Despite the development of a plethora of molecular urine markers, repetitive cystoscopy (WLC) and urine cytology remain the mainstay of surveillance in patients with high-risk (HR) non-muscle-invasive bladder cancer (NMIBC) [1,2]. However, WLC is invasive and has side effects like hematuria or urinary tract infection; it triggers anxiety among patients and imposes relevant costs to health care systems [3], [4], [5], [6].

In this context, it is of key importance to understand that WLC, the so called “gold standard,” has limitations: several studies and respective systematic reviews demonstrate that the sensitivity (Se) of WLC, routinely conducted as an office cystoscopy, will not exceed 75% in recurrent NMIBC if compared with blue light cystoscopy and subsequent TUR-B [7,8].

So far, urine markers may be used as an adjunct to routine follow-up to improve the sensitivity of WLC and, in consequence, improve early detection [9]. Based on respective analyses [10], [11], [12], the current EAU guideline concludes that some urine markers may have the performance to replace and/or postpone WLC in surveillance of low/intermediate risk NMIBC [1]. However, this statement has not validated by randomized controlled trials (RCTs), so far, and a detailed recommendation of a procedure is missing.

A marker-guided follow-up restricting WLC to patients with a positive urine marker test would represent a concrete scenario aiming at a decrease of the diagnostic workload [13] (Fig. 1). Combinations of marker-guided follow-up with a reduced number of WLCs might be another option (e.g., CeFub, SEALS Xpert trial) [14], [15], [16].

This simulation analyzes if and how a use of urine markers may contribute to and affect the follow-up of patients with HR NMIBC. This question has gained new interest with the advent of the recent modification of the EAU risk classification [1]. Regrouping of the small group of very HR tumors as a separate category dramatically lowers tumor progression rates in the new HR group [17] and requires reconsideration of the current surveillance.

The aim of this study was to assess the potential impact of modern commercial urine markers in the management of patients with HR NMIBC considering different surveillance strategies. Based on reported results on tumor recurrence and marker performance, we simulated the consequences regarding diagnosis of tumor recurrence and frequency of WLC for different strategies over a 1-year interval.