Daniel Shapiro, MD, on emerging biomarkers, combination strategies in RCC

In this interview, conducted at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California, Daniel Shapiro, MD, FACS, discussed how emerging biomarker strategies and evolving combination therapies are reshaping risk stratification and treatment decision-making in kidney cancer. Shapiro is an assistant professor of urology and radiology at the University of Wisconsin-Madison School of Medicine and Public Health.

Shapiro emphasized that accurately predicting recurrence risk following nephrectomy remains a major clinical challenge, particularly for patients with non-metastatic disease. Emerging biomarker approaches—including circulating tumor DNA (ctDNA) and KIM-1 assays—offer the potential to refine risk stratification by providing more individualized assessments of recurrence risk. These tools, along with investigations into the tumor microenvironment and immune infiltration, may enhance clinicians’ ability to identify which patients are most likely to benefit from additional therapy.

He highlighted that these advances are especially important in the context of expanding adjuvant treatment options. Building on findings from KEYNOTE-564 (NCT03142334), which demonstrated both disease-free and overall survival benefits with pembrolizumab (Keytruda),¹ newer data such as LITESPARK-022 (NCT05239728) suggest further improvements with combination approaches like pembrolizumab plus belzutifan (Welireg).² As therapeutic options grow more effective and potentially more complex, Shapiro underscored the need for improved patient selection to balance efficacy with the risk of unnecessary toxicity.

Looking more broadly at treatment evolution, Shapiro described rapid progress in combination strategies across both metastatic and earlier-stage disease. Trials such as LITESPARK-011 in the metastatic setting and LITESPARK-022 in the adjuvant setting illustrate the growing role of combination regimens. However, he stressed that many patients, particularly in the adjuvant setting, may still be cured with surgery alone. As such, integrating biomarker-driven risk assessment into clinical decision-making will be critical to avoid overtreatment, guide shared decision-making, and optimize outcomes as the therapeutic landscape continues to evolve.

REFERENCES

1. Choueiri TK, Tomczak P, Park SH, et al. Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma. N Engl J Med. 2024;390(15):1359-1371. doi:10.1056/NEJMoa2312695

2. Choueiri TK, Motzer RJ, Karam JA, et al. Adjuvant pembrolizumab plus belzutifan versus pembrolizumab for clear cell renal cell carcinoma (ccRCC): The randomized phase 3 LITESPARK-022 study. Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 26-28, 2026. San Francisco, California. Abstract LBA418. https://meetings.asco.org/meetings/2026-asco-genitourinary-cancers-symposium/334/16925?presentation=256660