The Impact of Patient Characteristics, Risk Factors, and Surgical Intervention on Survival in a Cohort of Patients Undergoing Neoadjuvant Treatment for Cervical Cancer.

ABSTRACT

Introduction: Cervical cancer is among the most frequent types of neoplasia worldwide and remains the fourth leading cause of cancer death in women, a fact that raises the necessity for further development of therapeutic strategies. NCCN guidelines recommend radiation therapy with or without chemotherapy as the gold standard for locally advanced cervical cancer. Also, some studies claim that performing surgery after chemo-radiation therapy does not necessarily improve the therapeutic outcome. This study aims to determine the impact of the risk factors, various characteristics, and surgical treatment for patients in different stages of the disease on survival rate. Material and methods: Our study started as a retrospective, observational, unicentric one, carried out on a cohort of 96 patients diagnosed with cervical cancer from the surgical department of the Bucharest Oncological Institute, followed from 1 January 2019 for a period of 3 years. After the registration of the initial parameters, however, the study became prospective, as the patients were closely monitored through periodical check-ups. The end-point of the study is either the death of the participants or reaching the end of the follow-up period, and, therefore, we divided the cohort into two subgroups the ones who survived after three years and the ones who did not. All 96 patients, with disease stages ranging from IA2 to IIIB, underwent radio-chemotherapy followed by adjuvant surgery. Results: Among the 96 patients, 45 (46%) presented residual tumor after radio-chemotherapy. Five patients (5%) presented positive resection margins at the post-operative histopathological examination. The presence of residual tumor, the FIGO stage post-radiotherapy, positive resection margins, and lympho-vascular and stromal invasions differed significantly between the subgroups, being more represented in the subgroup that reached the end-point. Variables correlated with the worst survival in Kaplan-Meier were the pelvic lymph node involvement-50% at three years (p-0.015)-and the positive resection margins-only 20% at three years (p < 0.001). The univariate Cox model identified as mortality-associated risk factors the same parameters as above, but also the intraoperative stage III FIGO (p < 0.001; HR 9.412; CI 2.713 to 32.648) and the presence of post-radiotherapy adenopathy (p-0.031; HR 3.915; CI 1.136 to 13.487) identified through imagistic methods. The independent predictors of the overall survival rate identified were the positive resection margins (p-0.002; HR 6.646; CI 2.0 to 22.084) and the post-radiotherapy stage III FIGO (p-0.003; HR 13.886; CI 2.456 to 78.506). Conclusions: The most important predictor factors of survival rate are the positive resection margins and the FIGO stage after radiotherapy. According to the NCCN guidelines in stages considered advanced (beyond stages IB3, IIA2), the standard treatment is neoadjuvant chemoradiotherapy. In our study, with radical surgery after neoadjuvant therapy, 46% of patients presented residual tumor at the intraoperative histopathological examination, a fact that makes the surgical intervention an important step in completing the treatment of these patients. In addition, based on the patient's features/comorbidities and the clinical response to chemotherapy/radiotherapy, surgeons could carefully tailor the extent of radical surgery, thus resulting in a personalized surgical approach for each patient. However, a potential limitation can be represented by the relatively small number of patients (96) and the unicentric nature of our study.