Toxicity Outcomes After Low-Dose-Rate vs. High-Dose-Rate Brachytherapy Boost in Combination With External Beam Radiation for Intermediate and High-Risk Prostate Cancer

Abstract

The addition of a brachytherapy boost to external beam radiation therapy (EBRT) reduces prostate cancer (PCa) recurrence compared with dose-escalated EBRT alone. However, combination therapy is associated with worse genitourinary (GU) toxicity compared with EBRT monotherapy. Whether brachytherapy boost technique, specifically low-dose-rate (LDR-BT) versus high-dose-rate (HDR-BT), impacts treatment-related toxicity is unclear and the subject of this analysis.This single institutional cohort study included 104 adult men with intermediate/high risk PCa treated with combination EBRT plus brachytherapy boost, with either LDR-BT or HDR-BT, between 2012 and 2018. Patient-reported outcomes (PRO) were assessed by the International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) surveys at 3-6-month intervals for up to three years following treatment, with higher scores indicating more severe toxicity. Provider-reported GU and gastrointestinal (GI) toxicities were assessed and graded per CTCAE V5.0 at each follow-up. Linear mixed models comparing PROs between LDR-BT versus HDR-BT were fitted. Stepwise multivariable analysis (MVA) was performed to account for age, gland size, androgen deprivation therapy (ADT) use, and alpha-blocker medication use. Incidence rates of grade 2+ GU/GI toxicity was compared using Chi-square test or Fisher's exact test.The median complete follow up time for LDR-BT and HDR-BT cohorts was 17 and 18.4 months, respectively. There was no difference in alpha-blocker use at baseline between groups (P = 0.16). Median prostate gland size was larger in the HDR-BT cohort compared with the LDR-BT cohort (39.99cc vs 26.58cc for HDR-BT vs LDR-BT, respectively; P < 0.001). The use of LDR-BT was associated with a greater change in IPSS (P = 0.003) and EPIC-CP urinary irritative score (P = 0.002) compared with HDR-BT, but effect size diminished over time (LDR-BT versus HDR-BT: baseline to 6-/24-month mean IPSS change, +6.4/+1.4 versus +2.7/-3.0, respectively; mean EPIC-CP irritative/obstructive change, +2.5/+0.1 versus +0.9/+0.1, respectively). These results remained significant on MVA. Incidence of post-treatment grade 2+ GU toxicity was significantly higher in the LDR-BT group (77.5% versus 42.9% for LDR-BT and HDR-BT, respectively; P < 0.001). There were no significant differences between LDR-BT and HDR-BT in EPIC-CP (total, urinary incontinence, bowel function, sexual, vitality) or provider-reported grade 2+ GI toxicity.In this single institution cohort, HDR-BT was associated with lower patient- and provider-reported GU toxicity compared with LDR-BT. However, differences in patient-reported toxicity diminished by 24 months post-treatment.