Ovarian cancer population screening and mortality after long-term follow-up in the UK collaborative trial of ovarian cancer screening (UKCTOCS): a randomised controlled trial

Ovarian cancer is most commonly diagnosed at an advanced stage (3 or 4) and remains the deadliest gynecologic malignancy. When diagnosed at stage 1, a survival rate of greater than 90% has been demonstrated, compared with a 5-year survival rate of 27% and 13% for stage 3 and stage 4 disease, respectively. Despite international efforts to identify robust screening methods and increase early-stage detection, to date no evidence that screening saves lives has been presented. The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is a randomized controlled trial that demonstrated no evidence associated with screening for ovarian cancer and reduction in ovarian cancer-related deaths at primary analysis but requires further follow-up. This secondary analysis of the UKCTOCS randomized controlled trial aimed to provide a follow-up and report on the long-term mortality effects of ovarian cancer screening. The UKCTOCS is a multicenter randomized trial of 202,638 women aged 50 to 74 years assigned to 2 annual screening groups (multimodal screening [MMS] vs ultrasound screening [USS]). Women in the United Kingdom were recruited from 13 National Health Service (NHS) centers and randomized to MMS, USS, or no screening in a 1:1:2 ratio. Annual screening in the MMS group involved serum CA125 measurements used in conjunction with the risk of ovarian cancer (ROCA) calculation to guide follow-up involving either no additional screening, repeat CA125 ROCA in 3 months, or transvaginal USS as a second test. Annual screening in the USS group involved transvaginal ultrasound with follow-up involving either continuation of annual screening, repeat in 3 months, or requiring a scan with a senior ultrasonographer within 6 weeks. The primary study outcome was death due to ovarian cancer or tubal cancer. A total of 202,638 women were randomized between April 2001 and September 2005, with screening concluding in December 2011 and follow-up continuing until June 2020. The final analysis cohort consisted of 202,562 women, 50,625 in the MMS group, 50,623 in the USS group, and 101,314 in the no screening group. Compliance with screening was 81% in the MMS group versus 78% in the USS group, with a median of 8 annual screens per participant. The median follow-up was 16.3 years (interquartile range, 15.1–17.3). A total of 2055 participants were diagnosed with ovarian or tubal cancer. At 9.5 years after screening, there was a 47.2% (95% confidence interval, 19.7–81.1) greater incidence of stage 1 disease and a 24.5% (-41.8 to -2.0) lower incidence of stage IV disease in the MMS group compared with the no screening group. Overall, a 39.2% (95% confidence interval, 16.1–66.9) greater incidence of stage I or II disease and a 10.2% (-21.3 to 2.4) lower incidence of stage III or IV disease was observed in the MMS group compared with the no screening group. At follow-up conclusion, 1206 women had died of ovarian cancer (296/50,625 [0.6%] in the MMS group, 291/50,623 [0.6%] in the USS group, 619/101,314 [0.6%] in the no screening group) with no significant difference between the MMS (P = 0.58) and USS (P = 0.36) groups compared with the no screening group. The results of this large-scale ovarian cancer screening trial demonstrate that, on long-term follow-up, while the screening strategies defined here resulted in a greater likelihood of diagnosing early stage disease, neither MMS nor USS resulted in a significant reduction in deaths from ovarian or tubal cancer.