Medical Marijuana: Research Not Anecdotes

For patients with cancer, marijuana may be valuable in controlling pain and chemotherapy-induced nausea and vomiting. Furthermore, it may have efficacy as an appetite stimulant. No randomized clinical trial has investigated the utility of whole-plant medical marijuana to alleviate these symptoms in patients with cancer, however. Research by clinical and basic scientists in the United States is needed to identify the appropriate dose of the drug and its appropriate use in symptom and disease management. First, however, the federal government needs to remove marijuana from a schedule I category in the Federal Controlled Substances Act so that such research can be performed.

Marijuana has been used by man for thousands of years. It has been smoked, eaten, vaped, and rubbed, but never thoroughly studied in clinical or basic science research. Medical marijuana is the only drug that is available to millions of Americans who live in states where adult use is legal. This is despite the fact that the drug has not received U.S. government approval. In 1973, when President Richard Nixon declared a war on drugs and expanded the U.S. Food and Drug Administration (FDA), the marijuana plant was classified as a schedule I drug among far more dangerous drugs (ie, heroin and LSD). Schedule I drugs are those having no currently accepted medical use in the United States, a lack of accepted safety for use under medical supervision, and a high potential for abuse.

Reputation as ‘Gateway Drug’ Lingers

The declaration of marijuana as a “gateway drug” has further vilified it. Even though the Institute of Medicine has refuted the myth of marijuana being a gateway drug, its reputation as such lingers. In 1999, the Institute of Medicine stated: “There is no conclusive evidence that the drug effects of marijuana are causally linked to the subsequent abuse of other illicit drugs.1” But research from Israel has started not only to dispute many of the unproven (yet promoted by many), unfounded pronouncements about marijuana, and it has begun to define advantages of the chemicals within the marijuana plant.2

OF NOTE

FDA Controlled Substance Schedules

·       Drugs and other substances that are considered controlled substances under the Controlled
Substances Act are divided into five schedules (I to V).

Schedule I Controlled Substances

·       Substances in schedule I have no currently accepted medical use in the United States, a lack of accepted safety for use under medical supervision, and a high potential for abuse.

·       Some examples of substances listed in Schedule I are heroin, LSD, and marijuana (cannabis).

·       For more information, visit https://www.deadiversion.usdoj.gov/
schedules.

The National Institute on Drug Abuse has promoted some sobering data about marijuana, purporting that 30% of those who use marijuana may have some degree of marijuana use disorder. People who begin using marijuana before the age of 18 are four to seven times more likely to develop a marijuana use disorder than adults. Estimates of the number of people addicted to marijuana are controversial, in part because epidemiologic studies of substance use often consider dependence as a proxy for addiction, even though it is possible to be dependent without being addicted.3 Furthermore, the National Institute on Drug Abuse quoted studies suggesting 9% of people who use marijuana will become dependent on it, rising to about 17% in those who start using marijuana in their teens.4

In 2015, about 4 million people in the United States met the diagnostic criteria for a marijuana use disorder, but just 138,000 of these individuals voluntarily sought treatment for their marijuana use.4,5

Closer Look at the Science

Humans have an endocannabinoid system that affects nearly all parts of the body. This system is a network of receptors spread throughout the entire body that control some of the most vital functions, including the immune system, memory, appetite, sleep, mood, and pain sensation. Receptors have also been found to impact metabolism, movement, temperature, learning, inflammation, neural development, neuroprotection, cardiovascular function, digestion, and reproduction. Thus, it is understandable why many research and clinical scientists are eager to have the federal classification of marijuana as a schedule I drug be removed so a thorough understanding of the substance could be achieved through research.

Understanding Marijuana

There are two broad species of marijuana: one is Cannabis indica, from which hemp is made, and the other is Cannabis sativa, which contains its halogenic properties. Within the marijuana plant, there are nearly 110 different chemicals. The chemicals familiar to most are halogenic tetrahydrocannabinol (THC or CB1), the cannabinol (CBN or CB2), and the mixed chemical, which has a powerful impact on both receptors, cannabidiol (CBD). There are many other chemicals within this family and subgroups as well, but I will focus on the common drug effects of these familiar chemicals.

Common effects of tetrahydrocannabinol are euphoria and relaxation, sleep and drowsiness, appetite stimulant, pain relief, antiemetic, and muscle relaxant. The common effects of cannabidiol are antianxiety, neuroprotective, anticonvulsant, antipsychotic, pain relief, and anti-inflammatory. Thus, different concentrations of tetrahydrocannabinol or cannabidiol in the product to be consumed will cause a different effect on a patient’s diseases or symptoms.

For patients with cancer, marijuana may be helpful in controlling pain and chemotherapy-induced nausea and vomiting. Furthermore, it may have efficacy as an appetite stimulant.

Furthermore, the Institute of Medicine studied available data and stated there is conclusive evidence that cannabis has a therapeutic effect on chronic pain, multiple sclerosis muscle spasms, as well as chemotherapy-induced nausea and vomiting, and it does not cause cancer.6 The Institute of Medicine also noted that there is no conclusive evidence that marijuana reduces, causes, improves, or worsens heart attacks, strokes, diabetes, respiratory diseases, immune competence, and testicular cancer.7 Marijuana is, however, potentially detrimental to mental health (schizophrenia, social anxiety disorders, depression) as well as prenatal, perinatal, and neonatal care. It is also detrimental to driving.

Marijuana and the Opioid Crisis

Cannabis may be helpful in the socially devasting opioid crisis. The statistics are frightening: In 2017, more than 64,000 Americans died of a drug overdose. More than 650,000 total prescriptions for opioids are written every day. The epidemic will continue in the months and years ahead without appropriate interventions to halt the widespread growth.

According to an article in JAMA Internal Medicine several years ago, “States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate compared with states without medical cannabis laws.”8 In addition, researchers from the University of California San Diego found that hospitalization rates of people suffering from opioid painkiller dependence and abuse dropped 23%, and opioid overdoses requiring hospitalization fell 13%, in states after marijuana was permitted for medicinal purposes.9 A more recent study in Colorado, which legalized marijuana in 2014, demonstrated a 6.5% reduction in opioid-related deaths after recreational marijuana was legalized in the state.10Nationwide, more than 4,000 lives might be saved if marijuana were available and used as a substitute for opioids.

Medical marijuana is currently available to approximately 200,000 million Americans who live in states where adult-use marijuana is legal, approximately 20% of Americans.11 The plea from many patients, providers, and governmental officials is fundamentally the same: Remove marijuana from a schedule 1 category in the Federal Controlled Substances Act so research can be performed by clinical and basic scientists in the United States. Only then will clinicians be able to prescribe a drug that is already available to millions of Americans in an evidence-based manner, in the right dose, and for the right symptoms and diseases. ■

Dr. Boxer, a urologist practicing in Los Angeles, is affiliated with VA Greater Los Angeles Healthcare System. He also is Medical Director of iAnthus Capital.

DISCLOSURE: Dr. Boxer is Medical Director of iAnthus Capital, a company that raises capital and invests in marijuana-licensed companies.

DISCLAIMER: The views expressed herein are those of the author and not necessarily the views of ASCO or The ASCO Post.

REFERENCES

1. Institute of Medicine: Marijuana and Medicine: Assessing the Science Base. Joy JE, Watson SJ, Benson JA [Eds]. National Academy Press, Washington, DC, 1999. 

2. Abuhasira R, Schleider LB, Mechoulam R, et al: Epidemological characteristics, safety and efficacy of medical cannabis in the elderly. Eur J Intern Med 49:44-50, 2018.

3. National Institute on Drug Abuse: The neurobiology of drug addiction. Available at www.drugabuse.gov/publications/teaching-packets/neurobiology-drug-addiction/section-iii-action-heroin-morphine/10-addiction-vs-dependence. Accessed August 6, 2018.

4. National Institute on Drug Abuse: Is marijuana addictive? Available at www.drugabuse.gov/publications/research-reports-mariuana/marijuana-addictive. Accessed August 6, 2018.

5. National Institutes of Health: Marijuana use disorder is common and often untreated. Available at www.nih.gov/news-events/news-releases/marijuana-use-disorder-common-often-untreated. Accessed August 6, 2018.

6. National Academics of Sciences, Engineering, and Medicine: The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research (2017). Available at www.ncbi.nlm.nih.gov/books/NBK425767//. Accessed August 6, 2018.

7. National Academics of Sciences, Engineering, and Medicine: Nearly 100 conclusions on the health effects of marijuana and cannabis-derived products presented in New Report: One of the most comprehensive studies of recent research on health effects of recreational and therapeutic use of cannabis and cannabis-derived products. Available at www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=24625. Accessed August 6, 2018.

8. Bachhuber MA, Saloner B, Cunningham CO, et al: Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Intern Med 174:1668-1673, 2014.

9. Cohen R: Would legalizing medical marijuana help curb the opioid epidemic? Reuters Health News, March 27, 2017. Available at https://www.reuters.com/article/us-health-addiction-medical-marijuana/would-legalizing-medical-marijuana-help-curb-the-opioid-epidemic-idUSKBN16Y2HV. Accessed August 6, 2018.

10. Livingston MD, Barnett TE, Delcher C, et al: Recreational cannabis legalization and opioid-related deaths in Colorado, 2000-2015. Am J Public Health 107:1827-1829, 2017.

11. Hudak J: Marijuana: A Short History. Brookings Institute, Washington, DC, 2016.

Telemedicine in Urology and Nephrology

Telemedicine in Urology and Nephrology

Richard James Boxer*

1Department of Urology, UCLA Medical School, USA

*Corresponding author: Richard James Boxer, Department of Urology, UCLA Medical School, USA, Email: richard.boxer1@gmail.com

Submission:  September 09, 2017; Published:  October 02, 2017

DOI: 10.31031/ETUN.2017.01.000502
Volume1 Issue1

Telemedicine is the greatest advance in the US to improving access to care. The use of this technology in urology and nephrology has allowed tens of thousands of patients to gain consultations regardless of whether they are in urban or rural areas.

Connected health is the umbrella term that includes telehealth, e-health, m-health, and telemedicine. The technology is quite simple: using video-conferencing, email, smart phones, handheld wireless technology such as tablets, or any other devices that allow instant communication. Tele-urology and tele-nephrology bring expert consultations to patients otherwise unable to get them. In addition, specialists can remotely consult with colleagues to obtain information to improve the quality of care for their patients.

The technology that is available today is helping bring about a fundamental change in U.S. health care. The current system of bringing patients to health care is changing because of technology. With innovations such as videoconferencing, telephone-based care management, and automated symptom monitoring, high-quality health care is becoming much more convenient and much more affordable, and providing greater access to care. Now, it is possible to bring health care to the patient instead of bringing the patient to health care. There is no scenario of the future of health care without connected health.

Better access to care

Interactive videoconferencing and Internet-based technologies are allowing physicians from a variety of specialties, including oncology, cardiology, urology, nephrology, dermatology, and neurology, to provide access to medical care to larger segments of the population, regardless of where patients are located. Currently, while a large number of people in the U.S. receive outstanding health care, it is often very expensive and inconvenient to access. And there are still tens of millions more Americans who don’t have access to the best specialists. Telemedicine provides patients with urologic and renal diseases greater access to better care.

For example, there is substantial evidence that outcomes are worse in rural or remote areas of the country. Telemedicine can decrease the travel burden on these patients thus giving them the opportunity to access state-of-the-art care.

In addition, Internet-based technologies, such as patient Web portals, will enable patients to learn more about their disease and treatment and how to manage their care, connect with providers, and receive social support through online support groups.

Remote Services

Go to

If a person is worried about a possible prostate cancer, for example, and can’t get a urologist for a diagnosis, he can upload any data points such as lab or images to his doctor’s office, and the physician and consulting urologist may make a decision about whether the patient needs to come to the office for an in-person consultation.

For patients with renal insufficiency who need to be monitored by their nephrologist, but either live long distances from their medical center or don’t need or cannot be physically in the nephrologists office, the nephrology team is able to virtually visit the patient in the patient’s home.

Alleviating the workforce shortage

Telemedicine has reduced the shortage of primary care physicians, where the workforce shortage is even greater than specialists. Currently, there is a disconnect between where the physician is located and where the patient is located. That disconnect can be reversed through telemedicine, through videoconferencing or telephone-based care management.

The technology of connected health increases the number of available time slots a doctor may use to care for patients. One of the great inefficiencies in medicine is that the doctor and the patient are disconnected through time or physical distance. Each appointment slot in a doctor’s office calendar that is not filled due to cancellations or inefficient scheduling results in another patient not receiving medical care. If these empty appointment slots can be filled with a virtual office visit, the doctor’s time is efficiently used and patients receive care.

In addition, the technology allows other populations of physicians, such as retired, disabled, or stay-at-home moms and dads, to continue to use their medical expertise by practicing medicine as virtual consultants as long as they maintain their board certification and keep current through CME courses.

Growth potential

The application is just beginning in urology and nephrology. I have a tele-urology practice that is located at the West Los Angeles Veterans Hospital. I have a greater than 95% satisfaction rate because the patients receive a consultation without having to be transported 3-5 hours in each direction for a 20 minute consultation. In primary care practice, there are about 200,000 telemedicine consultations a month in the U.S. vs 80 million inperson medical consultations each month, so the sky is the limit in terms of telemedicine growth potential.

In urology and nephrology, the use of communications technology can facilitate second opinions for patients seeking confirmation of their diagnosis or proposed treatment plan. There are companies specializing in obtaining remote second opinions. Patients upload their medical data to the company’s server, the company contacts and pays a world-class consulting specialists, and then the patients have a videoconferencing or telephonic interaction within a couple of days of their request. Individual or group practices of specialists can easily form their own telemedicine practice that generates income and referrals.

Both public and private insurance pays for telemedicine consultations. Careful documentation is, as always in medical practice, required.

The opportunities for any urologist or nephrologist to offer first or second opinions are nearly endless. In the near future every medical office, especially medical specialists’ offices, will have a dedicated room for virtual consults.

Supplementary care

Telemedicine is not meant to replace the physical interaction between the patient and doctor. The first interaction between a patient and the specialist does not necessarily always in-person. However, the patient must see a primary care physician prior to receiving a specialist consultation. The use of telecommunications technologies is reserved for follow-up, initial specialty (but followed up by in-person visit, second opinion, and supportive care.

