This is not the first report to reach such a disheartening conclusion, but it does come from a robust and representative dataset and offers additional insights into the reasons behind the reluctance to embrace [active surveillance in low-risk prostate cancer].
—Anthony L. Zietman, MD
Active surveillance is well established as an appropriate management option for men with low-risk prostate cancer and particularly for those over 65 years of age. Its legitimacy is now enshrined within National Comprehensive Cancer Network guidelines, in the American Society for Radiation Oncology Choosing Wisely campaign proclamations, and, indirectly, though the new American Urological Association guidelines on early detection of prostate cancer.1-3
A recent report by Hoffman et al, reviewed in this issue of The ASCO Post, uses the Surveillance, Epidemiology, and End Results database to look at a large number of contemporary men aged 66 years and older and concludes that for those with low-risk disease, active surveillance is far “more honored in the breach than in the observance.” This is not the first report to reach such a disheartening conclusion, but it does come from a robust and representative dataset and offers additional insights into the reasons behind the reluctance to embrace it.4
Why, despite accumulating evidence, might this state of affairs exist? The Hoffman et al report details a contemporary period of 2006–2009 for which Medicare data are available. The landmark PIVOT study, however, was not published until 2012, and it is possible that more recent data, if it had been available, might have shown different trends.5
Clinicians, it could be argued, may have been awaiting stronger evidence. It must be pointed out, however, that the early results of the Swedish randomized trial comparing simple observation with prostatectomy were available during this interval and, at that stage, showed no survival gains for aggressive treatment even for those with more advanced disease.6 Many large prospective active surveillance cohorts had also been published in high-profile journals. It seems, therefore, that a lack of data was not the issue.
Goals Other Than Cure
The first decade of this millennium was a time of extraordinarily exciting technologic advances in both radiation oncology and surgery, with unprecedentedly enthusiastic and rapid adoption of the new techniques into the clinic ahead of evidence. It may be that clinicians truly believed that the morbidity of their treatments was now so reduced that the scales tilted in favor of treatment.
After all, we treat everyone with mild hypertension or hyperlipidemia even though only a small proportion of the population with these conditions is destined to suffer serious consequences. We do this because the morbidity of the medications offered appears to be low and, when one considers the population rather than the individual advantages, the question is not “why?” but “why not?” Technology has not, unfortunately, rendered the consequences of a robotic prostatectomy or of intensity-modulated radiation therapy to be as innocent as a thiazide diuretic or a statin.
Some have argued that there are goals other than cure that are worth striving for in men with low-risk disease, such as freedom from anxiety and freedom from androgen deprivation. Freedom from anxiety is, I believe, the responsibility of the physician and not the treatment, and several quality-of-life studies show that a well-informed, well-counseled, and well-supported patient is perfectly happy with active surveillance.7
Freedom from androgen deprivation is a worthy goal, since it is likely that the adverse quality-of-life consequences of this particular form of therapy are far greater than initial treatment with surgery or radiation. It is unclear how often a man who is diagnosed with prostate cancer and left alone without curative treatment ultimately comes to androgen deprivation, but the Swedish trial suggests it may be a significant minority by 14 years—although it must be emphasized that these were not screened men.8 That proportion is likely to be much lower in a U.S. population.
Detractors of active surveillance point to the inaccuracy of needle biopsies in staging and grading prostate cancer when compared with prostatectomy specimens. That is indeed true, but is also true for all the active surveillance series in which very high rates of disease-specific survival at 10 years are routinely found despite this undergrading and understaging. Fear of missing higher-risk disease may lead to very aggressive surveillance with annual biopsies or magnetic resonance imaging, the prospect of which may also make treatment seem relatively appealing.
Cultural and Economic Obstacles
The biggest obstacles to the greater use of active surveillance in the United States are, regrettably, cultural and economic in nature, and the latter was hinted at in the Hoffman et al article. When a physician enjoys a financial gain if he treats and perceives the risk of a litigation loss if he does not, then the consequences are hardly difficult to predict. In our fee-for-service system, certain services are more generously reimbursed than others, and the face-time spent counseling a patient reimburses lowest of all.
