Interest of short hormonotherapy (HT) associated with radiotherapy (RT) as salvage treatment for metastatic free survival (MFS) after radical prostatectomy (RP): Update at 9 years of the GETUG-AFU 16 phase III randomized trial (NCT00423475).

Abstract

5001 Background: RT is the standard salvage treatment after RP. The role of HT is not formally demonstrated to date. This trial assessed the efficacy of RT alone vs RT+HT in terms of progression-free survival (PFS), metastase-free survival (MFS) and overall survival (OS) in patients with biological relapse (BR) after RP. After a median follow-up (FU) duration of 5.3 years, we previously reported [Carrie C, Lancet Oncol 2016] a benefit in PFS (80% vs 62% PFS free at 5 years; p < 0.0001) in the combined arm, whatever the risk subgroups. Methods: Patients (pts) were randomized (1:1) to RT alone or RT+HT (goserelin, for 6 months). The randomization was stratified according to radiotherapy modality and risk group. Low risk was defined as Gleason score < 8, surgical margins+, psa doubling time > 8 months and no seminal vesicle involment. Assuming a 45% 5-year PFS of 45% in the RT arm, the trial required 369 pts per arm to detect an improvement of 12% on PFS in RT+HT arm (90% power and 5% bilateral alpha risk), possibly translating into a 10% gain in OS (75% to 85% with 80% power). Biological relapse (BR) was defined according to ASTRO-consensus. Results: At the time of data cutoff (March 2019), the median duration follow-up was 112 months. We confirm the benefit of RT+HT on PFS (HR = 0.54 [CI95% = 0.43-0.68] ; p < 0.0001) whatever the risk subgroup (HR = 0.47 [CI95% = 0.28-0.80] and 0.56 [CI95% = 0.44-0.73] for low and high risk patients, respectively. Metastatic free survival (MFS) is significantly improved in the combined arm (HR = 0.73 [CI95% = 0.54-0.98] ; p = 0.034) with 69% [CI95% = 63-74] versus 75% [CI95% = 70-80] of MFS at 10 years for RT alone and RT+HT, respectively. Conclusions: Salvage radiotherapy combined with short term HT significantly improved 10-years metastatic free survival compared with salvage radiotherapy alone. GETUG-16 considered in the context of previously published results from RTOG-9601, confirm that this strategy can be considered as the new standard for salvage treatment after radical prostatectomy. Clinical trial information: NCT00423475.

Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

“…39 Post hoc subgroup analysis indicated that men with a pre-SRT PSA above 0.7 ng/ml, GS 8-10 and positive margins had the largest benefit from the addition of bicalutamide. 39 The GETUG-AFU 16 trial showed an improvement in metastasis-free survival (HR 0.73; 95% CI 0.54e0.98; P ¼ 0.034), 40 but not OS.…”

Combined Long-Term Androgen Deprivation and Pelvic Radiotherapy in the Post-operative Management of Pathologically Defined High-Risk Prostate Cancer Patients: Results of the Prospective Phase II McGill 0913 Study

“…Three large randomized phase III trials of salvage radiotherapy in prostate cancer have investigated combining prostate bed radiotherapy (PBRT) with androgen deprivation therapy (ADT) and/or pelvic lymph node radiotherapy (PLNRT). GETUG-AFU 16's salvage patients had a benefit in metastasis-free survival when short-term ADT (ST-ADT) was added to locoregional treatment (PBRT with PLNRT or previous dissection), compared to no ADT (1). RTOG 0534, also called SPPORT, noted improvements in biochemical progression-free survival (PFS) by adding PLNRT to the combination of PBRT and ST-ADT, compared to PBRT and ST-ADT only (2).…”

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer

“…86 The randomised phase III GETUG-AFU 16 trial showed ADT to improve metastasis-free survival (HR 0.73; 95% CI 0.54-0.98; P ¼ 0.034), but not overall survival. 87 In a United States study, comparison of pelvic node RT plus 6 months of ADT with prostate bed-only RT or prostate bed RT plus 6 months of ADT showed the addition of pelvic RT to improve freedom from failure and freedom from metastases compared with prostate bed-only RT (HR 0.52; 95% CI 0.30-0.92; P ¼ 0.014). 88 Thus, all the Asian experts accepted completely (100% consensus) 'recommendations 7a-e' below.…”