Use of CxBladder Monitor During the COVID-19 Pandemic Reduces Frequency of Surveillance Cystoscopy

The COVID-19 pandemic has brought about unprecedented changes in urologic care, including the need to find alternatives to traditional surveillance strategies for non-muscle invasive bladder cancer (NMIBC) in which cystoscopic examination usually plays a prominent role. With bladder cancer most frequently diagnosed in the 65-74 year-old age group, with a median age at diagnosis in the US of 73 years,¹ the bladder cancer patient population is one that is inherently apprehensive of the consequences of in-person interactions with physicians. Recent evidence suggests that even slight deviations or delays in surveillance may increase the risk of disease recurrence by 2-3-fold as well as the probability of progression by 6-7 fold.²

A number of non-invasive tests have been proposed to enhance surveillance capability for NMIBC without cystoscopy. One such test, CxBladder Monitor (Pacific Edge Diagnostics), is a commercially available, non-invasive, at-home urine test that evaluates the expression of five urinary mRNAs (insulin-like growth factor binding protein 5 [IGFBP5], homeobox protein Hox-A13 [HOXA13], midkine [MDK], cyclin-dependent kinase 1 [CDK1], and chemokine receptor type 2 [CXCR2]) and incorporates them into a mathematical algorithm that also includes clinical variables such as primary vs recurrent disease, and time since tumor occurrence, to generate a score to give a positive or negative result.³ CxBladder Monitor has an internally validated sensitivity of 93% with a negative predictive value (NPV) of 97%.⁴

Kevin D. Li, medical student researcher at University of California San Francisco (UCSF) School of Medicine presented the results of a single-site pilot study that showed how use of CxBladder Monitor reduces the intensity of surveillance cystoscopies in NMIBC patients.⁵ During March- June 2020, 56 patients with NMIBC due for surveillance cystoscopy were offered CxBladder Monitor testing prior to scheduling their cytoscopy appointment. Inclusion criteria for the study included time from diagnosis >6 months or > 9 months from a recurrent diagnosis, and >6 weeks from BCG or immunotherapy. The majority of patients (42, 75%) were male, their median age was 72 years, and the median time since initial diagnosis was 4 years. By AUA risk stratification, 20 patients were deemed high, 17 intermediate, and 14 low risk.

Among the 56 patients with CxBladder Monitor scores, 17 had a suspicious result (score ≥3.5) that required immediate cystoscopy, of whom 7 had cystoscopic findings requiring biopsy. Four patients exhibited positive cytology, including one patient with upper tract urothelial carcinoma. Of 35 patients who delayed cystoscopy, 34 had no findings on subsequent cystoscopy and 1 patient died from an unrelated cause.

Patients were sent a survey about the ease, cost, and usability of CxBladder Monitor, to which 41 patients (73%) responded.   Patients overwhelmingly found the test easy to use (median score 5/5, where 5 was easiest) and for most patients (26/29, 90%) the cost of the test was completely covered by insurance. Most patients (26/41, 73%) said that they would choose the test again in place of a surveillance cystoscopy.

The UCSF researchers concluded that their experience with CxBladder Monitor led to a reduction in the intensity of surveillance cystoscopy with high patient satisfaction and low out-of-pocket costs. Sensitivity and NPV in this pilot study were 100%, comparable with that seen in other studies, they noted. They also highlighted the position of CxBladder Monitor in the era of COVID-19. where patients and physicians are increasingly relying on telemedicine and working remotely. Overall, they believe that CxBladder Monitor is “emblematic of a new normal” in urology.

References

1. NCI-National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Bladder Cancer. https://seer.cancer.gov/statfacts/html/urinb.html Accessed December 3, 2021.
2. Culpan M, Keser F, Acar HC,, et al. Impact of delay in cystoscopic surveillance on recurrence and progression rates in patients with non-muscle invasive bladder cancer during the COVID-19 pandemic. Int J Clin Pract. 2021;75(9):e14490. DOI: 10.1111/ijcp.14490
3. Lough T, Luo Q, O’Sullivan P, et al. Clinical utility of Cxbladder monitor for patients with a history of urothelial carcinoma: a physician–patient real-world clinical data analysis. Oncol Ther. 2018;6(1):73-85. DOI: 10.1007/s40487-018-0059-5
4. Kavalieris L, O’Sullivan P, Frampton C, et al. Performance characteristics of a multigene urine biomarker test for monitoring for recurrent urothelial carcinoma in a multicenter study. J Urol. 2017;197(6):1419-1426. DOI: 10.1016/j.juro.2016.12.010
5. Li K, Chu C, Meng M, Porten S. Use of CxBladder monitor during the COVID-19 pandemic to reduce the frequency of surveillance cystoscopy. Poster #84 presented at the 22nd Annual Meeting of the Society of Urologic Oncology (SUO), December 1-3, 2021, Orlando, FL.