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Liquid biomarkers: What do we expect in the future?

Chaired by Prof. Lars Dyrskjøt (DK) and Prof. Arnulf Stenzl (DE), Plenary Session 7 was full of rapid-fire debate reviewing the use of liquid biomarkers in urothelial cancer, prostate cancer and kidney cancer.  This series of lectures focused on biomarkers in both blood and urine samples.

The session highlighted a number of patient cases, with each presenter reviewing the use of liquid biomarkers for tumour-agnostic and tumour-informed approaches, as well as sharing information on the latest novel intervention trials.  This article provides a selection of the information presented during the urothelial cancer presentation. To see the full session you can visit the EAU22 Resource Centre.

Prof. Dyrskjøt began with a brief overview on biomarkers: “One of the most interesting parts about circulating-tumour DNA (ctDNA) and cell-free DNA (cfDNA) is that it has a half-life of approximately two hours, which makes it possible to use it as a real time monitoring tool for measuring the amount of tumour in the body at any given time point. ctDNA is directly correlated with the invasiveness of the disease and tumour burden, as well as the tumour size, and it has the potential to be used throughout the disease course.”

According to Prof. Dyrskjøt, it can be used for cancer detection, screening and early diagnosis, molecular profiling or prognostication for surgery, using it for detection of residual disease after surgery, monitoring response during treatment, and also for monitoring clonal evolution after treatment resistance.


Prof. Jørgen Bjerggaard Jensen (DK) gave details and analysis on a 44-year old patient who had experience with the ctDNA dynamics in advanced bladder cancer. “Based on patients such as this, the Danish Bladder Cancer Group Study 14: Treatment Of Metastatic Bladder cancer at the time Of biochemical ReLApse following radical cystectomy (TOMBOLA) trial was designed. Hopefully these studies will show the true benefit of guiding treatment according to the ctDNA level in the future.”

In his lecture “Treatment monitoring of bladder cancer by urine testing”, Assoc. Prof. Joost Boormans (NL) talked about the unmet need in NMIBC to reduce the number of cystoscopies. “We do a lot of cystoscopies and the proportion of negative cystoscopies is high (no abnormal findings), cystoscopy is labour intensive, costly and operator-dependent. Could we replace cystoscopy by urine testing?”

According to Assoc. Prof. Boormans, the 2022 EAU Guidelines for surveillance of NMIBC  have included urine markers. “Four of the promising and commercially available urine biomarkers are Cxbladder Monitor, ADXBLADDER, Xpert Bladder Cancer Monitor and Bladder EpiCheck. Although not tested in RCTs, they have such high sensitivities and NPV’s for high-grade (HG) disease that these biomarkers may approach the sensitivity of cystoscopy. These four tests might be used to replace and/or postpone cystoscopy as they may identify the rare HG recurrences occurring in low/intermediate NMIBC.”


When drawing conclusions on urine markers for NMIBC , Prof. Boorman stated “ All reported studies have important limitations. Diagnostic performance assays are equal in moderate low-risk (LR) and intermediate-risk (IR) NMIBC. Sensitivity is better than cytology, especially in HG disease, specificity is less than cytology with high false positive rates, High NPV’s equals a reflection of low (HG) recurrence rates.

“For the future we must have prospective longitudinal clinical trials, pre-defined study population of LR, IR or HR NMIBC, SOC versus urine assay only/alternating, we need to look at diagnostic performance, cost and patient benefit”.

In his lecture “Is urine tumour DNA analysis in advanced disease informative?” Mr. Richard Bryan (GB) stated “Yes, urine-tumour DNA (utDNA) analysis in advanced disease is informative but it depends on the nature of the analysis or the gene panel used, and as we have heard, there are many different approaches to analysing tumour DNA in liquid biopsies. However, I do consider utDNA to faithfully recapitulate the mutations that will be found in the tumour itself.”

In conclusion

According to Prof. Dyrskjøt, the demonstration of clinical impact of ctDNA-based guidance is now needed. “We need to look at how we can improve overall survival. Can we improve quality of life? Can we reduce costs? The IMVIGOR 011 and TOMBOLA trials may provide answers to this. We must do the phase III trials.”

Prof. Dyrskjøt closed the session with the following: “we have seen multiple examples of promising biomarkers and liquid biopsies for different diseases. Multiple clinical trials are ongoing, and it’s going to be interesting to see in the coming years how we can actually get this approved for clinical use. We are probably not there yet for prime-time use”.