Late, persistent, substantial, treatment-related symptoms (LAPERS) following low-dose-rate brachytherapy for prostate cancer.

Abstract

246 Background: The late, persistent, substantial treatment-related symptoms (LAPERS) is a novel methodological approach to identify clinically relevant and long-lasting symptoms after treatment. It was first reported in a cohort of women with cervical cancer in the EMBRACE study. We applied the LAPERS methodology to report long-term outcomes following low-dose-rate brachytherapy (LDRBT) for prostate cancer (PCa). Methods: We studied a cohort of men with PCa treated with LDRBT in a single Australian institution, who completed the Expanded Prostate Cancer Index Composite short-from 26 (EPIC26) questionnaire before LDRBT, and at regular intervals after LDRBT. For LAPERS analyses, 1) we limited the analyses to men with baseline EPIC26, and at least 3 ‘late’ follow-up EPIC26 (from 6 months post-LDRBT onwards); 2) ‘substantial’ symptoms were defined as either ‘moderate’ (score 25) or ‘big problem’ (score 0) in EPIC26 urinary and bowel domain questions which assess the degree of symptom bother; 3) ‘persistent’ symptoms were defined as ‘substantial’ symptoms that present in at least half of the ‘late’ follow-up EPIC-26 assessments. This provides a binary (yes/no) LAPERS outcome. We estimated cumulative incidence of substantial symptom with the Kaplan-Meier methods. We reported on 1) proportion of men with LAPERS, 2) proportion with baseline-corrected LAPERS, 3) prevalence of substantial symptoms at specified timepoint, and 4) cumulative incidence of substantial symptoms. Results: 177 men were included in the study. The median follow-up was 60 months (IQR: 36-74 months). For overall urinary function, the proportion of men with LAPERS was 2.3% (baseline corrected LAPERS 2.3%). The prevalence of substantial urinary symptoms at 12, 24, 36, 48, and 60 months were 5.9%, 4.4%, 2.9%, 0.7%, 1.8%, and 5-year cumulative incidence was 17.8% (95%CI = 12.7-24.6%). For overall bowel function, the proportion of men with LAPERS was 2.3% (baseline-corrected LAPERS 1.7%). The prevalence of substantial bowel symptoms at 12, 24, 36, 48, 60 months were 7.6%, 3.0%, 3.6%, 3.6% and 2.2%, and 5-year cumulative incidence was 16.2% (95%CI = 11.3-23.2%). Conclusions: We observed considerable differences between LAPERS, prevalence and cumulative incidence of substantial symptoms in men with PCa treated with LDRBT. Cumulative incidence (‘time-to-first event’ analyses) may overestimate the burden of late toxicities as considerable proportion of patients do not experience persistent symptoms over time, and LAPERS is more reflective of ‘true’ late toxicities, taking into account the duration of symptoms.