Dr Galsky on the Current Roles of Biomarkers in Bladder Cancer

“We’ve had some challenges in terms of meeting that goal in bladder cancer, and we only have a few actionable biomarkers that indicate which patients should get which drugs.”

Matthew Galsky, MD, the director of Genitourinary Medical Oncology, co-director of the Center of Excellence for Bladder Cancer, the deputy director, and a professor of medicine (Hematology and Medical Oncology) at the Mount Sinai Tisch Cancer Center, discussed the role of biomarkers in the treatment and management of bladder cancer.

Biomarkers in bladder cancer are traditionally categorized as either prognostic or predictive, but a more clinically relevant framework may be to distinguish between biomarkers that identify which patients need treatment and those that determine which patients are most likely to benefit from specific therapies, Galsky began. This distinction is particularly important in the perioperative setting, where treatment decisions are often influenced by the risk of recurrence and the possibility that some patients may already be cured following surgery, he noted.

Biomarkers that predict benefit from treatment are intended to guide the selection of specific therapies, Galsky explained. However, progress in developing such biomarkers in bladder cancer has been relatively limited, and only a handful of actionable targets have entered clinical practice, he said. One of the most well-established examples is alterations in FGFR3, which can identify patients who may benefit from FGFR-targeted therapies. Another emerging biomarker is HER2 overexpression, which may help identify patients who are candidates for HER2-directed antibody-drug conjugates, he added. Despite these advances, the number of biomarkers that can reliably direct treatment selection remains relatively small, he underscored.

Equally important are biomarkers that determine which patients require additional therapy, Galsky said. This knowledge is especially relevant after definitive radical surgery in the perioperative setting, he added. Although many patients undergo surgery with curative intent and are ultimately cured, clinicians have historically lacked reliable tools to identify those individuals. As a result, some patients may receive systemic therapy despite having little or no chance of deriving benefit.

Circulating tumor DNA (ctDNA) has emerged as a potential way through which to address this challenge, Galsky said. Recent advances have demonstrated the potential of ctDNA testing to identify patients with residual microscopic disease who remain at risk for recurrence. Evidence supporting its clinical utility has begun to accumulate, particularly in the adjuvant setting. Findings from the phase 3 IMvigor011 study (NCT04660344) showed that patients with detectable ctDNA following surgery experienced an overall survival benefit when treated with immune checkpoint blockade compared with placebo, he noted. These results highlight the growing role of ctDNA-guided treatment strategies and suggest that biomarkers may increasingly be used not only to select therapies, but also to determine which patients truly need additional treatment, he concluded.

Check out the OncLive Biomarker Consortium site for more biomarker insights in bladder cancer and beyond!