A Nomogram Predicting Early Cervical Cancer Distant Recurrence

Abstract

Distant recurrence is the most common cause of treatment failure in locally advanced cervical cancer (LACC) following chemoradiation (CRT). We explored risk factors and developed a clinical nomogram predicting distant recurrence within 6 months of CRT completion.This was a retrospective case-control study of LACC patients treated with definitive CRT at a tertiary academic center from 1997-2020. Patients underwent FDG-PET at initial staging and approximately 3 months post treatment and had ≥ 3-month clinical follow-up. Patients were prescribed 50.4 Gy external beam radiation (EBRT) to the pelvic ± para-aortic (PA) lymph nodes (PA if involved on PET staging); both brachytherapy and cisplatin were delivered concurrently with EBRT. Patients who developed distant recurrence within 6 months were designated as cases and all others as controls. The dataset was randomly divided into 2/3 training and 1/3 testing. Binary logistic regression was applied to training data to determine significant predictor variables. Continuous variables were also assessed as categorical variables with cut points determined by Youden's method. Patients with missing data for significant predictors were excluded (110 training, 54 testing). The best model was defined by highest c-statistic and was applied to the testing data set.514 patients were identified of whom 45 (9%) developed distant recurrence within 6 months of CRT completion (15 biopsy proven, 30 clinically determined); 44 (98%) identified on 3 month post treatment PET. The dataset was divided into training (20 cases, 214 controls) and testing (10 cases, 106 controls). Age, treatment duration, histology (87% squamous), cervix SUVmax, pre/post squamous cell antigen did not differ across cases and controls in both training and testing data. Logistic regression applied to training data showed histology grade (poorly vs well/mod differentiated), PET positive lymph nodes (pelvic/para-aortic vs none) and PET initial tumor volume (≥50 vs < 50 cm3) had the most predictive multivariate beta coefficients (1.2, P = 0.025; 1.2, P = 0.016; 1.3, P = 0.028 respectively) with an overall c-statistic of 0.76. In the nomogram, each variable was assigned one point resulting in a total score range of 0-3 points, with higher scores indicating increasing risk. 3 points carried 29% positive predictive value (PPV), and 0 points indicated 100% negative predictive value (NPV) (Table 1). This nomogram was applied to the testing data and showed c-statistic 0.82 and 3 points PPV of 27% and 0 points NPV of 100%.More than a quarter of LACC patients with poorly differentiated histology, PET positive lymph nodes, and initial primary tumor volume greater than 50 cm3 experience distant recurrence within 6 months of completing CRT.