(1) We hypothesized that adding concurrent stereotactic ablative
radiotherapy (SAbR) would increase the time to progression in patients with metastatic castrate-resistant
prostate cancer (mCRPCA) treated with
sipuleucel-T. (2) Patients with a history of
prostate cancer (PC), radiographic evidence of metastatic disease, and rising
prostate-specific antigen (PSA) > 0.2 ng/dL on castrate
testosterone levels were enrolled in this single-arm phase II clinical trial and treated with
sipuleucel-T and SAbR. The primary endpoint was time to progression (
TTP). Cellular and humoral responses were measured using ELISpot and Luminex multiplex assays, respectively. (3) Twenty patients with mCRPC were enrolled and treated with SAbR to 1−3 sites. Treatment was well tolerated with 51, 8, and 4 treatment-related grade 1, 2, and 3 toxicities, respectively, and no grade 4 or 5 adverse events. At a median follow-up of 15.5 months, the median
TTP was 11.2 weeks (95% CI; 6.8−14.0 weeks). Median OS was 76.8 weeks (95% CI; 41.6−130.8 weeks). This regimen induced both humoral and cellular immune responses. Baseline M-MDSC levels were elevated in mCRPC patients compared to healthy donors (p = 0.004) and a decline in M-MDSC was associated with biochemical response (p = 0.044). Responders had lower baseline
uric acid levels (p = 0.05). No clear correlation with radiographic response was observed. (4) While the regimen was safe, the PC-
antigen-specific immune response induced by SAbR did not yield a synergistic clinical benefit for patients treated with
sipuleucel-T compared to the historically reported outcomes.