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. 2024 Sep;11(5):860-870.
doi: 10.1097/UPJ.0000000000000623. Epub 2024 Jun 12.

Surgical Outcomes and Genomic Insights of Nonclear Cell Renal Cell Carcinoma With Synchronous and Metachronous Nodal Disease

Lennert Eismann  1   2 , Mark Zucker  3 , Mark T Dawidek  1 , Stephen W Reese  1 , Lina Posada Calderon  1   4 , Andreas Aulitzky  1 , Christian G Stief  2 , Jonathan A Coleman  1 , Ritesh R Kotecha  5 , Maria Carlo  5 , Yingbei Chen  6 , Ed Reznik  4 , Paul Russo  1 , A Ari Hakimi  1
Affiliations

Surgical Outcomes and Genomic Insights of Nonclear Cell Renal Cell Carcinoma With Synchronous and Metachronous Nodal Disease

Lennert Eismann et al. Urol Pract. 2024 Sep.

Abstract

Introduction: Oncological outcomes in patients with nonclear cell renal cell carcinoma (non-ccRCC) treated with surgery for locoregional nodal disease (ND) remain incompletely characterized. The objective was to investigate the characteristics and outcomes of non-ccRCC patients treated with lymph node dissection (LND) and salvage-LND (S-LND).

Methods: A total of 1627 patients underwent nephrectomy for nonmetastatic non-ccRCC at Memorial Sloan Kettering Cancer Center between 2007 and 2023. Histology was grouped as papillary, chromophobe, unclassified, and rare subtypes. Retrospective evaluation identified 2.5% (n = 40) of patients with nodal disease at time of nephrectomy (synchronous-ND) and 1.1% (n = 18) with metachronous nodal disease limited to the retroperitoneum (metachronous-ND). Patients' demographics and tumor characteristics were recorded and evaluated by univariate and multivariate cox regression models. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Patients who underwent tumor DNA sequencing during their clinical course were considered for genomic analysis.

Results: OS trended toward longer in metachronous-ND (51 vs 105 months; P = .2), though 23% of patients with synchronous-ND were recurrence-free at 45 months median follow-up. In multivariate analysis, rare histologies were associated with decreased OS (P = .030) and metachronous-ND with improved OS (P = .036). RFS and OS after S-LND was 15 and 96 months, respectively. Late onset of metachronous-ND/recurrence was associated with improved OS (P = .008). Genetic alterations in SETD2, TP53, B2M, and FGFR3 were exclusively seen in synchronous-ND, and tumor mutation burden (TMB) was also higher in patients with synchronous-ND (P = .016).

Conclusions: Patients with metachronous-ND tend to have prolonged OS compared to synchronous-ND, but a substantial portion of patients with synchronous-ND still enter a durable disease-free state following LND. S-LND can likewise provide long-term survival, particularly in patients with longer time to metachronous nodal recurrence. Synchronous-ND was associated with SETD2, TP53, and NF2 alteration as well as higher TMB.

Keywords: lymph node excision; nephrectomy; renal cell carcinoma.

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Figures

Figure 1:
Figure 1:. Illustration of location of lymph node metastasis in patients with synchronous-ND (n=39) and patients with metachronous-ND/nodal recurrence isolated to the retroperitoneum (n=22).
A) The location of synchronous LNM of n=16 right-sided and n=22 left-sided tumors (Including one patient with bilateral disease and major tumor burden on the left side). B) The location of metachronous-ND and recurrence isolated to the retroperitoneum are displayed. In total, n=10 had history of right-sided and n=12 of a left-sided primary.
Figure 2a:
Figure 2a:. Recurrence-free survival (RFS) of patients with synchronous (blue) and metachronous (red) nodal disease from time of nephrectomy
Figure 2b:
Figure 2b:. Overall survival (OS) of patients with synchronous (blue) and metachronous (red) nodal disease from time of nephrectomy
Figure 3a:
Figure 3a:. Swimmer’s plot summarizing clinical course of patients treated with S-LND
Figure 3b:
Figure 3b:. Overall survival from S-LND (S-OS) of patients receiving S-LND stratified by time to recurrence.
According the median RFS from nephrectomy to metachronous-ND/recurrence (mRFS:13 mo) patients were stratified in an early and late onset subgroup.
Figure 4:
Figure 4:
Exploratory genomic analysis of patients with synchronous and metachronous nodal disease. A) reflects mutations of most frequently altered genes. B) and C) shows tumor mutational burden (TMB) in mu/Mb of the entire cohort comparing onset of nodal disease and outcome. D) shows the fraction of the genome that is copy-number altered (FGA) and E) Cancer-cell fraction (CCF) comparing patients according to their oncological outcome.
See this image and copyright information in PMC

Comment in

  • Editorial Commentary.
    Kronstedt S, Singer EA. Kronstedt S, et al. Urol Pract. 2024 Sep;11(5):869-870. doi: 10.1097/UPJ.0000000000000627. Epub 2024 Jun 5. Urol Pract. 2024. PMID: 38913562 No abstract available.

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