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

BACKGROUND. In 2022, a five-tiered CT algorithm was proposed for predicting whether a small (cT1a) solid renal mass represents clear cell renal cell carcinoma (ccRCC). OBJECTIVE. The purpose of this external validation study was to evaluate 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 that were seen on corticomedullary phase contrast-enhanced CT performed between January 2012 and July 2022 and subsequently underwent surgical resection. Five readers (three attending radiologists, two clinical fellows) independently evaluated masses for the mass-to-cortex corticomedullary attenuation ratio and heterogeneity score; these scores were used to derive the CT score by use of the previously proposed CT algorithm. The CT score's sensitivity, specificity, and PPV for ccRCC were calculated at threshold of 4 or greater, and the NPV for ccRCC was calculated at a threshold of 3 or greater (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 or less. Interreader agreement was assessed using the Gwet agreement coefficient (AC1). RESULTS. Overall, 61 of 97 masses (63%) were malignant and 43 of 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. A CT score of 2 or less had sensitivity ranging from 44% to 100% and specificity ranging from 77% to 98% for papillary RCC (representing nine of 97 masses). Interreader agreement was substantial for attenuation score (AC1 = 0.70), poor for heterogeneity score (AC1 = 0.17), fair for five-tiered CT score (AC1 = 0.32), and fair for dichotomous CT score at a threshold of 4 or greater (AC1 = 0.24 [95% CI, 0.14-0.33]). CONCLUSION. The five-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.