Advancing Precision Medicine in RCC: The Role of Biomarkers in Treatment Decisions

At the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium, a roundtable of expert panelists convened to discuss the latest research and practice updates related to advanced kidney cancer. Dr. Karine Tawagi of University of Illinois was joined by Drs. Regina Barragan-Carrillo, Benjamin Maughan, Laurence Albiges, and David McDermott in the discussion.

In the first part of the roundtable, the panel weighs the evolving role of biomarkers, particularly the promising blood-based biomarker KIM-1, highlighting its potential for predicting disease progression, guiding adjuvant therapy, and assessing treatment response—especially in immunotherapy settings—while emphasizing the need for prospective validation to integrate these findings into clinical practice.

View the next segment on COSMIC-313 and the Future of Triplet Therapy in RCC: Efficacy, Toxicity, and Biomarkers.

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Dr. Tawagi: I want to begin by opening the discussion on the current state and future directions of biomarkers in RCC. What are your thoughts?

David McDermott: As a field, we are currently behind others. We have spent a significant amount of time and effort investigating tumor-based biomarkers, and while we have identified some that may enrich for benefit, they are not yet ready for clinical implementation. For example, PD-L1 positivity likely increases the chance of responding to PD-L1 blockade, but at the moment, it is not a strong enough marker for routine clinical use. Researchers have attempted to build on this by examining gene expression and mutations, but we are not quite there yet.

One of the exciting aspects of this meeting, building on findings from previous meetings, is the emergence of more blood-based biomarkers. There is an update on KIM-1, a serum biomarker that has been evaluated in various kidney cancer settings. KIM-1 is produced by the kidney in response to injury, hence its name, Kidney Injury Molecule-1. It is highly elevated in patients with clear cell and papillary kidney cancer, as it is expressed on the proximal tubule where these tumors originate. Interestingly, the first detection of elevated KIM-1 levels occurred in patients before they had even developed kidney cancer.

A fascinating study conducted by colleagues in France, through the IARC, a WHO-based consortium, analyzed blood samples from patients across Europe. They found that patients with high KIM-1 levels five years prior were more likely to develop kidney cancer, which is remarkable.

Subsequently, KIM-1 has been evaluated in both the adjuvant and metastatic settings. To summarize, if KIM-1 is elevated, patients are more likely to benefit from PD-L1 blockade. Additionally, if KIM-1 levels decrease in response to treatment, that is likely a positive indicator. The key update from this meeting is the CheckMate 214 trial with ipilimumab and nivolumab. It demonstrated that patients whose KIM-1 levels were initially high but then declined had a greater likelihood of response, prolonged progression-free survival, and prolonged overall survival.

Although this research is retrospective and requires further prospective validation, it suggests we may be on the verge of identifying biomarkers that can inform critical clinical decisions. These include determining who requires adjuvant treatment, assessing whether adjuvant or metastatic treatment is effective, deciding if additional therapy is necessary, and even identifying patients who might safely forgo adjuvant treatment. There is considerable enthusiasm in this area, but confirmatory trials are essential for validating KIM-1 and other biomarkers, such as circulating tumor DNA.

Dr. Albiges: Yes, the excitement surrounding KIM-1 stems from its ease of assessment through blood or serum testing. Additionally, as a protein, it is feasible to develop an assay for routine testing, and it is cost-effective. The IMmotion010 trial, which investigated adjuvant atezolizumab, demonstrated that KIM-1 was the protein most likely to be differentially expressed at the time of disease progression or relapse. Importantly, when patients are monitored longitudinally, KIM-1 could help identify those at risk of relapse. This could serve as a strategy to define minimal residual disease, guide adjuvant therapy decisions, and facilitate long-term patient monitoring.

IMmotion010 highlighted this potential, and similar findings emerged from the CheckMate 914 trial, which compared adjuvant nivolumab alone, nivolumab plus ipilimumab, and placebo.

The CheckMate 214 data in the metastatic setting is particularly compelling. As you emphasized, KIM-1 was highly relevant in predicting response to treatment, but only in the nivolumab plus ipilimumab arm, not with sunitinib. This suggests that KIM-1 may not only serve as a surrogate marker for MRD or the presence of disease but may also be predictive of response to immunotherapy rather than tyrosine kinase inhibitors. This is significant because we are actively searching for predictive biomarkers. While prospective validation is necessary, the enthusiasm surrounding the possibility of a blood-based biomarker is growing.

Dr. Tawagi: Absolutely, that is extremely exciting. Perhaps in the future, we will have a risk-adapted adjuvant trial incorporating KIM-1 or similar biomarkers.