Growth kinetics of high-grade serous ovarian cancer using longitudinal clinical data - implications for early detection

Abstract High-grade serous ovarian cancer (HGSOC) is the most lethal gynaecological cancer with patients routinely diagnosed at advanced stages with widespread disease. Evidence from screening trials indicates that early diagnosis may not reduce cancer-related deaths, possibly due to an underestimation of the true extent of the disease at screening. We aim to characterise the growth kinetics of HGSOC to understand why early detection has failed so far and under what conditions it might prove fruitful. We analysed a dataset of 597 patients with a confirmed HGSOC diagnosis, and identified 37 cases with serial CT scans. We calculated the growth rates of lesions in the ovaries/pelvis and the omentum and estimated the time to metastasis using a population-level Gompertz model. Finally, we simulated ultrasound and CA125 based screening in a virtual population of patients. Growing lesions in the ovaries and the omentum doubled in volume every 2.3 months and 2 months respectively. At both sites, smaller lesions grew faster than larger ones. The 12 cases with growing lesions in both disease sites had a median interval of 11.5 months between disease initiation and the onset of metastasis. Our simulations suggested that over 33% of patients would develop metastases before they could be screen detected. The remaining patients provided a median window of opportunity of only 4.7 months to detect the tumours before they metastasised. Our results suggest that HGSOC lesions have short time to metastasis intervals, preventing effective early detection using current screening approaches. Competing Interest Statement James Brenton is a co-founder and shareholder of Tailor Bio Ltd. Mireia-Crispin Ortuzar is a co-founder and Chief Digital Officer of 52 North Health. There are no further conflicts of interests to declare. Funding Statement This study was funded by Cancer Research UK through the Alliance for Cancer Early Detection. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The data for this work were collected previously as part of the CTCR-OV04 study. The OV04 study was given ethical approval by the Cambridgeshire Research Ethics Committee (REC reference number 08 /H0306/61). Patients provided written consent to their data being anonymously used in secondary studies, such as this work, and for their anonymized data to be shared with other researchers. No patient data were collected as part of this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Competing Interests: James Brenton is a co-founder and shareholder of Tailor Bio Ltd. Mireia-Crispin Ortuzar is a co-founder and Chief Digital Officer of 52 North Health. There are no further conflicts of interests to declare. Data Availability All data produced in the present work are contained in the manuscript. Code for the simulations and model fitting are available upon reasonable request.