Patient-Reported Outcomes as Prognostic Indicators for Overall Survival in Cancer

Importance Patient-reported outcomes (PROs) are health data that are collected directly from patients to assess symptoms, functional status, and quality of life. While studies have reported associations between PROs and survival, the prognostic significance of specific PRO domains has not been systematically quantified. Objective To evaluate the association between baseline PROs and overall survival (OS) in patients with cancer and quantify the prognostic significance of various PRO domains through a systematic review and meta-analysis of randomized clinical trials (RCTs). Data Sources A systematic literature search of PubMed (MEDLINE), Ovid Embase, and the Cochrane Library was conducted to identify eligible studies published between January 1, 2000, and June 1, 2024. The data were analyzed on January 15, 2025. Study Selection Eligible studies were prospective RCTs that enrolled adult patients with cancer (18 years or older) that included at least 1 baseline PRO measure, reported OS as an outcome, and conducted multivariate analyses that adjusted for clinical and disease-related confounders. Data Extraction and Synthesis Data from eligible RCTs were extracted independently and in duplicate by 4 reviewers. Studies using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire were meta-analyzed using a random-effects model with an inverse variance–weighted approach. Main Outcome and Measure The primary outcome was the association between baseline PROs and OS reported using pooled hazard ratios (HRs) and 95% CIs. Results A total of 69 RCTs comprising 44 030 patients were included in the systematic review, with 31 RCTs (44.9%) meeting criteria for the meta-analysis. Higher global health status scores and quality of life were associated with improved OS (hazard ratio [HR], 0.99; 95% CI, 0.98-0.99). Among functional scales, physical functioning (HR, 0.94; 95% CI, 0.92-0.96) and role functioning (HR, 0.96; 95% CI, 0.94-0.98) were associated with improved OS. Conversely, higher symptom burden, including nausea and vomiting (HR, 1.12; 95% CI, 1.04-1.21), fatigue (HR, 1.05; 95% CI, 1.00-1.10), and pain (HR, 1.07; 95% CI, 1.04-1.11), was associated with worse OS. The overall pooled effect demonstrated that increasing individual symptom severity was associated with higher mortality risk (HR, 1.03; 95% CI, 1.01-1.04). The Egger test showed no evidence of publication bias. Conclusions and Relevance This systematic review and meta-analysis found that PROs offer independent prognostic information for cancer survival. These findings support the integration of PRO assessments into clinical decision-making and risk stratification in oncology.