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•The authors of this multicenter, randomized, phase III trial compared continuous long-term adjuvant androgen deprivation therapy (ADT) and intermittent ADT in 280 men with locally advanced prostate cancer and PSA response following 6-months of neoadjuvant ADT. All patients received 8 months of external-beam radiation therapy combined with adjuvant ADT. After a median follow-up of >8 years, the modified biochemical relapse–free survival rates were similar between groups but did not meet noninferiority criteria since the estimated upper limit of the hazard ratio was 1.722, exceeding the predetermined statistical noninferiority threshold of 1.5. There was no difference in overall survival.
•Although the noninferiority of intermittent ADT was not confirmed, this does appear to be a promising treatment strategy.
– Paul J. Hampel, MD
BACKGROUND
To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT).
METHODS
A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death.
RESULTS
The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722).
CONCLUSIONS
Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa.
Citation: Cancer 2020 Jun 23;[EPub Ahead of Print], K Ito, M Kobayashi, M Komiyama, S Naito, K Nishimura, J Yonese, K Hashine, S Saito, G Arai, M Shinohara, N Masumori, N Shimizu, T Satoh, A Yamauchi, T Tochigi, Y Takezawa, H Fujimoto, A Yokomizo, KI Kakimoto, I Fukui, K Karasawa, T Tsukamoto, M Nozaki, M Hasumi, H Ishiyama, M Ohtani, M Kuwahara, M Harada, Y Ohashi, T Kotake, T Kakizoe, K Suzuki, H Yamanaka
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