Specialists commonly have nurse practitioners, physician assistants, nutritionists, various therapists, social workers, and other professionals on their oncology team. Any of these professionals could perform virtual patient care, but the initial interaction must be by the specialist.

Cost Issues

Go to

Bringing virtual health care to the patient reduces brickand- mortar overhead and increases efficiencies for improved access to care. Everyone wins in the connected health scenario. Patients receive rapid access to appropriate care, more doctors are immediately introduced into the system, and potentially reversing the dire predictions of workforce shortages, and physicians are better compensated for improved efficiencies.

Wall Street Journal: Can Marijuana Alleviate the Opioid Crisis?

Can Marijuana Alleviate the Opioid Crisis?

The federal government should stop blocking research into the drug’s medical potential.

By 

Richard Boxer

Nov. 19, 2017 1:23 p.m. ET

Jennifer, a 37-year-old Virginia school teacher now unable to work due to unrelenting pain caused by a genetic spinal disease, stared hopelessly at the bottle of opioids her doctor had prescribed her. Beset by desperation discomfort, she faced a difficult choice. The opioids would provide limited relief but came with a high risk of addiction. Or she could try marijuana, which would likely be safer but put her on the wrong side of the law.

Jennifer chose marijuana. She drove to Washington, D.C., where the drug is sold legally, and visited three medical marijuana storefronts offering ridiculously named products like “Kush,” “Diesel” and “Head Trip.” While the offerings were of unknown concentrations and efficacy for her pain, they worked to a greater degree and with fewer side effects than any previous medication Jennifer had tried. Her experience (she is the daughter of a patient in Los Angeles, where I practice) inspired me to advocate for further research into clinical uses of the drug for pain relief.

For the most part, doctors and patients rely on anecdotal information when deciding on a treatment path involving cannabinoids. No rigorous scientific studies have been published that corroborate claims about marijuana’s medical benefits when prescribed and used properly. The federal government should remove the drug from Schedule I of the Federal Controlled Substances Act so researchers can lawfully assess its medical potential.

In September, Sen. Orrin Hatch introduced a bill “to improve the process for conducting scientific research on marijuana as a safe and effective medical treatment.” The Marijuana Effective Drug Study Act of 2017 has bipartisan support. “To be blunt, we need to remove the administrative barriers preventing legitimate research into medical marijuana,” Sen. Hatch said in a press release.

Any research on medical marijuana must first assess the potential for addiction to other, harder drugs. The notion that marijuana is a “gateway” is so far unsupported. “There is no conclusive evidence that the drug effects of marijuana are causally linked to the subsequent abuse of other illicit drugs,” wrote researchers for the Institute of Medicine in 1999. Still, the idea lives on, underscoring the need for real research.

Not only is marijuana a potentially effective pain treatment, it may also help alleviate the opioid crisis. States that have legalized medical marijuana enjoy significantly lower levels of opioid consumption and overdose deaths than states that continue to penalize possession and use, according to the Journal of the American Medical Association: “States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate . . . compared with states without medical cannabis laws.”

Researchers from the University of California, San Diego found that hospitalization rates of people suffering from painkiller abuse and addiction dropped 23% and overdoses requiring hospitalization fell 13% in places where medical marijuana was made legal. And a recent study found that Colorado, which legalized the drug for recreational use in 2014, experienced a 6.5% reduction in opioid-related deaths.

Last year alone, more than 64,000 Americans died from drug overdoses. Recognizing the link between decriminalizing marijuana and reducing opioid overdoses could save thousands of lives. With 650,000 prescriptions for opioids filled each day (3,900 for new patients) the epidemic seems likely to continue. Although scientific proof is no guarantee of an end to partisan squabbling, evidence-based medical data may offer hope for a consensus about the effectiveness of cannabis in the alleviation of human suffering.

Jennifer is not a criminal. She uses marijuana to relieve her debilitating pain because it is effective, non-addictive and almost impossible to overdose on. By preventing essential research on the medical uses of the drug, the federal government forces Jennifer, and thousands like her, into an impossible position.

Dr. Richard Boxer is a clinical professor at UCLA’s David Geffen School of Medicine and medical adviser to iAnthus Capital Management, which invests in the cannabis industry.

 

Achieving Universal Coverage Without Turning to a Single Payer Lessons From 3 Other Countries

JAMA

http://jamanetwork.com/journals/jama/fullarticle/2607482

Viewpoint

February 27, 2017

Regina E. Herzlinger, DBA1; Barak D. Richman, JD, PhD2; Richard J. Boxer, MD3

The most popular parts of the Affordable Care Act (ACA) are the most expensive. Universal coverage is a top priority not only for Democrats but also for President Trump. Both Republicans and Democrats want to preserve many costly coverage features of the ACA, including those that prevent insurers from precluding people with preexisting conditions and those that eliminate lifetime or annual coverage limits. The challenge is how to preserve these features and make insurance affordable.

A primary obstacle to achieving affordable universal coverage is the high costs of those with diseases or costly traumatic events—approximately 20% of individuals accounting for approximately 80% of health care spending.1So, a key question is how to pay for their care.

Some nations in the Organisation for Economic Co-operation and Development (OECD) rely on a governmental single-payer model to achieve universal coverage, but this approach is politically infeasible in the United States. As the United States relies on private-sector insurance, 3 other countries that use private-sector insurance to offer affordable universal coverage provide some potentially helpful lessons.

Paying for Costly Patients

Some advocate creating risk pools for enrollees with preexisting conditions. This strategy removes individuals with high health care costs from the broad pool of enrollees and uses government funds to subsidize their insurance premiums. In turn, the cost of insurance is substantially reduced for the rest of those who are insured.

This strategy, however, requires substantial infusions of funds. In 2016, the costliest 5% of patients younger than 65 years (the age before Medicare begins) accounted for nearly 50% of all expenditures for that age group,2 yet their insurance premiums can realistically cover only a small fraction of their costs. Accordingly, when states experimented with high-risk pools before the ACA, the costs proved to be unsustainable: net losses for 35 state high-risk pools combined were more than $1.2 billion, or $5510 per enrollee, in 2011.3 The expenses forced states to limit enrollment in these high-risk pools, leaving out many costly patients. By the time the ACA was implemented, the combined enrollment in 35 state high-risk pools included only about 2% of non–group health insurance participants. By comparison, a recent report estimated that 27% of individuals in the United States younger than 65 years have health conditions “that would likely leave them uninsurable if they applied for individual market coverage under pre-ACA underwriting practices.”4

If high-risk pools are part of the solution to attaining universal coverage, federal funding is essential. But federal policy makers are unlikely to commit a sufficient amount of funds to make this approach successful. One plan proposes $25 billion in state grants over 10 years to fund high-risk pools, but this sum is likely insufficient considering that insurance companies received $8 billion from the federal government through the ACA in 2014 and 2015 in reinsurance payouts for their costliest ACA patients.5

Another strategy to pool costly patients would channel them into Medicare and rely on the federal government as the ultimate risk bearer. But Medicare premiums are artificially controlled by passing some present spending onto future generations. Trustees project Medicare’s 75-year total spending in excess of dedicated revenues at $27.9 trillion, and the Centers for Medicare & Medicaid Services Office of the Actuary projects this amount at $36.8 trillion.6 Adding costly individuals to Medicare would only exacerbate these intergenerational problems.

This leaves a third strategy: the individual mandate—or as the Supreme Court characterized it, an annual tax assessed against individuals who have not purchased qualified health insurance within the calendar year. Although vilified by some, the mandate is attractive for several reasons. It is relatively easy to implement, is effective in pooling risk, and reflects the values of individual responsibility. Coverage is primarily funded by the enrollees rather than by general taxation. For these reasons, some nations that are committed to a private health insurance sector have achieved universal coverage and effective risk pooling by mandating the purchase of insurance.

Examples of the Individual Mandate and Penalties

Switzerland, Singapore, and Germany have achieved universal coverage and made insurance affordable even for their citizens with highest health care costs by instituting an individual mandate. One major difference, however, is that unlike the ACA, the mandates instituted by these countries are reinforced with effective penalties for nonparticipation, thus ensuring that lower-cost enrollees—generally healthier individuals—balance out the costs of the others who require more medical resources.

• In Switzerland, citizens must purchase health insurance. If they do not, government authorities automatically enroll them, selecting the insurance provider on the individuals’ behalf. Moreover, insurers can implement debt enforcement proceedings against anyone failing to pay their premiums and collect a penalty in addition to back premiums. The Swiss government subsidizes premium payments for more than a quarter of the population, including retirees who purchase the same insurance as workers.

• Singapore institutes compulsory contributions from employers on behalf of their employees to create medical savings accounts. Employees maintain these accounts for health care expenses such as health and disability insurance premiums, hospitalization, surgery, rehabilitation, end-of-life care, and outpatient services. Those failing to pay their premiums are subject to garnished wages and other legal actions that can force payment of back premiums, penalties, and interest. Unemployed or low-income individuals are eligible for government subsidies that enable them to pay for the premiums.

• In Germany, insurance is funded by compulsory contributions to private insurers levied as 7.3% of income. Unemployed individuals have their contribution taken out of their unemployment benefits coupled with means-based sliding-scale subsidies, and uninsured self-employed persons who later attempt to purchase insurance face payment of back premiums for the period in which they were uninsured.

To be sure, these health care systems differ from that in the United States in other important ways. For instance, all allow individual tax deductions for health insurance expenditures and thus have evolved from an employer-based to a consumer-based system, whereas the United States limits the individual market with constraints on such deductions. In addition, these countries have many more insurers than the United States, and consumers benefit from vigorous competition among them.7 Germany in 2015, for example, had 124 sickness funds and 42 private health insurance companies, and the average resident of Switzerland in 2011 could choose from 59 health insurers offering coverage, with the 5 largest insurers covering 43% of the population. By comparison, in California, a state with approximately half Germany’s population, only 7 firms covered more than 95% of privately insured individuals in 2011, with the 3 largest firms covering 75%. In Massachusetts, with a population slightly smaller than Switzerland’s, 3 insurance companies enrolled 79% of individuals with private insurance.

As with the ACA, these nations provide financial support for insurance mandate purchases. Singaporean employers contribute to their employees’ medical savings accounts, and German employers match their employees’ payroll contributions to insurance premiums.

In sum, health insurance models in Switzerland, Singapore, and Germany suggest that an individual mandate, with adequate subsidies, can achieve affordable universal coverage. But the recipe for their success also includes firm penalties. They also suggest that the ACA’s individual mandate failed to pool risk adequately, in large part because its penalties were too weak. In 2014, approximately 7.5 million individuals paid the penalty rather than purchasing insurance, and of the approximately 15 million uninsured people who were ineligible for Medicaid, an estimated 7.1 million would pay a penalty lower than the cost of the least expensive plan.8 The Internal Revenue Service’s recent announcement that, to comply with President Trump’s January 20, 2017, executive order rolling back the ACA, it might not pursue individuals who fail to provide evidence of health insurance will further dilute the current individual mandate.9 Achieving universal coverage, like these 3 nations, requires a more forceful approach.

Conclusions

Although insurance mandates and penalties may seem unattractive, policies that induce citizens to purchase insurance are as old as the republic and as common as the most popular programs. In 1790, President George Washington required that ship owners purchase medical insurance for their seamen, and Medicare has long assessed penalties on healthy people who do not enroll by age 65 years. If the goal is universal health coverage that provides care even for patients with the highest health care costs without relying on public insurance programs, the financial burden must be spread across the whole population. This requires either massive government spending, whether through high-risk pools or Medicare, or requiring individuals to purchase insurance.

It is time to stabilize the premiums of the universal insurance market by neutralizing the political disagreements surrounding the ACA’s mandate and penalties. As these 3 countries demonstrate, maintaining the popular aspects of the ACA requires keeping its less popular part, and achieving the stated goal of universal coverage requires a serious commitment to individual responsibility.

Article Information

Corresponding Author: Richard J. Boxer, MD, David Geffen School of Medicine at UCLA, 1143 Linda Flora Dr, Los Angeles, CA 90049 (rboxer@mednet.ucla.edu).

Published Online: February 27, 2017. doi:10.1001/jama.2017.1475

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Herzlinger reported owning shares in some health care firms as part of broad diversified investment portfolios. No other disclosures were reported.

References

1.National Institute for Health Care Management. The concentration of health care spending.https://www.nihcm.org/pdf/DataBrief3%20Final.pdf. Published July 2012. Accessed February 15, 2017.

2.Mitchell  EM. Concentration of Health Expenditures in the US Civilian Noninstitutionalized Population, 2014. Rockville, MD: Agency for Healthcare Research & Quality; 2016.https://meps.ahrq.gov/data_files/publications/st497/stat497.pdf. Accessed February 3, 2017.

3.Riley  T, Cardwell  A. High risk pools déjà vu—lessons from states, questions for policymakers.http://www.nashp.org/high-risk-pools-deja-vu-lessons-from-states-questions-for-policymakers/#_ftnref3. Published January 31, 2017. Accessed February 15, 2017.

4.Claxton  G, Cox  C, Damico  A, Levitt  L, Pollitz  K. Pre-existing conditions and medical underwriting in the individual insurance market prior to the ACA.http://kff.org/health-reform/issue-brief/pre-existing-conditions-and-medical-underwriting-in-the-individual-insurance-market-prior-to-the-aca/. Published December 12, 2016. Accessed February 3, 2017.

5.Herman  B. CMS readies $7.7 billion for ACA reinsurance payouts. Modern Healthcare.http://www.modernhealthcare.com/article/20160212/NEWS/160219952. Published February 12, 2016. Accessed January 26, 2017.

6Senate Republican Finance Committee Staff. 2015 Medicare/Social Security Trustees’ report analysis.https://www.finance.senate.gov/imo/media/doc/2015%20Trustees%20Report%20SS%20Medicare.pdf. Accessed January 26, 2017.

