“BCG failure is defined as any high-grade disease occurring during or after BCG therapy” said Dr. Chiara Mercinelli (IT) in her lecture on ‘Failure after BCG systemic treatment”. How does this happen? According to Dr. Mercinelli, BCG treatment increases the expression of PD-L1, Tregs, and tumour-associated macrophages, creating an immunosuppressive microenvironment over time. “This PD-L1 upregulation is one of the key mechanisms of immune escape and ultimately explains why some patients become BCG-unresponsive.”

What are the options? Dr. Mercinelli shared the key results of several novel therapies, before summarising these key take-home messages:

• Systemic checkpoint inhibitors restore T-cell function and can enhance or complement the anti-tumour activity of intravesical agents.
• Pembrolizumab is already FDA-approved for CIS BCG-unresponsive, confirming a clinical role for systemic therapy (complete clinical response at 6 months: 36%).
• Trials combining local and systemic therapy (CG0070 + pembrolizumab) show the highest clinical response rates in early-phase trials. Targeted therapy is a valid approach in the NMIBC population.
• Robust randomised trials to compare intravesical and systemic versus intravesical alone are urgently needed to define optimal sequencing and combination strategies.

Prof. Carmen Jeronimo (PT) presented on “Urinary biomarkers for monitoring of NMIBC”. She noted that NMIBC represent the majority of all bladder cancers and have a high recurrence (up to 70%) and variable progression (up to 20%), necessitating life-long surveillance. In her opinion, biomarkers offer the potential to reduce unnecessary cystoscopies and anticipate the identification of high-risk patients in NMIBC. “Urinary biomarkers are ideal for risk-adaptive surveillance – balancing patient burden and recurrence detection.”

She emphasised the need for further validation of the best-performing biomarkers in diverse real-world settings (different populations, different hospitals) and their implementation in clinical practice. She also highlighted that combing biomarker panels with AI driven multimodal surveillance could help individualise NMIBC follow-up.

What is the most cost-effective treatment in NMIBC failure?

According to Prof. Ashish Kamat (US), current options for patients in NMIBC failure are extensive and include immunotherapies, chemotherapy, a combination of both, gene therapies, targeted therapies, device-assisted therapies, and radiotherapy plus immunotherapy. But patients face many treatment considerations, including short-term cure versus short-term gain, quality of life, logistical challenges, anxiety, potential long-term side effects from drugs, and financial toxicity.

Prof. Kamat shared new research (Myers, Talwar et al. 2025) assessing the financial toxicity of five treatments: radical cystectomy, nadofaragene, nogapendekin/BCG, pembrolizumab and gemcitabine/docetaxel, as well as the study CISTO (Gore J, et. al 2025) on the financial impact of bladder-sparing therapy versus radical cystectomy.

He concluded that cost-effectiveness varies by treatment strategy and patient goals, but radical cystectomy remains the most cost-effective overall. Among bladder-sparing therapies, gemcitabine/docetaxel is the most-cost effective single-line option. He noted that multiple sequential therapies offer limited (financial) value, and in his final in comment he stressed that shared decision making is as important as ever.

Visit the EMUC25 Resource Centre to see their full presentations.

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In the plenary session on bladder cancer, a succession of esteemed experts highlighted some new developments in their field.

Urinary markers

Prof. Lars Dyrskjøt (Aarhus, DK) started the session with an update on the research he and his team are undertaking in urinary markers in non-muscle invasive bladder cancer. He explored the diagnostic, prognostic and predictive values of urine testing.

“Multiple urine tests are available, with relatively high sensitivity and specificity. We need randomised intervention trials to demonstrate that cystoscopy could be skipped in some cases. Quality-of-life and health economy analysis should be included in the design of these trials,” explained Prof. Dyrksjøt.

“Screening may be difficult – but promising results have been shown in patients with haematuria. Analysis of cell-free DNA in urine (supernatant) may identify high-risk patients.”

Significantly, urine markers may also help an earlier selection of patients for more aggressive treatment. Finally, urine analysis during BCG of T-cell exhaustion biomarkers may inform on treatment response.

Prof. Susanne Osanto (Leiden, NL), who chaired the session hailed Prof. Dyrksjøt’s “tremendous work in genomics in BCa.” Earlier on Friday, Prof. Arnulf Stenzl (Tübingen, DE) referred to the Aarhus TOMBOLA trial, saying that there were “high hopes that that will show possibilities of liquid biopsy for indication and monitoring.”

New research

Prof. Morgan Rouprêt (Paris, FR) followed the talk on urinary markers with a fresh look at the role of transurethral tumour removal for bladder preservation strategies, stressing the importance of functional outcomes as well.

Dr. Markus Eckstein (Erlangen, DE) presented a pathologist’s perspective on molecular subtyping and gene profiling. In his pre-recorded presentation he outlined that subtypes of NMIBC and MIBC are based on profound biological features and that consensus subtypes should be used, if possible.

It would have to be discussed if subtypes can be assessed via immunohistochemistry. The prognostic impact also differs between NMIBC and MIBC, while the predictive impact is still promising. As in so many cases with new research, Dr. Eckstein concluded that prospective validation in clinical trials is still missing.

Prof. Thomas Powles (London, GB) was on hand to update the audience on optimal patient selection for adjuvant treatments. While covering a huge amount of considerations, some of the most important conclusions were that tissue-based biomarker PD-L1 was perhaps not the best choice despite being the only approved biomarker in Europe. A new tool for patient selection is ctDNA as demonstrated in the recent IMvigor010 trial. Notably, EMUC22 has the first research on neoadjuvant immune combination therapy: “triplet therapy” in the VOLGA trial (LP166).

• EMUC22 delegates can watch back Plenary Session 3 in its entirety once it becomes available in the EMUC22 Resource Centre.

The post Plenary Session 3 report: New strategies in BCa appeared first on EMUC25.

Core of the lecture
“My lecture will focus on urine biomarkers in NMIBC. Most studies in the field have focused primarily on urine DNA isolated from intact cells in the urine (urine pellets). These inform us about the presence of tumour in the bladder, and may be used for optimised surveillance,” stated Prof. Dyrskjøt. “We have performed studies of cell-free DNA in urine which may originate from the blood stream, and indicate if the disease is already invasive/metastatic. Consequently, this may be used for additional monitoring of disease state, and not just presence of tumour cells.”

Inspiration for the research
The research by Prof. Dyrskjøt and his team was inspired by the liquid biopsy/plasma analysis in the detection of circulating tumour DNA.  He explained, “This was mostly focused on the late stage of the disease, for the detection of residual tumour after surgery, and for the detection of metastatic disease. Using biobank materials from patients with long-term follow-up, it was possible to select patients to investigate this mutated DNA in both urine and plasma samples from patients that were initially diagnosed with early stage disease.”

Potential of the findings
If validated in larger cohorts, cell-free analysis of tumour DNA in urine and plasma may be used for monitoring disease aggressiveness in NMIBC, and may complement other standard urine tests for tumour detection.

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Get the rest of the essentials during Prof. Dyrskjøt’s highly-informative lecture on Friday, 15 November during the Plenary Session “Novelties in muscle-invasive bladder cancer”.

Explore the rest of the EMUC19 Scientific Programme for vital information on GU cancers. We look forward to welcoming you in Vienna!

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