Pushing the limits of metastasis-directed treatment in metastatic renal cell carcinoma in the era of targeted therapy

Objective: To assess the role of metastasis directed therapy and in particular surgical metastasectomy (MxT) in metastatic renal cell carcinoma (mRCC) in the era of targeted therapy.

Method: The files of all patients who underwent MxT for treatment of mRCC in University Hospitals Leuven between 1989 and 2015 were reviewed.

Results: One hundred and thirty eight patients met the inclusion criteria. Mean age at MxT was 59.3 (IQR: 57.5-61.0) years. Median follow-up was 50.1 (42.3-63.8) months. Due to adequate patient selection, 91.9% of MxT achieved no evidence of disease status, which resulted in long median overall survival of 87.8 (63.8-113.4) months and median cancer specific survival of 92.8 (69.5-123.4) months. On multivariate analysis, primary tumor stage >pT2 (hazard ratio [HR] 2.79 [1.47-5.28] P= 0.002), unreached no evidence of disease status (HR 8.62 [3.19-23.32] P< 0.001), presence of nonpulmonary metastasis (HR 2.29 [1.02-5.10] P= 0.0449) and sarcomatoid dedifferentiation in the primary tumor (HR 4.52 [1.15-17.69] P= 0.03) significantly impacted overall survival. Survival did not differ for MxT performed before and after the advent of vascular endothelial growth factor receptor-tyrosine kinase inhibitors.

Discussion: Our study confirms the validity of MxT in mRCC in the tyrosine kinase inhibitors era. MxT should be considered in mRCC whenever the patient is fit enough to undergo surgery and complete removal of metastasis is considered possible, independent of number, location, and chronology of appearance of metastasis. Patients with pulmonary metastasis only, seem to be the best candidates for surgical MxT.