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Ovarian cancer screening: Will it impact mortality?
Synopsis: Despite the survival differences between early and advanced stage ovarian cancer and the promise of "stage migration" with general population screening, modeling suggests the impact will be modest due to identification of low-risk disease.
Source: Havrilesky LJ, Sanders GD, Kulasingam S, et al. Development of an ovarian cancer screening decision model that incorporates disease heterogeneity. Cancer 2011;117:545-553.
Recent investigation into the molecular pathogenesis of epithelial ovarian cancer has implicated two dominant phenotypes. One manifests by late presentation, advanced stage, and an aggressive clinical course (Type I), and one manifests with a more indolent nature, which, despite an innate chemo-resistance, is associated with long survival (Type II).
By studying the history of ovarian cancer, the authors evaluated the impact of screening on mortality. They considered a 1-phenotype and a 2-phenotype model, the latter including the assumptions on outcome based on the contribution of Type II cancers. To calibrate their data, they used data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database. They also assumed their "screening model" would perform in line with the multimodal screening algorithm (MMS) in the U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) study, and they adjusted the SEER prevalence ovarian cancer rate to match the UKCTOCS study.
The authors showed their validation test of screening performance would increase stage I/II cancers to about 41%, in line with the UKCTOCS study. Positive predictive value also was close (26%-27% vs. 35%). Overall survival for ovarian cancer predicted based on the 1-phenotype and 2-phenotype model was similar to that expected from the SEER data. The impact on mortality from an implemented postmenopausal annual screening program resulted in an 11% (2-phenotype model) to 15% (1-phenotype model) reduction in mortality. Modeling different screening characteristics (sensitivity and specificity) and frequencies adjusted these measures only slightly, with the exception of the screening frequencies, which had its greatest impact with every-three-months evaluation.