How do we safely preserve ovaries in patients with cervical adenocarcinoma: risk factors and predictive models.

Objective: To study and predict the risk of ovarian metastasis (OM) in patients with cervical adenocarcinoma (ADC). Methods: Patients with ADC who received surgical treatment from January 2015 to December 2022 in the Obstetrics and Gynecology Hospital of Fudan University were included in the study. Patients were further divided into OP (ovaries were preserved in surgery) and BSO (bilateral salpingo-oophorectomy) groups. For the patients who accepted BSO, 60% of the patients were randomly grouped into a training cohort, and predictive prognostic models were constructed with 10-fold cross-validation through random forest, LASSO, stepwise, and optimum subset analysis. The model with the highest area under receiver operator curve (AUC) was screened out in the testing cohort. The nomogram and its calibration curve presented the possibility of OM in future patients. The prognoses between the different populations were compared using Kaplan-Meier analysis. All data processing was carried out in R 4.2.0 software. Results: A total of 934 patients were enrolled in our cohort; 266 patients had their ovaries preserved and 668 patients had BSO according to the previous criteria reported The clinical safety with these criteria was secured, while the 5-year overall survival had no significant difference between the BSO and OP groups (p = 0.069), which suggested that the current criteria could be extended and are more precise. Four predictive models for ovarian metastasis by machine learning were constructed in our study, and the random forest model that obtained the highest AUC in both training and testing sets (0.971 for training and 0.962 for testing set) was taken as the best model. The optimal cut-off point of the ROC curve (specificity 99.5% and 90% sensitivity) was utilized to stratify the patients into high- and low-risk OM. Further comparing the survival curves of the high and low-OM risk groups, it was found that both DFS and OS were significantly prolonged in the low-risk group (p < 0.01). On the basis of this random forest model, a nomogram was used to calculate the OM risk, and the results were validated with calibration. The predictive model was further applied to the whole cohort (934 patients), and we identified the OM low-risk population (n = 822) and the patients with high risk who should be recommended for BSO (n = 112). No significant difference was found in the 5-year survival between the low-risk group with our model and the patients who already had ovaries preserved according to the previous criteria (n = 266). Conclusion: The predictive model constructed in our study could identify the low-risk population of OM in patients with ADC, which remarkably extended the number with the previous criteria, for whom we could potentially preserve ovaries to help improve their life quality.