From the Journals

Poor outcomes for RCC with nodal involvement: Time to reconsider staging criteria?



Among patients with stage III renal cell carcinoma (RCC) by current staging criteria, survival outcomes are worse for those who have pathological nodal involvement, results of a retrospective study suggest.

Survival was significantly shorter for stage III patients with nodal involvement versus those with no involvement, and was “equivalent” to survival in stage IV RCC patients, according to study author Jose A. Karam, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his coauthors.

“If these findings are validated in other studies, consideration should be given to reclassifying patients with stage III, pN1 disease as having stage IV disease,” Dr. Karam and his coauthors wrote in Cancer.

Dr. Karam and his colleagues looked at records for patients with RCC of any histologic subtype who had undergone radical or partial nephrectomy between 1993 and 2012. Their analysis included a total of 389 patients with stage III disease, including 274 with node-positive disease (pT3N0M0) and 115 with node-negative disease (pT123N1M0), along with 523 patients who had stage IV disease.

They found that median overall survival was just 2.4 years (95% confidence interval, 1.7-4.1) for stage III, node-positive disease patients, compared with 10.2 years (95% CI, 8.7-not estimable [NE]) for stage III, node-negative disease and 2.4 years (95% CI, 2.1-3.0) for stage IV disease.

There was a significant difference in overall survival between the three groups, but no significant difference between patients with stage III node-positive disease and stage IV disease, the investigators wrote.

Similarly, median cancer-specific survival was 2.8 years (95% CI, 1.8-4.8) for stage III node-positive disease, not reached (95% CI, 10.2-NE) for stage III node-negative disease, and 2.4 years (95% CI, 2.1-3.0) for stage IV disease, the investigators wrote.

In multivariate analysis, pathological lymph node involvement in the stage III patients was independently associated with worse overall and cancer-specific survival.

Dr. Karam and his coauthors wrote that it may be prudent to revise the current staging system to reclassify node-positive patients if further research confirms their findings. By the current American Joint Committee on Cancer tumor, nodes, and metastases staging manual, patients can be classified as stage III on the basis of either primary tumor status (pT3) or pathological lymph node involvement, they said.

The incidence of pathological, node-positive disease in RCC ranges from 2%-10% in studies, with 5-year survival rates that are “poor” at 5%-30%, the authors noted in their report.

“Even in the targeted therapy era, adjuvant therapy with tyrosine kinase inhibitors does not appear to improve on these outcomes in patients with pN-positive disease,” they wrote.

Funding support for the research came from the National Institutes of Health/National Cancer Institute. Dr. Karam reported serving as a consultant/advisory board member for Pfizer, EMD Serono, Novartis, and Roche/Genentech, and that the MD Anderson Cancer Center has received clinical trial research funding from Roche/Genentech, though none of these disclosures were related to the current report.

SOURCE: Karam JA et al. Cancer. 2018 Oct 1. doi: 10.1002/cncr.31661.

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