Localized Prostate Cancer: The Battle of Treatment Options Enters the Larger Arena

So here we go again with one more round in the battle of treatment options for localized prostate cancer. While more than 3 decades of such sparring has gotten us no closer to evidence-based conclusions, one might say that these matches do serve the purpose of bringing out the best and the worst of the therapeutic contenders. Provoked by an invitation to extol the virtues of one treatment method over another, the authors commence with the usual vigor to bias the existing data in support of their opinion. Rather than tediously rebutting each and every point with my own contrary but likewise “data-supported” opinion, I would instead like to make a few points and offer what I hope are constructive alternatives.

Interpreting the Data

As Drs. Rayala and Richie point out, no randomized studies in the current era have compared definitive treatments for this disease. There is one bona fide trial, however, that did compare radical prostatectomy to watchful waiting, and it even has long-term follow-up. The results of this trial showed a meager 5.4% benefit in prostate cancer–specific survival for all surgical patients at 12 years after enrollment. In patients 65 years or older, there was, for all practical purposes, no benefit at all-one-tenth of 1%.[1] If we were to take the worst case for radiation and assume that there is no benefit over surveillance, one might then extrapolate that the maximum possible advantage of surgery over radiation would be approximately 5% using the Bill-Axelson data.[1] Surely that would cause any patient to seriously consider the associated quality-of-life issues. Perhaps some urologists have already recognized this, as evidenced by the thousands of patients who are currently being directed to urologist-owned, free-standing radiation therapy centers.

Lacking randomized trials that compare treatment options, the next level of evidence for the superiority of one treatment over another comes from retrospective studies such as the one by D’Amico et al,[2] which the authors of the “Prostatectomy Reigns Supreme” article point out is not contemporary with current radiation doses. They continue this thought, saying that with higher doses, toxicity is “known to be worse,” referencing the randomized dose-escalation study report that I authored.[3] Conveniently, however, Rayala and Richie fail to mention a very important point. In the referenced study, a 1990s radiation technique was used, and the discussion section of the paper clearly states that past outcomes have been used to derive parameters to substantially decrease complications and improve current radiation technique la intensity-modulated radiation therapy (IMRT). Many subsequent reports have, in fact, shown that delivering higher radiation doses with a low complication rate is routine in the current era. This is a good example of the misinterpreted bits of information that can be assembled to make one’s chosen point in this debate.

Difficult Choice

Considering all of the available information, which is too lengthy to present here, the 2007 American Urologic Prostate Cancer Clinical Guideline Panel concluded that “study outcomes data do not provide clear-cut evidence for the superiority of any one treatment” for localized prostate cancer.[4] Performing their own in-depth research, the Agency for Healthcare Research and Quality recently published a similar report, stating that “no one therapy can be considered the preferred treatment for localized prostate cancer due to limitations in the body of evidence as well as the likely tradeoffs an individual patient must make between estimated treatment effectiveness, necessity, and adverse effects”.[5] In view of this, we try to steer men toward a Multidisciplinary Prostate Cancer Clinic where patients can engage in decision-making and hear recommendations from multiple specialists, who try to personalize options but also reach consensus as much as possible. Additionally, we aim to enroll patients on a multidisciplinary quality-of-life study, which includes all definitive prostate cancer treatments available at our institution.

The difficult choice a man with prostate cancer faces has been discussed in public venues such as the New York Times and the Wall Street Journal. Most recently, it has been suggested that this disease, with its plethora of treatment choices each associated with a different monetary cost, be used as the “acid test” of health-care reform.[6] Obviously, the spotlight is upon us. The questions previously lurking in the back of our minds are now being openly pondered: Should every treatment be allowed, even if superiority has not been proven and the cost is substantially higher? Is treatment truly necessary, and why is surveillance not encouraged more often? Surely, this gets us to the heart of some very difficult ethical and quality-of-life issues.

Conclusion

In summary, many have recognized the fact that no one treatment for prostate cancer is superior or the right choice for all patients. Simultaneously, the current health-care climate has thrust prostate cancer into the high-profile arena. It appears that our heretofore professional treatment option jousts may in fact become a much larger-scale battle. It’s time-actually way past time-to get over it. It’s time to work in a multidisciplinary manner to help patients make treatment decisions based on their particular set of tumor, medical, psychological, and social circumstances, while using clinical studies to collect comparative information and quality-of-life data. Let’s hope that we continue to have the luxury to do this, and that future treatment decisions are not based more on cost than on the patients’ best interests.

Financial Disclosure: Dr. Kuban is a member of an advisory board for Calypso Medical.

References:

1. Bill-Axelson A, Holmberg L, Filen F, et al: Radical prostatectomy versus watchful waiting in localized prostate cancer: The Scandinavian Prostate Cancer Group-4 randomized trial. J Natl Cancer Inst 100:1144-1154, 2008.
2. D’Amico AV, Wittington R, Malkowicz SB, et al: Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 280:969-974,1998.
3. Kuban DA, Tucker SL, Dong L, et al: Long-term results of the M.D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 70:67-74, 2008.
4. Thompson I, Thrasher JB, Aus G, et al: Guidelines for the management of clinically localized prostate cancer: 2007 update. J Urol 177:2106-2131, 2007.
5. Wilt TJ, Shamliyan T, Taylor B, et al: Comparative effectiveness of therapies for clinically localized prostate cancer. Comparative Effectiveness Review No. 13. Rockville, Md; Agency for Healthcare Research and Quality; February 2008. Available at http://effectivehealthcare.ahrq.gov. Accessed August 6, 2009.
6. Leonhardt D: In health reform, a cancer offers an acid test. The New York Times, July 7, 2009.