Management of small renal masses is a challenging clinical dilemma with no clear optimal management strategy. There is a high likelihood, up to 30% in some series,¹ that a given small renal mass is benign, and one-third of partial nephrectomies are performed for benign renal masses.² Although there has been a movement over the last several years toward performing partial nephrectomies robotically, a procedure with comparatively lower morbidity than those done open, the procedure is not without risk of considerable morbidity. The risk of postoperative hemorrhage requiring transfusion is reported to be between 3% and 10% in robotic partial nephrectomies, and the procedure carries an estimated urine leak rate of 0.6%-2.5%.³ In addition to subjecting patients with benign renal masses to these risks, the financial implications of performing unnecessary surgery are not trivial, with total cost of robotic partial nephrectomy estimated to be approximately $25,000.⁴ Clearly, an improved strategy to maximize treatment of high-risk malignant lesions while minimizing overtreatment of benign disease is necessary. Recent technological advances, namely positron emission tomography/CT with radiolabeled girentuximab, which targets carbonic anhydrase IX, a highly specific enzyme for clear cell renal cell carcinoma (RCC), have been highly promising. In the phase 3 ZIRCON study, the results of which were recently presented,⁵ the end point was met with 86% sensitivity, 87% specificity, 93% positive predictive value, and 75% negative predictive value (NPV) for detection of clear cell RCC. Despite the emergence of exciting new technologies to aid in the diagnostic dilemma for small renal masses, the role of renal mass biopsy (RMB) must be further delineated.

Renal biopsy has come under scrutiny over the years, and society guidelines are not clear on its role in the diagnostic workup of small renal masses. Per National Comprehensive Cancer Network guidelines, biopsy of small lesions may be considered to obtain or confirm diagnosis of malignancy and guide surveillance or ablative techniques (eg, cryoablation, radiofrequency ablation). Furthermore, if urothelial cancer is suspected, biopsy can be considered in the setting of metastasis or if the patient is unable to tolerate ureteroscopy.⁶ Per AUA guidelines recently updated in 2020, patients should be counseled on the positive predictive value, NPV, risks of biopsy and potential for nondiagnostic biopsy. Biopsy should be performed if the mass is suspected to be hematological, metastatic, inflammatory, or infectious. Additionally, biopsy candidates include patients undergoing thermal ablation and those with solid or Bosniak 3-4 complex cystic masses who are considering active surveillance and are thought to have high oncologic risk.⁷

A critical evaluation of the perceived disadvantages of RMB is needed to better understand the feasibility of regularly incorporating it into the small renal mass algorithm. A major historical concern with RMB was tumor seeding along the biopsy tract. The modern technique of using a coaxial sheath and withdrawing the biopsy needle through that sheath has virtually eliminated the risk of tumor seeding, with modern rates reported to be in the range of 1:10,000.⁸

There are additional procedural risks associated with RMB, including renal hematoma (4.9%), postprocedural pain (1.2%), gross hematuria (1.0%), pneumothorax (0.6%), and blood loss requiring transfusion (0.4%).⁹ These risks are significantly lower than corresponding risks of a partial nephrectomy. For example, as noted above, bleeding requiring transfusion in robotic partial nephrectomy occurs at a more than 10-fold higher rate, as noted above. From a diagnostic standpoint, issues include a nondiagnostic rate of RMB of around 8%, although this rate can be as high as 20% in some series. However, in the event of nondiagnostic biopsy, a diagnosis was able to be obtained in the event of a single repeat biopsy 80% of the time.⁹

Low NPV is another concern with RMB, with reported NPV of 63% in a large systematic review, meaning that 37% of those with a negative biopsy ended up having malignant pathology at the time of surgery. However, this figure is problematic and is subject to inaccuracy because rarely do benign biopsies have surgical pathology available. In fact, only 16% of benign cases from the above review had available surgical pathology.⁹ Another consideration is the difficulty in distinguishing oncocytic neoplasms from malignant entities such as chromophobe RCC by biopsy. However, emerging literature suggests no difference between growth rates of oncocytoma and chromophobe RCC, and that biopsy-proven oncocytic neoplasms can be managed with surveillance without development of metastatic disease or disease-related morbidity or mortality.¹⁰

Given the morbidity and financial implications of surgery, with novel developments like radiolabeled girentuximab still in their infancy, a growing body of data to challenge many of the historical controversies surrounding RMB, and the potential for RMB to drive cost savings in the care of patients with small renal masses by 20%,¹¹ we feel that the evidence supports a growth in the role of RMB in the management of small renal masses.