Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-Term Update of NRG Oncology RTOG 9202

Abstract

Purpose Trial**** was a phase III randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced non-metastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease. Materials and Methods Men (N=1,554) with adenocarcinoma of the prostate (cT2c-T4, N0- Nx) with a prostate specific antigen (PSA) <150ng/ml and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short term ADT (STAD: 4 months of flutamide 250mg three times per day and goserelin 3.6mg per month) and definitive RT verses long term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin). Results Among 1,520 protocol eligible and evaluable patients, median follow up for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease free survival (29% relative reduction in failure rate, p<0.0001), local progression (46% relative reduction, p=0.02), distant metastases (36% relative reduction, p<0.0001), disease specific survival (30% relative reduction, p=0.003), and overall survival (12% relative reduction, p=0.03). Other cause (non-prostate cancer) mortality did not differ (5% relative reduction, p=0.48). Conclusions LTAD and RT is superior to STAD and RT for the treatment of locally advanced non-metastatic adenocarcinoma of the prostate and should be considered the standard of care.

Large institutional variations in use of androgen deprivation therapy with definitive radiotherapy in a population‐based cohort of men with intermediate‐ and high‐risk prostate cancer

“…Equally critical in the evaluation of the pattern of use of ADT is the timing and duration of ADT. For men with high-risk PCa, multiple randomized controlled trials, including RTOG 92-02, EORTC 22961 and TROG 03.04, have all shown that short-term ADT (3-6 months) is inferior to long-term ADT (1.5-3 years) [6,7,9,33], and for men with intermediate-risk PCa, there are some data suggesting that 6-8 months of ADT is superior to 3 months of ADT [3,8]; however, there is little evidence as to whether longer-term ADT in men with intermediate-risk PCa provides further clinical benefits. Unfortunately, given the nature of data captured in PCOR-Vic, there are no data on duration or type of ADT used for each patient, which is another limitation of this study.…”

“…Multiple randomized controlled trials to date have consistently shown that adding ADT to RT is associated with improved overall survival in men with intermediate-to high-risk PCa [1][2][3][4][5]; however, controversies remain regarding the role of ADT given the potential side effects, deterring some radiation oncologists from prescribing ADT with RT. There are also ongoing controversies regarding timing, duration [6][7][8][9] and type of ADT prescribed [10][11][12]. Recent findings from the US National Cancer Database (NCDB) have shown that, over time, there is a decreasing trend in the use of ADT with RT in men with intermediate-risk PCa [13].…”

Optimal Androgen Deprivation Therapy Combined with Proton Beam Therapy for Prostate Cancer: Results from a Multi-Institutional Study of the Japanese Radiation Oncology Study Group

“…Several randomized trials and meta-analyses performed in the 1990s and 2000s showed a significant benefit of androgen deprivation therapy (ADT) combined with RT in terms of biochemical control and overall survival (OS) among patients with intermediate-risk and high-risk PC [4][5][6][7]. Because the relatively low irradiation doses (65-70 Gy) were used in those trials, the optimal duration of ADT to use in combination with high-dose RT remains unknown [8].…”

Optimizing the role of androgen deprivation therapy in advanced prostate cancer: Challenges beyond the guidelines

“…In all studies, there was greater benefit with adjuvant ADT given for at least 3 months compared with no ADT, and the panel concluded that optimal dosing of ADT for use with RT is 4 to 6 months for intermediate-risk patients and 18 to 36 months for high-risk patients. [23][24][25][26][27][28][29] The first dose of ADT should be administered 1 to 2 months before beginning RT. ability to measure PSA with ultrasensitive assays advances, these definitions may change.…”