Critical Appraisal of Leibovich 2018 and GRANT Models for Prediction of Cancer-Specific Survival in Non-Metastatic Chromophobe Renal Cell Carcinoma

Simple Summary To date, guideline-recommended prognostic models predicting cancer-control outcomes in chromophobe kidney cancer patients have never been validated in a large-scale contemporary North American cohort. We addressed this knowledge gap and performed a formal validation of Leibovich 2018 and GRade, Age, Nodes and Tumor (GRANT) prognostic models with cancer-specific survival as an outcome. Moreover, we proposed a novel nomogram for the prediction of the same outcome. Within the Surveillance, Epidemiology, and End Results database (2000-2019), we identified 5522 unilateral surgically treated non-metastatic chromophobe kidney cancer (chRCC) patients. This population was randomly divided into development vs. external validation cohorts. In the development cohort, the original Leibovich 2018 and GRANT categories were applied to predict 5- and 10-year cancer-specific survival (CSS). Subsequently, a novel multivariable nomogram was developed. Accuracy, calibration and decision curve analyses (DCA) tested the Cox regression-based nomogram as well as the Leibovich 2018 and GRANT risk categories in the external validation cohort. The accuracy of the Leibovich 2018 and GRANT models was 0.65 and 0.64 at ten years, respectively. The novel prognostic nomogram had an accuracy of 0.78 at ten years. All models exhibited good calibration. In DCA, Leibovich 2018 outperformed the novel nomogram within selected ranges of threshold probabilities at ten years. Conversely, the novel nomogram outperformed Leibovich 2018 for other values of threshold probabilities. In summary, Leibovich 2018 and GRANT risk categories exhibited borderline low accuracy in predicting CSS in North American non-metastatic chRCC patients. Conversely, the novel nomogram exhibited higher accuracy. However, in DCA, all examined models exhibited limitations within specific threshold probability intervals. In consequence, all three examined models provide individual predictions that might be suboptimal and be affected by limitations determined by the natural history of chRCC, where few deaths occur within ten years from surgery. Further investigations regarding established and novel predictors of CSS and relying on large sample sizes with longer follow-up are needed to better stratify CSS in chRCC.

Automated summary

To date, guideline-recommended prognostic models predicting cancer-control outcomes in chromophobe kidney cancer patients in North America have not been validated. In this study, we validated the Leibovich 2018 and GRANT prognostic models and proposed a novel nomogram for cancer-specific survival in a large-scale North American cohort. The accuracy of the Leibovich 2018 and GRANT models was relatively low, while the novel nomogram showed higher accuracy. However, all models had limitations in certain threshold probability intervals, highlighting the need for further investigations and larger sample sizes to better predict cancer-specific survival in chromophobe kidney cancer.