Preoperative multiplex nomogram for prediction of high-risk nonorgan-confined upper-tract urothelial carcinoma.

BACKGROUND

Accurate risk stratification prior to radical nephroureterectomy remains a challenge with upper-tract urothelial carcinoma (UTUC). Herein, we generated an optimized preoperative tool predicting high-risk nonorgan-confined (NOC)-UTUC.

MATERIALS AND METHODS

Retrospective evaluation of 699 patients undergoing radical nephroureterectomy at 3 academic centers. Multiplex preoperative patient, imaging, endoscopic, and laboratory values were evaluated. Model derivation and validation were based on a split-sample method. Patients were divided randomly into a development (training) cohort (70% of patients) and validation (test) cohort (30% of patients). Univariate and multivariate logistic regression addressed the prediction of NOC disease (pT3/pT4 and/or pN+) based on training cohort. A backward stepdown selection process achieved the most informative nomogram. The ROC analysis identified a cut-off point predicting high-risk disease. The test cohort served as "external" validation to verify the findings based on the training cohort. Bootstrap resampling was conducted for both internal and "external" validation to evaluate the model fitting.

RESULTS

Total of 566 patients included for analysis, mean age 69.7 years, 85% Caucasian, 64% male, 62% high grade. NOC-UTUC was found in 184 (32.5%) patients on final pathology. Of 184 patients with NOC-UTUC, an equal number of renal pelvis and ureter only tumors (n = 74; 40.2% for each location) were noted; 36 (19.6%) had tumors in both locations. Multivariate model based on development cohort (n = 396) demonstrated clinical stage (odds ratio [OR] 14.0, P < 0.01), biopsy tumor grade (OR 3.3, P = 0.01), tumor architecture (OR 2.65, P = 0.09), and Hgb (OR 0.8, P = 0.02) level were independently associated with NOC disease. A preoperative nomogram incorporating these 4 variables achieved 82% accuracy, 48% sensitivity, and 95% specificity in predicting NOC-UTUC. The cut-off point for predicting high-risk disease was ≥0.49.

CONCLUSIONS

We established and validated an accurate tool for the prediction of locally advanced NOC-UTUC. This preoperative nomogram can be used to more optimally select patients for preoperative systemic chemotherapy, and facilitate clinical trial enrollment.