Propensity-Weighted Survival Analysis of SBRT vs. Conventional Radiotherapy in Unfavorable Intermediate-Risk Prostate Cancer

Background : Prostate stereotactic body radiotherapy (SBRT), which delivers high-dose precision treatment in ≤5 fractions, is a shorter, more convenient, and less expensive alternative to conventionally fractionated radiotherapy (CRFT; ∼44 fractions) or moderately hypofractionated radiotherapy (MFRT; 20-28 fractions). SBRT has not been widely adopted but may have radiobiologic advantages over CFRT/MFRT. We hypothesized that SBRT would be associated with improved overall survival (OS) vs. CFRT or MFRT ± androgen deprivation therapy (ADT) for unfavorable-intermediate-risk prostate cancer (UIR-PCa). Methods : Men with UIR-PCa treated with SBRT (35-40Gy in ≤5 fractions) or biologically effective doses (BED) of CFRT (72-86.4Gy in 1.8-2.0Gy/fraction) or MRFT (≥60Gy in 2.4-3.2Gy/fraction; BED ≥120) were identified in the National Cancer Database (NCDB). Unweighted and propensity-weighted multivariable Cox analysis (MVA) was used to compare OS hazard ratios. Results : 28,028 men with UIR-PCa who received CFRT with (n=12,872) or without ADT (n=12,984); MFRT with (n=251) or without ADT (n=281); and SBRT with (n=212) or without ADT (n=1,428) were identified. Relative to CFRT without ADT, CFRT+ADT (HR 0.92, 95%CI 0.87-0.97, P=.002) and SBRT without ADT (HR 0.74, 95%CI 0.61-0.89, P=.002) were both associated with improved OS on MVA. Relative to CFRT+ADT, SBRT without ADT correlated with improved OS on MVA (HR:0.81, 95%CI 0.67-0.99, P=.04). Propensity-weighted MVA demonstrated that SBRT (HR:0.80, 95%CI 0.65-0.98, P=.036) and ADT (HR:0.91, 95%CI 0.86-0.97, P=.002) correlated with improved OS. SBRT was not associated with improved OS vs. MFRT. Conclusion : SBRT, which offers a cheaper and shorter treatment course that mitigates COVID-19 exposure, was associated with improved OS vs. CFRT for UIR-PCa. These results confirm guideline-based recommendations that SBRT is a viable option for UIR prostate cancer. The results from this large retrospective study require further validation in clinical trials. Micro-Abstract : In the era of COVID-19, there has been a large shift toward delivering larger doses of radiation over fewer treatments using stereotactic body radiation therapy (SBRT). There is a strong radiobiologic basis for using SBRT, as prostate cancer cells are more sensitive to higher doses of radiation delivered over fewer treatments. Here we show that men with unfavorable intermediate-risk prostate cancer (UIR-PCa) treated with SBRT lived significantly longer when treated with SBRT relative to longer courses of radiotherapy. While we await results from several ongoing clinical trials, this study lends support to the use of SBRT in men with UIR-PCa.