High-Grade Serous Ovarian Cancer: Impact of Multimodal Screening on Survival

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In an analysis of the UKCTOCS study reported in The Lancet Oncology, Menon et al found that patients with high-grade serous tubo-ovarian cancer detected on multimodal screening may have a survival benefit over those whose disease was diagnosed without screening.

The investigator stated, “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. …[W]e did exploratory analyses of patients with high-grade serous ovarian cancer to understand the reason for the discrepancy.”

Study Details

In UKCTOCS, patients aged 50 to 74 years with intact ovaries recruited between April 2001 and September 2005 were randomly assigned 2:1:1 to receive either no screening, annual multimodal screening, or annual ultrasound screening through December 2011. The current analysis involves patients diagnosed with high-grade serous cancer in the multimodal screening group and the no screening group, with follow-up through June 2020.

Key Findings

Diagnosis of high-grade serous cancer occurred in 259 (0.5%) of 50,625 patients in the multimodal screening group and in 520 (0.5%) of 101,314 in the no screening group.

Among patients in the multimodal screening group vs the no screening group diagnosed with high-grade serous cancer, 75% vs 86% had advanced disease (P = .0003), 61% vs 42% underwent primary surgery (P < .0001),  46% vs 30% had no residual disease after debulking surgery (P < .0001), 74% vs 64% received treatment including both surgery and chemotherapy (P = .0032), and 55% vs 56% received first-line combination chemotherapy (P = .69).

Median follow-up from random assignment of patients with high-grade serous cancer in the multimodal screening and no screening groups was 9.51 years (interquartile range = 6.04–13.00 years). At time of analysis, a delayed overall survival benefit was observed in the multimodal screening group. For the multimodal group vs no screening group, overall survival was 83% vs 83% at 5 years after random assignment (absolute difference = –0.3%, 95% confidence interval [CI] = –5.6% to 5.3%), 46% vs 45% at 10 years (absolute difference = 1.5%, 95% CI = –5.9% to 9.0%), 24% vs 18% at 15 years (absolute difference = 6.7%, 95% CI = 0.40%–13.0%), and 21% vs 14% at 18 years (absolute difference = 6.9%, 95% CI = 0.61%–13.2%).

The investigators concluded, “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 tumor 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.”

Usha Menon, FRCOG, of the MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the National Institute for Health Research, Medical Research Council, Cancer Research UK, and The Eve Appeal. For full disclosures of the study authors, visit

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