Introduction: Studies have explored the use of renal mass biopsy (RMB) for the management and surveillance of small renal masses (SRM), given that 20–25% are benign. However, concerns remain regarding its accuracy; while a definitive diagnosis can be confirmed by nephrectomy, there is a surgical selection bias not to operate in negative cases, resulting in an unknown rate of true- vs. false-negatives on RMB. We hypothesized that patients undergoing repeat RMB would demonstrate lower selection bias and evaluated its role as a pathological surrogate to determine initial RMB sensitivity and specificity.

Methods: Clinical and pathological covariates for patients with a SRM receiving initial RMB, repeat RMB, and nephrectomy were extracted from our institutional database (1994–2020). After categorizing benign and malignant lesions, the primary outcome was to calculate sensitivity and specificity of the initial biopsy against each of: 1) repeat biopsy; and 2) surgical pathology.

Results: A total of 977 patients with SRMs had ≥1 biopsy, of which 216 had ≥2 biopsies (after a median of 119 days) and 442 underwent nephrectomy. Only 3% of cases were benign at nephrectomy, confirming a strong surgical selection bias, vs. 17% of repeat RMB. Using repeat RMB as a pathological surrogate, the sensitivity and specificity of initial RMB were 98.1% and 89.5%, respectively (vs. 99.2% and 100% when calculated against nephrectomy). In particular, 1.5% of cases were identified as false-negatives on repeat RMB compared to none by nephrectomy.

Conclusions: By studying repeat RMB as a novel pathological surrogate, this study overcomes the surgical selection bias in the nephrectomy gold standard. The conventional approach using final surgical pathology revealed an extremely low benign/negative rate and resulted in an inflated specificity. This effect is largely corrected by repeat RMB, suggesting that it may be a preferable gold standard in certain diagnostic scenarios. Furthermore, our results confirm that false-negatives on initial biopsy are rare (1.5%) and reinforce the accuracy of RMB.