Jillian T Henderson1, Elizabeth M Webber1, George F Sawaya2. 1. Kaiser Permanente Research Affiliates Evidence-based Practice Center, Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon. 2. Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco.
Abstract
Importance: Ovarian cancer is relatively rare but the fifth-leading cause of cancer mortality among United States women. Objective: To systematically review evidence on benefits and harms of ovarian cancer screening among average-risk women to inform the United States Preventive Services Task Force. Data Sources: MEDLINE, PubMed, Cochrane Collaboration Registry of Controlled Trials; studies published in English from January 1, 2003, through January 31, 2017; ongoing surveillance in targeted publications through November 22, 2017. Study Selection: Randomized clinical trials of ovarian cancer screening in average-risk women that reported mortality or quality-of-life outcomes. Interventions included transvaginal ultrasound, cancer antigen 125 (CA-125) testing, or their combination. Comparators were usual care or no screening. Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers. Meta-analytic pooling of results was not conducted because of the small number of studies and heterogeneity of interventions. Main Outcomes and Measures: Ovarian cancer mortality, false-positive screening results and surgery, surgical complications, and psychological effects of screening. Results: Four trials (N = 293 587) were included; of these, 3 (n = 293 038) assessed ovarian cancer mortality, and 1 (n = 549) reported only on psychological outcomes. Evaluated screening interventions included transvaginal ultrasound alone, transvaginal ultrasound plus CA-125 testing, and CA-125 testing alone. Test positivity for CA-125 was defined by a fixed serum level cutpoint or by a proprietary risk algorithm based on CA-125 level, change in CA-125 level over time, and age (risk of ovarian cancer algorithm [ROCA]). No trial found a significant difference in ovarian cancer mortality with screening. In the 2 large screening trials (PLCO and UKCTOCS, n = 271 103), there was not a statistically significant difference in complete intention-to-screen analyses of ovarian, fallopian, and peritoneal cancer cases associated with screening (PLCO: rate ratio, 1.18 [95% CI, 0.82-1.71]; UKCTOCS: hazard ratio [HR], 0.91 [95% CI, 0.76-1.09] for transvaginal ultrasound and HR, 0.89 [95% CI, 0.74-1.08] for CA-125 ROCA). Within these 2 trials, screening led to surgery for suspected ovarian cancer in 1% of women without cancer for CA-125 ROCA and in 3% for transvaginal ultrasound with or without CA-125 screening, with major complications occurring among 3% to 15% of surgery. Evidence on psychological harms was limited but nonsignificant except in the case of repeat follow-up scans and tests, which increased the risk of psychological morbidity in a subsample of UKCTOCS participants based on the General Health Questionnaire 12 (score ≥4) (odds ratio, 1.28 [95% CI, 1.18-1.39]). Conclusions and Relevance: In randomized trials conducted among average-risk, asymptomatic women, ovarian cancer mortality did not significantly differ between screened women and those with no screening or in usual care. Screening harms included surgery (with major surgical complications) in women found to not have cancer. Further research is needed to identify effective approaches for reducing ovarian cancer incidence and mortality.
Importance: Ovarian cancer is relatively rare but the fifth-leading cause of cancer mortality among United States women. Objective: To systematically review evidence on benefits and harms of ovarian cancer screening among average-risk women to inform the United States Preventive Services Task Force. Data Sources: MEDLINE, PubMed, Cochrane Collaboration Registry of Controlled Trials; studies published in English from January 1, 2003, through January 31, 2017; ongoing surveillance in targeted publications through November 22, 2017. Study Selection: Randomized clinical trials of ovarian cancer screening in average-risk women that reported mortality or quality-of-life outcomes. Interventions included transvaginal ultrasound, cancer antigen 125 (CA-125) testing, or their combination. Comparators were usual care or no screening. Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers. Meta-analytic pooling of results was not conducted because of the small number of studies and heterogeneity of interventions. Main Outcomes and Measures: Ovarian cancer mortality, false-positive screening results and surgery, surgical complications, and psychological effects of screening. Results: Four trials (N = 293 587) were included; of these, 3 (n = 293 038) assessed ovarian cancer mortality, and 1 (n = 549) reported only on psychological outcomes. Evaluated screening interventions included transvaginal ultrasound alone, transvaginal ultrasound plus CA-125 testing, and CA-125 testing alone. Test positivity for CA-125 was defined by a fixed serum level cutpoint or by a proprietary risk algorithm based on CA-125 level, change in CA-125 level over time, and age (risk of ovarian cancer algorithm [ROCA]). No trial found a significant difference in ovarian cancer mortality with screening. In the 2 large screening trials (PLCO and UKCTOCS, n = 271 103), there was not a statistically significant difference in complete intention-to-screen analyses of ovarian, fallopian, and peritoneal cancer cases associated with screening (PLCO: rate ratio, 1.18 [95% CI, 0.82-1.71]; UKCTOCS: hazard ratio [HR], 0.91 [95% CI, 0.76-1.09] for transvaginal ultrasound and HR, 0.89 [95% CI, 0.74-1.08] for CA-125ROCA). Within these 2 trials, screening led to surgery for suspected ovarian cancer in 1% of women without cancer for CA-125ROCA and in 3% for transvaginal ultrasound with or without CA-125 screening, with major complications occurring among 3% to 15% of surgery. Evidence on psychological harms was limited but nonsignificant except in the case of repeat follow-up scans and tests, which increased the risk of psychological morbidity in a subsample of UKCTOCS participants based on the General Health Questionnaire 12 (score ≥4) (odds ratio, 1.28 [95% CI, 1.18-1.39]). Conclusions and Relevance: In randomized trials conducted among average-risk, asymptomatic women, ovarian cancer mortality did not significantly differ between screened women and those with no screening or in usual care. Screening harms included surgery (with major surgical complications) in women found to not have cancer. Further research is needed to identify effective approaches for reducing ovarian cancer incidence and mortality.
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