7.Blümel  M, Busse  R. The German Health Care System, 2015. In: Mossialos E, Wenz M, Osborn R, Sarnak D, eds. 2015 International Profiles of Health Care Systems. New York, NY: Commonwealth Fund; 2016:69-70.http://www.commonwealthfund.org/~/media/files/publications/fund-report/2016/jan/1857_mossialos_intl_profiles_2015_v7.pdf. Accessed February 6, 2017.

8.Rae  M, Damico  A, Cox  C, Claxton  G, Levitt  L. The cost of the individual mandate penalty for the remaining uninsured.http://kff.org/health-reform/issue-brief/the-cost-of-the-individual-mandate-penalty-for-the-remaining-uninsured/. Published December 9, 2015. Accessed January 26, 2017.

9.Suderman  P. Major blow to Obamacare mandate: IRS won’t reject tax returns that don’t answer health insurance question.http://reason.com/blog/2017/02/14/irs-blow-to-obamacare-individual-mandate. Published February 14, 2017. Accessed February 16, 2017.

Wall Street Journal: It’ll Take More Than a Band-Aid to Fix Medicaid: Save the program by giving states money to provide high-deductible plans with health savings accounts.

By   REGINA HERZLINGER and RICHARD BOXER

Feb. 5, 2017 6:12 p.m. ET

One of the most fraught questions in Donald Trump’s Washington is how Republicans will reform health care. No aspect of the debate over ObamaCare presents as much risk, or opportunity, as what to do with the law’s expansion of Medicaid, which gave government health insurance to millions of Americans. It won’t be easy, but President Trump and Congress have an opportunity to control Medicaid costs, improve the health of enrollees—and also win bipartisan support.

Republicans should combine two ideas popular in their party: block grants and health savings accounts. The former would let states tailor their Medicaid policies to their local communities, while the latter would give enrollees the ability to choose their own insurers and providers. In essence, Washington could give the states Medicaid block grants, allocated per capita, to provide beneficiaries with high-deductible insurance and health savings accounts.

Premiums on ObamaCare’s insurance exchanges are rising in part because so few providers participate. Our plan would allow Medicaid enrollees to shop for their high-deductible plans on exchanges. More people shopping would draw more insurers, thereby increasing competition and containing costs.

A 2015 study in the American Journal of Health Economics simulated what would have happened if all the insurers active on the exchanges in 2011 had participated statewide through 2014. The results? Premiums for silver coverage would have fallen by more than 10%, saving the government $1.7 billion in subsidies.

Health savings accounts, which force medical providers to compete for consumers who pay out of their own pocket, also reduce overall costs. When employers introduce such accounts, health-care costs are reduced by about 5% for each of the next three years, according to a 2015 study from the National Bureau of Economic Research.

Two years ago Indiana implemented a modified version of the program we propose, the Healthy Indiana Plan, or HIP 2.0. Comparing enrollees who used health savings accounts with those who didn’t showed that the former used more primary and preventive care, adhered better to their drug regimens, missed fewer appointments and showed up less frequently at the emergency room.

Although the Hoosier State’s “basic” traditional Medicaid was free, those in HIP 2.0 were charged 2% of their income but did not have to make copayments. If payments weren’t made for six months they would lose insurance. Yet the program remained popular: 70% of enrollees contributed and 86% described themselves as satisfied, according to a survey from the Lewin Group last summer.As more data are gathered, policy makers can better understand what beneficiaries want and how Medicaid dollars can be efficiently spent to meet their health needs.

Combining high-deductible plans and health savings accounts could also improve the health of enrollees. Current Medicaid coverage overemphasizes costly treatments. Duke University professor Barak Richman has long argued that the program doesn’t take full advantage of low-cost, high-value services, such as home care. Demonstration projects such as Medicaid’s Cash and Counseling program have shown that beneficiaries can fulfill unmet needs and improve their quality of life when they have more control over their medical dollars.

The high-deductible plan should be required to cover preventive care, as well as maintenance medications. And as with other health savings accounts, unspent funds could be rolled over to the next year or used for purchases beyond prescribed medical expenditures.

Current Medicaid rules also often pay for services that beneficiaries find unnecessary. For example, a 2015 paper for the National Bureau of Economic Research found that Oregon recipients gained only 20 to 40 cents in value for services that cost Medicaid $1. The integrity of the Medicaid program depends on bringing real value to its beneficiaries.

Democrats often say that block grants allow states to divert federal dollars away from Medicaid beneficiaries. But allocating the funds directly to beneficiaries through health savings accounts should allay concerns and draw more moderate Democrats to support the reform.

Combining high-deducible insurance plans and health savings accounts—and block-granting them per capita for use on exchanges—isn’t the sexiest proposal. But it would allocate scarce dollars more efficiently, address the nexus of poverty and illness, and make insurance markets work again. It could also pass even in a deeply divided Congress.

Ms. Herzlinger is a professor of business administration at Harvard Business School. Dr. Boxer is a professor at the UCLA School of Medicine.

Making the ACA Affordable — bipartisan lessons from abroad

Making the ACA Affordable — bipartisan lessons from abroad

BY REGINA HERZLINGER, ERIC BALDWIN AND RICHARD BOXER

The Hill - 12/21/16 12:20 PM EST

The two major barriers to maintaining the portions of the Affordable Care Act (ACA) that are widely popular — even among Republicans — are its sky high costs and the bitter partisan rancor about how to fix them.

We can learn how to attain bipartisan solutions for universal health care coverage at reasonable costs from three other countries whose healthcare systems are similar to the ACA’s: Switzerland, Germany, and Singapore.

Each has achieved universal access to high-quality healthcare at significantly lower costs than in the U.S., and has done so largely through private insurance, rather than a governmental single-payer system, currently a non-starter in the U.S. They have accomplished this by balancing a commitment to individual responsibility and choice with solidarity.

A successful ACA must have these features. Its high costs have occurred in large part because many younger, healthier people could readily opt out, and did so. 

Only 28 percent of those purchasing health care through the ACA marketplaces for 2016 were young adults (aged 18-34), significantly less than the 38 percent the Obama administration estimated were needed to enable insurers to charge reasonable premiums and earn reasonable profits.

Many Americans — some 5.6 million in 2015 — instead opted to pay the penalty for being uninsured, currently set at about $700, but averaging $442 after subsidies, and 10 percent for the non-subsidized.

Combined with the ACA’s prohibitions against denying coverage or basing premiums on subscriber's health — popular aspects of the law that President-elect Trump has signaled he wants to maintain — an older, sicker, high cost population is enrolled in the ACA.

Insurers that found it difficult to earn a reasonable profit on individual plans exited the marketplace or aggressively raised premiums. Higher premiums and less insurance plan choices make it even more likely that younger, healthier people will avoid purchasing insurance. The remaining sickly insurance pool will inevitably require additional, massive public funding.

The Germans and Swiss show us how to avoid this problem. When they opted for a system funded through private insurance purchased directly by individuals and families, like that of the ACA, they understood that the costs of a health insurance system could be managed only if it required participation by all and exacted stiff penalties for non-participation.

The Swiss must buy health insurance from a large number of private insurers. If they do not, government authorities automatically and swiftly enroll them, selecting the insurance provider on the individual's’ behalf. Insurers can implement debt enforcement proceedings against anyone failing to pay their premiums, including court proceedings and asset seizure. They are also assessed a penalty in addition to their back premiums. Poorer residents receive subsidies— the Republicans would do this as tax credits — to help pay their premiums, representing almost 16 percent of 2014 payments.

Germany’s insurance is funded by compulsory contributions to private insurers levied as a fixed percentage of income taken from workers’ wages with the employee and employer each contributing half, akin to the payroll tax in the U.S.

Employees pay a maximum of 7.3 percent of their income for insurance premiums and d cost-sharing is capped at two percent of household income. The unemployed have their contribution taken out of their unemployment benefits. Uninsured self-employed persons who later attempt to purchase insurance face payment of back premiums for the period they were uninsured, thus discouraging the healthy from gaming the system.

About eight percent of the population receives some means-tested subsidies to assist with premium payments, and government premium subsidies accounted for less than four percent of healthcare financing.

Both countries feature the competitive insurance markets Republicans favor: there are 124 insurers in Germany and 61 in Switzerland, a much greater choice than Americans have. Individuals directly choose their insurer and plan, which must compete on quality, service, and (in Switzerland) structure and price. Not surprisingly, the healthcare costs of these high-income countries, as a percentage of GDP, are significantly lower than ours and the CAGR of per capita health care cost relative to GDP is the lowest among developed European countries.

Singapore has also achieved universal coverage at low cost — less than five percent of 2014 GDP — by balancing mandated health insurance purchase with vigorous commitment to the Health Savings Accounts Republicans favor.  Compulsory tax-free contributions from employers and employees maintain adequate balances. Account funds can be used for healthcare expenses such as health insurance and disability insurance premiums, hospitalization, surgery, rehabilitation, end-of-life care, and outpatient services. Premiums are kept low because the insurance plans include significant cost-sharing, in keeping with the commitment to personal responsibility.

As in Switzerland and Germany, the government of Singapore has outlined strong recovery measures for those failing to pay their premiums, including garnishing wages; subtracting arrears from any payouts made on hospitalization claims; recovering funds from any government payments made to the defaulter; taking court action to recover back premiums; and imposing financial penalties, including interest.    

As these countries demonstrate, maintaining the popular aspects of the ACA in a cost-controlled way requires commitment to individual responsibility and choice along with a commitment to solidarity. Although these values are sometimes identified as conservative or liberal, as the examples of Switzerland, Germany, and Singapore show, they are shared by people around the world. 

Indeed, the Republicans are already back-dooring their way toward universal coverage with proposed tax credits for the uninsured and high risk pools for the sick. By balancing these values, both parties can work together to implement universal healthcare access at reasonable cost. If they do, we might finally see a demonstration of effective Congressional collaboration.

Regina Herzlinger is a Harvard Business School professor, she was the first woman to be tenured and chaired at Harvard Business School and the first to serve on many established and start up corporate healthcare /medical technology boards. Richard Boxer is an attending urologist with the Los Angeles Veterans Administration Hospital and Voluntary Professor of Urology at UCLA. Stephen Bonner is the former CEO of Cancer Treatment Centers of America.

New York Times OP-ED Nov. 2, 2016 "How Health Care Hurts Your Paycheck"

New York Times

OP-ED

How Health Care Hurts Your Paycheck

By REGINA E. HERZLINGER, BARAK D. RICHMAN and RICHARD J. BOXER

NOV. 2, 2016

If there is a coherent theme to this year’s election, it is the growing economic frustration of working Americans. While trade has been the chief scapegoat, a major culprit has received much less attention: the rising cost of health insurance.

Recent news of large price increases for plans on the Affordable Care Act’s insurance exchanges was the latest example of an unsustainable trend. But those exchanges sell insurance to only about 12 million individuals. Most people with private health insurance, about 150 million individuals, receive coverage through employers. And for those people, prices have been rising for years.

A Kaiser Foundation report released in September explained that since 1999, health care premiums for employer-sponsored insurance programs have risen more than three times faster than wages. Today’s workers are paying an average of $18,000 for health insurance that covers fewer services each year, as employers shift costs to their employees through higher deductibles, co-payments and shares of premiums.

Unlike the plans purchased on insurance exchanges, where individuals pay directly for their policies, employers pay for most private health insurance on their employees’ behalf. Economics research suggests that for each dollar an employer spends on an employee’s health insurance premium, roughly one dollar is removed from that person’s take-home pay. But these costs remain hidden. Workers know their take-home pay has stagnated, but they may not attribute that stagnation to health care costs.

Workers have little control over this enormous expense made on their behalf. Most have few, if any, health insurance options and cannot trade dollars spent on insurance for higher take-home pay. They cannot shop around for or economize on what is probably their most expensive annual purchase. In turn, insurers are not pressured to offer more affordable insurance products.

A minor tweak to our tax code could go a long way to bring more choice, affordability and personal control to how workers purchase health insurance. Current law allows individuals to avoid taxes on money spent on insurance premiums only if their employers purchase insurance on their behalf. What if employers transferred to their employees the amount they now spend on coverage and the law allowed employees to deduct that spending from their taxes?

And what if those laws allowed employees to opt not to spend that entire sum on health insurance, but instead take some home as wages? If an employee in a marginal tax bracket of 25 percent were given an $18,000 budget to purchase insurance, but opted for a plan that costs only $14,000, she could take an additional $3,000, post-tax, home to her family.

This slight change would turn the economic tables for the millions of Americans who get health insurance through their employers. Abundant research has shown that low- and middle-income workers have a strong preference for low-cost plans, much more than what their employers currently offer. If workers know they can increase take-home wages by purchasing less expensive insurance, they will demand more insurance options, and insurers are likely to respond. To avoid the chance that cash-strapped families purchase inadequate plans, insurance plans would have to meet the Affordable Care Act’s minimum standards. The law’s requirement to purchase insurance, with penalties for non-purchase, would lessen the possibility that workers would keep all the money rather than buy insurance.

Freeing workers’ choices for insurance would also bring pressures on insurers to create new products that control costs, such as bundling of homeowners, auto and health insurances, or enabling people between 55 and 64 years old to access Medicare. State legislatures would feel similar pressures to adjust regulations to support competitive insurance marketplaces.

Stiffer competition and cost pressures on insurers, in turn, would force providers to offer more efficient care, such as by replacing outpatient and emergency room visits with telemedicine technology.

Our proposal charts a bipartisan path, bolstering the Democratic mandate for universal care working within the Affordable Care Act, while heeding the Republican call for competition and choice. It also presses further than the main presidential candidates. Hillary Clinton proposes reducing the cost of pharmaceuticals, eliminating taxes on high-end policies, improving cost transparency and allowing people over 55 to buy into Medicare. Donald J. Trump, who wants to repeal the Affordable Care Act, calls for creating tax-free health savings accounts and facilitating cross-state competition. Both recommend assorted tax credits. Each of these approaches aims to soften the effects of rising prices. But neither empowers workers to invigorate the marketplace and make prices more competitive.

America has prospered because it has harnessed the power of competitive markets to enable growth, and it is not hyperbole to say that middle-class disaffection threatens the very compact that generated this prosperity. Competitive markets do not merely force companies to act efficiently and produce valuable offerings. In assuring Americans that they can control their budgets and have a voice in their life decisions, they also serve as a reliable counterforce to the economic discontent that has roiled this election season.

