Miest, Tanner S

ObjectivesTo evaluate the timing and distribution of first renal cell carcinoma metastasis after nephrectomy stratified by nodal status.MethodsWe evaluated patients treated with nephrectomy for sporadic, unilateral renal cell carcinoma between 1970 and 2011 who subsequently developed distant metastasis to three or fewer sites. Site‐specific metastases‐free 2‐year survival rates were estimated using the Kaplan–Meier method. Associations of nodal status with time to metastasis were evaluated using multivariable Cox regression models.ResultsA total of 1049 patients met the inclusion criteria (135 pN1, 914 pN0/x patients). The median time to identification of first distant metastasis for pN1 patients was 0.4 years (interquartile range 0.2–1.1 years) versus 2.2 years (interquartile range 0.6–6.0 years) in pN0/x patients. The most common site of metastasis was to the lung, but this occurred earlier in pN1 patients (median 0.3 years vs 2.0 years). pN1 was associated with significantly lower site‐specific 2‐year metastases‐free survival when compared with pN0/x for lung (37% vs 70%, P < 0.001), bone (63% vs 87%, P < 0.001), non‐regional lymph nodes (60% vs 96%, P < 0.001) and liver metastases (79% vs 91%, P < 0.001). On multivariable analysis, pN1 status remained significantly associated with lung, bone, and non‐regional lymph node (all P < 0.001) metastases, but it was no longer associated with liver metastases (P = 0.3).ConclusionspN1 nodal status in M0 patients treated with nephrectomy for renal cell carcinoma is associated with more frequent early metastasis to sites conferring poor prognosis when compared with pN0/x. Our findings highlight the importance of rigorous, early surveillance though the multimodal use of a comprehensive history, physical, laboratory and radiological studies, as outlined in societal guidelines.