If one factors in curious perverse incentives (such as dubious self-referral practices) that exist within our system, then the problem is amplified.9 Prostate cancer does not have a good record in this regard—and the massive use of androgen deprivation prevalent in the 1990s was terminated suddenly in 2003 by federal fines, a change in reimbursement, and the closing of a legal loophole.10
Reasons for Optimism
I remain optimistic, however, that things will change for the better. New, high-quality evidence will emerge in the next 2 years from the ProtecT randomized trial taking place in the United Kingdom.11 This beautifully organized trial has studied screening in an enormous cohort of men, and there is a further randomization to surgery, radiation, or active surveillance for those in whom cancer is detected. It completed accrual ahead of schedule and, while we must not anticipate its findings, its wealth of data will drive future practice.
In another recent development, several groups have clearly documented that multidisciplinary clinics increase the uptake of active surveillance.12 This is likely because two or three physicians from different specialties seeing a patient together and singing harmoniously the same active surveillance song provide great reassurance for patients. It is also probable that effective, synchronous multidisciplinary clinics keep all the physicians honest and prevent exaggerated claims about any one therapy.
Also critical to patterns of practice will be health-care payment reform, which now seems inevitable. We don’t know when it will come or what exact form it will take, but it is likely that attempts will be made to align financial incentives with best practices.
Hoffman et al point out the extraordinary physician variation in the management of prostate cancer and, after illustrating that it has a strong economic basis, recommend public reporting of a physicians’ cancer management profiles. This would represent a “name and shame” approach that might provide a solution while we await payment reform. If physicians cannot do the right thing for the right reasons, then the second-best resolution would be that they at least do the right thing for the wrong reasons. ■
Disclosure: Dr. Zietman reported no potential conflicts of interest.
1. Mohler JL, Kantoff PW, Armstrong AJ, et al: Prostate cancer version 2.2014. J Natl Compr Canc Netw 12:686-718, 2014.
2. American Society for Radiation Oncology/Choosing Wisely Initiative: Five things physicians and patients should question. September 23, 2013. Available at www.choosingwisely.org/doctor-patient-lists/american-society-for-radiation-oncology/
3. Carter HB, Albertsen PC, Barry MJ, et al: Early detection of prostate cancer: AUA guideline. J Urol 190:419-426, 2013.
4. Hoffman KE, Niu J, Shen Y, et al: Physician variation in management of low-risk prostate cancer: A population-based cohort study. JAMA Intern Med. July 14, 2014 (early release online).
5. Wilt TJ, Brawer MK, Jones KM, et al: Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 367:203-213, 2012.
6. Bill-Axelson A, Holmberg L, Ruutu M, et al: Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 352:1977-1984, 2005.
7. Burnett KL, Parker C, Dearnaely D, et al: Does active surveillance for men with prostate cancer carry psychological morbidity. BJU Int 100:540-543, 2007.
8. Bill-Axelson A, Holmberg L, Garmo H, et al: Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med 370:932-942, 2014.
9. Mitchell J: Urologists’ use of intensity-modulated radiation therapy for prostate cancer. N Engl J Med 369:1629-1635, 2013.
10. McKoy JM, Lyons EA, Obadina E, et al: Caveat medicus: Consequences of federal investigations of marketing activities of pharmaceutical suppliers of prostate cancer drugs. J Clin Oncol 23: 8894-8905, 2005.
11. Lane JA, Hamdy FC, Martin RM, et al: Latest results from the UK trials evaluating prostate cancer treatment and screening: The CaP and ProtecT studies. Eur J Cancer 46:3095-3101, 2010.
12. Aizer AA, Paley JJ, Zietman AL, et al: Multidisciplinary care and the pursuit of active surveillance in low-risk prostate cancer. J Clin Oncol 30: 3071-3076, 2012.
Dr. Zietman is Shipley Professor of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston.