Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease

• the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) was designed to determine if population screening can reduce deaths due to the disease

Methods:

• randomised controlled trial, postmenopausal women aged 50-74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland
• exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk
• the trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio
• follow-up was through national registries
• primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020
• analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test
• investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group

Findings:

• between April 17, 2001, and Sept 29, 2005, of 1243282 women invited, 202638 were recruited and randomly assigned, and 202562 were included in the analysis:
  • 50625 (25.0%) in the MMS group, 50623 (25.0%) in the USS group, and 101314 (50.0%) in the no screening group. At a median follow-up of 16.3 years (IQR 15.1-17.3), 2055 women were diagnosed with tubal or ovarian cancer:
    • 522 (1.0%) of 50625 in the MMS group,
    • 517 (1.0%) of 50623 in the USS group,
    • 1016 (1.0%) of 101314 in the no screening group
  • compared with no screening
    • there was a 47.2% (95% CI 19.7 to 81.1) increase in stage I
    • 24.5% (-41.8 to -2.0) decrease in stage IV disease incidence in the MMS group
    • overall the incidence of stage I or II disease was 39.2% (95% CI 16.1 to 66.9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10.2% (-21.3 to 2.4) lower
    • 1206 women died of the disease:
      • 296 (0.6%) of 50625 in the MMS group,
      • 291 (0.6%) of 50623 in the USS group,
      • 619 (0.6%) of 101314 in the no screening group
    • no significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0.58) or USS (p=0.36) groups compared with the no screening group

Interpretation

• the study authors concluded:
  • reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended

Reference:

1. Menon U, Gentry-Maharaj A, Burnell M, Singh N, Ryan A, Karpinskyj C, Carlino G, Taylor J, Massingham SK, Raikou M, Kalsi JK, Woolas R, Manchanda R, Arora R, Casey L, Dawnay A, Dobbs S, Leeson S, Mould T, Seif MW, Sharma A, Williamson K, Liu Y, Fallowfield L, McGuire AJ, Campbell S, Skates SJ, Jacobs IJ, Parmar M. 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. Lancet. 2021 Jun 5;397(10290):2182-2193.