Abstract: The increasing use of cross-sectional imaging has led to an increase in the diagnosis of incidental small renal masses (SRMs). About 20% of such masses are benign, while a significant proportion of malignant SRMs demonstrate slow growth kinetics and non-aggressive histologic features. Given these characteristics, lesions that were traditionally treated surgically are increasingly managed with less aggressive approaches. Further contributing to the evolving management paradigm is accumulating evidence supporting the safety of active surveillance and the efficacy of percutaneous renal mass biopsy in guiding management decisions. This review first discusses the epidemiology and diagnostic work-up of SRMs. The available management options are then examined, with emphasis placed on the clinical factors considered in selecting an appropriate approach. The existing evidence and long-term outcomes of each strategy are discussed. Finally, an overview of the current paradigm for the management of a patient with a SRM is provided. The goal is to provide physicians with the necessary understanding to appropriately manage this increasingly common condition.
407 Background: Genetic alterations predicting response to targeted therapy are an area of active interest in developing novel therapies for patients with metastatic urothelial carcinoma (mUC). With the objective of characterizing the frequency of actionable alterations (AA) and the evidence supporting targeted therapy for these AAs, we report our experience with next-generation sequencing in mUC. Methods: Patients with sequenced mUC lesions were identified from our prospectively-maintained database. All AAs with clinical or biologic evidence supporting the alteration as predicting response to targeted therapy were identified and stratified by Oncology Knowledge Base (OncoKB) level of evidence (table). The relationship between strength of evidence and administration of targeted therapy was examined. Results: Ninety-nine of 134 patients (74%) harbored at least one AA, with 162 total AAs identified. Twenty level 2B AAs were identified, reflecting the highest level evidence in this cohort, with ERBB2 amplification (9), TSC1/TSC2 (6), and BRCA1/BRCA2 mutations (3) most common. Twenty-eight level 3A, 51 level 3B, and 62 level 4 AAs were also identified. Seventeen patients received targeted therapy, which was administered with greater frequency among patients with level 3B or higher AAs (21% vs 3%). Conclusions: Most patients with mUC harbor at least one AA, suggesting multiple targeted therapeutic opportunities in mUC. These findings highlight the need for additional clinical trials and the role of genetic testing in identifying candidates for targeted therapy. [Table: see text]
Nima Almassi and Joel Sheinfeld have no conflicts of interest to report. John P. Mulhall serves as a consultant for Vault Health. Samuel A. Funt has received research support from AstraZeneca and Genentech/Roche, has served in a consulting or advisory role for Decibel, AstraZeneza, and Immunai, and has stock or other ownership interests in Urogen, Allogene Therapeutics, Neogene Therapeutics, Vaxigene, Kronos Bio, and Vida Ventures.
