# Reassessing prognostic markers in metastatic renal cell carcinoma in the era of immune checkpoint inhibitors: the enduring value of body composition, nutritional, and inflammatory indices

## TL;DR

This study shows that body composition, nutrition, and inflammation markers still predict survival in kidney cancer patients treated with immune checkpoint inhibitors.

## Contribution

The study validates traditional prognostic markers in the context of modern ICI-based therapies for metastatic renal cell carcinoma.

## Key findings

- Low visceral and subcutaneous adipose tissue indices were linked to shorter survival in mRCC patients.
- Nutritional and inflammatory indices like PNI, GNRI, GPS, and SII strongly predicted overall survival.
- PNI and SATI showed the best performance in stratifying survival outcomes in ICI-treated patients.

## Abstract

Immune checkpoint inhibitors (ICIs) are now the standard first-line treatment for metastatic renal cell carcinoma (mRCC), yet many risk factors identified during the tyrosine kinase inhibitor era remain unvalidated in current practice. This study aimed to evaluate the prognostic value of body composition, nutritional, and inflammatory indices in the era of ICI-based first-line therapy.

We retrospectively analyzed 136 mRCC patients who received systemic therapy. Body composition indices (skeletal muscle index [SMI], visceral adipose tissue index [VATI], subcutaneous adipose tissue index [SATI]), nutritional markers (prognostic nutritional index [PNI], geriatric nutritional risk index [GNRI]), and inflammatory markers (Glasgow Prognostic Score [GPS], systemic inflammatory index [SII], and other indices) were assessed for their association with overall survival (OS). We also compared their prognostic impact on patients treated with non-ICI-based and ICI-based regimens as first-line therapy.

Low VATI (HR 1.64, P = 0.030), and low SATI (HR 2.22, P < 0.001) were associated with shorter survival. PNI (HR 1.70, P < 0.001) and GNRI (HR 1.57, P < 0.001) showed strong prognostic value, as did GPS (HR 2.43, P < 0.001) and SII (HR 2.11, P < 0.001) in the overall cohort. In the ICI-based regimen group, PNI, GNRI, and SATI demonstrated higher prognostic performance (C-indices 0.736, 0.730, and 0.690, respectively), with PNI and SATI providing clear OS stratification.

Several indices reflecting body composition, nutritional status, and systemic inflammation remain valuable prognostic markers in patients with mRCC receiving ICI-based first-line therapy.

The online version contains supplementary material available at 10.1007/s10147-025-02855-6.