# Cancer-Specific Mortality in Sarcomatoid Renal Cell Carcinoma: A Histological Subtype-Controlled Analysis

## TL;DR

This study finds that sarcomatoid dedifferentiation in kidney cancer is strongly linked to higher cancer-specific deaths, especially in non-clear cell types.

## Contribution

The study reveals that sarcomatoid dedifferentiation has a stronger impact on mortality in non-clear cell RCC than in clear cell RCC.

## Key findings

- Sarcomatoid dedifferentiation is associated with a 1.6-fold higher cancer-specific mortality in clear cell RCC.
- In non-clear cell RCC, sarcomatoid dedifferentiation is linked to a 2.0-fold higher cancer-specific mortality.
- The negative effect of sarcomatoid dedifferentiation is more pronounced in non-clear cell RCC than in clear cell RCC.

## Abstract

Introduction: Sarcomatoid dedifferentiation may be identified in both clear cell renal cell carcinoma (ccRCC) and non-clear cell RCC (nccRCC). Within the SEER database (2010–2021), we tested the effect of sarcomatoid dedifferentiation in first ccRCC and subsequently in nccRCC on cancer-specific mortality (CSM). Methods: Separate propensity score matching (PSM) and multivariable competing risks regression (CRR) analyses were first applied to ccRCC with vs. without sarcomatoid dedifferentiation and subsequently to nccRCC with vs. without sarcomatoid dedifferentiation. Results: Sarcomatoid dedifferentiation was present in 2496 (3.0%) of 82,146 ccRCC patients and in 501 (1.9%) of 26,584 nccRCC. In ccRCC, after 1:2 PSM, 2496 (100%) patients with sarcomatoid dedifferentiation vs. 4992 (6.2%) patients without sarcomatoid dedifferentiation were included. At 60 months, CSM was 45.7% vs. 33.6% in ccRCC patients with vs. without sarcomatoid dedifferentiation. In CRR sarcomatoid dedifferentiation independently predicted 1.6-fold higher CSM (HR 1.6, p < 0.001). In nccRCC, after 1:2 PSM 501 (100%) patients with sarcomatoid dedifferentiation vs. 1002 (3.8%) patients without sarcomatoid dedifferentiation were included. At 60 months, CSM was 41.7% vs. 28.1% in nccRCC patients with vs. without sarcomatoid dedifferentiation. In CRR sarcomatoid dedifferentiation independently predicted 2.0-fold higher CSM (HR 2.0, p < 0.001). Conclusion: Sarcomatoid dedifferentiation is invariably associated with higher CSM in both ccRCC and nccRCC. However, the detrimental effect of sarcomatoid dedifferentiation in CSM is more pronounced in nccRCC than in ccRCC.