Long-term oncologic outcomes were superior with adjuvant androgen-deprivation therapy (ADT) over neoadjuvant ADT when combining hormone therapy with radiation therapy (RT) in localized prostate cancer, according to findings from a pooled analysis of 2 randomized phase 3 trials.1
At a median follow-up of 15 years, the pooled analysis showed statistically significant improvements with adjuvant ADT over neoadjuvant ADT in biochemical failure, distant metastasis, and progression-free survival rates.
“We demonstrate for the first time that sequencing of ADT with RT significantly impacts long-term oncologic outcomes in localized prostate cancer, favoring an adjuvant- rather than neoadjuvant-based approach, without increasing late toxicity. This data has important implications to ongoing and future clinical trial design,” first study author Daniel E. Spratt, MD, professor of radiation oncology at the University of Michigan, Ann Arbor, and coinvestigators wrote in their study conclusion.
The first trial used for the pooled analysis was a phase 3 trial by Malone et al2 which randomized patients with localized prostate cancer to neoadjuvant/concurrent or concurrent/adjuvant ADT for 6 months with prostate only radiotherapy. These data were combined with the prostate only radiotherapy arms of the phase 3 RTOG 9413 trial,3 in which patients were randomized to 4 months of either adjuvant ADT or neoadjuvant/concurrent ADT.
In the pooled analysis, the “neoadjuvant” group included patients in the neoadjuvant/concurrent arms of both prior studies, and the “adjuvant” group included patients from the adjuvant arm of RTOG 9413 and the concurrent/adjuvant arm of Malone et al’s study.
Overall, there were 1065 patients included in the pooled analysis, comprising 531 patients who received neoadjuvant ADT and 534 patients who received adjuvant ADT. Baseline patient and tumor characteristics were well balanced between the 2 arms.
The biochemical failure rate at 15 years was 33% with adjuvant ADT versus 43% with neoadjuvant ADT (HR, 1.37; P = .002). At 15 years, 12% of patients receiving adjuvant ADT had distant metastasis compared with 18% of patients who received neoadjuvant ADT (HR, 1.40; P = .04). The 15-year PFS rates were 36% versus 29%, respectively (HR, 1.25; P = .01).
Prostate cancer–specific mortality (PCSM) rates were also lower with adjuvant ADT at 15% versus 20% with neoadjuvant ADT; however, the difference was not statistically significant (HR, 1.29; P = 0.10). Of note, the difference in PCSM rate favoring adjuvant ADT did approach statistical significance in patients with high-risk disease (HR, 1.39; P = .053).
Although the 15-year overall survival rate was higher with adjuvant ADT, the difference was not statistically significant: 39% versus 34% (HR, 1.11; P = .20).
Regarding toxicity, late grade ≥3 gastrointestinal (P = .21) or genitourinary (P = .98) adverse events were not significantly higher with adjuvant ADT.
1. Spratt DE, Malone S, Roy S, et al. Short-Term adjuvant versus neoadjuvant hormone therapy in localized prostate cancer: a pooled individual patient analysis of two randomized phase 3 trials. Int J Radiat Oncol Biol Phys. 2020;108(3):S17. doi.org/10.1016/j.ijrobp.2020.07.2099
2. Malone S, Roy S, Eapen L, et al. Sequencing of androgen-deprivation therapy with external-beam radiotherapy in localized prostate cancer: A phase III randomized controlled trial. Clinical Trial J Clin Oncol. 2020;38(6):593-601. doi: 10.1200/JCO.19.01904
3. Roach M, Moughan J, Lawton CAF, et al. Sequence of hormonal therapy and radiotherapy field size in unfavourable, localised prostate cancer (NRG/RTOG 9413): long-term results of a randomised, phase 3 trial. Lancet Oncol. 2018;19(11):1504-1515. doi: 10.1016/S1470-2045(18)30528-X