Androgen Deprivation and Radiotherapy with or Without Docetaxel for Localized High-risk Prostate Cancer: Long-term Follow-up from the Randomized NRG Oncology RTOG 0521 Trial

Sartor, O; Karrison, TG; Sandler, HM; Gomella, LG; Amin, MB; Purdy, J; Michalski, JM; Garzotto, MG; Pervez, N; Balogh, AG; Rodrigues, GB; Souhami, L; Reaume, MN; Williams, SG; Hannan, R; Jones, CU; Horwitz, EM; Rodgers, JP; Feng, FY; Rosenthal, SA

Author(s): Sartor, O; Karrison, TG; Sandler, HM; Gomella, LG; Amin, MB; Purdy, J; Michalski, JM; Garzotto, MG; Pervez, N; Balogh, AG; Rodrigues, GB; Souhami, L; Reaume, MN; Williams, SG; Hannan, R; Jones, CU; Horwitz, EM; Rodgers, JP; Feng, FY; Rosenthal, SA;
Details: Publication Year 2023-08,Volume 84,Issue #2,Page 156-163
Journal Title: European Urology
Publication Type: Research article
Abstract: BACKGROUND: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer. OBJECTIVE: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT. DESIGN, SETTING, AND PARTICIPANTS: High-risk localized prostate cancer patients (>50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was overall survival (OS). Analyses with Cox proportional hazards were performed as prespecified in the protocol; however, there was evidence of nonproportional hazards. Thus, a post hoc analysis was performed using the restricted mean survival time (RMST). The secondary endpoints included biochemical failure, distant metastasis (DM) as detected by conventional imaging, and disease-free survival (DFS). RESULTS AND LIMITATIONS: After 10.4 yr of median follow-up among survivors, the hazard ratio (HR) for OS was 0.89 (90% confidence interval [CI] 0.70-1.14; one-sided log-rank p = 0.22). Survival at 10 yr was 64% for ADT + EBRT and 69% for ADT + EBRT + docetaxel. The RMST at 12 yr was 0.45 yr and not statistically significant (one-sided p = 0.053). No differences were detected in the incidence of DFS (HR = 0.92, 95% CI 0.73-1.14), DM (HR = 0.84, 95% CI 0.73-1.14), or prostate-specific antigen recurrence risk (HR = 0.97, 95% CI 0.74-1.29). Two patients had grade 5 toxicity in the chemotherapy arm and zero patients in the control arm. CONCLUSIONS: After a median follow-up of 10.4 yr among surviving patients, no significant differences are observed in clinical outcomes between the experimental and control arms. These data suggest that docetaxel should not be used for high-risk localized prostate cancer. Additional research may be warranted using novel predictive biomarkers. PATIENT SUMMARY: No significant differences in survival were noted after long-term follow-up for high-risk localized prostate cancer patients in a large prospective trial where patients were treated with androgen deprivation therapy + radiation to the prostate +/- docetaxel.
Publisher: Elsevier
Keywords: Male; Humans; Docetaxel/therapeutic use; *Androgen Antagonists/adverse effects; Androgens/therapeutic use; *Prostatic Neoplasms/drug therapy/radiotherapy; Follow-Up Studies; Prospective Studies; Androgen deprivation therapy; Docetaxel; Prostate cancer; Radiation; Randomized; Survival
Department(s): Radiation Oncology
PubMed ID: 37179241
Publisher's Version: https://doi.org/10.1016/j.eururo.2023.04.024
Open Access at Publisher's Site: https://doi.org/10.1016/j.eururo.2023.04.024
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-10-12 05:13:37

Last Modified: 2023-10-12 05:16:23