Abstract CT104: Ovarian cancer screening and mortality in the UK collaborative trial of ovarian cancer screening (UKCTOCS): A randomised controlled trial

Abstract

Abstract Background: Ovarian cancer has poor prognosis, with 60% of patients dying within 5 years. Early detection of ovarian cancer through blood tests may reduce mortality through detection earlier in the disease process than occurs with clinical detection. Since survival time in screening trials is measured from time of randomization rather than diagnosis as is done in therapeutic trials, there is a well established delayed effect of screening. The impact on prevalent cases, women with undiagnosed disease at study entry, is likely to be less than for disease arising after start of screening. One intervention arm of this trial was designed to establish the effect of early detection by screening with blood tests on ovarian cancer mortality. We estimated its impact on cases arising after screening begins (pre-specified) and accounting for the delayed effect (post-hoc). Methods: We recruited postmenopausal women aged 50-74 years from 13 centres in the UK and randomly allocated participants to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS with no screening. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. For this report, we focused on the impact of screening on cases arising after the randomization in the MMS arm where we excluded cases arising prior to randomization, and on the delayed effect for which we applied the weighted log-rank test with weights which increased over time to account for the delayed effect. Results: For the MMS comparison, we randomly allocated 202 638 women: 50 640 (25.0%) to MMS, and 101 359 (50.0%) to no screening. More than 99.9% women were eligible for analysis. Screening ended on Dec 31, 2011, and included 345 570 MMS annual screening episodes. At a median follow-up of 11.1 years, we diagnosed ovarian cancer in 968 women: 338 in the MMS group, and 630 in the no screening group. Of these women, 148 (0.29%) women in the MMS group, and 347 (0.34%) in the no screening group had died of ovarian cancer. A standard Cox proportional hazards model, which does not account for the delayed effect nor for the lesser impact on prevalent cases gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p = 0.10) with MMS. However, the pre-specified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p = 0.021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favor of MMS. The post-hoc weighted log-rank test had a significant p-value of 0.023 with weights equal to ovarian cancer mortality pooled over the MMS and control arms. Conclusion: Accounting for the delayed effect of screening and estimating the impact excluding prevalent cases yielded a significant but delayed impact of MMS screening in years 7-14. Further follow-up is needed however before firm conclusions can be reached on the efficacy of ovarian cancer screening. Citation Format: Ian J. Jacobs, Usha Menon, Andy Ryan, Aleksandra Gentry-Maharaj, Matthew Burnell, Jatinderpal K. Kalsi, Alistair J. McGuire, Mahesh Parmar, Steven J. Skates. Ovarian cancer screening and mortality in the UK collaborative trial of ovarian cancer screening (UKCTOCS): A randomised controlled trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT104.