Tumour stage, treatment, and survival of women with high-grade serous tubo-ovarian cancer in UKCTOCS : an exploratory analysis of a randomised controlled trial

Background In UKCTOCS, there was a decrease in the diagnosis of advanced stage tubo-ovarian cancer but no reduction in deaths in the multimodal screening group compared with the no screening group. Therefore, we did exploratory analyses of patients with high-grade serous ovarian cancer to understand the reason for the discrepancy.Methods UKCTOCS was a 13-centre randomised controlled trial of screening postmenopausal women from the general population, aged 50-74 years, with intact ovaries. The trial management system randomly allocated (2:1:1) eligible participants (recruited from April 17, 2001, to Sept 29, 2005) in blocks of 32 using computer generated random numbers to no screening or annual screening (multimodal screening or ultrasound screening) until Dec 31, 2011. Follow-up was through national registries until June 30, 2020. An outcome review committee, masked to randomisation group, adjudicated on ovarian cancer diagnosis, histotype, stage, and cause of death. In this study, analyses were intention-to -screen comparisons of women with high-grade serous cancer at censorship (Dec 31, 2014) in multimodal screening versus no screening, using descriptive statistics for stage and treatment endpoints, and the Versatile test for survival from randomisation. This trial is registered with the ISRCTN Registry, 22488978, and ClinicalTrials.gov, NCT00058032.Findings 202 562 eligible women were recruited (50 625 multimodal screening; 50 623 ultrasound screening; 101 314 no screening). 259 (0 center dot 5%) of 50 625 participants in the multimodal screening group and 520 (0 center dot 5%) of 101 314 in the no screening group were diagnosed with high-grade serous cancer. In the multimodal screening group compared with the no screening group, fewer were diagnosed with advanced stage disease (195 [75%] of 259 vs 446 [86%] of 520; p=0 center dot 0003), more had primary surgery (158 [61%] vs 219 [42%]; p<0 center dot 0001), more had zero residual disease following debulking surgery (119 [46%] vs 157 [30%]; p<0 center dot 0001), and more received treatment including both surgery and chemotherapy (192 [74%] vs 331 [64%]; p=0 center dot 0032). There was no difference in the first-line combination chemotherapy rate (142 [55%] vs 293 [56%]; p=0 center dot 69). Median follow-up from randomisation of 779 women with high-grade serous cancer in the multimodal and no screening groups was 9 center dot 51 years (IQR 6 center dot 04-13 center dot 00). At censorship (June 30, 2020), survival from randomisation was longer in women with high-grade serous cancer in the multimodal screening group than in the no screening group with absolute difference in survival of 6 center dot 9% (95% CI 0 center dot 4-13 center dot 0; p=0 center dot 042) at 18 years (21% [95% CI 15 center dot 6-26 center dot 2] vs 14% [95% CI 10 center dot 5-17 center dot 4]).Interpretation To our knowledge, this is the first evidence that screening can detect high-grade serous cancer earlier and lead to improved short-term treatment outcomes compared with no screening. The potential survival benefit for women with high-grade serous cancer was small, most likely due to only modest gains in early detection and treatment improvement, and tumour biology. The cumulative results of the trial suggest that surrogate endpoints for disease-specific mortality should not currently be used in screening trials for ovarian cancer.Funding National Institute for Health Research, Medical Research Council, Cancer Research UK, The Eve Appeal.Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.