The use of cytoreductive nephrectomy in patients with renal cell carcinoma

ABSTRACT

Introduction: The systemic options for managing metastatic renal cell carcinoma (mRCC) have expanded considerably over the past decade. Initially limited to cytokines, clinicians may now choose from several classes of targeted therapies and, most recently, immune checkpoint inhibitors.

Areas covered: In this review, we discuss the role and timing of cytoreductive nephrectomy (CN) and its evolution starting with cytokines, and then alongside the emergence of targeted therapy and novel immunotherapy with immune checkpoint inhibitors. Patient selection remains the most critical determinant in offering CN, and the anticipated survival benefits of CN must be weighed against the surgical morbidity and potential delay to receipt of systemic therapies.

Expert opinion: Proper patient selection is key for decision-making in mRCC. Prospective data is urgently needed to define the role of CN in the contemporary immunotherapy era, with greater personalization of prognostic models.

KEYWORDS:

• Renal cell carcinoma
• metastatic
• cytoreductive nephrectomy
• targeted therapy
• patient selection

Article highlights

• Several classes of targeted therapies have emerged over the last decade for mRCC.

• The recent approval of immune checkpoint inhibitors, including nivolumab monotherapy and combination ipilimumab and nivolumab, revolutionized the treatment paradigm for mRCC.

• The role and timing of CN in combination with systemic therapies has been debated, and the survival benefits of CN must be weighed against the associated surgical morbidity and potential delay to receipt of effective systemic therapies.

• The recent CARMENA trial showed non-inferior outcomes of sunitinib alone compared to combination CN and sunitinib, but the results must be interpreted cautiously, given the inclusion of poor risk patients, large metastatic burden outside of the primary tumor site, accrual issues, and notable protocol deviations.

• While CN is not appropriate for every patient with mRCC, it still arguably plays an important role for prolonging survival in many, and appropriate patient selection and consideration of risk factors are absolutely paramount in treatment planning.

• The timing of CN remains unclear in the contemporary immunotherapy era, and prospective data are urgently needed to define its role in this setting.

• The response to up-front systemic therapy may inform the clinician regarding the role of CN (limited data). Hence, emergency CN to slow down the progression of mRCC in patients not responding to targeted therapy is not indicated, in fact, it can further harm patients.

• Population-based data suggest the benefit of CN in non-clear cell mRCC, particularly since the rate of response to targeted therapies do not exceed 10%

• The integration of genomic biomarkers and other personalized parameters into prognostic models may help better define patient selection and timing for CN in mRCC.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.