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

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.