Individualised Indications for Cytoreductive Nephrectomy: Which Criteria Define the Optimal Candidates?

Abstract

Context: The current role of cytoreductive nephrectomy (CN) is controversial.

Objective: Review of the available evidence about criteria defining CN optimal candidates.

Evidence acquisition: Collaborative critical narrative review of the literature focusing on CN oncological outcomes, perioperative morbidity, eligibility criteria, presurgical systemic therapy, and surgical factors.

Evidence synthesis: In contrast to observational studies, the Clinical Trial to Assess the Importance of Nephrectomy (CARMENA) trial demonstrated noninferiority of targeted therapy alone relative to CN with targeted therapy. CN is associated with a significant risk of perioperative mortality (0-13%) and major complications (3-36%). Metastatic burden, haematological parameters, performance status, sarcopenia, and genetic mutations have been proposed as CN eligibility criteria. Comprehensive models including local and systemic factors are recommended. The Immediate Surgery or Surgery after sunitinib Malate In Treating Patients with Kidney Cancer (SURTIME) trial reported similar progression-free rate after immediate or deferred CN, and suggests that presurgical systemic therapy can identify candidates for CN, avoiding unnecessary surgery in nonresponders without increasing the risk of perioperative complications. Minimally invasive and nephron-sparing CNs are established surgical strategies in selected patients.

Conclusions: No benefit of upfront CN is observed for intermediate- and poor-risk patients who require systemic therapy in randomised controlled trials, and systemic therapy deserves priority over CN in patients with metastatic renal cell carcinoma. These findings are not applicable to all patients with metastatic kidney cancer. CN has a role in favourable cases not requiring immediate systemic therapy or in symptomatic patients. Individual patient selection to identify those patients who might profit the most from CN is critical; however, clinical decision making should be based on comprehensive models. Presurgical systemic therapy is a promising option to avoid unnecessary CN, which is associated with major morbidity.

Patient summary: Consideration for systemic therapy deserves priority over cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma. In patients eligible for systemic therapy, CN does not offer a survival benefit. The indications for CN should be evaluated on an individual basis. Risk scores and response to presurgical systemic therapy can be used for subsequent decision making.

Keywords: Cytoreductive nephrectomy; Kidney cancer; Metastatic renal cell carcinoma; Presurgical therapy; Systemic therapy; Targeted therapy.