Subdivision of IIIC Stage for Endometrioid Carcinoma to Better Predict Prognosis and Treatment Guidance

Objective: The prognostic value of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) IIIC staging in endometrioid carcinoma patients remains debatable. The current study aimed to compare the prognosis between IIIC1 and IIIC2 patients with endometrioid carcinoma and attempt to conduct a new subdivision. Methods: By using the Surveillance, Epidemiology, and End Results (SEER) database, patients with endometrioid-type endometrial cancer diagnosed from 2004 to 2015 were identified and randomly divided into training and validation sets. We developed a Fine–Gray competing risk model to compare the cancer-specific mortality (CSM). The IIIC subdivision system was built based on the independent prognostic factors. The cumulative incidence curves were compared using Gray's test or log-rank test. Nomogram for predicting 3- or 5-years CSM was constructed and subsequently validated internally and externally. Results: The IIIC subdivision defined by FIGO staging, including IIIC1 and IIIC2, exhibited no association with CSM in multivariate analysis [subdistribution hazard ratio [SHR] = 1.03, 95% CI [0.85–1.26], P = 0.760]. The IIIC category was subdivided into three subcategories based on the tumor (T) and nodes (N) stage, including IIICa (T1N1 and T1N2), IIICb (T2N1 and T2N2), and IIICc (T2N1 and T2N2). The prognosis across new IIIC subcategories with CSM remained significant [IIICb vs. IIICa: SHR = 1.53, 95% CI [1.18–1.98], P = 0.001; IIICc vs. IIICa: SHR = 2.64, 95% CI [2.13–3.28], P < 0.001]. Postoperative adjuvant chemotherapy or radiotherapy alone did not improve survival for patients categorized as IIICa or IIICb, and all IIIC patients benefited most from combination of postoperative chemotherapy and radiotherapy [IIICa: SHR = 0.59, 95% CI [0.43–0.82], P = 0.001; IIICb: SHR = 0.66, 95% CI [0.45–0.97], P = 0.036; IIICc: SHR = 0.44, 95% CI [0.34–0.58], P < 0.001]. A nomogram based on competing risk model was built to predict the long-term survival of IIIC patients, with a concordance index above 0.70 both in training and validation set. Conclusion: There was no prognostic difference between FIGO IIIC1 and IIIC2 patients with endometrioid-type endometrial cancer. A new subdivision of IIIC category facilitates prognosis prediction and treatment modalities. A combination of postoperative chemotherapy and radiotherapy exerted as the optimal choice for endometrioid cancer patients with IIIC stage.