Surgical Management of Advanced Kidney Cancer: The Role of Cytoreductive Nephrectomy and Lymphadenectomy

Despite the evolution of systemic therapy from the immunotherapy to targeted therapy eras, surgical management remains a mainstay of treatment of patients with locally advanced, lymph node-positive, and distant metastatic renal cell carcinoma. Balancing patient and disease characteristics with the potential morbidity of surgery has gained increasing attention to better define the role of cytoreductive nephrectomy and lymphadenectomy. In this review, we critically evaluate the literature for the potential therapeutic role of cytoreductive nephrectomy and lymphadenectomy in advanced kidney cancer, highlighting current evidence, limitations, and best-management practices. Although retrospective data supported a similar survival benefit for cytoreductive nephrectomy in the targeted therapy era as it did for the initial immunotherapy era (1992 to 2006), level 1 evidence from the randomized Clinical Trial to Assess the Importance of Nephrectomy (CARMENA) demonstrated no benefit for intermediate- and poor-risk patients in the setting of sunitinib therapy. Level 1 evidence among a favorable-risk subset is still awaited from the trial Targeted Therapy With or Without Nephrectomy in Metastatic Renal Cell Carcinoma: Liquid Biopsy for Biomarkers Discovery (TARIBO). Another trial, Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME), has compared upfront cytoreductive nephrectomy prior to targeted therapy with the initial initiation of targeted therapy followed by deferred cytoreductive nephrectomy. Lymphadenectomy is yet another controversial but less well-defined management option for patients with kidney cancer. The role of lymphadenectomy has been studied in both the localized and advanced settings over the past few decades, with a strong suggestion of no therapeutic benefit for patients with cT1-2N0M0 and cM1 disease, and with uncertain benefit in patients with high-risk disease (ie, locally advanced or cN1M0), leading to weak statements among clinical guidelines.