Development of an ovarian cancer screening decision model that incorporates disease heterogeneity

Abstract

BACKGROUND: Pathologic and genetic data suggest that epithelial ovarian cancer may consist of indolent and aggressive phenotypes. The objective of the current study was to estimate the impact of a 2-phenotype paradigm of epithelial ovarian cancer on the mortality reduction achievable using available screening technologies. METHODS:The authors modified a Markov model of ovarian cancer natural history (the 1-phenotype model) to incorporate aggressive and indolent phenotypes (the 2-phenotype model) based on histopathologic criteria. Stage distribution, incidence, and mortality were calibrated to data from the Surveillance, Epidemiology, and End Results Program of the US National Cancer Institute. For validation, a Monte Carlo microsimulation (1000,000 events) of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) multimodality prevalence screen was performed. Mortality reduction and positive predictive value (PPV) were estimated for annual screening. RESULTS: In validation against UKCTOCS data, the model-predicted percentage of screen-detected cancers diagnosed at stage I and II was 41% compared with 47% (UKCTOCS data), and the model-predicted PPV of screening was 27% compared with 35% (UKCTOCS data). The model-estimated PPV of a strategy of annual population-based screening in the United States at ages 50 to 85 years was 14%. The mortality reduction using annual postmenopausal screening was 14.7% (1-phenotype model) and 10.9% (2-phenotype model). Mortality reduction was lower with the 2-phenotype model than with the 1-phenotype model regardless of screening frequency or test sensitivity; 68% of cancer deaths are accounted for by the aggressive phenotype. CONCLUSIONS: The current analysis suggested that reductions in ovarian cancer mortality using available screening technologies on an annual basis are likely to be modest. A model that incorporated 2 clinical phenotypes of ovarian carcinoma into its natural history predicted an even smaller potential reduction in mortality because of the more frequent diagnosis of indolent cancers at early stages. Cancer 2011;117:545-53.

A branching process model of ovarian cancer

“…They found that annual screening had the potential to result in up to a 43% reduction in ovarian cancer mortality but at an incremental cost of $73,500 per year of life saved in the general population (or $36,000 in the high-risk population). A follow-up study [11] which separated ovarian cancer cases into two phenotypes found less benefit from annual screening since a large percentage of the early-stage detections occurred for the less aggressive phenotype.…”

Ultrasound Monitoring of Extant Adnexal Masses in the Era of Type 1 and Type 2 Ovarian Cancers: Lessons Learned From Ovarian Cancer Screening Trials

“…Recently, it has been reported that ovarian cancer screening detects more indolent and less aggressive Type 1 cancers [45] and that the frequency of Type 2 cancer is ~75% is higher than Type 1 with higher mortality rate for Type 2 cancer due to its faster rate of growth and metastasis. This result is in contrast to findings from the Kentucky Ovarian Cancer Screening trial where 83.3% of early stage malignancies were aggressive Type 2 cancers [5,35,36,38].…”

Current Status of Problem of Early Diagnosis of Ovarian Cancer and Its Solutions (Literature Review)

“…При использовании протеомных методов поиска биомаркеров A-SAA был выявлен как один из потен-циальных биомаркеров РЯ [48], рака легких [49], по-чки [50], носоглотки [51].…”

“…A-SAA был идентифицирован в качестве маркера метастазирования аденокарциномы простаты в кост-ную ткань [48]. Для рака легкого показано прогресси-рующее увеличение концентрации A-SAA с прогрес-сированием рака.…”