Prostate Radiotherapy With Adjuvant Androgen Deprivation Therapy Improves Metastasis Free Survival Compared To Neoadjuvant ADT: An Individual Patient Meta-Analysis

The utility of ADT for localized prostate cancer in the neoadjuvant versus concurrent versus adjuvant setting has remained a contentious issue for urologic oncologist for decades.  In a recent publication in the Journal of Clinical Oncology, published January 2021, investigators pulled together individual patient data from 2 trials, the Ottowa 0101 and NRG oncology’s radiation therapy oncology group 9413 trials.  These trials were slightly different. The Ottowa 0101 trial had randomly assigned patients to neoadjuvant or concurrent versus concurrent or adjuvant short-term ADT.  The second trial, used a 2 x 2 factorial design, included a random assignment of neoadjuvant or concurrent versus adjuvant short-term ADT.  The neoadjuvant or concurrent ADT arm of both trials were combined into a neoadjuvant group for the meta-analysis.  The arms receiving adjuvant ADT were combined into an adjuvant group for the meta-analysis.  The primary endpoint was progression free survival

After a median follow-up of 14.9 years, 1,065 patients records were reviewed.  531 received neoadjuvant ADT while 534 received adjuvant ADT.  Progression free survival was significantly improved in the adjuvant group, 15-year PFS 29% versus 36%, with a hazard ratio of 1.25, 95% confidence interval 1.07–1.47, with a P-value of 0.01.  Biochemical failure, distant metastasis, and metastasis-free survival were all significantly improved in the adjuvant group.  The respective hazard ratios and p-values were as follows: 1.30 and P= 0.002, 1.40 and P = 0.04 and 1.17 and P = 0.050.  No differences in toxicity were noted.

The authors concluded “the sequencing of ADT with prostate directed radiotherapy has significant association with long-term progression free survival and metastasis-free survival in localized prostate cancer.  Our findings favor the use of an adjuvant over a neoadjuvant approach.”