Results from a secondary analysis of the RTOG 9408 trial found that the addition of androgen deprivation therapy (ADT) to radiation therapy had no benefit for patients with favorable intermediate-risk prostate cancer (JAMA Netw Open. 2020 Sep 1;3(9):e2015083. doi:10.1001/jamanetworkopen.2020.15083).
“Use of [ADT] during radiotherapy is controversial in intermediate-risk prostate cancer. Retrospective data suggest that ADT benefits patients with unfavorable, but not favorable, intermediate-risk cancer but are limited by selection bias and limited follow-up,” explained Zachary S Zumsteg, MD, Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California, and colleagues.
The RTOG 9408 trial was a randomized trial evaluating radiotherapy with or without 4 months of ADT for patients with localized prostate cancer. This approved secondary analysis of the trial examined the effect of ADT on long-term outcomes of intermediate-risk prostate cancer classified as favorable and unfavorable.
A total of 890 patients were stratified as having either favorable intermediate-risk (FIR; n = 377) or unfavorable intermediate-risk (UIR; n = 513)) prostate cancer according to primary Gleason score, percentage of positive biopsy cores, and number of intermediate-risk factors. The median follow-up duration for this analysis was 17.8 years.
Patients with UIR disease were shown to have a higher risk of distant metastasis, (hazard ratio [HR], 2.36; 95% CI, 1.44 to 3.89; P = .001), prostate-cancer specific mortality (HR, 1.84; 95% CI, 1.29 to 2.62; P = .001), and all-cause mortality (HR, 1.19; 95% CI, 1.02 to 1.40; P = .03) compared with patients with FIR disease.
For patients with FIR disease, ADT did not improve distant metastasis (HR, 1.55; 95% CI, 0.64 to 3.74; P = .33), prostate cancer specific mortality (HR, 0.63; 95% CI, 0.35 to 1.15; P = .13), or all-cause mortality (HR, 1.02; 95% CI, 0.80 to 1.30; P = .90). However, for patients with UIR disease, ADT improved DM (HR, 0.48; 95% CI, 0.28 to 0.83; P = .008) and prostate cancer specific mortality (HR, 0.40; 95% CI, 0.26 to 0.60; P <.001), but not all-cause mortality (HR, 0.84; 95% CI, 0.68 to 1.03; P = .09).
Additionally, the 15-year restricted mean survival time was longer with ADT vs without ADT for patients with UIR disease (10.5 vs 9.8 years; difference, 0.7 year; 95% CI, 0.001 to 1.6 years; P = .0497), but no significant difference was observed for patients with FIR disease (11 vs 10.7 years; difference, 0.3 year; 95% CI, −0.6 to 1.2 years; P = .50).
“In summary, to our knowledge, these results are the highest quality to date supporting a dichotomization of intermediate-risk prostate cancer into favorable and unfavorable subgroups, and support National Comprehensive Cancer Network recommendations to limit ADT use for patients with UIR disease,” Dr Zumsteg and colleagues concluded.
“Future studies exploring genomic classifiers to further personalize therapy in intermediate-risk prostate cancer should be performed,” they added.—Janelle Bradley
