External Validation of Early Quality of Life (QOL) Declines Correlated with Late QOL after Intensity Modulated, Low Dose Rate Brachytherapy, or Stereotactic Radiation for Prostate Cancer within a Prospective Trial

Abstract

There is data on early toxicity associated with late toxicity, but there is currently a lack of data on quality of life (QOL) outcomes and evaluation for possible surrogacy between early and late toxicity. This is an evaluation of early QOL for prostate cancer across RT options with a validation within QOL from a SBRT prospective trial. An initial cohort of 898 patients (PROSTQA study and 3 institutions with prospective QOL data were pooled for analysis for IMRT (n = 162), LDR brachytherapy (n = 271), or SBRT (Robotic n = 392 and Linac n = 72) to the prostate with or without seminal vesicles) were evaluated for patient reported outcomes. Expanded Prostate Cancer Index (EPIC) QOL data for urinary, bowel, vitality, and sexual function was evaluated by pre-specified relevant thresholds for meaningful clinical differences (MCD) compared to baseline. Patients were evaluated for QOL at 1-2 month from the start of radiotherapy and at 24 months from the start of radiotherapy. Multivariate analysis (MVA) used general linear models to assess the correlation between QOL changes. This was then externally validated with QOL analysis from a prospective trial of robotic SBRT to the prostate alone to 38 Gy in 4 fractions of 259 patients assessing QOL at 1-month post-radiotherapy to predict late declines QOL at 24 months. A total of 898 patients were within the initial cohort, 94% had evaluable QOL at 24 months. On MVA, after controlling for age, baseline function, PSA, Gleason score, T-stage, prostate volume, and RT technique, an early MCD was the strongest predictor of late MCD at 24 months in all assessed domains and radiation modalities: odds ratio (OR) 3.7 [95% CI 2.2-6.4] for urinary irritation, OR 4.5 [2.9-6.9] for urinary incontinence, OR 2.4 [1.6-3.5] for bowel, OR 3.7 [2.5-5.5] for sexual function, and OR 3.4 [2.3-4.9] for hormone. Within the validation cohort of 259 patients, 83% had evaluable QOL at 24 months. Early declines of a MCD were again associated with late declines noted across all domains of QOL: OR 3.1 [95% CI 1.7-5.8] for urinary irritation, OR 2.7 [1.5-4.8] for urinary incontinence, OR 2.0 [1.1-3.7] for bowel, OR 4.0 [2.1-7.7] for sexual function, and OR 3.0 [1.2-7.3] for hormone. Early QOL decline was the strongest predictor of QOL impacts at 2 years across all domains and this appeared consistent across standard radiation treatment modalities. This was externally validated within these domains suggesting early declines in QOL are surrogates and predict for late declines.Abstract 141; TableIncidence and Correlation of an MCD in Early and Late QOLEPIC DomainEPIC MCD ThresholdEarly Decline MCDLate Decline MCDOR [95% CI]Early Decline MCDLate Decline MCDOR [95% CI]Initial CohortValidation CohortUrinary Irritative678%36%3.7 [2.2-6.4]63%39%3.1 [1.7-5.8]Urinary Incontinence7.537%24%4.5 [2.9-6.9]32%41%2.7 [1.5-4.8]Bowel554%29%2.4 [1.6-3.5]41%26%2.0 [1.1-3.7]Sexual1136%41%2.9 [2.3-3.8]30%49%2.4 [0.89-6.6] Open table in a new tab