[Establishment of a prognostic nomogram and discussion on optimal treatment for cervical adenocarcinoma:a...

Objective: To establish and validate a predicting nomogram for cervical adenocarcinoma based on surveillance, epidemiology and end results (SEER) database and Chinese single-center data, and to explore the optimal treatment for cervical adenocarcinoma. Methods: This study selected 2 478 cervical adenocarcinoma patients from the SEER database as the training cohort, and 195 cervical adenocarcinoma patients from Cancer Hospital of Dalian University of Technology, Liaouing Cancer Hospital and Institute as an external validation cohort. Clinicopathological information and follow-up data of the two cohorts were collected. The radiotherapy group was defined as receiving comprehensive treatment based on concurrent chemoradiotherapy after initial diagnosis, while the surgery group was defined as receiving comprehensive treatment based on radical surgery. Log-rank test and cox regression were used to evaluate factors affecting the prognosis of cervical adenocarcinoma patients. A nomogram was drawn to predict the 3-year and 5-year overall survival rates of cervical adenocarcinoma patients, and then internal validation of the training cohort from SEER database and external validation of the hospital cohort were conducted. Results: (1) In the SEER database training cohort, there were 385 patients (15.54%, 385/2 478) in the radiotherapy group and 2 093 patients (84.46%, 2 093/2 478) in the surgery group. Overall survival time of the radiotherapy group was (55.8±51.3) months, while that of the surgery roup was (94.4±61.7) months, the difference between the two groups was statistically significant (χ²=256.44, P<0.001). Log-rank test showed that age, marital status, maximum of tumor diameters, pathological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and treatments were all significant factors affecting the overall survival time of cervical adenocarcinoma patients (all P<0.001). Multivariate Cox regression analysis showed that elder (>50 years old), single status, huge tumors (>4 cm), high pathological grades (G₂, G₃), and advanced FIGO stages (≥Ⅱa2 stage) were independent risk factors for the overall survival time of cervical adenocarcinoma patients (all P<0.05); compared with radiotherapy, surgery was a protective factor for the prognosis of cervical adenocarcinoma patients (HR=0.619, 95%CI: 0.494-0.777; P<0.001). Further analysis of locally advanced stage and Ⅲc stage of patients showed that surgery was a protective factor for the prognosis of cervical adenocarcinoma patients with a maximum tumor diameter >4 to <6 cm (HR=0.414, 95%CI: 0.182-0.942; P=0.036) in locally advanced stage and Ⅲc T1 to T2 stage (HR=0.473, 95%CI: 0.307-0.728; P=0.001). (2) The external validation cohort consisted of 39 patients (20.00%, 39/195) in the radiotherapy group and 156 patients (80.00%, 156/195) in the surgery group. The overall survival time of patients in the radiotherapy group was (51.7±34.3) months, while that of the surgery group was (63.1±26.6) months (χ²=28.41, P<0.001). Further analysis was conducted on locally advanced stage and Ⅲc stage patients, and multivariate Cox regression analysis was performed after propensity score matching, which showed that surgery was a protective factor for the prognosis of cervical adenocarcinoma patients with a maximum tumor diameter >4 to <6 cm in locally advanced stage (HR=0.141, 95%CI: 0.023-0.843; P=0.032) and Ⅲc T1 to T2 stage (HR=0.184, 95%CI: 0.036-0.947; P=0.043). (3) Establishment and internal and external validation of nomogram: based on the six factors screened out by the multivariate Cox regression model, the nomogram was developed to predict the prognosis of cervical adenocarcinoma patients. The consistency index of the internal and external validation were 0.801 and 0.766, respectively, and the calibration curves matched well with the ideal fitting line. Conclusions: The key to the treatment of cervical adenocarcinoma is to prioritize radical surgery for patients with conditions for radical tumor resection. Compared with concurrent chemoradiotherapy, patients with locally advanced stages (Ⅰb3, Ⅱa2), and Ⅲc (T1, T2) stages cervical adenocarcinoma could benefit from comprehensive treatment based on radical surgery. The nomogram of this study has been validated internally and externally, and show good survival prediction efficacy for cervical adenocarcinoma patients.