Screening for Ovarian Cancer: An Updated Evidence Review for the U.S. Preventive Services Task Force [Internet]

Excerpt

Importance: Ovarian cancer, while not common, is the fifth-leading cause of cancer death among United States women. In 2012 the U.S. Preventive Services Task Force (USPSTF) determined that harms of ovarian cancer screening outweighed benefits based on trial evidence, and recommended against screening average-risk women.

Objective: To update the previous systematic review and inform USPSTF ovarian cancer screening guidance.

Data Sources: MEDLINE, PubMed, and the Cochrane Collaboration Registry of Controlled Trials from January 1, 2003, through January 31, 2017, and prior literature identified in the previous review conducted for the USPSTF.

Study Selection: English-language trials of benefits and harms of screening for ovarian cancer in average-risk women reporting health outcomes (e.g., mortality and quality of life). Interventions compared with the control condition were transvaginal ultrasound screening alone, ultrasound screening with cancer antigen 125 (CA-125) testing, and CA-125 screening alone—either with a single measurement threshold value or measures of change over time.

Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles, and then extracted data from fair- and good-quality trials.

Main Outcomes and Measures: Ovarian cancer mortality and incidence (defined as ovarian, fallopian tube, and peritoneal cancer), ovarian cancer survival, harms associated with false positive test results, false positive surgery, screening and surgical complications.

Results: Four RCTs (n = 293,587) were included; three reported ovarian cancer mortality (KQ1) and all reported potential harms of screening (KQ2). Three trials were rated good-quality and the small trial (n= 549) reporting only on psychological harms of screening was rated fair-quality. Two trials were conducted in the United States and two in the United Kingdom, primarily with postmenopausal, average-risk women. The Prostate, Lung, Colorectal and Ovarian (PLCO) (n = 68,557) included 4-6 rounds of annual CA-125 (≥35 U/mL threshold) and transvaginal ultrasound screening, with up to 13 years of trial data. The U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) (n = 202,546) included 7–11 rounds of either annual transvaginal ultrasound screening or CA-125 screening using the Risk of Ovarian Cancer Algorithm with up to 14 years of trial data. A smaller U.K. Pilot trial (n = 21,935) included three rounds of annual screening with CA-125 (≥30 U/mL threshold) and up to 8 years of trial data. In all three screening trials, there was not a statistically significant difference in ovarian cancer mortality associated with screening. Mortality estimates from the PLCO (RR =1.18 [95% CI, 0.82 to 1.71]) or in either arm of the UKCTOCS: ultrasound (HR = 0.91 [95% CI, 0.76 to 1.09]) and CA-125 (HR = 0.89 [95% CI, 0.74 to 1.08]) were based on more rounds of screening and larger study populations. Harms of screening in these two large screening trials included surgical investigations among screen-positive women without cancer, which ranged from 1 percent of trial participants without cancer screened with CA-125 testing in the UKCTOCS, and 3.2 percent for the ultrasound arm of the UKCTOCS and in the PLCO screening intervention. Serious surgical complications of occurred for just over 3 percent of women without cancer in the UKCTOCS intervention arms, and in 15 percent of women in the PLCO intervention arm. In the two largest trials, cumulative false-positive rates ranged from 9.8% to 44%. Evidence on psychological harms was limited but nonsignificant, except in the case of repeat followup scans and tests, which increased the risk of psychological morbidity in a subsample of the UKCTOCS participants based on the General Health Questionnaire 12 (score ≥4) (OR 1.28 [95% CI, 1.18 to 1.39]).

Conclusions and Relevance: Since the previous review for the USPSTF, results from a large trial conducted in the United Kingdom were published. Ovarian cancer mortality did not differ between control and intervention screening conditions in any of the included trials, including two good-quality studies with adequate power to detect differences. Harms of screening include surgery following a false-positive test, often resulting in removal of one or both ovaries and/or fallopian tubes, and the potential for major surgical complications. Reports from the UKCTOCS of a potential delayed effect of screening on ovarian cancer mortality require further followup data to evaluate, but the causal mechanism for a delayed screening effect is unclear. Major trials of promising ovarian cancer screening tools have null findings to date among healthy average-risk women, and there are considerable harms associated with screening.