Victoria Cooley

A Prospective Study Consortium for the Discovery and Validation of Early Detection Markers for Ovarian Cancer – Baseline Findings for CA125

Abstract Purpose: Epithelial ovarian cancer (EOC) is a lethal malignancy. Cancer antigen 125 (CA125), the “best” available marker for detecting EOC, has insufficient sensitivity and specificity for earlier-stage disease and is not a meaningful screening tool, motivating the search for further biomarkers. Cancer biomarker discovery is enhanced by “omics” technologies. Discovery studies for EOC biomarkers should be conducted in prediagnosis blood samples from prospective cohorts to maximize the likelihood of identifying markers that can detect disease before usual diagnosis and in earlier disease stage while reducing methodologic biases. Experimental Design: Individual cohorts with prediagnosis blood samples have insufficient sample size for such studies. Thus, we established “Prospective Early Detection Consortium for Ovarian Cancer” (“PREDICT”)—a collaboration of nine prospective studies—to assemble a sufficient number of EOC cases with blood samples collected ≤18 months before diagnosis plus controls. The 457 cases and 1,687 controls have circulating CA125 measured using a clinical assay. Results: The discrimination capacity for single CA125 measurements in samples collected <6 months prior to diagnosis was high (AUC; PREDICT overall = 0.92; range across cohorts of nonpregnant individuals = 0.89–0.98) and declined with extended time between blood collection and diagnosis. Between-cohort variability in CA125 levels and predictive performance was observed. Conclusions: Ongoing investigations in PREDICT are evaluating the early detection potential of tumor-associated autoantibodies and miRNAs using CA125 as a benchmark. PREDICT is a well-characterized resource for identifying and validating detection markers for EOC that may then be used in multimodal screening as a complement to CA125 and combined with imaging.

Ovarian cancer survival in Germany: a nationwide analysis by stage and histotype

Previous population-based studies on ovarian cancer survival have evaluated less granular disease staging categories and histologic sub-types than are in current use, and there is a need to assess survival in the context of more contemporary treatment practices and histotype classifications. Using flexible parametric models, we assessed the 1-, 3-, 5-, and 10-year net survival and excess mortality hazards of 54,267 incident invasive ovarian cancer cases by stage and histology and 9478 borderline cases diagnosed between January 1, 2010 and December 31, 2021 recorded in Germany. Net survival differed markedly by stage, with consistently favorable long-term survival for early-stage (I to II) and poor outcomes for advanced-stage (III to IV) disease across histotypes. Although most stage I tumors showed high 10-year net survival (≥ 77%), carcinosarcomas represented a notable exception. Net survival declined with advancing stage, with 10-year estimates ranging from 46% to 76% for stage II, 18% to 55% for stage III, and poor 5-year survival for stage IV tumors (15% to 41%). Considering patterns by time since diagnosis, the excess mortality hazard was the highest across all histotype-stage groups during the first 3 years with variability suggestive of histotype-specific treatment resistance and disease recurrence. The influence of stage decreased over the follow-up, with the largest impact mostly observed during the first year after diagnosis. Net survival for borderline tumors was high (10-year survival = 92.9%). Net survival was favorable for patients with early-stage disease. Variability was observed across histotypes by stage. The early post-diagnosis period is a critical window for excess mortality, and the development of histotype-specific treatments is needed.