External beam radiation therapy improves survival in low-volume metastatic prostate cancer patients: a North American population-based study.

Background: We hypothesized that the survival benefit of external beam radiation therapy (EBRT) recorded in European low-volume metastatic prostate cancer (mPCA) patients, will apply to similar North American patients.
Methods: Newly diagnosed mPCa patients with M1a/b substages, treated with EBRT or no EBRT were abstracted from the Surveillance, Epidemiology, and End Results database (2004-2016). Kaplan-Meier plots and Cox-regression models targeted overall mortality (OM) and cancer specific-mortality (CSM) according to EBRT administration. M1 substages and PSA stratified analyses were performed. Internal validation relied on 2000 bootstrap resamples.
Results: Of 15,494 patients, 1156 (7.5%) were M1a vs 14,338 (92.5%) were M1b. PSA at diagnosis ≤10.0 ng/ml was recorded in 1463 (9.4%) patients. In all 15,494 patients, EBRT did not affect OM (hazard ratio [HR] 1.0; p = 0.5). However, in M1a patients and M1b patients with PSA ≤ 10.0 ng/ml EBRT was associated with lower OM (HR 0.73, CI 0.62-0.86; p < 0.001) but not in M1b patients with PSA > 10.0 ng/ml. The PSA cut-off of ≤ 10.0 ng/ml represented the most statistically significant cut-off for OM prediction in M1b patients. Moreover, internal validation with 2000 bootstrap resamples confirmed these findings. Finally, all results were virtually the same, when CSM represented the endpoint of interest.
Conclusions: We validated the OM reduction associated with EBRT in M1a and M1b patients with PSA ≤ 10.0 ng/ml but not in M1b patients with PSA > 10.0 ng/ml. In consequence, it appears that a smaller subset of North American mPCa patients benefit of EBRT than originally reported in European patients. Further North American validation studies are essential.