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

Abstract

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.

Keywords: cancer-specific mortality; chromophobe kidney cancer; prognostic model.

Figure 1

Development cohort: Kaplan–Meier plots with log-rank test depicting cancer-specific survival over ten years in patients with unilateral surgically treated non-metastatic chromophobe renal carcinoma diagnosed in 2000–2019 Surveillance, Epidemiology, and End Results database. (a) Overall; (b) according to Leibovich 2018 risk categories; (c) according to GRANT risk categories.

Figure 2

Nomogram predicting cancer-specific survival in surgically treated non-metastatic chromophobe renal cell carcinoma at five and ten years after surgery.

Figure 3

External validation cohort: Leibovich 2018 and GRANT prognostic models calibration plots. CSS: cancer-specific survival. (a) Cancer-specific survival at five years according to Leibovich 2018; (b) cancer-specific survival at ten years according to Leibovich 2018; (c) cancer-specific survival at five years according to GRANT; (d) cancer-specific survival at ten years according to GRANT.

Figure 4

External validation cohort: nomogram calibration plots. CSS: cancer-specific survival. (a) Cancer-specific survival at five years; (b) cancer-specific survival at ten years.

Figure 5

External validation cohort: decision curve analyses quantifying and comparing the performance of the prognostic models relative to random predictions of cancer-specific mortality: (a) 5-year survival; (b) 10-year survival.