BERKELEY, CA (UroToday.com) -
Post-prostatectomy Management of Patients with Adverse Pathologic Features: Why is there no Consensus?
In this study, we surveyed United States prostate cancer specialists to assess post-prostatectomy radiotherapy practice patterns and the opinions on which they are based.1 We detected significant variability in practice patterns among clinicians; there were only a handful of questions for which answers were nearly uniform (e.g., only 3% of respondents stated that they would never use adjuvant radiotherapy [ART]). We also found that typical treatment recommendations differed dramatically between specialties. This could be explained by the fact that radiation oncologists and urologists have different perceptions of both the efficacy and toxicity of post-prostatectomy radiotherapy.
Many radiation oncologists now consider ART as standard of care for patients with one or more adverse pathologic features (positive surgical margin, extracapsular extension, or seminal vesicle invasion). This stems from three remarkably similar randomized trials that examined the use of ART following prostatectomy.2-4 In each trial, patients with one or more adverse pathologic features were randomized to receive postoperative radiotherapy to a dose of 60-64 Gy - or observation. ART improved biochemical progression-free survival in each study, with absolute improvements of 18-28% after 5 years. In the study with the most mature data, ART was found to confer an 11% improvement in overall survival with a median follow-up of 12.5 years.5 Based on the results of these three pivotal trials, current NCCN guidelines recommend ART following prostatectomy for all men with adverse pathologic features.6
Closer examination of those studies, however, provides fodder for opponents of ART. Only the German study excluded patients with detectable postoperative PSA; in both the EORTC and the SWOG study approximately 1/3 of patients had postoperative PSA levels of 0.2 ng/mL or greater. By current standards, those patients received (or did not receive, depending on randomization) salvage radiotherapy rather than ART. In addition, patients who relapsed following observation may not have received optimal salvage therapy; 53% and 63% of such patients received pelvic radiotherapy in the EORTC and SWOG trials, respectively. In the absence of disseminated disease, all such patients should receive salvage radiotherapy under current NCCN recommendations.6 These criticisms of the ART studies, which would have been impossible to anticipate at the time the trials were designed, may contribute to the fact that many clinicians do not routinely recommend ART following prostatectomy and instead advocate for close PSA surveillance.
Two ongoing trials address the question of ART versus PSA surveillance and salvage radiotherapy.7 In TROG 08.03, 470 patients with adverse pathologic features following prostatectomy and postoperative PSA ≤0.1 ng/mL will be randomized to receive ART or active surveillance with early salvage RT for patients whose PSA reaches 0.2 ng/mL. Both ART and salvage radiotherapy will be directed to the prostate bed, with a total dose of 64 Gy in 32 fractions. The primary endpoint is biochemical failure, defined as a PSA ≥0.4 ng/mL and rising following radiotherapy. The study is expected to be completed in 2020.
A similar trial is also being conducted in France.7 The main difference in the French trial is that patients on both arms will receive short-term androgen deprivation therapy along with postoperative radiotherapy. The primary endpoint is event-free survival, defined as lack of clinical progression, biochemical progression, and death. Estimated enrollment will be 718 patients, and the study is scheduled to be completed in 2022.
It is clear that the debate over ART versus close surveillance and salvage radiotherapy will not be settled by randomized trials in the near future. Until definitive data are available, we believe that all prostatectomy patients who are found to have adverse pathologic features should be evaluated in a multidisciplinary setting. Based on available randomized trial data, ART remains the standard of care. Patients who are instead managed with PSA surveillance should be aware that the safety of this approach has not yet been established.
- Showalter TN, Ohri N, Teti KG, et al. Physician Beliefs and Practices for Adjuvant and Salvage Radiation Therapy After Prostatectomy. Int J Radiat Oncol Biol Phys, 2010.
- Wiegel T, Bottke D, Steiner U, et al. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol 2009;27:2924-2930.
- Bolla M, van Poppel H, Collette L, et al. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet 2005;366:572-578.
- Thompson IM, Jr., Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA 2006;296:2329-2335.
- Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol 2009;181:956-962.
- NCCN Clinical Practice Guidelines in Oncology. Version 4.2011.
Nitin Ohri, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.