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.

Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer.

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.

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.

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).

After 10.4 yr of median follow-up among survivors, the hazard ratio (HR) for OS was 0.89 (90% confidence interval [CI] 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.

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.

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.

European urology. 2023 May 11 [Epub ahead of print]

Oliver Sartor, Theodore G Karrison, Howard M Sandler, Leonard G Gomella, Mahul Amin, James Purdy, Jeff M Michalski, Mark G Garzotto, Nadeem Pervez, Alexander G Balogh, George B Rodrigues, Luis Souhami, M Neil Reaume, Scott G Williams, Raquibul Hannan, Christopher U Jones, Eric M Horwitz, Joseph P Rodgers, Felix Y Feng, Seth A Rosenthal

Tulane University Health Services Center, New Orleans, LA, USA. Electronic address: ., University of Chicago and NRG Oncology Statistics and Data Management Center, Chicago, IL, USA., Cedars-Sinai Medical Center, Los Angeles, CA, USA., Thomas Jefferson University Hospital, Philadelphia, PA, USA., UC Davis Medical Center, Sacramento, CA, USA., Washington University School of Medicine, St. Louis, MO, USA., Oregon Health & Science University, Portland, OR, USA., Cross Cancer Institute, Edmonton, Alberta, Canada., Tom Baker Cancer Centre, Calgary, Alberta, Canada., London Health Sciences Centre, London, Ontario, Canada., McGill University, Montreal, Quebec, Canada., The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada., Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., University of Texas Southwestern Medical School, Dallas, TX, USA., Sutter Cancer Center (accruals under Radiological Associates of Sacramento), Sacramento, CA, USA., Fox Chase Cancer Center, Philadelphia, PA, USA., UCSF Medical Center, San Francisco, CA, USA.