CUA 2017: Role of Androgen Deprivation in Salvage Radiotherapy

Toronto, Ontairo (UroToday.com) Dr. Tamim Niazi, from McGill University provided an excellent summary of the literature on the role for androgen-deprivation therapy (ADT) in patients undergoing salvage radiotherapy (RT).

First, he reviewed the literature for adjuvant RT. While there is clearly evidence for the benefit of adjuvant radiotherapy for high-risk patients based on SWOG 8794/PR-2, EORTC 22911, and ARO 96-02. The benefit is primarily for biochemical recurrence-free survival (BCR survival), progression-free survival (PFS) and metastases-free survival. In both studies, there was no overall survival benefit (OS), though it likely would have reached significant with longer follow-up in the PR2 study. 

He then went into the discussion of patients getting salvage RT, with a focus on the role of ADT. In the GETUG-AFU 16 trial,1 high-risk patients post-prostatectomy with a rising PSA between 0.2-2.0 ng/dL were randomized to either RT alone or RT + goserelin. PFS was 80% vs. 62% in favor of goserelin, but no different in OS. There was a slight risk in cardiac adverse events (hypertension), but no specific cardiac events (MI, etc.). There were also no additional GU or GI adverse events as a result of the addition.

Then he addressed the RTOG 9601 study.2 This study began accruing many years ago, as such the ADT utilized was bicalutamide – partly due to the time period and partly due to pharmaceutical funding. However, this does limit the results somewhat as bicalutamide is no longer the standard of care ADT regimen. In this study, 760 patients were randomized to RT alone (no pelvic node RT due to prior pN0 status) or RT with bicalutamide. The initial report in 2011 suggested improved freedom from progression, less metastases, and improved actuarial OS. Importantly, while cancer-specific mortality was less in the bicalutamide arm, the non-prostate cancer specific deaths were similar between the groups – suggesting bicalutamide did not increase adverse event profiles leading to death. Based on this, they concluded that 24 months of ADT (bicalutamide) to salvage RT resulted in significantly higher rates of OS and lower incidence of metastatic cancer and death. 

Future and ongoing randomized trials (including the RADICALS trial) may help address the duration of ADT with salvage RT. While the results suggest benefit of ADT, the duration is not yet clear. 

This was a nice summary of the role of ADT for salvage RT, and its potential sensitizing role. It looks like it is here to stay, though commentary from the crowd did indicate some degree of clinical flexibility depending on patient presentation. Some providers were less likely to give it in patients with minimal high-risk features. 

Presented By: Tamim Niazi, MD, Assistant Professor of the Department of Oncology, McGill University, Montréal, Québec

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto  Twitter: @tchandra_uromd at the  72nd Canadian Urological Association Annual Meeting - June 24 - 27, 2017 - Toronto, Ontario, Canada

References:

1. Carrie C, Hasbini A, de Laroche G, Richaud P, Guerif S, Latorzeff I, Supiot S, Bosset M, Lagrange JL, Beckendorf V, Lesaunier F, Dubray B, Wagner JP, N'Guyen TD, Suchaud JP, Créhange G, Barbier N, Habibian M, Ferlay C, Fourneret P, Ruffion A, Dussart S. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol. 2016 Jun;17(6):747-56. doi: 10.1016/S1470-2045(16)00111-X. Epub 2016 May 6.

2. Shipley WU, Seiferheld W, Lukka HR, Major PP, Heney NM, Grignon DJ, Sartor O, Patel MP, Bahary JP, Zietman AL, Pisansky TM, Zeitzer KL, Lawton CA, Feng FY, Lovett RD, Balogh AG, Souhami L, Rosenthal SA, Kerlin KJ, Dignam JJ, Pugh SL, Sandler HM; NRG Oncology RTOG. Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer. N Engl J Med. 2017 Feb 2;376(5):417-428. doi: 10.1056/NEJMoa1607529.