The Long-Term Prognostic Significance of Circulating Tumor Cells in Ovarian Cancer—A Study of the OVCAD Consortium

SIMPLE SUMMARY: In ovarian cancer, often diagnosed at an advanced stage and associated with poor overall survival, with just a third of women surviving five years, the controversial prognostic value of circulating tumor cells (CTCs) is still discussed. Currently CTC diagnostics use either molecular approaches or immunofluorescent staining. Our study shows that, given the heterogeneity and extreme scarcity of CTCs, a multifactorial analysis of CTCs is key. Combining both approaches, qPCR and IF, increased sensitivity and may better capture a treatment-related shift in the molecular phenotypes of CTCs. In addition to a long progression-free interval, the absence of CTCs after treatment was an independent predictor of an excellent outcome in patients who had already survived for five years. Thus, a multifactorial CTC approach can identify patients who have elevated risk of recurrence and death and who may require risk-adapted treatment strategies. ABSTRACT: Introduction: We previously reported the prognostic impact of circulating tumor cells (CTCs) in a multicenter study on minimal residual disease in primary ovarian cancer. With additional follow-up data, we evaluated the combined CTC approach (CTCs(combo)), in particular for the patients who had survived more than five years. Material and Methods: Blood samples taken at baseline and six months after adjuvant treatment (follow-up) were assessed by quantitative PCR (qPCR) measuring PPIC transcripts and immunofluorescent staining (IF). A positive result with either IF or qPCR was classified as CTC(combo)-positive. Further, PPIC was assessed in the primary tumor tissue. Results: The concordance of IF and qPCR was 65% at baseline and 83% after treatment. Results showed that 50.5% of the baseline and 29.5% of the follow-up samples were CTC(combo)-positive. CTCs(combo) after treatment were associated with increased mortality after adjusting for FIGO stage (HR 2.574, 95% CI: 1.227–5.398, p = 0.012), a higher risk of recurrence after adjusting for peritoneal carcinosis (HR 4.068, 95% CI: 1.948–8.498, p < 0.001), and increased mortality after five survived years. Discussion: The two-sided analytical approach revealed CTC subpopulations associated with ovarian cancer progression and may illuminate a potential treatment-related shift in molecular phenotypes. That approach can identify patients who have elevated risk of recurrence and death due to ovarian cancer and who may require risk-adapted treatment strategies.