Introduction:

Non-clear cell renal cell carcinoma (non-ccRCC) accounts for up to 25 % of all RCC. The evidence for systemic therapy in non-ccRCC is scarce and suggests limited efficacy. Therefore, surgical resection remains an essential component of management, especially in patients with a limited burden of metastatic disease. The impact of loco-regional nodal involvement and the role of salvage-lymph node dissection in recurrent retroperitoneal nodal disease in patients with non-ccRCC remains poorly defined. 

Methods:

We queried our institutional database of 1,443 patients who had undergone radical nephrectomy for non-ccRCC at Memorial Sloan Kettering Cancer Center between 2007 and 2023. We identified 38 (3%) patients with de novo nodal disease resected at the time of nephrectomy (cohort 1) and 22 (1,5%) patients who developed recurrent nodal disease limited to the retroperitoneum (cohort 2) on follow-up. Histology was grouped as papillary RCC, chromophobe RCC, unclassified RCC and rare subtypes (e.g. FH deficient, translocation RCC). Patients’ demographics and tumor characteristics were recorded and evaluated using univariate and cox regression models. Recurrence-free (RFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method. For 55% (34/60) of patients genetic testing was available and explorative analysis was performed. 

Results:

Cohort 1 and 2 were similar in age, gender, BMI, T-stage, histology, and surgical approach (Table 1). OS was longer for cohort 2 (median OS 104 vs 25 months; p=0.032; Figure 1). In cohort 1, 26% (n=10) remained disease free after the initial surgery. On multivariate analysis, rare histology was associated with worse OS (p=0.035), whereas recurrent nodal disease was associated with improved OS (p=0.014) compared with de novo disease. In cohort 2, 91% (n=20) received salvage-LND. The RFS and OS after salvage-LND were 15 and 96 months respectively. Later onset of recurrent nodal disease (>15months) was associated with improved OS (p=0.009). Genetic analysis revealed a trend toward higher mutations frequency in SETD2, TP53 and NF2 in cohort 1 (Figure 2). 

Conclusion:

In conclusion, recurrent nodal disease is associated with better survival compared with de novo nodal disease in patients with non-ccRCC. Nonetheless, a significant portion of patients with de novo nodal disease have improved outcomes and prolonged survvial, with 26% remaining disease-free. Similarly, salvage-LND also provides durable management for a subset of recurrent patients with recurrent disease. Mutations in SETD2, TP53, and NF2 tended to be more frequent in patients with de novo nodal disease.

Funding: German Research Foundation