Regina E. Herzlinger is a professor of business administration at Harvard University. Barak D. Richman is a professor of law and business administration at Duke University. Richard J. Boxer is a professor at the David Geffen School of Medicine at U.C.L.A.

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Using Telemedicine to Reduce Wait Times for Veterans

Although it’s not a replacement for all face-to-face care, telemedicine could make a significant impact for those with simpler needs.

John Farrow, a 67-year-old Vietnam veteran, had not been able to sleep for days. A week ago, his primary care doctor at his local outpatient Veterans Administration (VA) clinic told him that his prostate-specific antigen (PSA) blood level was rapidly increasing, and his prostate was abnormal on examination. His brother and father had similar findings years ago, and they had prostate cancer.

To learn more, Mr. Farrow (not his real name) would need to see a specialist in West Los Angeles, the closest fully staffed VA in the state. But to get there, he’d have to drive 5 hours from his home in Atascadero, California, and back.

Over the past year, the VA has been accused of wrongdoing, ranging from administrative inefficiency to straight-out fraud. According to reports, many veterans were made to wait for months before receiving care—delays that are thought to account for upward of a few dozen preventable deaths. Three of the patients had prostate and bladder diseases and died as a result of delay in treatments.

The unconscionable behavior of a few has thrown a shadow across the efforts of the dedicated caregivers who work in earnest to fulfill the VA’s stated mission: “To serve those who serve.” But it has also given us a chance to rethink how we approach our service in the future.

Amid this fallout, Congress has allocated an additional $15 billion to help the VA address these issues.1 The challenge now is in using that funding effectively and efficiently to reshape its approach to patient care.

The New World of Connected Health

One avenue the VA could take to modernize its operations, provide more patients timely care, maintain quality standards, and save money at the same time is telemedicine. The new world of connected health has given rise to novel approaches, ranging from the simple availability of doctors via instant chat to military applications allowing instantaneous response and relief for wounded soldiers. This technology let’s them contact teletrauma specialists directly from the field, drastically improving the odds of survival.

Thus far, the VA’s use of telemedicine has been effective but limited. At the West Los Angeles VA, a new teleurology clinic opened 18 months ago, allowing veterans to opt for private video consultations with board-certified physicians instead of in-person meetings. Already, these efforts have brought down wait times from an average of 7 weeks to about 1.5 weeks—an 85% decrease. Not only that, but it has also increased the number of initial patient visits by nearly 10%—a remarkable number considering that 3,000 veterans seek new urologic consultations at the West Los Angeles VA alone.

As any doctor will tell you, getting patients to come in sooner has a tremendous impact on their odds for survival before the illness progresses too far. Early diagnosis could mean the difference between a bad cough and pneumonia or between a sore leg and a pulmonary embolism.

Although it’s not a replacement for all face-to-face care, telemedicine could make a significant impact for those with simpler needs. Digital health care is just as effective as in-person care in these scenarios, according to the American Medical Association.

In 2016, nearly 100 million outpatient visits will occur at the VA.2 Included in that number are a projected 800,000 televisits across 44 specialties. Based upon studies in the private sector, where 80 million doctor visits occur each month, estimates show that as many as 30% of visits could be performed via technology.3 Thus, in the VA system, there will be less than 5% of the potential televisits.

Changing that ratio could mean not only that more veterans will be able to see doctors sooner, but that they may be more likely to see them in the first place. In the long haul, it could significantly expand veterans’ access to quality care and add efficiencies across the system.

Telemedicine in Action

For Mr. Farrow, the choice was easy to make.

After our 30-minute video session, I ultimately recommended that he receive a biopsy, followed by a telemedicine visit to discuss the results of the test. In the end, he came to Los Angeles for the procedure—an outcome that could have taken two 10-hour drives and another 6 weeks of waiting had he gone the traditional route. Removing that wait time allowed him to make up his mind more quickly—and to receive care more swiftly.

“He would not admit it, but the stress of not knowing immediately was nearly overwhelming,” Mrs. Farrow confided to me during the initial consultation. “I never saw him that way before. Now, I can tell there has been a cloud lifted from him.” ■

Disclosure: Dr. Boxer reported no potential conflicts of interest.

References

1. VA got $15B from Congress, 
still can’t fix problems. Newsmax. April 30, 2015. Available at http://www
.newsmax.com/Newsfront/va-billions-wait-times/2015/04/30/id/641658/. Accessed April 20, 2016.

2. U.S. Department of Veterans Affairs: Trends in the utilization of VA programs and services. Available athttp://www.va.gov/vetdata/docs/quickfacts/Utilization_trends_2012.pdf. Accessed April 20, 2016.

3. New England Healthcare Institute: A matter of urgency: Reducing emergency department overuse. An NEHI Research Brief, March 2010. Available at http://www.nehi.net/writable/
publication_files/file/nehi_ed_overuse_issue_brief_032610finaledits.pdf. Accessed April 20, 2016.

Vaccinations: Protect you and your community

Each year the Centers for Disease Control (CDC) encourages Americans to receive the flu vaccine to significantly reduce the chance of contracting the miserable illness that causes fever 100o F or higher, chills, muscle aches, cough, congestion, runny nose, headaches, sore throat, and fatigue.  The flu is not just an annoyance: More than 200,000 people are hospitalized in the United States from flu complications each year. The flu also can be deadly. Over a period of 30 years, between 1976 and 2006, estimates of yearly flu-associated deaths in the United States range from a low of about 3,000 to a high of about 49,000 people during the most severe season.

Most people who skip the influenza vaccination every year because of myths: they will never get the flu; the flu isn't dangerous; the vaccination gives you the flu; I will notget terribly sick from the flu if I'm infected.

Of all these reasons, only the last is true -- and only for a certain group of people. For healthy young adults, it is unlikely that the flu will be deadly or dangerous enough to require hospitalization. But there is an extremely good reason to get vaccinated:

Receiving the flu vaccine does more than provide a very high rate of immunity to you, it affords your loved ones and your entire community reduced chances of getting the flu.  The process of conferring immunity to those within a highly immunized population is called “herd” or community immunity. Even those who are not eligible for certain vaccines—such as infants, pregnant women, people allergic to eggs from which the vaccine is created, or immune-compromised individuals (AIDS, cancer) —get some protection because the spread of contagious disease is contained.

The principle of community immunity applies to control of a variety of contagious diseases, including influenza, measles, mumps, polio, and pneumococcal disease.

Reluctance to get a shot every year is part of the reason why national flu vaccination rates are so dismal -- about 40 percent of the country each year -- far below the 80 percent to 90 percent needed to achieve herd immunity and protect the most vulnerable in the population.

In the illustration  (http://www.vaccines.gov/basics/protection/) the top box depicts a community in which no one is immunized and an outbreak occurs. In the middle box, some of the population is immunized but not enough to confer community immunity. In the bottom box, a critical portion of the population is immunized, protecting most community members.

Diabetes, Demystified

Diabetes, Demystified

Diabetes is short for diabetes mellitus, meaning “sugar runs through,” which is a very appropriate name for the disease that affects nearly every vital organ in the body.

The two types of diabetes are:

Type 1: (formerly called juvenile-onset or insulin-dependent diabetes), accounts for 5 to 10% of those who have diabetes. In Type 1 diabetes, the body’s immune system destroys the cells that release insulin, eventually eliminating insulin production from the body. Without insulin, cells cannot absorb sugar (glucose), which they need to produce energy.

Type 2: (formerly called adult-onset or non-insulin-dependent diabetes) can develop at any age. It most commonly occurs in adulthood, although more children are developing the disease. Type 2 diabetes accounts for 90 to 95% of people who have diabetes. In Type 2 diabetes, the body becomes resistant to insulin produced by the body. As type 2 diabetes gets worse, the pancreasmay make less and less insulin. This is called insulin deficiency, and some patients then require insulin.

Both types of diabetes greatly increase a person’s risk for a range of serious complications. Although monitoring and managing the disease can prevent complications, diabetes remains the leading cause of blindness and kidney failure. It also continues to be a critical risk factor for heart disease, stroke, and foot or leg amputations.

Type 1 diabetes cannot be prevented. It may run in families and thus be genetic. However, Type 2 diabetes may be prevented or effectively treated by appropriate diet and body weight.

How is diabetes diagnosed?

The A1C test is a common blood test used to diagnose Type 1 and Type 2 diabetes and then to gauge how well the patient is being managed. Specifically, the A1C test measures what percentage of your hemoglobin — a protein in red blood cells that carries oxygen — is coated with sugar (glycated). The higher the A1C level, the poorer the blood sugar control and the higher your risk of diabetes complications.

It is essential that a person reduce the disease’s impact by always being vigilant to symptoms as well as being committed to a sensible diet. This is a full time job.

Although it is not a guarantee, the best way to prevent or mitigate complications of diabetes is to keep your body mass index (BMI) under 25 (http://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htm), and exercise regularly.

3 Risks to Men’s Health That Are Worth Talking About

3 Risks to Men’s Health That Are Worth Talking About

A man’s health is predicated upon his genetic make-up and his willingness to guard his most precious gift by not abusing his body with obesity, smoking, street drugs, being sedentary, and taking insane risks.

No one suggests a dull life, just one that makes common sense. A person cannot alter his genes, but he can make the most of whatever he is given.

While smoking and obesity are the two greatest preventable threats to all Americans (according to Centers for Disease Control, there is one specific illness that impacts a man’s life: prostate cancer.

1 in 9 white men will develop prostate cancer, while black men have 1 chance in 9 of developing the disease. Furthermore, if a man has a brother or father who has prostate cancer, he has twice as likely a chance of getting the disease.

There is no known prevention, but early detection through annual visits to the doctor will reduce the chance that prostate cancer will lead to death.

Unfortunately, 225,000 American men will be diagnosed with prostate cancer and 40,000 will die of the disease each year. Vigilance is critical. New medications and the slowness of the disease to grow is a reason why the vast majority of men die with prostate cancer, not from it.

Erectile dysfunction (impotence) is an important condition that negatively impacts a man’s quality of life. Fortunately, there are many medications that can treat the condition to make a large number of men capable of having intercourse. Thus, it is a treatable, although not curable condition. And as if smoking does not wreck enough havoc on a man, it is the major cause of impotence as well.

An enlarged prostate is yet another risk for men. Benign prostatic hyperplasia, as its medically known, can cause difficulty urinating. By age 60, over one-half of men have BPH; by age 85, the number climbs to 90%, according to the American Urological Association (AUA). Medications and (less likely) surgery may be necessary to relieve the symptoms of decreased urinary stream, frequency of urination during the day and/or night, the sense of incomplete emptying, urgency to void, and possibly incontinence. All these symptoms are due to the prostate obstructing the bladder outflow.

The good news is that many of a man’s health problems can be either avoided or improved. All it takes is the desire to care for oneself, vigilance, and periodic checkup.

House Calls, a win-win for Healthcare in America

House Calls, a win-win for Healthcare in America

In a recent New York Times OP-ED, “Bring Back House Calls,” by Sandeep Jauharot, he describes one of the key advantages of house calls, as reducing the readmission rates that annually cost Medicare $17 billion. Additionally, he mentions, “The key to improving the hospital-to-home transition is a better understanding of the home component. For doctors, patients’ homes shouldn’t be a black box.”

Sandeep hits on a critical point, house calls will improve home care and reduce hospital readmissions; although, it is the use of that ‘black box’ and the doctor’s black bag that are critical to enabling urgent care in the home and monitoring to become an essential part of the healthcare ecosystem.

It is with that in mind, that Pager (www.pager.com), a technology company started 2 years ago with a founder that developed the Uber app, began this exact service in Manhattan, now San Francisco and soon to be in many other major cities. The premise of Pager, and to Sandeep’s article, is that consumers want better care that runs in parallel to the on-demand desire for convenience, affordability and access to quality healthcare.

The Pager ‘black bag’ is not the “Marcus Welby” model of old — it comes fully equipped to provide urgent care on wheels. Pager can treat lacerations, nearly any infection, sprains, and other illnesses that would normally require an urgent care or emergency department facility. Blood drawing, immunizations, wrapping sprains, and treating most of the common medical problems are daily affairs for Pager doctors.

A few other companies have recently entered the market, validating the concept that Pager began. Hospitals, particularly Accountable Care Organizations that are at financial risk for expensive venues of care, are enthusiastically embracing the house call. Using the technology that Pager has created, hospitals can now offer multiple venues for their patients to access care: telephonic or video (telemedicine), home care, urgent care, doctors’ offices, or emergency rooms. Patients receive excellent care at the convenient right time, in the most cost-effective site.

Hospitals and large medical groups have identified the technology and house call delivery as not only cost-effective, but also a marketing tool to differentiate itself in the local market where all healthcare is determined. It becomes a referral engine: if a patient is seen by a primary physician in the home, a trust is built, and if the patient also has a medical or surgical problem, the patient would be referred to a specialist in the medical group or hospital. Further, the patient likely does not have a primary care doctor and could become a patient affiliated with the doctor’s practice. Any initial loss of money by the group or hospital for the house call, is effectively overcome by the marketing benefits of those who use the service.

House calls benefit the entire eco-system of health care: first and foremost, the patient; the doctor and his/her group or hospital, the insurance company to reduce expensive venues of care; and the health care economy as a whole. Truly, a win/win/win/win for all.

Richard Boxer is the Chief Medical Officer at Pager. He is the founder of Boxer Health Strategies and actively practices medicine. He was Surgeon General of the United States Finalist and was a Senior Advisor to the Health Security Act of 1993 for President Clinton’s administration.

Wall Street Journal OP-ED Aug. 3, 2015

·       http://www.wsj.com/articles/when-a-doctor-is-always-a-phone-call-away-1438551044

When a Doctor Is Always a Phone Call Away

Many of the 136 million ER visits in 2011 could have been replaced with a $50 telemedicine consultation.

By 

RICHARD BOXER

Aug. 2, 2015 5:30 p.m. ET

52 COMMENTS

A 39-year-old truck driver was hauling through the Midwest in the middle of the night in 2011 when he began to feel a bit of indigestion. Then a lot of indigestion. He pulled over, recalling that his company had recently signed on with Teladoc, for which I was then the chief medical officer. The service allowed him to get a doctor on the phone within 15 minutes. He called and described his symptoms: nausea, chest pain, a little numbness in his left arm. He was having a heart attack, and his GPS guided him to the nearest emergency room.

