Journal
EUROPEAN UROLOGY
Volume 75, Issue 1, Pages 35-41Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.eururo.2018.08.033
Keywords
Androgen deprivation therapy; Gleason score; High-grade; Prostate cancer; Prostate-specific antigen
Categories
Funding
- Prostate Cancer Foundation
- Wood Family Foundation
- Baker Family
- Freeman Family
- Gina Ventre Fund
- Frashure Family
- Fitz's Cancer Warriors
- Campbell Family
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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. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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