Kemal Caglar Gogebakan

Estimating the Opportunity for Early Detection of Ovarian Cancer Using Individual-Patient Data from a Large Randomized Controlled Trial

Abstract Background: The UK Collaborative Trial of Ovarian Cancer Screening did not detect a reduction in ovarian cancer mortality with either multimodal screening (MMS) or transvaginal ultrasound screening (USS) compared with no screening. The trial data provide an invaluable resource to quantify the opportunity for interception in ovarian cancer. Methods: We used Bayesian inference to estimate ovarian cancer natural history based on individual screening and cancer diagnosis records from the UK Collaborative Trial of Ovarian Cancer Screening, a randomized controlled ovarian cancer screening trial conducted in England, Wales, and Northern Ireland. The trial included 202,638 women ages 50 to 74 years with no family history of ovarian cancer, randomized in a 1:1:2 ratio to annual MMS (serum CA125 interpreted using the risk of ovarian cancer algorithm), annual USS, or no screening. The current analysis included 199,499 women, with 674,806 screens and 2,025 cancer diagnoses. Results: Among high-grade serous cancers (HGSC), the estimated preclinical detectable phase was 1.7 years (95% credible interval, 1.3–2.2), compared with 7.8 years (95% credible interval, 5.7–10.6) for non-HGSCs. The preclinical detectable phase depended on screening modality: for HGSCs, it was longer in the MMS arm (2.2 years) compared with the USS arm (0.8 years), whereas for non-HGSCs, it was shorter in the MMS arm (2.7 years) compared with the USS arm (8.2 years). Conclusions: The interception opportunity for ovarian cancer strongly depends on histologic subtype and screening modality. Impact: Achieving a clinically significant benefit of ovarian cancer early detection will require prolonging the interception window through judicious combination of first- and second-line tests.

Short-term Endpoints for Cancer Screening Trials: Does Tumor Subtype Matter?

Abstract Multicancer early detection tests are precipitating a reexamination of potential short-term endpoints for cancer screening trials. A reduction in advanced stage incidence is a prime candidate, and stage-shift models that substitute early-stage for late-stage survival have been used to predict mortality reduction due to screening. However, standard stage-shift models often ignore prognostic subtypes, effectively implying that cancers detected early also have an associated subtype shift. To illustrate the differences between mortality predictions from stage-shift models that ignore versus preserve prognostic subtype, we use ovarian cancer partitioned by histologic subtype and prostate cancer partitioned by grade. We infer general conditions under which stage-shift models that preserve prognostic subtype are likely to predict mortality reductions that differ from those that ignore subtype and examine the implications for short-term endpoints based on stage in cancer screening trials.