Getting that doctor on the phone saved his life, and potentially the lives of whoever his 10-ton rig might have plowed into had he keeled over behind the wheel. If efficient and affordable quality treatment is the goal, telemedicine should be the future of health care.

ENLARGE

PHOTO: GETTY IMAGES

When it comes to health care, “efficient” is a word that frightens people, calling to mind a soulless bureaucracy with an eye on the company’s bottom line. But it is inefficiency that is overburdening the medical system. Consider a woman with a urinary-tract infection who has to leave work to obtain a prescription from a doctor for a drug she already knows she needs. Or a man with a fever and hacking cough who has good health insurance, but who goes to the emergency room because his doctor’s office is closed.

Americans are struggling to obtain affordable, convenient care, and 103 million people in the U.S. live in areas with a shortage of primary health-care providers, according to the Health Resources and Services Administration. Yet the country is dependent on expensive, brick-and-mortar facilities that require time-consuming travel.

Primary-care doctors tend to cluster in urban areas. If you get sick in rural Wyoming, even during the workweek, your only choice might be the emergency room. In 2011, the Centers for Disease Control and Prevention reports, 136 million people were seen in an ER; many of those visits could have been replaced with a $50 telemedicine consultation.Researchers at the University of Rochester found that 28% of the visits at one pediatric emergency room involved ailments such as ear infections or sore throats that could be diagnosed over the phone.

These problems are exacerbated by the increase in the elderly population, coupled with tens of millions of patients newly insured by the Affordable Care Act. A study in theAnnals of Family Medicine projects that the U.S. will need 52,000 more primary-care doctors by 2025. Those positions aren’t filled easily. It takes 12 years and hundreds of thousands of public dollars to educate one primary-care doctor.

But there is an untapped resource: the many doctors leaving their practices, fed up with the regulations and other hassles, but who love their patients, and the older physicians eyeing retirement because they no longer want to maintain an office. Why not let these doctors offer their expertise to patients by smartphone?

Doctors who contract with a telemedicine company can opt for a specific block of time when they are “on call” to patients, picking up the phone and answering questions in 10- to 15-minute intervals. The doctor is paid and the patient gets a prompt and inexpensive answer to a concern.

Home care of individuals with major chronic conditions would also substantially benefit from telemedicine. Millions of houses have cable and satellite connections that can be used to monitor patients wearing wireless devices, allowing health professionals to intercede at the first sign of trouble. This can reduce rates of hospitalization by half or more, some studies suggest.

While there is worry about the quality of these interactions, telemedicine companies assess their doctors routinely and maintain strong quality-assurance programs. Every doctor is taught in medical school that 80% of diagnoses are obtained through a medical history and symptoms, and not by what a doctor sees, touches or tests.

Telemedicine will never completely supplant face-to-face visits, and most doctors naturally would prefer to treat a patient in person. The American Medical Association, for instance, has encouraged restriction of telemedicine to patients who have an established relationship with a doctor, and some state medical boards try to enforce that view.

But the perfect cannot be the enemy of the good—and by continuing to practice medicine as usual, we are making it so. Millions of Americans live in areas that are short of primary-care doctors, and millions more go to the emergency room when they have a sore throat. Entrepreneurs have responded by creating methods of connecting patients to doctors remotely, which reduces costs and satisfies patients.

There is no scenario for sustaining or improving health care in America without telemedicine. State and federal governments, as well as the medical establishment, should embrace the technology. For one thing, they should change Medicare and Medicaid to allow reimbursement for telemedicine consultations, most of which are currently not covered. Ask that truck driver if he thinks talking to a doctor over the phone has value: He is still alive and trucking.

Dr. Boxer is the chief telehealth officer of Pager and chief medical officer of Well Via.

Corrections & Amplifications

An earlier version of this article misstated the name of the journal that published a study of the need for 52,000 more primary-care doctors by 2025. It is the Annals of Family

Biosimilars: Questions Remain

 

There must be a balance between encouraging the development of new, lifesaving, or life-improving drugs, and their cost. Whether biosimilars will help in achieving such balance remains to be seen. 
—Richard J. Boxer, MD, FACS

Biosimilars are biologic drugs that are similar to an already established “reference” or “innovator” biologic drug product and can be manufactured when an original biologic drug product’s patent expires. Reference to the innovator product is an integral component of approval for a biosimilar. The U.S. Food and Drug Administration (FDA) requires licensed biosimilar and interchangeable biologic products to meet the agency’s rigorous standards of safety and efficacy.

Laws and Definitions

According to the FDA,1 a biologic product may be demonstrated to be biosimilar if data show that, among other things, the product is “highly similar” to an already-approved biologic product. The biosimilar also must show it has no clinically meaningful differences from the innovator product in terms of safety and effectiveness. Only minor differences in clinically inactive components are allowable in biosimilar products.

The Affordable Care Act amended the Public Health Service Act to create an abbreviated licensure pathway for biologic products that are demonstrated to be “biosimilar to” or “interchangeable with” an FDA-licensed biologic product. This pathway is provided in the part of the law known as the Biologics Price Competition and Innovation Act.

A phrase used to describe the biosimilar creation—“the process is the product”—illustrates that it is critical to understand the biosimilar development process.2 Biosimilars are derived from many sources, including humans, animals, microorganisms, or yeast. Some, such as blood cells or stem cells, are extracted from living beings. Others are produced using advanced genetic technology. If the host cells, cell culture process, or purification methods are different, there may be clinically significant alterations in the safety and effectiveness of the drug.

Regulatory Guidance

Recently, the FDA clarified its views through regulatory guidance. The FDA suggested that manufacturers of biosimilar drug products would be allowed to extrapolate innovator data to support the approval of all indications the branded product is approved for. While they may reduce the overall resources required in bringing a biosimilar to market, other aspects of the guidance were not as favorable to these stakeholders. The guidance also suggested that the FDA does not believe the current technology is evolved enough to truly establish the interchangeability of a biosimilar with a branded product.3

The World Health Organization has stated, “The approach established for generic medicines is not suitable for development, evaluation, and licensing of similar biotherapeutic products since biotherapeutics consist of relatively large and complex proteins that are difficult to characterize.”4

Indeed, biosimilars are not generics. “It is important to note that a biosimilar is not just like a generic drug,” according to Leah Christl, PhD, Associate Director for Therapeutic Biologics in the FDA’s Office of New Drugs. “Because of the differences in complexity of the structure of the biologic and the process used to make a biologic, biosimilars are not as easy to produce as generics, which are copies of brand-name drugs.”5

Thus, uncertainties about interchangeability and their implications for biosimilar development remain to be resolved. In the meantime, federal regulators are charged to determine whether a biosimilar product is sufficiently similar clinically to an innovator biologic drug to merit the same approval for use.

Cost Considerations

Questions about interchangeability aside, it is predicted that biosimilars will save patients money. Biosimilars are expected to save $13 billion over the next 10 years, according to the Congres­sional Budget Office. The initial promise of biosimilars was that they would save patients 30% to 40%. (As a point of reference, generic drugs, which have 85% of the U.S. pharmaceutical market, cost about 80% to 85% less than their corresponding brand-name products, according to the FDA.3)

Unfortunately, bringing biosimilars to market is proving far more complex than anticipated, and therefore, 10% to 20% less than the cost of the branded medication is a more reasonable expectation. In Europe, biosimilars have often been associated with only a 10% discount from the brand-name product.3

Express Scripts, a pharmacy benefits manager, has stated that biosimilars will provide $250 billion in U.S. health-care savings over the next decade if 11 biologics gain biosimilar competition,6 but the RAND Corporation projects much lower savings—about $44 billion—from the introduction of biologics.7

Another class of new biologic drugs is called “biobetter drugs.” A biosimilar drug is a mere structural imitation; a biobetter drug possesses some molecular modification that constitutes an improvement over the original innovator drug. Such improvements may range from a longer half-life (allowing for less frequent dosing) to more potency with less toxicity. Biosimilar drugs and biobetter drugs offer the very real possibility of quality alternatives and even enhanced treatments at better prices.

More Key Issues

Another important question is, will biosimilar drugs stymie innovation in research and development? Clearly, there must be a return on investment for original biologic medication, and it can take hundreds of millions of dollars to prove a drug’s efficacy and bring it to market. The cost of discovery is staggering, but the cost of copying, even though biosimilars are not chemically exact copies, is significantly less.

There must be a balance between encouraging the development of new, lifesaving, or life-improving drugs and their cost. Whether biosimilars will help in achieving such balance remains to be seen. ■

Disclosure: Dr. Boxer reported no potential conflicts of interest.

References

1. U.S. Food and Drug Administration: Biosimilars. Available at www.fda.gov. Accessed June 23, 2015.

2. Thelwell C, Longstaff C: Biosimilars: The process is the product. The example of recombinant streptokinase. J Thromb Haemost 12:1229-1233, 2014.

3. Howell P: How much cheaper will biosimilars be? March 2, 2012. Available atwww.fiercepharma.com. Accessed June 23, 2015.

4. Expert Committee on Biological Standardization: Guidelines on Evaluation of Similar Biotherapeutic Products (SBPs). Geneva, Switzerland, World Health Organization, 2009. Available at www.who.int. Accessed June 23, 2015.

5. U.S. Food and Drug Administration: Biosimilars: More treatment options are on the way. March 6, 2015. Available at www.fda.gov. Accessed June 23, 2015.

6. Milman J: The cheaper cancer drug that could pave the way for much more affordable medicine.The Washington Post. January 5, 2015.

7. RAND Corporation: Biosimilar medications could create billions in health care savings. November 3, 2014. Available at rand.org. Accessed June 23, 2015.

Dr. Boxer is Visiting Professor of Urology and Scholar in Residence (Business of Science Center) at the David Geffen School of Medicine at UCLA. He is also Professor of Clinical Urology at the University of Wisconsin–Madison.

Disclaimer: This commentary represents the views of the author and may not necessarily reflect the views of ASCO.

Cost vs Our Values in Cancer Care

 

Science always races ahead of our moral, philosophical, and ethical understanding. 
—Richard J. Boxer, MD, FACS

An 80-year-old patient with metastatic prostate cancer asked me to discontinue his treatments, which were costing him more than $1,000 every 3 months. Although he had Medicare, he did not have secondary insurance. I told him that I would seek compassionate-care payment from the pharmaceutical company, but he insisted. I was perfectly willing to accept Medicare as the only payment, but in the perverse rules of the Centers for Medicare and Medicaid Services, it is a crime to accept Medicare as payment in full because then I am “overcharging” Medicare. A colleague tells me that being compassionate by not charging the patient the co-pay is a crime in Nebraska. This is the best definition of “No good deed goes unpunished.”

The gentleman knew he was going to die soon and that the money expended now for a few more months of life would be essential for his wife after he was gone. He died later that year, without receiving any more treatment.

Societal Costs of Cancer Care

Science always races ahead of our moral, philosophical, and ethical understanding. Can we honestly say that the present or future $100,000/year miracle medication that gives an additional 4 months of life is rational given our nation’s fiscal constraints? Does it make sense to prolong a life (or prolong the onset of death) by a few months with such a hefty price tag when the money might be better spent to address the desperate needs of many others in the country?

The cost of cancer care as measured by the value in increased life, especially quality of life, has commonly been a discussion about the impact on the individual, and there is great reason for that. However, there should be room for the cost to society in that discussion. Science creates targeted therapies, but should there be a targeted future with a rationale?

Cost-effectiveness analysis, intensely discussed 7 years ago, provoked our understanding of the issue of value (of care) and values (of humanity).1 Studying the effect of new treatments on quality-adjusted life-years brings some measure of rationale to the discussion. However, as Douglas Owens said in his editorial, “Cost-effectiveness analysis is a tool that cannot substitute for value judgments. We must still decide how much money we are willing to spend to improve our health.”1

So where does this leave our cancer care community? We must continue to push the envelope in basic and clinical research to find the next discovery that will lead to improved treatments, prevention of disease, cures, and quality-adjusted life-years but should never forget that we live in a complex society, where the value placed on life should not prolong inevitable death at the expense of society as a whole. ■

Disclosure: Dr. Boxer reported no potential conflicts of interest.

Reference

1. Owens DK: Interpretation of cost-effectiveness analyses. J Gen Intern Med 13:716-717, 1998.

Dr. Boxer is Voluntary Professor of Urology and Scholar in Residence (Business of Science Center) at the David Geffen School of Medicine at UCLA. He is also Professor of Clinical Urology at the University of Wisconsin-Madison.

How Technology Is Helping Bring Health Care to Patients

The term “telemedicine,” which is sometimes used interchangeably with “telehealth” and “m-health” (for mobile health) and is now collectively called “connected health,” involves the use of information and communications technology to connect patients with their providers through a variety of electronic devices, including interactive videoconferencing, e-mail, smart phones, handheld wireless tools such as tablets, and other types of telecommunications technology. Another term gaining traction is “tele-oncology”—the application of telemedicine in the advancement of cancer care, including diagnostics, treatment, and supportive care.

Telemedicine can offer oncologists a way to consult remotely with specialists in other disciplines in other parts of the country or the world to help in their assessments and diagnoses. For patients with cancer, telemedicine can expand access to care, facilitate their reporting of treatment side effects and outcomes, and even improve their quality-of-life.

Results from the Indiana Cancer Pain and Depression study,1 which evaluated the use of telephone-based care management and automated symptom monitoring to reduce depression and pain in patients with cancer, show that these symptoms were significantly improved.

“The technology that is available today is helping bring about a fundamental change in U.S. health care,” said Richard J. Boxer, MD, FACS, Visiting Professor of Urology, David Geffen School of Medicine at University of California, Los Angeles, and Visiting Scholar, the Business of Science Center, UCLA. “The current system of bringing patients to health care is changing because of technology. With innovations such as videoconferencing, telephone-based care management, and automated symptom monitoring, high-quality health care is becoming much more convenient and much more affordable, and providing greater access to care. Now, it is possible to bring health care to the patient instead of bringing the patient to health care. I cannot envision the future of health care without connected health.”

