Validation of the integrated prediction model algorithm for outcome of cytoreduction in advanced ovarian cancer.
Authors: Piedimonte Sabrina , Bernardini Marcus , Ferguson Sarah , Laframboise Stephane , Bouchard-Fortier Genevieve , Cybulska Paulina , Avery Lisa , May Taymaa , Hogen Liat Frida 
Published: June 2022

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Background: In advanced ovarian cancer, the decision for primary cytoreductive surgery(PCS) or neoadjuvant chemotherapy(NACT) remains a challenge and may impact survival. We previously developed the integrated prediction model(IPM) using a 4-step algorithm of unresectable stage IVb, patient factors, surgical resectability and surgical complexity to predict outcome of optimal cytoreduction in advanced epithelial ovarian cancer(AEOC) and triage patients to NACT or PCS. The objective of the current study was to validate this model on a retrospective historical cohort of patients. Methods: This is a retrospective cohort study of 107 patients with AEOC treated at the Princess Margaret Cancer Centre between January 2017 and September 2018 undergoing PCS or NACT. All diagnostic imaging was retrospectively reviewed to assign surgical resectability score (SRS) for sites of disease and the surgical complexity score (SCS) for procedures anticipated to be required to achieve optimal cytoreduction based on pre-operative imaging. Those scores were modified from previously validated tools. Patient factors (PF) included age, ECOG and albumin. We previously developed an IPM algorithm to achieve outcome of optimal cytoreduction and determined cut-offs using the Youden index J. Triaging patients to PCS without stage IVb unresectable disease, PF≤ 2, SRS≤5 and SCS≤ 9 led to an 85% specificity and 75% accuracy for outcome of optimal cytoreduction < 1 cm. The current validation study was performed reporting sensitivity, specificity, negative (NPV) and positive predictive value (PPV) on an external cohort. Results: Among 107 patients, 61 had PCS and 46 had NACT followed by ICS. Patients treated with NACT were significantly older (63.5 vs 61 years, p = 0.037), more likely stage IV (52% vs 18%, p < 0.001), had a higher proportion of ECOG > 1 (30% vs 11%, 0.045), a lower pre-operative album (37 vs 40, p < 0.001) and higher CA-125 (970 vs 227.5, p < 0.001) compared to PCS. They also had higher PF (2 vs 0, p = 0.013), SRS (4 vs 1, p < 0.001) and SCS (8 vs 5, p = < 0.001). There was no significant difference in outcome of cytoreduction; the optimal cytoreduction rate was 85% vs 87%, p = 0.12 between PCS and ICS patients. In this validation cohort, triaging patients without unresectable stage IVb disease, PF≤ 2, SRS≤ 5 and SCS≤ 9 to PCS had a sensitivity of 91% to correctly identify patients who will have optimal cytoreduction of < 1 cm at PCS and a specificity of 81%. The PPV was 83%, NPV was 90% and accuracy was 86%. Application of the IPM would have prevented 5 suboptimal patients and correctly triaged them to NACT. Conclusions: We validated a triage algorithm integrating patient factors, surgical complexity and surgical resectability for patients with AEOC to achieve optimal cytoreduction at PCS with high sensitivity and specificity. This may therefore be used in a clinical setting to decide between PCS and NACT.