Association of Baseline Health-Related Quality of Life Metrics With Outcome in Localized Prostate Cancer

Abstract

While health-related quality of life (HR-QoL) outcomes are pivotal in oncology, the prognostic significance of patient-reported HR-QoL metrics is largely undefined in localized prostate cancer (LPCa). In this exploratory analysis, we report the association of baseline HR-QoL metrics with overall survival (OS) and risk of late radiation-induced toxicity in men with LPCa treated with combination of radiotherapy (RT) and androgen deprivation therapy (ADT).This is a secondary analysis of a phase III randomized controlled study conducted in two tertiary cancer centers. LPCa patients with Gleason score ≤7, clinical stage T1b to T3a, and prostate-specific antigen < 30 ng/mL were randomized to neoadjuvant and concurrent ADT for 6 months starting 4 months before prostate RT or concurrent and adjuvant ADT for 6 months starting simultaneously with prostate RT. HR-QoL scores were estimated using European Organization for Research and Treatment of Cancer QoL questionnaire. A multi-state Markov model was used to determine the association of baseline HR-QoL metrics with OS and a multilevel multivariable Cox regression to determine the association with incidence of delayed-onset grade ≥3 radiotherapy-related toxicities. To adjust for multiple analyses, P-value < 0.025 was considered as statistically significant. Conditional approach was used to calculate 15-year adjusted OS for patients with and without financial difficulty and patients with and without dyspnea at baseline.Overall, 393 patients with baseline HR-QoL data were included in this analysis - 194 in the neoadjuvant arm and 199 in the adjuvant arm. Baseline financial difficulty (hazard ratio [HR]: 1.020, 95% confidence intervals [CI]:1.010-1.030, P = 0.02), and dyspnea (HR: 1.020, 95% CI:1.003-1.030, P = 0.01) were associated with inferior OS. Adjusted OS for patients with and without financial difficulty at baseline was 15.5% and 45.7%, respectively (P < 0.01). Adjusted OS for patients with and without baseline dyspnea was 21.2% and 46.6%, respectively. Baseline dyspnea was associated with higher incidence of grade ≥3 toxicity (HR: 1.020, 95% CI: 1.010-1.030, P = 0.023).In a cohort of LPCa patients treated with RT and short-term ADT, a 10-point increase in baseline financial difficulty or a 10-point increase in baseline dyspnea was associated with a 20% increased risk of death. With each 10-point increase in baseline dyspnea, we noted an 20% increase in the associated risk of grade ≥3 delayed-onset radiotherapy-related toxicity. These findings underscore the importance of integrating these baseline patient-reported metrics in selecting patients, making informed treatment-decisions, and optimizing overall outcome in men with localized prostate cancer.