The ASCO Post talked with Dr. Boxer, who was Chief Medical Officer at Teladoc, a telemedicine company, from 2006 to 2013, and is currently a consultant for several technology-enabled health-care services companies, including Pager (www.getpager.com) and 2nd.MD )www.2nd.MD.com), about how telemedicine may impact cancer care in the future.

Better Access to Care

How can telemedicine provide better quality health care to patients?

Interactive videoconferencing and Internet-based technologies are allowing physicians from a variety of specialties, including oncology, cardiology, dermatology, and neurology, to provide access to medical care to larger segments of the population, regardless of where patients are located. Currently, while a large number of people in the U.S. receive outstanding health care, it is often very expensive and inconvenient to access. And there are still tens of millions more Americans who don’t have access to the best oncologists. Telemedicine will provide patients with cancer greater access to better care.

For example, there is substantial evidence that cancer outcomes are worse in rural or remote areas of the country. Telemedicine or tele-oncology can decrease the travel burden on these patients.

In addition, Internet-based technologies, such as patient Web portals, will enable patients to learn more about their cancer and treatment and how to manage their care, connect with providers, and receive social support through online support groups.

Remote Services

Please explain how cancers might be diagnosed or monitored remotely.

If a person is worried about a possible skin cancer, for example, and can’t get to her dermatologist for a diagnosis, she can upload a photo of the skin lesion to her doctor’s office, and the physician and consulting dermatologist may make a decision about whether the patient needs to come to the office for an in-person skin check.

For patients with cancer who need to be monitored by their oncology team, but either live long distances from their medical center or don’t need or cannot be physically in the oncologist’s office for a checkup, the oncology team would be able to virtually visit the patient in the patient’s home.

Alleviating the Workforce Shortage

In March, ASCO published its report The State of Cancer Care in America: 2014,2 which detailed a potential workforce shortage of oncologists over the next decade just as the demand for oncology services will be surging. Can telemedicine or tele-oncology help mitigate the problem of a physician workforce shortage?

Yes. This will be especially true for primary care physicians, where the workforce shortage is even greater than it is in oncology. Currently, there is a disconnect between where the physician is and where the patient is. That disconnect can be reversed through telemedicine, or tele-oncology, through videoconferencing or telephone-based care management.

The technology of connected health, increases the number of available time slots a doctor may use to care for patients. One of the great inefficiencies in medicine is that the doctor and the patient are disconnected through time or physical distance. Each appointment slot in a doctor’s office calendar that is not filled due to cancellations or incomplete scheduling results in another patient not receiving medical care. If these empty appointment slots can be filled with a virtual office visit, the doctor’s time is efficiently used and the patient receives care.

In addition, the technology allows other populations of physicians, such as retired, disabled, or stay-at-home moms and dads, to continue to use their medical expertise by practicing medicine as virtual consultants as long as they maintain their board certification and keep current through CME courses.

Growth Potential

How prevalent is telemedicine in the practice of oncology?

 The application is just beginning in oncology. In primary care practice, there are about 50,000 telemedicine consultations a month in the U.S. vs 80 million in-person medical consultations each month, so the sky is the limit in terms of telemedicine growth potential.

In oncology, the use of communications technology can facilitate second opinions for patients seeking confirmation of their diagnosis or proposed treatment plan. There are companies specializing in obtaining remote second opinions. Patients upload their medical data to the company’s server, the company contacts and pays a world-class consulting oncologist, and then the patients have a videoconferencing or telephonic interaction within a couple of days of their request.

The opportunities for any oncologist to offer first or second opinions are nearly endless. I predict that every medical office, especially medical specialists’ offices, will have a dedicated room for virtual consults.

Supplementary Care

Are patients likely to use virtual technology to supplement the physical interaction they receive from their oncologist and other members of their medical team?

Tele-oncology or telemedicine is not meant to replace the physical interaction between the patient and doctor. The first interaction between a patient and the doctor is always in-person. The use of telecommunications technologies is reserved for follow-up, second opinion, and supportive care.

Oncologists commonly have nurse practitioners, physician assistants, nutritionists, various therapists, social workers, and other professionals on their oncology team. Any of these professionals could perform virtual patient care.

Cost Issues

Can telemedicine reduce health-care expenses?

Yes. Bringing virtual health care to the patient reduces brick-and-mortar overhead and increases efficiencies for improved access to care. Everyone wins in the connected health scenario. Patients receive rapid access to appropriate care, more doctors are immediately introduced into the system, potentially reversing the dire predictions of workforce shortages, and physicians are better compensated for improved efficiencies.

Disclosure:

References

1. Kroenke K, Theobald D, Wu J, et al: Effect of telecare management on pain and depression in patients with cancer: A randomized trial. JAMA 304:163-171, 2010.

2. The State of Cancer Care in America, 2014: A report by the American Society of Clinical Oncology. J Oncol Pract 10:119-142, 2014.

Renal Carcinoma: State-of-the-Art Treament

A Conversation With David I. Quinn, MBBS, PhD, FRACP, and With Arie Belldegrun, MD, FACS, and Allan Pantuck, MD, MS, FACS

Dr. Boxer:  Dr. David Quinn, would you describe the newest medical oncology approach to metastatic renal carcinoma?

Recurrent or metastatic renal cell cancer therapy

The current first line therapy for most patients with good to intermediate risk mRCC is a VEGFrTKI. There are a small group of good performance status patients who should consider high dose interleukin 2 therapy but the toxicity and inpatient therapy commitment precludes many patients. The selection of the specific VEGFrTKI used for first line therapy has evolved. Level 1 evidence has been established for sunitinib in this setting since 2007 but more recently data from the COMPARZ study[1] suggests that pazopanib has similar efficacy to sunitinib with a better side effect profile in many patients. Lower levels of evidence support the use of other VEGFrTKIs such as sorafenib and axitinib and also the VEGF ligand inhibitor, bevacizumab, in the first line setting. For patients with poor risk mRCC, an intravenous mTOR inhibitor has level 1 evidence to support is use over interferon-a. There is lower level evidence to support the use of VEGFrTKIs in the poor risk setting also.

Second therapy selection depends on first line that preceded it and some would argue that the efficacy and tolerability of the first line agent should also inform second line selection. For patients that received first line HDIL2, VEGFrTKIs have level 1 evidence in the second line with axitinib being the common choice based the AXIS study[2] data. For patients that received a VEGFrTKI first line, there is a choice between another VEGFrTKI or an mTORi in the second line. This choice is the subject of division among RCC experts and represents an area of equipoise and debate. Data from the Record-1 study provides level 1 evidence for the oral mTORi everolimus over best supportive care alone after a VEGFrTKI. Data from the AXIS study supports the use of axitinib over sorafenib in this setting. Interestingly, the PFS for everolimus and axitinib after sunitinib therapy in these different trials approximated 4 months. A trial of everolimus versus axitinib after a single VEGFrTKI might be definitive but has not been undertaken. The INTORSECT trial[3] compared the intravenous mTORi temsirolimus to the VEGFrTKI sorafenib after sunitinib therapy. There was minimal difference in the PFS between the 2 agents but patients given sorafenib in this trial had a 4-month better overall survival. Extrapolating these data to clinical practice is difficult although many oncologists have noted benefit for sorafenib with a response to first line sunitinib that exceeded 6 months in the INTORSECT trial. Poor risk patients given temsirolimus in the first line are routinely given a VEGFrTKI in the second line if their performance status is adequate.

Third line therapy is dependent on prior therapy. Both mTORis and VEGFrTKI have activity. Based on RECORD-1[4] everolimus has activity compared to BSC while the recently reported GOLD study[5] showed that use of sorafenib resulted OS of 11 months patients treated with prior VEGF and mTOR directed therapies.

Beyond third line therapy may be warranted in some patients who have had good disease control duration or responses to prior VEGF or mTOR directed agents and good performance status. Many clinicians use sorafenib or bevacizumab in this setting although there is no evidence base to support this.

Dr. Boxer:

Drs. Allan Pantuck and Arie Belldegrun, immunotherapy and vaccination for cancer has been an area of great pursuit and of your interest.  Would please explain your efforts and where you think the new era of treating metastatic RCC?

      Cancer Immunotherapy—the harnessing of the immune system as an effective treatment for cancer--was recently selected by the journal Science as the top scientific achievement Breakthrough of the Year for 2013 (1). With this declaration, we are entering into a new era of enthusiasm about the use of immunotherapy in the treatment of cancer, and this shift will undoubtedly significantly impact upon the treatment of advanced renal cell carcinoma (RCC) as much as any other cancer type over the next decade. Historically, metastatic RCC did not fit the standard oncologic paradigm, and proved to be largely resistant to the usual treatment regimens employed in combating other types of cancer.  Trials of cytotoxic chemotherapy, radiation therapy, and hormones all failed to demonstrate any appreciable effects on survival.  Instead, in the 1980s and 1990s, RCC, along with melanoma, became the model for the development of immune based therapies. 

      The first iteration in the development of cancer immunotherapy treatment regimens, the use of non-specific cytokine treatments that included interleukin-2 (IL-2) and interferon (IFN), created an important treatment option for patients with metastatic RCC that remained the mainstay of treatment for nearly 15 years. Until the approvals of the first anti-angiogenic VEGF tyrosine kinase inhibitors in 2005 and 2006, high-dose, bolus intravenous (IV) IL-2 was the only treatment approved by the United States Food and Drug Administration (FDA) for patients with metastatic RCC, an approval granted by the FDA in 1992 for its ability to produce durable complete responses in a small subset of patients.    Data from seven phase II clinical trials involving a total of 255 patients with metastatic RCC demonstrated an overall response rate of 15%, which included complete response (CR) in 7% of the patients and partial response (PR) in 8% of the patients (2,3).  Subsequent modern trials with high-dose, bolus IL-2 such as the Cytokine Working Group’s Select trial, have demonstrated response rates nearing 30% and of greater quality and durability (4).  Taken together, these studies clearly demonstrated the benefit that immunotherapy can provide for a subset of patients with metastatic RCC. 

Although immunotherapy was once the standard of care, the advent of oral therapies that target angiogenesis and other signal transduction pathways and that produced significant clinical benefits in larger patient subsets prompted a reassessment of the role of immunotherapy in advanced RCC. Due to their broad activity and relatively tolerable toxicity profiles, the last 10 years saw a shift away from the use of cytokine-based treatment of mRCC to the use of these newer targeted oral therapies. In contrast to the results achieved with IL-2, however, the cytostatic molecularly targeted therapies (eg, sorafenib, sunitinib, everolimus) do not produce durable remissions when therapy is discontinued, and treatment resistance inevitably develops. In the past years, however,  an improved understanding of immunology and tumor biology have led to the development of novel immunotherapeutic treatment strategies that include vaccines such as Provenge, the first and thus far only therapeutic cancer vaccine to achieve FDA approval (in 2010), as well as immune checkpoint inhibitors (eg ipilimumab approved in 2011, nivolumab), and the adoptive transfer of engineered T cells (eg tumor infiltrating lymphocytes, or T cells engineered to express a recombinant T cell receptor or chimeric antibody receptor) (5 for a review of current novel combination strategies integrating immunotherapies in GU malignancoies). It is the latter two strategies in particular that have generated the newfound enthusiasm for cancer immunotherapy.

Checkpoint Blockade to Eliminate Immune Suppression

Since the groundbreaking work of James Allison and others in the 1990s unravelling the molecular mechanisms governing the host response to tumors and identifying the signaling pathways involved in limiting the immune response, a successful therapeutic strategy has emerged based on the development of various agents that enhance the anti-cancer immune response by taking the breaks off these immunosuppressive, inhibitory (“checkpoint”) pathways (reviewed in 6). To date, the most clinically important checkpoint molecules mediating tumor-induced immune suppression are cytotoxic T-lymphocyte antigen-4 (CTLA-4) as well as the programmed death-1 (PD-1) receptor and its ligands. CTLA-4 acts as a signal dampener acting primarily within the lymph nodes to regulate the early activation of naive and memory T cells. PD-1, by contrast, is induced on T cells after activation in response to inflammatory signals and limits T-cell function in peripheral tissues (7). The anti–CTLA-4 monoclonal antibody (mAb) ipilimumab improved survival in a phase 3 trial in patients with metastatic melanoma (8) and was subsequently approved by the United States Food and Drug Administration in 2011 for the treatment of patients with that indication. However, the fully human anti–PD-1 mAb BMS-936558/MDX-1106/ONO-4538 (nivolumab), has already demonstrated impressive antitumor activity in phase 1/1b studies of not only RCC, but also castrate resistant prostate cancer, non–small cell lung cancer (NSCLC), and colorectal cancer (CRC) (9). What is notable about the clinical results using checkpoint inhibitor therapy is the high level of anti-tumor activity (eg, the spectrum of tumors that appear to be responsive, and the durability of the responses). For example, reductions in tumor size of more than 80% in the majority of patients in one study (10), and in another study of patients with advanced melanoma, four year survival in approximately 20% of subjects (8).

Adoptive Immunotherapy

Adoptive immunotherapy refers to the passive transfer of immune cells with antitumor activity into a tumor-bearing host.  Currently, there are 3 main strategies that have been extensively studied for the adoptive immunotherapy of cancer.  The first use of adoptive immunotherapy of cancer was based on the use of tumor infiltrating lymphoctyes (TIL).  The anti-tumor activity of TIL is thought to be mediated through interaction between the tumor cell and the T cell receptor (TCR) and is MHC restricted (11).  Though early trials of TIL in mRCC such as the UCLA experience combining TIL with low dose IL-2 plus IFN demonstrated the feasibility of this approach, with an intriguing 35% response rate that includes durable remissions (12), a subsequent  multi-center phase III trial randomizing subjects with mRCC to low dose IL-2 alone vs. low dose IL-2 plus TIL was negative (13). After randomization of a total of 160 subjects, intent to treat analysis revealed response rates of 9.9 vs. 11.4% (IL-2 vs, IL-2/TIL).  Moreover, this trial was fraught with difficulty especially with regards to the successful preparation of TIL at a centralized facility.  Of the subjects randomized to the TIL arm, 41% did not receive these cells due to processing difficulties.  To date, TIL therapy has proven effective only in the treatment of metastatic melanoma, primarily since it has not proven to be possible to consistently and successfully isolate, culture, establish, and expand large populations of tumor-reactive T cells having anti-cancer activity from the tumors of the majority of patients having other tumor types. 

