Docetaxel with androgen deprivation therapy (ADT) and radiotherapy (RT) for high-risk localized prostate cancer (HRLPC): An ICECaP individual patient-data (IPD) meta-analysis of randomized controlled trials (RCTs).

5013 Background: There is no established role for the use of docetaxel with ADT and RT for HRLPC, with mixed results seen in prior RCTs. Prior work from ICECaP (Ravi et al, Eur Urol 2024) has shown that patients (pts) with very high-risk disease (i.e. 2 or 3 risk factors [RFs]: Gleason ≥8, PSA >20, ≥cT3 and/or cN1) have the poorest outcomes with RT+ADT for HRLPC, with 5-year metastasis-free survival (MFS) of ≤80%. We aimed to perform an IPD meta-analysis of the role of docetaxel with ADT+RT for HRLPC and specifically evaluate whether patients with very high-risk disease benefit from the addition of docetaxel. Methods: IPD from RCTs involving pts with HRLPC treated with RT+ADT +/- docetaxel collated by ICECaP were analyzed. “High-risk” disease was defined as presence of 1 RF and “very high-risk” disease as 2-3 RFs and/or cN1 disease. The primary outcomes of interest were MFS and overall survival (OS). Hazard ratios (HR) for MFS and OS were estimated using Cox regression, stratified by year of randomization and adjusted for age at randomization and ECOG performance status. 5-year MFS and OS rates were estimated using the Kaplan-Meier method. Subgroup analyses were performed according to the severity of disease (high- and very high-risk), and p-values for interaction were tested using the likelihood ratio test. Results: 1690 pts treated on 4 RCTs (GETUG-12, DFCI 05-043, STAMPEDE, RTOG-0521) between 2002-2015 were eligible. Median age was 65, median PSA was 23 (IQR 10-48); 154 (9%) pts had cN1 disease and 1444 (85%) received long-term ADT with RT. Median follow-up was 10 years (range: <1-15). Overall, the addition of docetaxel to RT+ADT was not associated with a significant benefit in MFS (HR=0.89 [0.76-1.05], p=0.160) or OS (HR=0.88 [0.74-1.05], p=0.167). Though there was some evidence for favoring docetaxel in pts with very high-risk disease (n=1054; MFS HR=0.86 [0.71-1.05]; OS HR=0.85 [0.68-1.07]) compared to high-risk disease (n=636; MFS HR=0.97 [0.74-1.27]; OS HR=0.95 [0.71-1.28]), there was no evidence of a significant difference in treatment effect by risk group (p-interaction >0.1). 5- and 10-yr MFS and OS in pts with high- and very high-risk disease, stratified by receipt of docetaxel, are shown in the Table. Conclusions: Some HRLPC pts with very high-risk disease may benefit from the addition of docetaxel to RT+ADT. Biomarker evaluation within this group may identify those who are candidates for treatment intensification with docetaxel with RT+ADT (+/- androgen receptor pathway inhibitors) in HRLPC. % (95% CI) High risk Very high-risk RT+ADT RT+ADT+docetaxel RT+ADT RT+ADT+docetaxel 5yr MFS 87 (82-90) 90 (86-93) 74 (71-78) 80 (76-83) 5yr OS 90 (86-93) 93 (90-96) 84 (80-86) 89 (86-92) 10yr MFS 67 (61-72) 71 (65-76) 51 (46-55) 55 (49-60) 10yr OS 74 (69-79) 77 (72-82) 62 (57-67) 67 (62-72)