Bladder Cancer Awareness Month: The rise of biomarkers and precision care

As bladder cancer treatment becomes increasingly complex, biomarkers and novel therapeutics are poised to play a defining role in guiding the next generation of care. In the second part of this Bladder Cancer Awareness Month Q&A (see part 1 here), Song Jiang, MD, PhD, of Northwestern University Feinberg School of Medicine, explores how tools such as circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA) may help refine patient selection, particularly for bladder-preserving strategies.

He discusses how these markers could inform decisions around adjuvant therapy and the potential to safely avoid overtreatment in select patients. Jiang also highlights the growing impact of antibody-drug conjugates, targeted therapies, and immunotherapy combinations in advanced disease, as well as the promise of multidisciplinary collaboration in optimizing outcomes. Looking ahead, the integration of biomarker-driven strategies with innovative therapeutics signals a shift toward more precise, individualized care, aimed not only at improving survival but also at preserving quality of life.

Urology Times: How important do you think biomarkers such as circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA) will be in selecting patients for potential bladder preserving strategies in muscle-invasive bladder cancer?

Jiang: Highly important. The folks who have conducted those trials had the foresight to include those biomarkers as possible predictive tools. CheckMate 274 [NCT02632409], the adjuvant trial, had shown that ctDNA was highly predictive for occult metastatic disease.¹ Those were the folks in the trial who benefited the most from adjuvant therapy. That's going to be important in the perioperative space to continue to look at and monitor those patients with ctDNA. The NIAGARA trial of gemcitabine, cisplatin, and durvalumab [Imfinzi] had shown that utDNA was a predictor of pathologic [complete response].² With negative utDNA, it was reflective of the local response. That's going to be a powerful tool.

With regard to bladder preservation, for those folks who are marker negative, meaning they are ctDNA negative and utDNA negative, there were great responses and an exceptionally low rate of development of metastatic disease. In the bladder preservation trials, that was a predictor of a good response. That brings up the question of, No. 1, do they need adjuvant therapy if they're double negative after neoadjuvant treatment and definitive local treatment? And then the other question is, if, after neoadjuvant therapy, you're completely marker negative, does that make you more of a candidate for surveillance alone? Those are open questions, and there are trials going on that are going to address those questions in the near future. It's something to be on the lookout for and that we're really excited about.

Urology Times: Antibody-drug conjugates, targeted therapies, and novel immunotherapy combinations are expanding options in advanced disease. Which emerging approaches do you believe could have the biggest impact on the field in the next few years?

Jiang: From a scientific standpoint and from a biology standpoint, the ongoing research in antibody-drug conjugates is exciting. Folks are creating bivalent antibodies targeting all sorts of different target antigens carrying different cytotoxic payloads. I think it brings in a truly exciting realm of possibilities. So many smart scientists are leveraging immunology and T-cell receptor biology and combining them in targeted therapies based on molecular phenotype. The use of these drugs in combination is going to move the needle quite a bit in the treatment of advanced bladder cancer. That's my hunch; it's cool technology, and I think it's going to create a lot of different avenues that we're seeing in other diseases. In colorectal cancer and melanoma, they're really leveraging these different antibody-drug conjugate combinations to treat disease.

Urology Times: What gives you the most optimism about the future of bladder cancer care? What progress would you like to see over the next decade?

Jiang: Overall, I think the field is moving toward sparing more bladders and sparing more functional bladders. That’s going to be the future of bladder cancer care, frankly, as well as using biomarkers to be able to achieve a risk-adapted approach to intervention, including radiation or surgery. The idea is to be able to use ctDNA or utDNA almost like how we use (PSA) [prostate-specific antigen] in prostate cancer. That's going to be exciting in the future.

From a non–muscle-invasive bladder cancer standpoint, my mentor in fellowship, Eugene Pietzak, [MD,] made the comment when I started with him, that he hoped that we wouldn't be doing BCG anymore—that it would become obsolete. That probably is the next progression, that BCG monotherapy will become obsolete, and we will have more shelf-stable drugs that are not as susceptible to shortages and that are equal or, if not, better, in terms of efficacy for NMIBC patients.

Urology Times: Is there anything else that you wanted to add?

Jiang: Bladder cancer requires multidisciplinary care. What I've been proud of and what I've seen in practice, more so than I even realized in training, is the amount of multidisciplinary communication in working with medical oncologists and radiation oncologists. That's paramount in modern medicine. We don't work in a silo. Communicating with our colleagues in different fields is going to be important, especially in a complex disease process like bladder cancer.

Secondly, I'll just reiterate that it's really cool to see how basic science and translational research have become so fruitful in the clinical setting with these new therapies. The ability to engineer things like BCG, T-cell receptors, and immunotherapeutics to make them more targeted and have fewer off-target effects is a testament to our investment in science.

REFERENCES

1. Galsky MD, Gschwend JE, Milowsky MI, et al. Adjuvant nivolumab versus placebo for high-risk muscle-invasive urothelial carcinoma: 5-year efficacy and ctDNA results from CheckMate 274. Ann Oncol. 2026;37(1):69-78. doi:10.1016/j.annonc.2025.09.139
2. Van Der Heijden MS, Galsky MD, Joshi R, et al. Urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) in patients (pts) with muscle-invasive bladder cancer (MIBC) who received perioperative durvalumab (D) in NIAGARA. J Clin Oncol. 2026;44(suppl 7):636. doi:10.1200/JCO.2026.44.7_suppl.636