The other two strategies of adoptive T cell immunotherapy have found ways to circumvent this problem (14). T cell receptor (TCR) therapy utilizes patients easily acquired peripherally acquired T cells which are then genetically engineered using viral vectors to transduce and express a specific recombinant T cell receptor capable of recognizing a specified tumor antigen (eg CAIX, MART-1, NY-ESO, etc). Already, clinical trials of TCR therapies has shown unexpected anti-cancer activity in a number of solid tumor indications including melanoma, and other unanticipated cancer types such as colorectal and synovial sarcoma (15, 16).  While TCR-transduced T cells are engineered to express a particular TCR, they still require tumor recognition in the context of MHC restriction and can therefore be utilized only in a subset of patients and are vulnerable to the well-known mechanism of tumor evasion by the immune recognition, MHC down regulation. The last strategy for adoptive T cell therapy circumvents these issues as well. In this final option, peripherally acquired T cells are transduced by a “chimeric” antigen receptor (CAR) that combines the variable region of an antibody domain with a CD3 T-cell signaling molecule, with more recent second and third generation CAR iterations also including other co-stimulatory molecules such as CD28 and 4-IBB (17). The ability of the CAR receptor to recognize tumor antigens and engage native TCR-mediated activation is derived from non-MHC restricted antibody binding, which is capable of antigen recognition and binding with exquisite sensitivity. Moreover, like TCR, clinical trials of modern CAR have demonstrated great potential across a spectrum of tumor types, with the greatest success thus far being seen in a variety of hematologic malignancies expressing the CD19 antigen (18, 19).

The use of TCR and CAR technology has only yet begun to be applied to RCC (20). The next decade will witness a new renaissance in the use of immunotherapy of RCC based on combinations of non-specific immunotherapies such as IL-2, targeted immunotherapies utilizing engineered T cells, augmentation of the anti-cancer immune response through the use of immune checkpoint blockade, and likely even combinatory approaches simultaneously using standard molecularly targeted approaches.

*Acknowledgements: The authors (AP&AB) are scientific founders, equity holders, and Executive/Director (AB) of Kite Pharma Inc., a Los Angeles based biotechnology company dedicated to the development of adoptive TCR and CAR engineered T cell cancer therapies.

References:

1.Couzin-Frankel J: Cancer Immunotherapy. Science 2013;342a;1432-1433. Gleave ME, Elhilali M, Fradet Y, et al. Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. Canadian Urologic Oncology Group. N Engl J Med. 1998;338:1265-1271.

2. Fyfe et al: Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 1995;13688-696.

3. Fisher RI, Rosenberg SA, Fyfe G: Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am 2000;S155-57.

4. McDermott DF et al: The high-dose aldesleukin (HD-IL-2) “SELECT” trial in patients with metastatic renal cell carcinoma [abstract 4514]. Presented at the American Society of Clinical Oncology Annual Meeting, Chicago, USA; June 4-8, 2010.

5. Drakaki A, McDermott DF: Novel immunotherapies in GU malignancies. Curr Oncol Rep 2013;15224-231.

6. McDermott DM, Atkins M. PD-1 as a Potential Target in Cancer Therapy. Cancer Medicine 2013; 2(5): 662–673.

7. Topalian, SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1 (PDL-1) pathway to activate anti-tumor immunity. Curr Opin Immunol 2012;24:207-212.

8.  Hodi et al. Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. N Engl J Med 2010; 363:711-723.

9. Topalian et al: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2013; 366:2443-2454.

10. Wolchok JD et al: Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013;369:122-133.

11. Finke, JH, Rayman, P, Hart, L, et al. Characterization of tumor infiltrating lymphocyte subsets from human renal cell carcinoma: specific reactivity defined by cytotoxicity, interferon gamma secretion, and proliferation.  J. Immunother. 15, 91, 1994.

12. Figlin, R.A., Pierce, W.C., Kaboo, R., et al. Treatment of metastatic renal cell carcinoma with nephrectomy, interleukin-2, and cytokine-primed or CD8(+) selected tumor infiltrating lymphocytes from primary tumor. J. Urol. 158, 740-5, 1997.

13. Figlin, R.A., Thompson, J.A., Bukowski, M.D., et al. A multi-center, randomized, phase III trial of CD8+ tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J. Clin. Oncol. 17(8), 251-9, 1999.

14. Humphries C. Honing that killer instinct. Nature 2013;504:S13-S15.

15. Robbins PF et al: Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011 Mar 1;29(7):917-24.

16. Parkhurst MR et al: T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther. 2011 Mar;19(3):620-6.

17. Sampson JH et al: EGFRvIII mCAR-mediated T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss. Clin Can Res 2013.

18. Kochenderfer JN et al: B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric antigen receptor transduced T cells. Blood 2012:1192709-2720.

19. Porter et al: Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. New Engl J Med 2011;365:725-733.

20. Lamers et al: Treatment of Metastatic Renal Cell Carcinoma With Autologous T-Lymphocytes Genetically Retargeted Against Carbonic Anhydrase IX: First Clinical Experience. J Clin Oncol 2006;24: e20-e22.

{C}[1]{C} Pazopanib versus sunitinib in metastatic renal-cell carcinoma.

Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R,Pandite LN, Choueiri TK. N Engl J Med. 2013 Aug 22;369(8):722-31. doi: 10.1056/NEJMoa1303989

{C}[2]{C} Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial.

Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Lancet. 2011 Dec 3;378(9807):1931-9. doi: 10.1016/S0140-6736(11)61613-9. Epub 2011 Nov 4.

[3]{C} Randomized Phase III Trial of Temsirolimus Versus Sorafenib As Second-Line Therapy After Sunitinib in Patients With Metastatic Renal Cell Carcinoma. JCO Oct 20, 2013:3791-3799; DOI:10.1200/JCO.2012.47.4940.

{C}[4]{C} Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N,Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group. Lancet. 2008 Aug 9;372(9637):449-56. doi: 10.1016/S0140-6736(08)61039-9. Epub 2008 Jul 22

{C}[5]{C} ESMO @ ECC 2013: Similar Phase III Results Reported for Dovitinib vs. Sorafenib Treatment in Patients with Metastatic Renal Cell Carcinoma http://www.esmo.org/Conferences/European-Cancer-Congress-2013/News/Similar-Phase-III-Results-Reported-for-Dovitinib-vs.-Sorafenib-Treatment-in-Patients-with-Metastatic-Renal-Cell-Carcinoma

Prostate Cancer: State-of-the-Art Update on Prostate Cancer

The 2014 Genitourinary Cancers Symposium, held in San Francisco from January 29 to February 1, brought together more than 3,100 participants from around the world involved in the care of patients with genitourinary malignancies. The abstract presentations and plenary discussions offered the latest clinical and basic science data that will affect patient management immediately and well into the future.

During the course of the meeting, as Associate Editor of The ASCO Post,  I had the opportunity to speak with several of the world’s leading authorities about the state of the art in screening, diagnosis, and treatment for prostate and kidney cancers. In this first installment of our two-part report on genitourinary malignancies, we talk to Peter T. Scardino, MD, FACS, Chair of Surgery and former Chair of Urology at Memorial Sloan Kettering Cancer Center in New York, and Howard M. Sandler, MD, MS, FASTRO, Chair of Radiation Oncology at Cedars-Sinai Medical Center, and a member in the Cedars-Sinai Samuel Comprehensive Caner Institute, Los Angeles, about the latest approaches to managing prostate cancer.

Peter T. Scardino, MD, FACS
Chair of Surgery, Memorial Sloan Kettering Cancer Center, New York

PSA Screening

What is your current perspective on screening for prostate cancer?

Screening for prostate cancer with prostate-specific antigen (PSA) will continue to be practiced and will be endorsed by national screening agencies once the problems of current screening methods are resolved. A man’s PSA level at midlife (age 45–50) is a more powerful predictor of his lifetime risk of dying of prostate cancer than his family history or ethnicity. As the power of PSA to predict risk for death from prostate cancer becomes clearer, PSA levels at midlife will be used to risk-adjust screening intensity and duration.

Men with a PSA level below the median at age 45 to 50 can be screened every 5 years until age 60. If their PSA level remains below the median at 60, no further screening will be necessary. Men with intermediate PSA levels (1–3 ng/mL) will be screened less frequently than they are today, every 2 to 4 years, to reduce the risk of false-positives. And men with PSA levels greater than 3 ng/mL will be considered for biopsy after an evaluation that includes the use of new marker panels such as phi (Prostate Health Index, Beckman Coulter) and the 4K (four-kallikrein) panel (in development at OPKO Diagnostics), both of which have been shown to markedly increase the specificity of PSA testing and reduce the need for biopsies.

These new testing guidelines will allow many men with elevated PSA levels to avoid a biopsy and yet be followed safely, without the risk of missing high-grade cancers. New urinary molecular markers, in addition to prostate cancer antigen 3 (PCA3), will be developed to better predict which men with an elevated PSA level should have a biopsy.

Imaging Studies

What are your thoughts about imaging studies for prostate cancer?

Imaging will continue to improve, particularly magnetic resonance imaging (MRI), which when performed as a multiparametric test, is reasonably accurate for the detection of clinically significant cancers. Not only could multiparametric MRI be used in men with an elevated PSA to identify appropriate patients for biopsy, it will also be used with ultrasound fusion or MRI guidance to change the strategy for biopsy from systematic random biopsies back to targeted biopsies, as performed in previous decades when finger guidance was the prime technique for biopsy targeting.

Used together with MRI, molecular positron-emission tomography (PET) imaging will provide more accurate detection of clinically significant cancers within the prostate that will allow better local staging and treatment planning with surgery or radiation, as well as accurate tumor localization and characterization for effective focal ablation. Even more exciting, optical imaging of prostate cancer during a surgical procedure will allow more complete excision of the cancer and of the normal gland (to avoid “benign” PSA relapse requiring salvage radiotherapy), as well as targeted dissection of involved regional lymph nodes, which will become essential once prospective studies document the therapeutic value of lymphadenectomy.

Focal Therapy

Could you discuss current concepts in focal therapy for prostate cancer?

Technology now exists to ablate regions within the prostate using a variety of modalities, including lasers, photodynamics, high-intensity focused ultrasound, cryotherapy, and electroporation, among others. These approaches have already proven capable of thoroughly ablating regions within the prostate with much less impact on sexual, urinary, and bowel function than radical surgery or radiotherapy.

The limiting factor for focal therapy has been our inability to identify the exact location, size, and extent of cancer within the prostate, as well as its biologic potential, but better anatomic imaging (MRI) and molecular imaging will overcome this problem, and partial ablation of the prostate will become as readily accepted as partial nephrectomy for renal tumors, if well designed trials establish the clinical benefit of focal ablation.

Molecular Profiling

How is molecular profiling being used in prostate cancer management?

Once a cancer is identified within the prostate, the most difficult decision is whether to monitor the patient in an active surveillance program or to proceed immediately with radical surgery or radiotherapy. The decision hinges on the assessment of the biologic potential or level of aggressiveness of the cancer, which can be difficult to determine with standard clinicopathologic measures.

Molecular profiling of prostate cancer is now commercially available, with RNA profiles developed by Genomic Health (Oncotype DX) and Myriad (Prolaris), and numerous other techniques currently in development. These profiling strategies provide prognostic information independent of Gleason grade and PSA levels.

With improved profiling, patients can be triaged to active surveillance or to radical therapy more appropriately and with greater confidence. I see a rapid expansion of molecular profiling for prostate cancer using such techniques as copy number alteration and mutation analysis, expression arrays, methylation abnormalities, and metabolomics, as well as microscopic image analysis.

Active Surveillance

Please describe the current role of active surveillance in prostate cancer.

As a consequence of these technologic innovations, active surveillance will expand rapidly and be offered to more than half of patients diagnosed with prostate cancer. These patients will be safely monitored over long periods of time, with treatment delayed until evidence of a cancer with aggressive characteristics.

Clinical trials will define more clearly the eligibility criteria for active surveillance, both for the patient (age and comorbidity) and the tumor (grade, biologic aggressiveness, and imaging characteristics). Of course, a substantial minority of patients on active surveillance will develop more aggressive prostate cancers that will require definitive therapy, and the risk will likely increase among survivors followed for more than a decade, given the logarithmic growth rate of cancer.

Radical Prostatectomy

How is the use of radical prostatectomy evolving in prostate cancer treatment?

Radical prostatectomy procedures will become more complex, as patients with more advanced disease are selected for treatment. More extensive lymphadenectomy will become routine as detection methods improve, including intraoperative imaging of the cancer, and the therapeutic value of lymphadenectomy becomes apparent.

Function-preserving radical prostatectomy will become more challenging with complete ablation of large extracapsular tumors; techniques such as nerve grafting to replace resected cavernous nerves and methods to strengthen the distal urinary sphincter will become even more important. Surgery for resection of the primary tumor will become accepted as effective multimodality therapy proves capable of curing many men with locally extensive or limited metastatic prostate cancer.

The remarkable advances in systemic therapy for prostate cancer, including potent new antiandrogens (enzalutamide [Xtandi]), inhibitors of testosterone synthesis (abiraterone [Zytiga]), classic chemotherapy (taxanes, including docetaxel and cabazitaxel [Jevtana Kit]), and immunotherapy (vaccines such as sipuleucel-T [Provenge] and checkpoint blockade with ipilimumab [Yervoy] and anti–PD-1 antibody), will be used in combination with radical surgery for locoregional disease in patients with locally extensive and limited metastatic disease who cannot be cured by local therapy alone.

Howard M. Sandler, MD, MS, FASTRO
Chair of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles

Evolution of Radiotherapy

How has the use of radiation therapy in prostate cancer changed in the new millennium?

