From the Guidelines
Cytoreductive nephrectomy (CN) is a treatment option for selected patients with metastatic renal cell carcinoma (RCC), particularly those with a potentially surgically resectable primary tumor mass and limited metastatic disease.
Key Considerations
- The role of CN in the management of metastatic RCC has evolved with the introduction of new systemic therapies, including immunotherapy and targeted agents 1.
- CN can be considered for patients with one IMDC risk factor (intermediate risk disease), as it may improve overall survival (OS) in this subgroup 1.
- CN should be considered for patients with hematuria or pain, as it can be a palliative option for symptom control 1.
- The sequencing of CN and systemic therapy is important, with some studies suggesting that deferred CN may be associated with improved OS 1.
Evidence Summary
- The CARMENA study showed that sunitinib alone was noninferior to sunitinib after CN in patients with metastatic RCC, with a median OS of 18.4 months versus 13.9 months, respectively 1.
- The SURTIME study demonstrated that the sequencing of CN and sunitinib did not affect progression-free survival (PFS), but deferred CN was associated with improved OS 1.
- A NCDB analysis found that CN plus immunotherapy was associated with longer OS compared to immunotherapy alone in patients with clear cell metastatic RCC 1.
Clinical Implications
- CN should be considered as part of a multidisciplinary approach to the management of metastatic RCC, taking into account the patient's overall health, tumor characteristics, and treatment goals 1.
- Patient selection is crucial to ensure that CN is offered to those who are most likely to benefit from it, including those with limited metastatic disease and good performance status 1.
From the Research
Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma
- Cytoreductive nephrectomy (CN) can be an important component of a multidisciplinary treatment approach to metastatic renal cell carcinoma (RCC) in carefully selected patients 2.
- The results of retrospective single institution series and randomized multicenter phase III trials suggest that removal of the primary tumor, even in the setting of metastatic disease, can significantly prolong survival and delay time to progression 2.
- CN may also enhance the response to systemic therapy in the postoperative period 2.
Patient Selection for Cytoreductive Nephrectomy
- Careful patient selection is critical to the success of CN, with factors such as performance status, comorbidities, and extent of metastatic disease influencing the decision to proceed with surgery 2, 3.
- Patients with poor prognostic features, such as brain, liver, or bone metastases, or atypical histology, should not be considered for initial CN and instead receive upfront systemic therapy 2.
- Patients who do not demonstrate these poor prognostic features should be considered for upfront CN as part of their overall treatment approach 2.
Timing of Cytoreductive Nephrectomy
- The timing of CN relative to systemic therapy may not be significantly related to overall survival, with similar benefits seen for upfront and deferred CN 4.
- However, the CARMENA and SURTIME trials have challenged the utility of CN in clinical practice, suggesting that CN combined with targeted therapy may not yield a survival advantage over targeted therapy alone in intermediate and poor risk metastatic RCC patients 3.
Survival Benefits of Cytoreductive Nephrectomy
- Upfront CN has been associated with improved overall survival in patients with metastatic RCC, with median overall survival ranging from 26.6 to 36.8 months in patients undergoing CN compared to 12.2 to 20.8 months in those without CN 4, 5.
- The use of immunotherapy-based therapies, such as IO+TKI combination or TKI monotherapy, may be a better choice than IO+IO combination for patients who are not candidates for CN 5.