Development of a Novel Risk Score to Select the Optimal Candidate for Cytoreductive Nephrectomy Among Patients with Metastatic Renal Cell Carcinoma. Results from a Multi-Institutional Registry (REMARCC)

The role of cytoreductive nephrectomy is currently evolving in the immunotherapy era, nevertheless, it might remain a critical aspect of care for metastatic renal cell carcinoma (mRCC). To date, patients’ risk stratification (favorable; intermediate or poor) is established on the basis of two prognostic models for mRCC: Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic RCC Database Consortium IMDC criteria. These scores contain five or six pretreatment clinical factors and the degree of disability from cancer-related symptoms (performance status), however, no disease (location or volume of metastatic locations) or pathology specific features. Therefore, a patient with a solitary metastasis might be stratified as one with several organ metastatic locations.

Currently, no clear indication of metastatic burden or metastatic site can be derived from the available tools. The metastatic burden has been without translation on the IMDC stratification. CARMENA prospective trial failed to show superiority of cytoreductive nephrectomy in combination with sunitinib while the randomized controlled trial SURTIME highlighted the tentative relevance of deferred CN in patients with mRCC and initial responses to sunitinib. Nevertheless, both CARMENA and SURTIME confirm the fact that personalized patient stratification remains an unmet need.

REMARCC is a multi-institutional retrospective registry of patients with mRCC undergoing CN in the targeted therapy era. We were able to develop a novel risk score for an optimal selection of candidates for CN that includes, besides clinical factors, also location and burden of metastatic disease. REMARCC underlines that up to 17% of patients that would not undergo surgery according to current stratification scores were reclassified as good prognosis. The study highlights how metastatic burden is relevant in the risk classification for primary mRCC. The model confirmed that the site of metastases influences overall mortality.

Nowadays, medical therapies are constantly evolving and adapting to patients. The decision to proceed with nephrectomy and the time of surgery remains to be elucidated with current ongoing prospective trials on sequencing therapies. Solid prognostic/predictive biomarkers are still missing, however, some efforts are being made. Gene mutations such as PBRM1, BAP1, and TP53 might bring a ray of light to further improve risk stratification for patients with mRCC.

Written by: Giacomo Rebez, Michele Marchioni, M. Carmen Mir

Deparmtent of Urology. Fundación Instituto Valenciano Oncología, Valencia, Spain

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