Sarcomatoid Features May Be a Biomarker in Chromophobe RCC

Patients who have metastatic chromophobe renal cell carcinoma (ChrRCC) that harbors sarcomatoid features (SF) benefited from immunotherapy (IO)-containing regimens vs patients without SF, according to a multi-institutional retrospective analysis presented by Sahil D. Doshi, MD, during the 2025 International Kidney Cancer Symposium in Denver, Colorado.¹

These findings suggest that SF may be a predictive biomarker for immunotherapy in metastatic ChRCC.

Among patients with no SF (n = 138) who were stratified by IO vs non-IO therapy, among patients without SF, treatment with an IO regimen (n = 45) vs non-IO (n = 93) had an inconclusive effect on overall survival (OS; HR, 0.85; 95% CI, 0.49-1.47; P = .56).¹

Looking at SF (n = 52), comparing IO vs non-IO regimens, “we saw that patients treated with IO regimens had a statistically significant superior OS compared with those with non-IO regimens,” Doshi, a genitourinary medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, said. The hazard ratio was 0.29 (95% CI, 0.14-0.61; P = .001). “We also adjusted for IMDC risk in de novo metastatic disease, and the significance remained with a hazard ratio of 0.3,” continued Doshi.

Further, time to first-line treatment failure and OS were evaluated for sarcomatoid vs no sarcomatoid and IO vs no IO (n = 190). Doshi reported that the magnitude of benefit to IO therapy was greater in the SF group as compared with the no SF group (Cox interaction P = .02).

In patients with target lesion information, RECIST 1.1 analysis revealed that in the no sarcomatoid and no IO group (n = 96), 22% had a partial response, 47% had stable disease, 31% had progressive disease, and 22% had an objective response rate (ORR; 95% CI, 14%-30%).

In the no sarcomatoid and no IO subgroup (n = 44), the ORR was 23% (95% CI, 10%-35%), with 23% of patients exhibiting a partial response, 61% demonstrating stable disease, and 16% with progressive disease.

In the no sarcomatoid group (n = 21), the ORR was 19% (95% CI, 2%-36%), with 19% of patients demonstrating a partial response, 62% showing stable disease, and 19% of patients with progressive disease.

Patients with sarcomatoid and no IO (n = 18) had an ORR of 11% (95% CI, 0%-26%), 11% had a partial response, 22% had stable disease, and 67% had disease progression. In the sarcomatoid and IO group (n = 11), the ORR was 36% (95% CI, 8%-65%), 36% had a partial response, 9% had stable disease, and 55% had progressive disease.

Study Design

Patient records in 9 cancer centers in the US and Europe were evaluated, and the presence or absence of SF was determined by local pathology reports. Frontline systemic therapy options were categorized by IO-containing or non-IO containing regimens. Time-to-treatment failure and OS were estimated using the Kaplan-Meier method.

Patient Demographics

The median age of the overall cohort (n = 202) was 55 years (range, 28-55). Fifty-two patients had SF, and 138 did not. This characteristic was unknown in 12 patients. Overall, 91% of patients had undergone a nephrectomy, and 31% had de novo metastatic disease.

Seventy-nine percent of the total patients had metastases in 1 to 2 sites; in the SF population and the no SF population, it was 69% and 83%, respectively. Lymph node involvement affected 51%, 56%, and 46% of the populations, respectively.

In the total population, IMDC risk categories were favorable (32%), intermediate (33%), poor (16%), and unknown (19%). Thirty-four percent had been previously treated with IO-containing therapy. In the SF and no SF populations, 44% and 33% had received prior IO-containing therapy.

Previous studies have reported retrospective outcomes for first-line systemic therapy for patients with metastatic ChRCC and found improved outcomes with doublet therapies as compared with single-agent regimens.²

For example, for IMDC risk stratified by SF vs no SF, “we see that patients with sarcomatoid features had a higher proportion of intermediate IMDC risk and poor risk disease,” Doshi said.

In patients without SF, outcomes were similar between IO vs non-IO containing regimens; in patients with SF, there was a treatment benefit with IO-containing regimens.

“We believe [these data] should be further explored, with implications for treatment selection and clinical trial design,” Doshi concluded.

REFERENCES

1. Doshi SD. A multi-institution analysis of outcomes for 202 patients with metastatic chromophobe renal cell carcinoma with and without sarcomatoid features. Presented at 2025 International Kidney Cancer Symposium: North America; November 13-15, 2025; Denver, Colorado.

2. Bakouny Z, Braun DA, Shukla SA, et al. Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma. Nat Commun. 2021;12(1):808. doi:10.1038/s41467-021-21068-9