Nomogram-based prediction of overall survival (OS) of patients (pts) with metastatic urothelial carcinoma (UC) receiving first-line platinum-based chemotherapy: retrospective international study of invasive/advanced cancer of the urothelium (RISC)

Abstract

Background: The available prognostic models of OS for pts with metastatic UC were derived from clinical trial populations of cisplatin‐treated pts only. We aimed to develop a new model based on 'real world' pts. Methods: Individual pt‐level data from 29 centers was collected. Pts had to be treated for metastatic UC at the participating sites between 01/2006 and 01/2011. Selection criteria included metastatic UC, and first‐line cisplatin‐ or carboplatin‐based chemotherapy. The overall sample was randomly split into a development and a validation cohort. Generalized Boosted Regression Modeling was used first to exclude variables not associated with OS. Backward variable selection was then undertaken. Platinum‐type was incorporated in the analysis as a stratification factor. Two nomograms were built to estimate OS probability, the first based on baseline factors and the second incorporating objective response (OR). The performance of the present nomogram and that of the other available models was assessed for accuracy (Brier score), calibration (Hosmer‐Lemeshow test), and discrimination (Harrell c‐index). Results: 1,020 pts were analyzed (development: 687; validation: 333). In the platinum‐stratified Cox model, significant variables for OS were: performance status (p < .001), white blood cell count (p = 0.013), body mass index (p = 0.003), ethnicity (p = 0.012), lung, liver, or bone metastases (p < .001), and prior peri‐operative chemotherapy (p = 0.012). The c‐index was 0.66. The distribution of the nomogram scores was associated with OR (p < .001) and incorporating OR in the model further improved the c‐index (0.67, with 4‐month landmark analysis). The two nomograms both performed better than the available models in terms of accuracy and discrimination in the validation cohort. Conclusions: We developed and validated two nomograms that accounted for novel prognostic factors and can be used before and after completion of chemotherapy, respectively. These two nomograms may be suitable tools to enhance patient stratification and inform pts in the clinic.