Comparing Physician-Reported Toxicity In Men With Localized Prostate Cancer Undergoing External Beam, Brachytherapy, Or Combination Radiation Therapy

The purpose of this study is to compare physician-reported gastrointestinal (GI), genitourinary (GU) and sexual toxicity outcomes of men with localized prostate cancer undergoing dose-escalated external beam radiation therapy (EBRT), high-dose-rate (HDR) brachytherapy or low-dose-rate (LDR) brachytherapy monotherapy (HDRm or LDRm), EBRT with HDR BT boost (HDRb), and EBRT with LDR BT boost (LDRb). We performed a retrospective cohort study of a prospectively collected database of patients with localized prostate adenocarcinoma treated with EBRT, HDRm, LDRm, HDRb, or LDRb between 2004-2019 at our institution. Hormone therapy was delivered per physician discretion. Physician-reported GI, GU, and sexual toxicity were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at time points of 3 months, 6 months, 12 months, 18 months, and 24+ months. Stratified Fisher exact tests and generalized linear mixed effects models were used to assess for differences in the physician-graded toxicity rate between radiation treatment modalities. 555 men with prostate cancer met selection criteria. 277 (49.9%) received EBRT, 76 (13.7%) received LDRm, 30 (5.4%) received LDRb, 130 (23.4%) received HDRm, and 42 (7.6%) received HDRb. Median follow-up was 33 months (interquartile range [IQR]: 15-59). 130 (23%) had low risk, 280 (50%) had intermediate risk, and 145 (26%) had high risk disease. After 24 months, Grade 3+ GI toxicity with LDRb (15%) was higher than those in the EBRT group (1.2%), and it was higher than those in the HDRb cohort (0%; p = 0.01). No other pairwise comparisons were significant. The risk of Grade 2+ GU toxicity was higher with LDRm over HDRm at months 3, 21, and 24 (p = 0.03; p = 0.02; p = 0.03). HDRm patients had higher incidence of Grade 2+ sexual toxicity than EBRT patients in the first 3 months (p = 0.02). Compared to patients receiving EBRT, patients receiving HDRb, HDRm, or LDRm had higher sexual toxicity by month 15 (p = 0.002; p < 0.001; p = 0.004). By month 21, patients receiving HDRm remained more likely than those receiving EBRT to have sexual toxicity (p = 0.01). There were no significant differences in the sexual toxicity rates between groups after 24 months. In men treated with radiation therapy for localized prostate cancer, there are differences in physician-reported toxicity across radiation treatment modalities. Our study suggests lower rates of chronic GI toxicity in patients treated with HDRb as compared to LDRb and EBRT, lower rates of acute and chronic GU toxicities in patients treated with HDRm as compared to LDRm, and similar long-term sexual toxicity among the groups. The differences in the physician-graded toxicity profiles between radiation treatment modalities can be used in shared decision-making when selecting the best radiation therapy option for each patient.