The Role of Lymph Node Downstaging Following Neoadjuvant Treatment in a Group of Patients with Advanced Stage Cervical Cancer.

Background and Objectives : Cervical cancer is the fourth most frequent type of neoplasia in women. It is most commonly caused by the persistent infection with high-risk strands of human papillomavirus (hrHPV). Its incidence increases rapidly from age 25 when routine HPV screening starts and then decreases at the age of 45. This reflects both the diagnosis of prevalent cases at first-time screening and the likely peak of HPV exposure in early adulthood. For early stages, the treatment offers the possibility of fertility preservation.. However, in more advanced stages, the treatment is restricted to concomitant chemo-radiotherapy, combined, in very selected cases with surgical intervention. After the neoadjuvant treatment, an imagistic re-evaluation of the patients is carried out to analyze if the stage of the disease remained the same or suffered a downstaging. Lymph node downstaging following neoadjuvant treatment is regarded as an indubitable prognostic factor for predicting disease recurrence and survival in patients with advanced cervical cancer. This study aims to ascertain the important survival role of radiotherapy in the downstaging of the disease and of lymphadenectomy in the control of lymph node invasion for patients with advanced-stage cervical cancer. Material and Methods : We describe the outcome of patients with cervical cancer in stage IIIC1 FIGO treated at Bucharest Oncological Institute. All patients received radiotherapy and two-thirds received concomitant chemotherapy. A surgical intervention consisting of type C radical hysterectomy with radical pelvic lymphadenectomy was performed six to eight weeks after the end of the neoadjuvant treatment. Results : The McNemar test demonstrated the regression of lymphadenopathies after neoadjuvant treatment- p : <0.001. However, the persistence of adenopathies was not related to the dose of irradiation ( p : 0.61), the number of sessions of radiotherapy ( p : 0.80), or the chemotherapy ( p : 0.44). Also, there were no significant differences between the adenopathies reported by imagistic methods and those identified during surgical intervention- p : 0.62. The overall survival evaluated using Kaplan-Meier curves is dependent on the post-radiotherapy FIGO stage- p : 0.002 and on the lymph node status evaluated during surgical intervention- p : 0.04. The risk factors associated with an increased risk of death were represented by a low preoperative hemoglobin level ( p : 0.003) and by the advanced FIGO stage determined during surgical intervention ( p -value: 0.006 for stage IIIA and 0.01 for stage IIIC1). In the multivariate Cox model, the independent predictor of survival was the preoperative hemoglobin level ( p : 0.004, HR 0.535, CI: 0.347 to 0.823). Out of a total of 33 patients with neoadjuvant treatment, 22 survived until the end of the study, all 33 responded to the treatment in varying degrees, but in 3 of them, tumor cells were found in the lymph nodes during the intraoperative histopathological examination. Conclusions : For advanced cervical cancer patients, radical surgery after neoadjuvant treatment may be associated with a better survival rate. Further research is needed to identify all the causes that lead to the persistence of adenopathies in certain patients, to decrease the FIGO stage after surgical intervention, and, therefore, to lower the risk of death. Also, it is mandatory to correctly evaluate and treat the anemia, as it seems to be an independent predictor factor for mortality.