This patient has an intermediate-risk tumour according to the EAU guidelines, as he has recurrent pTa LG NMIBC. The patient finds multiple cystoscopies burdensome.
Do the EAU guidelines support alternating a urinary biomarker with cystoscopy?
According to the EAU guidelines, surveillance with cystoscopy is still standard of care for NMIBC [1]. However, the EAU guidelines state that 4 promising and commercially available urinary biomarkers, Bladder EpiCheck, Cxbladder Monitor, ADXBLADDER and Xpert Bladder Cancer Monitor, although not tested in randomised controlled trials (RCTs), have such high sensitivities and negative predictive values (NPV) for high-grade (HG) disease that these biomarkers may approach the sensitivity of cystoscopy.
Therefore, these urinary biomarkers might be used to replace and/or postpone cystoscopy during surveillance as they may identify rare HG recurrences occurring in both low- and intermediate-risk NMIBC [1].
Additionally, cystoscopy is an invasive procedure that may cause significant anxiety and discomfort, thus negatively impacting the quality of life of Henry and his adherence to the follow-up schedule. An alternative surveillance schedule, in which a non-invasive urinary biomarker is alternated with cystoscopy can alleviate this burden by reducing the number of invasive procedures.
The EAU guidelines indicate that in patients initially diagnosed with Ta LG bladder cancer, a urinary marker or ultrasound of the bladder may be a mode of surveillance in case cystoscopy is not possible or refused by the patient [1].
Are all urinary biomarkers equal?
An independent systematic review and network meta-analysis reported on the pooled diagnostic values of the 4 EAU-recommended urinary biomarkers based on the individual validation studies [2,3].
Pooled sensitivity, specificity and NPV for NMIBC recurrence in all-risk patients of the EAU guideline-recommened markers [2,3]
Pooled diagnostic estimates were calculated from univariate statistics for 1,000 patients based on the pooled recurrence rate.
This study showed that Bladder EpiCheck has the highest sensitivity and NPV for detecting HG recurrences among the guideline-recommended tests [2,3].
The meta-analysis also demonstrated that per 1,000 patients, 740 cystoscopies could be avoided by using Bladder EpiCheck, and the low number of false positives ensures that only a limited number of patients will have unnecessary downstream cystoscopies (127 per 1,000 patients) [2,3].
Net benefits and interventions avoided with urinary biomarker tests during the follow-up of 1000 patients with NMIBC based on the pooled recurrence rate [2,3] 
These results indicate that the implementation of urinary biomarkers in the follow-up strategy of NMIBC patients could strongly decrease the number of invasive cystoscopies performed.
What is the impact on healtcare cost of alternating a urinary biomarker with cystoscopy?
The potential of urinary biomarkers in reducing the number of cystoscopies has an imporant impact not only on the patient’s quality of life and adherence to the follow-up schedules, but also on healthcare costs. A recent cost analysis study estimated a cost reduction of approximately 1.6 million euro/year in the Dutch healthcare system using a Bladder EpiCheck follow-up strategy (8%, 4%, 9% estimated cost reduction in low-, intermediate-, and high-risk patients, respectively) [4]. Importantly, the estimated delay in the detection of recurrent disease was small (3.9 months, 1.7 months, 1.3 months in low-, intermediate-, and high-risk patients, respectively).
Take away
Patients with intermediate-risk NMIBC deserve to be informed on urinary markers as an alternative in surveillance. Thanks to its high sensitivity and high NPV for detecting HG disease, and its high specificity, Bladder EpiCheck has the ability to reduce patient’s burden and potentially healthcare costs without compromising the early detection of HG recurrences.
References
- Gontero P, Compérat E, Escrig D et al. European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (TaT1 and CIS). Update March 2023. Available at: https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/
- Laukhtina E, Shim SR, Mori K, et al. Eur Urol Oncol 2021;4:927-42. PubMed
- Laukhtina E, Shim SR, Mori K, et al. Eur Urol Oncol 2022;5:480-1. PubMed
- Hekman MCH, Wijn SRW, Lotan Y, et al. World J Urol 2023;41:471-6. PubMed