Spatial and temporal intra-tumoral heterogeneity in advanced HGSOC: Implications for surgical and clinical outcomes

Limited evidence exists on the impact of spatial and temporal heterogeneity of high-grade serous ovarian cancer (HGSOC) on tumor evolution, clinical outcomes, and surgical operability. We perform systematic multi-site tumor mapping at presentation and matched relapse from 49 high-tumor-burden patients, operated up front. From SNP array-derived copy-number data, we categorize dendrograms representing tumor clonal evolution as sympodial or dichotomous, noting most chemo-resistant patients favor simpler sympodial evolution. Three distinct tumor evolutionary patterns from primary to relapse are identified, demonstrating recurrent disease may emerge from pre-existing or newly detected clones. Crucially, we identify spatial heterogeneity for clinically actionable homologous recombination deficiency scores and for poor prognosis biomarkers CCNE1 and MYC. Copy-number signature, phenotypic, proteomic, and proliferative-index heterogeneity further highlight HGSOC complexity. This study explores HGSOC evolution and dissemination across space and time, its impact on optimal surgical cytoreductive effort and clinical outcomes, and its consequences for clinical decision-making. [Display omitted] •Multi-site tumor profiling of high-disease-burden HGSOC patients across space and time•Distinct tumor evolution patterns identified from initial diagnosis to relapse•HRD scores and genomic biomarkers demonstrate spatial and temporal heterogeneity•No adverse tumor profiles identified that preclude patients from cytoreductive effort Cunnea et al. profile a cohort of advanced, high-tumor-burden high-grade serous ovarian cancer patients using systematic, multi-site, multi-level mapping to demonstrate tumor evolution from initial diagnosis through to matched relapse. They report distinct patterns of tumor evolution and extensive spatial and temporal heterogeneity in actionable genomic biomarkers.