External Validation of a Five-Tiered CT Algorithm for the Diagnosis of Clear-Cell Renal Cell Carcinoma: A Retrospective Five-Reader Study.

Background: A 5-tiered CT algorithm was proposed in 2022 for predicting whether a small (cT1a) solid renal mass represents clear-cell renal cell carcinoma (ccRCC). Purpose: To perform an external-validation study of the proposed CT algorithm for diagnosis of ccRCC among small solid renal masses. Methods: This retrospective study included 93 patients [median age, 62 years; 42 women, 51 men] with 97 small solid renal masses on corticomedullary-phase contrast-enhanced CT performed between January 2012 and July 2022 that underwent surgical resection. Five readers (three attending radiologists, two clinical fellows) independently evaluated masses for mass-to-cortex corticomedullary attenuation ratio and heterogeneity score; these scores were used to derive the CT score by the previously proposed CT algorithm. The CT score's sensitivity, specificity, and PPV for ccRCC were calculated at threshold of ≥4, and NPV for ccRCC was calculated at threshold of ≥3 (consistent with thresholds in studies of the MRI-based clear-cell likelihood score and the CT algorithm's initial study). The CT score's sensitivity and specificity for papillary RCC were calculated at a threshold of ≤2. Interreader agreement was assessed using Gwet's AC1. Results: Overall, 61/97 (63%) masses were malignant; 44/97 (44%) were ccRCC. Across readers, CT score had sensitivity ranging from 47% to 95% [pooled sensitivity, 74% (95% CI, 68-80%)], specificity ranging from 19% to 83% [pooled specificity, 59% (95% CI, 52-67%)], PPV ranging from 48% to 76% [pooled PPV, 59% (95% CI, 49-71%)], and NPV ranging from 83% to 100% [pooled NPV, 90% (95% CI, 84-95%)], for ccRCC. CT score ≤2 had sensitivity ranging from 44% to 100% and specificity ranging from 77% to 98% for papillary RCC (representing 9/97 masses). Interreader agreement was substantial for attenuation score (AC1=0.70), poor for heterogeneity score (AC1=0.17), fair for 5-tiered CT score (AC1=0.32), and fair for dichotomous CT score at threshold of ≥4 (AC1=0.24; 95% CI, 0.14-0.33). Conclusion: The 5-tiered CT algorithm for evaluation of small solid renal masses was tested in an external sample and showed high NPV for ccRCC. Clinical Impact: The CT algorithm may be used for risk stratification and patient selection for active surveillance by identifying patients unlikely to have ccRCC.