BackgroundRenal cell carcinoma (RCC) with isolated lymph node (LN) involvement has historically been associated with poor prognosis. However, a subset of patients may experience long-term survival. ObjectiveTo examine the natural history of RCC with isolated LN involvement following surgical resection with long-term follow-up, and to evaluate clinicopathologic features associated with disease progression and survival. Design, setting, and participantsA total of 138 patients with isolated pN1M0 RCC underwent partial or radical nephrectomy and LN dissection from 1980 to 2010. InterventionPartial or radical nephrectomy with LN dissection. Outcome measurements and statistical analysisMetastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were estimated using the Kaplan-Meier method. Associations between clinicopathologic features and oncologic outcomes were evaluated using Cox regression models. Results and limitationsMedian follow-up among survivors was 8.5 yr. The 5-yr and 10-yr MFS, CSS, and OS rates were 16% and 15%, 26% and 21%, and 25% and 15%, respectively. The median time to development of metastases was only 4.2 mo. On multivariable analysis, symptoms at presentation (hazard ratio [HR] 2.40; p=0.03), inferior vena cava tumor thrombus (HR 1.99; p=0.003), clear cell (HR 2.21; p=0.01) and collecting duct/not otherwise specified (HR 4.28; p<0.001) histologic subtypes, pT4 stage (HR 2.64; p=0.005), and coagulative tumor necrosis (HR 2.51; p<0.001) were independently associated with development of metastases. MFS rates at 1 yr after surgery were 71%, 63%, 33%, and 7% for patients with one, two, three, and four to five adverse features, respectively. Limitations include surgical selection bias. ConclusionsAlthough isolated pN1 disease portends a poor prognosis, a small subset of patients experience durable long-term survival after surgical resection of isolated lymphatic metastases. Adverse prognostic features may enhance patient risk stratification and facilitate multimodal management approaches. Patient summaryAlthough isolated lymph node metastases portend a poor prognosis, a small subset of patients experience long-term survival following surgical resection.