Radiation oncology for genitourinary tumors, mostly prostate cancer, has evolved over the past 2 decades from relatively crude radiation portals that affected large portions of pelvic-localized bowel uninvolved by prostate cancer (which led to acute and chronic gastrointestinal distress) to current highly targeted radiation treatments that focus with great precision on the prostate itself and a slim margin of surrounding extraprostatic tissue. This has resulted in a marked reduction in acute and chronic complications.

Interestingly, despite the older, two-dimensional approach using large radiation fields to treat pelvic lymphatic tissue, research showed that those large fields failed to encompass the prostate itself adequately due to uncertainties in prostate localization during the planning and treatment process. Those uncertainties were caused, in part, by the failure to account for prostatic motion due to variations in rectal and bladder filling. With current techniques, we can irradiate a smaller volume with more conformality, more precision, and fewer side effects and simultaneously treat to higher, more effective doses.

Stereotactic Body Radiotherapy

What is the role of stereotactic body radiotherapy in prostate cancer treatment?

Improvements in radiotherapy techniques led to important changes in the external-beam concept. While traditional radiation biology teaching suggests that fractionated treatment, such as 8 weeks of daily radiation sessions, provides a good risk-benefit ratio, the ability to treat small volumes with precision has led to the development of short, five-fraction approaches using a technique called stereotactic body radiotherapy (SBRT). The “body” is included in the name because this technique evolved from central nervous system or “head” tumor techniques.

The intensity of the five-fraction approach can lead to more genitourinary toxicity if the volume treated is too large or if the treatment is delivered imprecisely. However, there have been enough single-institution studies assessing the benefit of stereotactic body radiotherapy for prostate cancer that in 2013, the American Society for Radiation Oncology (ASTRO) said, “data supporting the use of SBRT for prostate cancer have matured to a point where SBRT could be considered an appropriate alternative for select patients with low- to intermediate-risk disease.”

Thus, over the next 2 years, one might expect a substantial increase in the use of stereotactic body radiotherapy for prostate cancer, given the convenience of the five-fraction approach compared with longer treatment strategies.

Looking Ahead

What other changes in radiotherapy for prostate cancer might be coming in the near future?

In addition to the increased use of stereotactic body radiotherapy, other new aspects of radiation oncology for prostate cancer include ongoing and future trials that will build on our current template of either short- or long-term androgen deprivation in combination with radiotherapy for intermediate-risk and high-risk cancer, respectively.

For example, the Radiation Therapy Oncology Group (RTOG) is examining the potential benefit of inhibiting androgen synthesis with TAK-700 for high-risk patients above and beyond the conventional androgen deprivation that is provided with luteinizing hormone–releasing hormone (LHRH) agonists or antagonists alone. This trial and others will be exploring how the current enriched environment of medications for the castration-resistant patient population might be beneficial—especially combined with radiotherapy—for the hormone-naive patient.

Prostate and Renal Cancer Update

The 10th Genitourinary Cancers Symposium, sponsored by ASCO, the American Society for Radiation Oncology, and the Society of Urologic Oncology, was held January 29–February 1, 2014, in San Francisco. The more than 630 abstracts presented addressed essential research in genitourinary malignancies, including data on some of the newest, most cutting-edge treatments available.

Several papers stand out in my mind as important, possibly groundbreaking, and may alter the approach to treating genitourinary malignancies. The five following abstracts were among the most noteworthy.

Enzalutamide for Chemotherapy-Naive Prostate Cancer

Abstract LBA1. Beer TM, Armstrong AJ, Sternberg CN, et al: Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): Results of phase III PREVAIL study.

The authors performed a randomized, double-blind, placebo-controlled phase III (PREVAIL) study in patients with metastatic castration-resistant prostate cancer. The patients were either asymptomatic or mildly symptomatic. They received enzalutamide (Xtandi), an androgen-receptor blocker (160 mg/d) or placebo, and had never received any other chemotherapy.

A total of 1,717 men (1,715 treated) were randomly assigned to the two arms between September 2010 and September 2012. The investigators found a 29% reduction in deaths in the enzalutamide group compared to the placebo group, and an 81% reduction in disease progression. The two primary endpoints in this trial were overall survival and radiographic progression-free survival.

Enzalutamide treatment resulted in 20% complete responses and 39% partial responses, compared with a 5% objective response rate in the placebo arm. Enzalutamide also significantly delayed the need for chemotherapy. On average, patients receiving enzalutamide needed chemotherapy 17 months later than those in the placebo arm.

The Independent Data Monitoring Committee deemed the benefit-risk ratio to favor enzalutamide and recommended stopping the study and allowing placebo patients to cross over to enzalutamide. The authors concluded, “Treatment with enzalutamide significantly improves overall survival and radiographic progression-free survival in men with chemotherapy-naive metastatic castration-resistant prostate cancer.”

Radium-223 Improves Survival in Prostate Cancer

Abstract 9. Nilsson S, Vogelzang NJ, Sartor AO, et al: 1.5-year post-treatment follow-up of radium-223 dichloride (Ra-223) in patients with castration-resistant prostate cancer (CRPC) and bone metastases from the phase 3 ALSYMPCA study.

In follow-up to the ALSYMPCA study of radium Ra 223 dichloride (Xofigo), the first alpha-emitting pharmaceutical approved by the U.S. Food and Drug Administration for treatment of patients with castration-resistant prostate cancer with symptomatic bone metastases, the investigators found the agent significantly improved overall survival by 3.6 months vs placebo.

They concluded, “Ra-223 is an effective and well-tolerated treatment for castration-resistant prostate cancer with symptomatic bone metastases. No major safety issues were identified within ~1.5 years after treatment in the ALSYMPCA safety population.”

Role of Total Androgen Blockade in Prostate Cancer

Abstract 4. Fossa SD, Widmark A, Klepp OH, et al: Ten- and 15-year prostate cancer-specific survival in patients with nonmetastatic high-risk prostate cancer randomized to lifelong hormone treatment alone or combined with radiotherapy (SPCG VII).

This important Scandinavian trial, a follow-up to previous study of the same group of patients [Widmark et al: Lancet 373:301-308, 2009], demonstrated a significant reduction in prostate cancer–specific mortality among patients with locally advanced or histologically aggressive prostate cancer who received total androgen blockade followed by radiotherapy and continuous antiandrogen therapy compared to patients given hormonal treatment only. Patients in the total androgen blockade arm had a 12% reduction in deaths. The patients were followed for a median of 10.7 years.

The abstract data are quite convincing. Among the 439 men receiving hormone therapy only, 118 died of prostate cancer, whereas of the 436 receiving combination therapy, only 45 died. For the patients receiving androgen ablation alone, cancer-specific mortality at 10 and 15 years was 18.9% and 30.7%. Patients receiving both radiotherapy and androgen ablation had a 10- and 15-year prostate cancer-specific mortality of 8.3% and 12.4%, respectively.

The authors concluded, “Addition of local radiotherapy to hormonal treatment in patients with non-metastatic locally advanced or high-risk prostate cancer more than halved the 10 and 15 year prostate cancer-specific mortality and substantially decreased overall mortality.”

Impact of Angiotensin System Inhibitors on Renal Cell Cancer Outcomes

Abstract 437. McKay RR, Rodriguez GE, Lin X, et al: Impact of angiotensin system inhibitors (ASI) on outcomes in patients with metastatic renal cell carcinoma (mRCC): Results from a pooled clinical trials database.

Treatment of metastatic renal cell carcinoma has been the focus of intense research using new and exciting vascular endothelial growth factor (VEGF)-targeted agents such as sunitinib (Sutent), sorafenib (Nexavar), axitinib (Inlyta), bevacizumab (Avastin); mammalian target of rapamycin (mTOR)-targeted agents such as temsirolimus (Torisel); and interferon alfa. At the same time, however, accumulating evidence has implicated common antihypertensive angiotensin system inhibitors (angiotensin-converting enzyme inhibitors and angiotension-receptor blockers such as lisinopril, captopril, and losartan) in the modulation of angiogenesis and tumorigenesis. The authors of this important retrospective study evaluated the role of these medications in the survival outcomes of patients with metastatic renal cell carcinoma.

The study evaluated the mortality outcomes of 4,736 patients on one or a combination of the above-mentioned targeted therapy medications, also treated with an angiotensin system inhibitor (n = 1,383) or without additional angiotensin system inhibitor treatment (n = 3,353).

The overall survival for patients receiving angiotensin system inhibitors was 27 months, compared with 17 months for those not using these agents. In addition, cancer was more likely to shrink in patients taking angiotensin system inhibitors. The researchers also analyzed data from patients taking any type of antihypertensive agent (n = 2,000) and found that overall survival for patients using angiotensin system inhibitors was 27 months compared to 18 months for those on other types of antihypertensive agents.

The authors stated, “Angiotensin system inhibitor use was associated with improved progression-free survival and overall survival when compared to patients who did not receive an angiotensin system inhibitor. This association was retained in multivariable analysis adjusted for age, gender, presence of bone metastases, and risk groups…. This is the largest retrospective study to date evaluating the role of angiotensin system inhibitors on outcomes in cancer patients. In this analysis, we demonstrate that concomitant use of angiotensin system inhibitors may improve survival outcomes in patients with metastatic renal cell carcinoma treated in the era of targeted therapy.”

Prognostic Model for Renal Cell Carcinoma

Abstract 398. Ko JJ, Xie W, Heng DY, et al: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model as a prognostic tool in metastatic renal cell carcinoma (mRCC) patients previously treated with first-line targeted therapy (TT).

Prognostic models may be very helpful to both patients and oncologists in the treatment of any disease, especially in metastatic renal carcinoma. The authors of this international study sought to validate the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in predicting the value of second-line targeted therapy in patients with disease progression on first-line targeted therapy.

Their study included 1,021 patients on second-line targeted therapy in 19 international centers. The IMDC identified five (of six) predefined factors (anemia, thrombocytopenia, neutrophilia, Karnofsky performance status less than 80%, and interval less than 1 year from diagnosis to treatment), measured at the time of second-line targeted therapy, as independent predictors of poorer overall survival. The sixth predefined factor, hypercalcemia, was not a statistically significant predictor in multivariable analysis.

The authors concluded, “The IMDC prognostic model has been validated in and can be applied to patients previously treated with targeted therapy, in addition to previously validated populations in first-line targeted therapy and non-clear cell setting.”

Diet and Lifestyle and the Impact on Prostate Cancer Cells: OP-ED

Dean Ornish et al at the University of California in San Francisco and the Preventive Medicine Research Institute in Sausalito, California, performed a 5-year study including 35 men on active surveillance (10 in a lifestyle-intervention group and 25 in a control group) with low-risk prostate cancer. The study was a follow-up of a 3-month study performed 6 years ago.2

The authors hypothesized that men compliant with a comprehensive diet and lifestyle change would have improvement in their peripheral blood telomere profile (length and activity), compared to a control group that did not participate in the lifestyle intervention. They noted that short telomere length in peripheral blood mononuclear cells is associated with aging and age-related diseases such as cancer, stroke, vascular dementia, and diabetes.

Considerable Commitment

The comprehensive lifestyle intervention required considerable commitment from the patients and the team of investigators to carry out the study procedures. The intervention consisted of whole foods, plant-based protein, fruits, vegetables, unrefined grains, and legumes, and was low in fat (approximately 10% of calories) and refined carbohydrates, with take-home meals being provided to patients for the first 3 months of the intervention. The intervention also consisted of moderate aerobic exercise (eg, walking 30 minutes per day on 6 days per week), stress management (eg, gentle yoga-based stretching, breathing, meditation, imagery, and progressive relaxation for 60 minutes daily), and increased social support (eg, 60-minute support group sessions once per week).

At each weekly support session, patients performed 1 hour of moderate exercise supervised by an exercise physiologist and 1 hour of stress-management techniques supervised by a certified stress-management specialist. They also attended a 1-hour support group led by a clinical psychologist at each session and a 1-hour lecture during dinner, generally from a dietitian, registered nurse, or physician. All members of the intervention staff were available to answer patient questions and to provide counseling at the weekly support sessions. Spouses and partners were encouraged to attend support sessions but were not required to do so.

Hypothesis-Generating Findings

The investigators reported that the comprehensive lifestyle group had a relative increase in telomere length compared to the control group, though there was no change in telomere activity and no statistical difference in telomerase activity between the groups. This was a pilot study and, therefore, should be considered hypothesis-generating.

Subjects in the control group had slightly higher weight and body mass index and were older than the intervention group (though these differences were not statistically significant), and this may have impacted the results. In addition, this was a nonrandomized trial. Perhaps the health-seeking personalities of the individuals who were willing to participate in the comprehensive lifestyle changes may have factored into the outcome.

Nonetheless, the findings are intriguing and form a strong basis for prospective randomized trials. We look forward to more studies on diet and lifestyle interventions in men with prostate cancer from this group of highly experienced and committed investigators.

Further Considerations

Whereas medical scientists will continue to prove benefits to diet and lifestyle changes, social scientists will need to create the incentives to cause people to change their lifestyles. Full knowledge that smoking and obesity cause innumerable diseases and hundreds of thousands of deaths has not dissuaded tens of millions of humans from abusing their bodies.

With the rapidly evolving field of computer and sensor technology, we would anticipate interactive computer-based, mobile programs as having a positive impact in the future. Hopefully there will soon be a highly effective “app for that.”

Disclosure:

References

1. Ornish D, Lin J, Chan JM, et al: Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. Lancet Oncol 14: 1112-1120, 2013.

2. Ornish D, Lin J, Daubenmier J, et al: Increased telomerase activity and comprehensive lifestyle changes: A pilot study. Lancet Oncol 9:1048-1057, 2008.

<FOOTNOTE FOR FIRST COLUMN OF COMMENTARY>
Dr. Boxer is Visiting Professor at the David Geffen School of Medicine at UCLA, Clinical Professor at the University of Wisconsin, Madison, and the Medical College of Wisconsin (Milwaukee), and former Professor of Clinical Urology at the University of Miami. He is also an Associate Editor of The ASCO Post. Dr. Aronson is Clinical Professor, UCLA Department of Urology, and Chief of Urologic Oncology, VA Medical Center, Greater Los Angeles Healthcare System.

<PULLQUOTE>
“Whereas medical scientists will continue to prove benefits to diet and lifestyle changes, social scientists will need to create the incentives to cause people to change their lifestyles.”