PurposeThe purpose was to evaluate survival outcomes between external beam radiotherapy (EBRT) plus brachytherapy and brachytherapy alone for intermediate-risk prostate cancer, using the National Cancer Data Base. Methods and MaterialsThe National Cancer Data Base was queried for cN0M0 intermediate-risk patients treated from 2004 to 2006, with available data for Gleason score (GS), prostate-specific antigen (PSA), tumor stage, and receipt of radiation therapy (RT) and androgen deprivation therapy. RT comparison groups were the following: EBRT (40–50.4 Gy) plus brachytherapy and brachytherapy alone. ResultsA total of 10,571 patients were included: 3,148 received EBRT plus brachytherapy and 7,423 received brachytherapy alone. Median followup was 84 months (2–122 months); median age was 68 years (40–90 years). Unadjusted 5- and 7-year overall survival (OS) rates between EBRT plus brachytherapy vs. brachytherapy alone were 91.4% vs. 90.2% and 85.7% vs. 82.9%, respectively (p < 0.001). EBRT plus brachytherapy was associated with longer OS compared with brachytherapy alone under multivariate (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.75–0.93; p = 0.001) and propensity score-matched analyses (HR, 0.85; 95% CI, 0.75–0.97; p = 0.006). Further subset analysis performed based on the Radiation Therapy Oncology Group 0232 inclusion criteria (GS 7 if PSA < 10 or GS < 7 if PSA 10–20) also demonstrated longer OS with EBRT plus brachytherapy (HR, 0.87; 95% CI, 0.77–0.98; p = 0.026). ConclusionsEBRT plus brachytherapy is associated with a modest OS improvement compared with brachytherapy alone in this population-based analysis. Although this benefit appears statistically significant, the relatively small difference in OS raises the question of overall clinical benefit with combined modality RT for intermediate-risk prostate cancer, given the potential increased risk for toxicities. Future results from Radiation Therapy Oncology Group 0232 should provide further insight on this topic.