Evaluating Biomarkers of Response to Immune Checkpoint Blockade in mRCC

For patients with metastatic renal cell carcinoma (mRCC), immune checkpoint blockade (ICB) treatments used alone and in combination with other therapies can dramatically improve outcomes. However, very few biomarkers exist to predict patient response to ICB therapy.

At the 2024 American Urological Association Annual Meeting, Stephen Reese, MD, and colleagues presented a comprehensive evaluation of various features that can serve as biomarkers of response to ICB therapy in patients with mRCC.

The researchers examined 185 patients with RCC who received a systemic ICB consisting of immuno-oncology (IO)/IO or IO/tyrosine kinase inhibitor therapy from 2005 to 2022. Of the total group of patients, 62 had a primary kidney tumor present.

In subgroups of patients with a primary tumor, radiographic information was recorded, including time of initial treatment through treatment failure and receipt of second-line therapy or surgical intervention, radiographic kinetics of response to therapy, Response Evaluation Criteria in Solid Tumors v1.1 measurements, and 145 radiomic features.

A landmark analysis was performed at 3 months. Features such as time to next treatment and overall survival (OS) were evaluated; pathologic data were also reviewed and recorded for each patient.

The researchers discovered 4 possible outcomes in metastatic and primary pairs linked to patient response to ICB therapy. At 3 months, response to the metastatic and primary lesion predicted time to next therapy and OS. Shrinkage in primary and metastatic disease predicted the best clinical outcomes, while progression in primary and metastatic disease predicted the worst outcomes.

Depth of response in primary tumor was also found to correlate with time to next therapy and OS (<75% at 3 months associated with best outcomes); both outcomes were highly significant (P<.01). The preoperative radiographic tumor volume was found to overestimate pathologic tumor volume for most patients, with an overall mean difference in volume of 622 cm³ (95% confidence level of mean difference: 285, 958).

Pathologic viable tumor volume was positively associated with preoperative contrast enhancement and change in contrast enhancement (Spearman correlation coefficient P=.41, P=.02). When examining radiographic features of response to systemic therapy, the researchers noted 4 first- and second-order radiomic features that identified patients with measurable residual disease on pathologic evaluation.

Further analyses can aid physicians in clinical decision-making regarding noninvasive determinations about prognosis and response to therapy.