Therapy for Non-Clear Cell Histologies in Renal Cancer

The advent of targeted systemic therapies has significantly improved treatment options for patients with metastatic renal cell carcinoma (RCC). Multiple agents that inhibit angiogenesis, cell growth, and proliferation via the VEGF and mTOR (TORC1) pathways have been USFDA-approved for locally advanced or metastatic renal cell carcinoma in recent years, although the majority of clinical trials have focused only on clear cell RCC. While clear cell RCC is the most common histologic subtype, nearly 25% of RCC cases are histologic variants representing a diverse group of diseases with different prognoses underlying biology and molecular targets and therapies. This review will focus on the incidence, clinical and pathologic features, pathogenesis, and treatment strategies of non-clear cell RCC in both the adjuvant and metastatic setting. These non-clear, cell subtypes include papillary type 1 and type 2, chromophobe, translocation carcinoma, and collecting duct RCC. Controlled studies in these relatively rare subgroups are needed to inform upon clinical practice, which is currently based on small series of uncontrolled studies. Ongoing clinical trials and areas of future research will be discussed.