Screening may reduce mortality in ovarian cancer17 Dec 2015
One of the largest ever randomized trials has concluded that ovarian cancer screening may reduce ovarian cancer mortality by an estimated 20% after follow up of up to 14 years. Longer follow-up is needed to determine the ultimate mortality reduction and if screening the general population is cost effective.
The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) tested the hypothesis that screening for ovarian cancer in the general population can reduce disease mortality without significant harm (in line with screening programs for other cancers).
Details of the clinical study
Following invitations to 1·2 million women aged 50-74 years identified through age/sex registers, 202 638 were recruited between 2001-2005 to this randomized controlled trial through 13 trial centers in England, Northern Ireland and Wales. Postmenopausal women not considered to be at risk for familial ovarian cancer, with no personal history of ovarian cancer or removal of both ovaries (bilateral oophorectomy) or active non ovarian malignancy were randomized in a 2:1:1 ratio to:
- No screening -- 101299 women analyzed
- Annual screening using serum CA125 (a biomarker blood test) interpreted using the Risk of Ovarian Cancer Algorithm (ROCA) with transvaginal ultrasound scan (TVS) as a second-line test (multimodal; MMS group) -- 50624 women analyzed or
- Annual TVS alone (USS group) -- 50623 analyzed.
Annual screening ended in December 2011 and follow-up lasted until 31st December 2014. Follow-up was through national cancer/death registries supplemented with postal questionnaires sent to all participants who were alive and had not withdrawn from the study. The primary outcome was death due to ovarian cancer (malignant neoplasm of ovary, fallopian tube or undesignated ovary/tube/peritoneum). An outcome review committee blinded to the randomization group assigned ovarian cancer diagnosis/death.
With the median follow-up was 11·1 years, the analysis of the results showed:
- Ovarian cancers were diagnosed in 630 (no screening) 338 (MMS) 314 (USS) women.
- The primary analysis using a statistical method known as a Cox model gave a mortality reduction over years 0-14 of 15% with MMS, and 11% with USS which were not significant.
- This mortality reduction was made up of an 8% and 23% relative reduction in mortality during years 0-7 and 7-14 respectively in the MMS versus no screening analysis; and of 2% and 21% respectively in the USS group.
- After excluding women who, when they joined the trial, had undiagnosed ovarian cancer, there was a significant reduction in deaths with an average mortality reduction of 20% and in years 7-14 of 28%.
- There was also a significant reduction in deaths in the MMS versus no screening group using a different statistical analysis called weighted log rank test. However, this was not a planned analysis and was undertaken only after the data were revealed.
- The preliminary estimate of the number needed to screen in the MMS group to prevent one ovarian cancer death at 14 years was 641.
- In respect to harms, in the MMS group from 10,000 women screened, 14 underwent screen-positive surgery that resulted in benign pathology or normal ovaries.
“Screening can reduce ovarian cancer deaths”
Professor Menon adds: "Our report on the mortality data from UKCTOCS is the first evidence from a randomized controlled trial that screening can reduce ovarian cancer deaths. The findings are of importance given the limited progress in treatment outcomes for ovarian cancer over the last 30 years."
The authors say "The evidence from UKCTOCS suggests that carefully conducted screening using a multimodal strategy detects ovarian cancer sufficiently early to alter the natural history of the disease and reduce mortality. This opens up a new era in ovarian cancer research and care. Whether or not population screening is justified will depend upon a range of factors including further follow-up to determine the full extent of the mortality reduction and health economic analyses. Meanwhile efforts can be made to refine ovarian cancer screening, develop tests with greater sensitivity and more lead time and improve ways to risk stratify the population."Source: Science Daily