The natural history of renal cell carcinoma with isolated lymph node metastases following surgical resection from 2006 to 2013

Introduction: Renal cell carcinoma (RCC) with isolated lymph node (LN) involvement (pN1 M0 RCC) is a rare clinical entity associated with a poor prognosis. Prior studies comprised cohorts treated predominantly prior to the introduction of targeted systemic therapy. We therefore examined the natural history of pN1M0 RCC following surgical resection in a contemporary cohort, and evaluated clinicopathologic features associated with survival. Patients and methods: We identified patients aged 18 to 89 years who underwent radical or partial nephrectomy with LN dissection for pN1 M0 RCC from 2006 to 2013 in the National Cancer Database. The associations of clinicopathologic features with overall survival (OS) were evaluated using Cox regression models, and a simplified risk score was developed. Results: A total of 2,679 patients were found to have pN1 M0 RCC after nephrectomy. Median follow-up was 19.2 (interquartile range 8.2, 39.8) months, during which time 1,782 patients died. One-, 5-, and 8-year OS rates were 68%, 28%, and 19%, respectively. On multivariable analysis, older age (HR 1.50; P< 0.001 for ≥70 vs, 18–<50 years old), rural location (HR 1.49; P= 0.01), larger tumor size (HR 1.29; P= 0.01 for 5–<10 cm; HR 1.34; P= 0.01 for 10–<15 cm; HR 1.43; P= 0.01 for ≥15 cm vs. <5 cm); higher pT stage (HR 1.25; P= 0.04 for pT3; HR 2.41; P< 0.001 for pT4 vs. pT1), positive surgical margins (HR 1.55; P< 0.001), number of positive LNs (HR 1.18; P= 0.01 for 2–3; HR 1.37; P< 0.001 for >3 vs. 1), and nonclear cell histologic subtype (HR 1.32; P< 0.001) were independently associated with decreased OS. A simplified risk score was developed based on the multivariable results. Five-year OS was 49%, 28%, 22%, and 10% for patients with scores of <4, 4 to 6, 7 to 9, and >9, respectively. Conclusions: In this large, contemporary cohort, pN1 M0 RCC was associated with a poor prognosis, with 5-year survival less than 30%. A simplified risk score was developed to facilitate postoperative risk-stratification and selection of patients for consideration of adjuvant therapy and clinical trial enrollment.