Androgen Deprivation Therapy and Overall Survival for Gleason 8 Versus Gleason 9-10 Prostate Cancer

Background: While the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) is known to improve overall survival (OS) in Gleason 8-10 (Grade Group 4-5) prostate cancer (PCa), it has been hypothesized that Gleason 9-10 disease, which is less differentiated than Gleason 8 disease, may be less sensitive to ADT.

Objective: To examine the association between ADT and OS for Gleason 8 versus Gleason 9-10 PCa.

Design, setting, and participants: A retrospective cohort study of 20 139 men from the National Cancer Database with localized or locally advanced, Gleason 8-10 PCa who received EBRT. Data were collected from 2004 to 2012.

Intervention: ADT.

Outcome measurements and statistical analysis: Cox proportional hazards regression was used to examine the association between ADT and OS.

Results and limitations: Overall, 9509 (78%) of the 12 160 men with Gleason 8 disease and 6908 (87%) of the 7979 men with Gleason 9-10 disease received ADT. On multivariable analysis, ADT was associated with a significant improvement in OS for Gleason 8 patients (adjusted hazard ratio 0.78, 95% confidence interval 0.70-0.87, p<0.001) but not for Gleason 9-10 patients (adjusted hazard ratio 0.96, 95% confidence interval 0.84-1.11, p=0.6), with a significant interaction (p_interaction=0.020). A higher Gleason score (8, 9, 10) correlated with an increased adjusted hazard ratio for the association between ADT and OS (p_interaction=0.042). Our study may be limited by the relatively short follow-up (median of 4.0 yr).

Conclusions: In contrast to the significant survival advantage of ADT for Gleason 8 disease, our results suggest that Gleason 9-10 disease derives less survival benefit from ADT and that a higher Gleason score predicts lesser benefit. Consideration should be given to treatment intensification for Gleason 9-10 patients through enrollment in clinical trials or potentially adding novel antiandrogens or docetaxel, which have shown efficacy in both castration-resistant and castration-sensitive settings.

Patient summary: In this study, we examined the effect of androgen deprivation therapy (ADT) for Gleason 8 (Grade Group 4) versus Gleason 9-10 (Grade Group 5) prostate cancer. We found that Gleason 9-10 disease may derive a smaller survival benefit from ADT than Gleason 8 disease.