Androgen deprivation therapy and the risk of death from prostate cancer among men with favorable or unfavorable intermediate-risk disease, "Beyond the Abstract," by Florence K. Keane, MD and Anthony V. D’Amico, MD, PhD

BERKELEY, CA (UroToday.com) - Intermediate-risk prostate cancer (PC) is a heterogeneous population with variable outcomes after standard PC treatments, which include external beam radiotherapy (EBRT), brachytherapy and androgen deprivation therapy (ADT) for 4 to 6 months in various combinations.[1] We previously validated the proposed division, by Zumsteg, et al., of intermediate-risk PC into favorable and unfavorable subgroups,[2] and demonstrated that men with unfavorable intermediate-risk prostate cancer have an increased risk of prostate cancer-specific mortality (PCSM) compared to those with favorable intermediate-risk PC.[3] While men with unfavorable intermediate-risk PC also had an increased risk of death when treated with low-dose RT alone vs RT and ADT, men with favorable intermediate-risk PC did not benefit from the addition of ADT to RT.

However, these patients were all treated with low-dose RT, not the currently accepted standard of dose-escalated RT. Therefore, we assessed and compared the risk of PCSM in men treated with dose-escalated RT in the following treatment combinations: brachytherapy with either neoadjuvant ADT or neoadjuvant EBRT in unfavorable intermediate-risk PC and brachytherapy with or without neoadjuvant ADT in favorable intermediate-risk PC.

In men with unfavorable intermediate-risk PC, the combination of short-course neoadjuvant ADT and brachytherapy was superior to neoadjuvant EBRT and brachytherapy in reducing the risk of PCSM. However, in men with favorable intermediate-risk PC, short-course neoadjuvant ADT did not reduce the risk of PC death when used in combination with brachytherapy.

The significance of these findings is as follows. First, given the reduced risk of PCSM in men with unfavorable intermediate-risk PC undergoing ADT and brachytherapy vs EBRT and brachytherapy, consideration to the former approach should be given now, particularly in healthy men with a long life expectancy given that the PC death rate estimates for the two treatment combinations begin to differ only 4 years after treatment. Validation of the superiority of ADT in addition to RT in unfavorable intermediate-risk PC awaits final reporting of RTOG 0815 (NCT00936390),[4] which is expected in 6 to 7 years. It is important to note, however, that if RTOG 0815 includes a significant number of patients with favorable intermediate-risk disease, it may be underpowered to detect an improvement in outcomes with the addition of ADT.

Second, the extremely low death rates in men with favorable intermediate-risk PC (< 1% at 8 years) seen in our study and in the study of Raldow et al.[5] begs the issue of whether active surveillance is appropriate for these men. We await reporting of the randomized ProtecT trial (NCT 02044172),[6] which is expected in 2016, for further data on the feasibility of active surveillance in this population.

References:

  1. Mohler JL, Kantoff PW, Armstrong AJ, Bahnson RR, Cohen M, D'Amico AV, et al. Prostate cancer, version 2.2014. J Natl Compr Canc Netw 2014;12:686–718.
  2. Zumsteg ZS, Spratt DE, Pei I, Zhang Z, Yamada Y, Kollmeier M, et al. A New Risk Classification System for Therapeutic Decision Making with Intermediate-risk Prostate Cancer Patients Undergoing Dose-escalated External-beam Radiation Therapy. Eur Urol 2013;64:895–902.
  3. Keane FK, Chen M-H, Zhang D, Loffredo MJ, Kantoff PW, Renshaw AA, et al. The likelihood of death from prostate cancer in men with favorable or unfavorable intermediate-risk disease. Cancer 2014;120:1787–93.
  4. Clinicaltrials.gov identifier: NCT00936390.
  5. Raldow AC, Zhang D, Chen MH, Braccioforte MH, Moran BJ and D’Amico AV. Risk Group and Death From Prostate Cancer: Implications for Active Surveillance in Men with Favorable Intermediate-Risk Prostate Cancer. JAMA Oncol 2015; doi:10.1001/jamaoncol.2014.284.
  6. Lane JA, Donovan JL, Davis M, et al. ProtecT study group. Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial. Lancet Oncol. 2014;15(10):1109-1118.


Written by:
Florence K. Keane, MD and Anthony V. D’Amico, MD, PhD 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.

Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA USA

Androgen deprivation therapy and the risk of death from prostate cancer among men with favorable or unfavorable intermediate-risk disease - Abstract

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