ASCO 2017: A secondary analysis of PSA response in NRG Oncology/RTOG 9902: A phase III trial of adjuvant chemotherapy with androgen suppression and radiation for high-risk prostate cancer

Chicago, IL (UroToday.com) Over the past several years, we have seen a remarkable shift towards multiple treatment regimens at the onset of high-risk prostate cancer (PCa) diagnosis, particularly in subsets of populations that likely derive the greatest benefit from up front aggressive therapy. Dr. Stephen Mihalcik presented his group’s work of a post-hoc secondary analysis of RTOG 9902, a phase III trial of adjuvant chemotherapy with androgen suppression and radiation for high-risk prostate cancer. The objective of this analysis was to assess a subset of patients by post-radiation PSA that may identify patients that benefit from treatment intensification with chemotherapy. 

RTOG 9902 was a randomized controlled trial of the addition of adjuvant chemotherapy (paclitaxel, oral etoposide, and estramustine x4 cycles) to 24 months of androgen suppression and radiation for patients with high-risk prostate cancer, beginning with an initial 4 months of androgen suppression and radiotherapy beginning after 2 months.1 After accruing 397 patients, the study closed early due to excess toxicity. At a median follow-up of 9.2 years, there was deemed to be no benefit to chemotherapy. For this study, post-radiation PSA status was dichotomized at > 0.2 ng/mL within 1 month of RT. Landmark analysis was used to redefine start times for disease-free survival (DFS), time to distant metastasis, and overall survival (OS) at 16 weeks post-radiation (36 weeks after randomization) when chemotherapy was planned to be completed. Patients were excluded from this analysis if they did not get radiation or experienced DFS events/lost to follow-up <36 weeks after randomization. 

There were 333 patients available for analysis of which 190 did not and 143 patients did receive chemotherapy. There were 37% of patients that had a post-radiation PSA ≤0.2, 34% > 0.2, and 29% no recorded PSA in the defined interval. Chemotherapy was associated with improved DFS for patients with PSA > 0.2 (HR 0.59, 0.38-0.91), but not for those with PSA ≤0.2 (HR 0.94, 0.60-1.46; interaction p = 0.13). For those with PSA > 0.2 ng/mL, this association persisted for patients who received the full course of chemotherapy and trended in the same direction for patients receiving 1-3 cycles. Furthermore, chemotherapy was associated with a trend toward improved time to distant metastasis in the PSA > 0.2 group (HR 0.56, 0.23-1.35) but not in the PSA ≤0.2 group (HR 1.31, 0.36-4.70), based on 32 patients with metastases. OS did not show the same pattern and was consistent between the two groups. This is an important post-hoc analysis, with strong methodologic design. A limitation of the study is the small number of events.

In summary, the authors concluded that men with high-risk PCa and suboptimal response to androgen suppression + radiation, as identified by post-radiation PSA > 0.2, may benefit from adjuvant chemotherapy. Prospective trials using contemporary chemotherapy (e.g. docetaxel) will help optimize treatment for these men. As the authors note, an ongoing clinical trial (NRG-GU002) has started enrolling patients and will address this issue.

Presented By: Stephen A. Mihalcik, MD, PhD, Harvard Radiation Oncology Residency Program, Massachusetts General Hospital, Boston, MA, USA

Co-Authors: Meredith M. Regan, Seth A. Rosenthal, Glenn J. Bubley, Kenneth J. Pienta, Leonard G. Gomella, David A. Grignon, Alan C Hartford, Mark S. Morginstin, Jeff M. Michalski, Raghu Rajan, Andrew Michael McDonald, Michael M. Dominello, James Norman Atkins, Christopher U Jones, Jennifer Moughan, Howard M. Sandler, Irving D. Kaplan

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA

Reference:
1. Rosenthal SA, Hunt D, Sartor AO, et al. A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902
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