Optimal management for high-risk prostate cancer is unclear. Using individual patient data from two contemporaneous North American cooperative group phase 3 randomized controlled trials (RCTs), we compared the outcomes of high-risk prostate cancer patients treated with radiotherapy-based and radical prostatectomy (RP)-based treatment strategies.

Data were collected from newly diagnosed high-risk prostate cancer patients enrolled in NRG/RTOG 0521 who received radiotherapy-based treatment (2005-2009), and those enrolled in CALGB 90203 who received surgery-based treatment (2006-2015). Patients received radiotherapy plus 24 mo of androgen deprivation therapy (ADT) ± six cycles of adjuvant docetaxel versus RP with personalized postoperative therapy ± neoadjuvant six cycles of docetaxel and 18-24 wk of ADT. The primary objective was to compare the cumulative incidence of distant metastasis considering death as a competing event using the inverse probability of treatment weighting (IPTW).

Overall, 1290 patients (radiotherapy n = 557, RP n = 733) were included with similar follow-up (median 6.4 [interquartile range {IQR}: 5.6-6.9] yr and 6.4 [IQR: 4.7-8.5] yr, respectively). Patients who received surgery had generally more favorable prognostic features and were younger relative to those who received radiotherapy. After IPTW, the cumulative incidence of distant metastasis was significantly lower in patients who underwent radiotherapy-based compared with RP-based treatment (8-yr distant metastasis: 15% [95% confidence interval {CI} 9.3-21] vs 22% [95% CI 18-26]; adjusted subdistribution hazard ratio [sHR] 0.58 [95% CI 0.42-0.81]; p = 0.001). We did not find any significant difference in the incidence of deaths after distant metastasis (adjusted sHR 0.98 [95% CI 0.61-1.58]) between the two groups.

High-risk prostate cancer patients enrolled in RCTs had a significantly lower incidence of distant metastasis with a radiotherapy-based treatment strategy than with an RP-based treatment strategy, while the risk of deaths after distant metastasis was similar in the two groups.