Overall Survival Following Treatment of Localized Prostate Cancer with Proton Therapy, External Beam Photon Therapy, or Brachytherapy: A National Cancer Data Base Analysis

Abstract

Given the lack of high level evidence about the effectiveness of proton therapy compared to photon-based radiation approaches for prostate cancer, the most appropriate role for proton therapy in this disease remains in question. While waiting for results from randomized clinical trials (e.g., NCT03561220), we examined overall survival (OS) following proton radiation (Proton) compared to external beam radiation (EBRT) and brachytherapy (Brachy) in patients with localized prostate cancer. The National Cancer Data Base (NCDB) was queried from 2004-2014. Patients with T1-3N0M0 without chemotherapy or surgery and age >=40 were included. Overall survival (OS) was defined as months from the date radiation started. For inclusion, Proton or EBRT patients were required to have a total radiation dose > 59 Gy. The Brachytherapy cohort included those treated with brachytherapy alone or in combination with EBRT. Summary statistics were applied to assess background differences. Cox proportional hazard model was used for evaluating the association with OS. Propensity score matching (PSM) was implemented to balance all observed baseline characteristics. A total of 275,944 eligible patients were identified, with a median follow up of 79.7 months. The median age was 68, 80.4% were white, 24.3% classified as NCCN high risk, and 40% received ADT. 4959 (1.8%) received Proton vs. 153,045 (55.5%) for EBRT vs. 117,940 (42.7%) for Brachy. Compared to the other radiation modalities, Proton patients tended to be younger, more likely to be treated at academic facilities, had private insurance, resided in higher income or education zip code, or had lower PSA or Gleason score. The 10-year survival rate was 86.5% (Proton) vs. 61.6% (EBRT) vs. 75.4% (Brachy) by KM method. In the multivariable model using Proton as reference, the hazard ratio (HR) was 1.26 (95%CI: 1.11-1.43) for Brachy and 1.59 (95%CI: 1.40-1.81) for EBRT. PSM yielded 1720 patients per cohort, and the HR was 1.23 (95%CI: 0.97-1.56) for Brachy and 1.43 (95%CI: 1.14-1.80) for EBRT. Among low risk patients, HR was 1.58 (95%CI: 1.23-2.02) for Brachy and 1.96 (95%CI: 1.53-2.51) for EBRT while it was 1.15(95%CI: 0.99-1.34) and 1.47 (95%CI: 1.26-1.7) respectively among intermediate or high risk patients. After correcting for background differences, on average, proton therapy provided significant long-term OS benefit among localized prostate cancer patients compared to EBRT, but may have a similar outcome as brachytherapy. In addition, proton therapy may hold higher magnitude of benefit for low risk patients than for intermediate or high risk patients. As disease-free survival (which is unavailable in NCDB) is an endpoint that accounts for competing morbidities better than OS, these results require validation in the randomized setting.