Athens, Greece (UroToday.com) In this debate, Dr. Renu Eapen recommended against the current use of urinary biomarkers in the management of bladder cancer. According to her, there has been a plethora of research and studies on potential urinary biomarkers that can be used in the treatment of bladder cancer. However, to date, none of the markers have been commonly adopted.
The ideal biomarker should be accurate, reproducible, fast and cheap. Unfortunately, to date, no marker has met these criteria.
There have been many reviews evaluating urinary biomarkers for bladder cancer. All show higher sensitivity than urine cytology, but all lack level 1 evidence of clinical benefit. It is unlikely that a single marker that meets all required attributed of a substantial marker exist, and it is more realistic that panels including several drivers from key pathways will likely hold promise. For a biomarker to be fully assimilated in standard care, it is not enough for it to show an association with the investigated outcome. The biomarker needs to improve clinical decision making in a cost-effective manner. It needs to show the superiority of a multivariable model over currently available techniques1.
The role of urinary biomarkers in screening is not clear. The effectiveness of screening programs is affected by the incidence and mortality of the disease. The low prevalence of bladder cancer – makes the role of screening unestablished. An additional limitation is that in high-risk populations the incidence is too low for broad screening to have an effect.
The role of urinary biomarkers in hematuria was discussed next. For microscopic hematuria we would ideally need a marker with very high specificity as the prevalence of the disease in the at-risk population is very low. For gross hematuria, the risk of bladder cancer is approximately 10% - the marker would need to show high sensitivity. Current biomarkers studied as potential adjuncts to cystoscopy are unlikely to impact diagnosis strategies. Lastly, prospective controlled trials are generally lacking, and there is no evidence that the use of biomarkers in screening/early detection has any impact on cancer-specific survival (CSS).
Next, Dr. Eapen discussed the potential role of biomarkers in replacing cystoscopy. For this to occur, urine biomarkers would need extremely high sensitivity and negative predictive value (NPV) to adequately replace cystoscopy. Various patient surveys have suggested that the required sensitivity would need to be as high as 95%.
Moving on to the role of biomarkers in surveillance, Dr. Eapen state that most single biomarkers have unsatisfactory performance, and the combination of markers is needed to improve the sensitivity. To date, there is simply insufficient evidence to suggest that urinary biomarkers can replace cystoscopy safely2. There is also a lack of evidence that there are any urinary biomarkers that have a substantial role in prognosis.
Specifically, the role of biomarkers in Bacillus Calmette-Guerin or BCG response has been studied as well. There has been some work done by Kamat et al. analyzing 143 patients during intravesical BCG therapy. FISH essays were collected and correlated with clinical outcomes of different points during treatment3. Patients with positive FISH were more likely to develop tumor recurrence than patients with negative FISH (46% vs. 10% at 6 weeks, and 57% vs. 8% at 3 months, p<0.001)3. However, according to Dr. Eapen these data still require external validation before utilized in a standard manner.
Even the current most commonly used urology guidelines state that none of the studied markers have been accepted for diagnosis or follow-up in routine practice or clinical guidelines (EAU guidelines). Furthermore, the EAU guidelines state that none of the currently available tests can replace cystoscopy in any constellation.
Due to these findings, Dr. Eapen concluded that to date, urinary markers are irrelevant in non-muscle invasive bladder cancer (NMIBC). There is a plethora of studies investigating the role of urinary biomarkers. No study has reached the required level of evidence of a change in clinical practice. Due to this, no marker is currently widely used or recommended in clinical practice. We need to await further studies assessing new markers and validation of previously studied markers before considering use.
Presented by: Renu Eapen, MD, Consultant Urologist in the Genitourinary Oncology service at the Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, New York, USA, Twitter: @GoldbergHanan at the 39th Congress of the Société Internationale d'Urologie, SIU 2019, #SIUWorld #SIU2019, October 17-20, 2019, Athens, Greece
References:
- Soria F, Krabbe L-M, Todenhöfer T, et al. Molecular markers in bladder cancer. World journal of urology 2019; 37(1): 31-40.
- Todenhöfer T, Hennenlotter J, Esser M, et al. Stepwise application of urine markers to detect tumor recurrence in patients undergoing surveillance for non-muscle-invasive bladder cancer. Dis Markers 2014; 2014: 973406-.
- Kamat AM, Willis DL, Dickstein RJ, et al. Novel fluorescence in situ hybridization-based definition of bacille Calmette-Guerin (BCG) failure for use in enhancing recruitment into clinical trials of intravesical therapies. BJU international 2016; 117(5): 754-60.