11Exploring Health-Related quality of life across the disease spectrum in renal cell carcinoma: a conceptual domain analysis

Abstract Background Understanding how health-related quality of life (HRQOL) concerns vary by disease stage is essential for developing patient-reported outcome measures (PROMs) that reflect the lived experiences of individuals with renal cell carcinoma (RCC). This study aimed to explore differences in the perceived relevance of HRQOL domains between patients with localized and metastatic RCC using a provisionally grouped item set derived from validated instruments. Methods This is a secondary analysis of a prospective international study conducted from August 2022 and October 2024, with participants from the United States, Europe, and Brazil (Bergerot et al., JCO 2025). In Phase 1, a 54-item was developed using the Functional Assessment of Cancer Therapy–Kidney Symptom Index (FKSI-19), the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), and the EuroQol (EQ-5D). Items were provisionally grouped into four conceptual domains: physical disease-related symptoms (DRS-P), emotional symptoms (DRS-E), treatment side effects (TSE), and function/well-being (FWB). Patients with localized or metastatic RCC rated item relevance. We calculated the mean number of relevant items per domain and conducted ANOVAs to compare groups, reporting partial eta squared (η²) for effect size. Results A total of 200 patients (localized n = 83; metastatic n = 117) were included. Patients with metastatic RCC reported greater relevance of physical symptoms (DRS-P: M = 39.2, SD = 6.0) compared to those with localized disease (M = 35.3, SD = 6.7; F(1,198)=17.53, P .001, η²=0.081). Similarly, metastatic patients reported higher treatment side effect burden (TSE: M = 12.2, SD = 2.3 vs. 10.6, SD = 2.5; F(1,198)=19.47, P .001, η²=0.089). No significant difference was observed in emotional symptoms (DRS-E; P = .260). Conversely, patients with localized RCC more often endorsed concerns related to function and well-being (FWB: M = 17.6, SD = 3.5) than those with metastatic disease (M = 15.5, SD = 2.9; F(1,198)=20.52, P .001, η²=0.094). Conclusions Given the differences in trajectory and treatment modalities across localized and metastatic RCC, our findings underscore the evolving nature of HRQOL concerns across the RCC continuum. While physical symptoms and treatment side effects were highly relevant across both groups, their prominence among metastatic patients suggests the burden of advanced disease and systemic therapies. In contrast, patients with localized disease prioritized functional limitations and emotional concerns, potentially linked to surveillance-related anxiety. These insights support the need for stage-specific PROMs and highlight the importance of integrating both physical and emotional dimensions of care in RCC. Validation of such a tool for both localized and metastatic RCC is underway in forthcoming studies.