Biomarkers for detection and surveillance of bladder cancer

Abstract

Introduction: Bladder cancer is the fourth most common cancer in men and the ninth most common cancer in women in Canada. Early detection of tumours is essential for improved prognosis and long-term survival. The standard method for detection and surveillance is cystoscopy together with urine cytology. Cystoscopy is relatively sensitive but is expensive and invasive. Urinary cytology is a noninvasive method that has poor sensitivity but high specificity; it is relied on for the detection of carcinoma in situ. Currently, several urinary based bladder tumour biomarkers with USFDA/Health Canada approval are available commercially, but none have been widely adopted by urologists despite their offering high sensitivity and/or specificity. We present here a review of recent studies evaluating 7 commercial biomarker assays for the detection and/or surveillance of bladder cancer.Results: Sensitivity and specificity ranges, respectively, for each marker were reported as follows: BTA Stat (Polymedco), 52.5%–78.0% and 69.0%–87.1%; BTA Trak (Polymedco), 51%–100% and 73%–92.5%; cytology, 12.1%–84.6% and 78.0%–100%; hematuria dipstick, 47.0%–92.6% and 51.0%–84.0%; NMP22 Bladder Cancer Test (Matritech), 34.6%–100% and 60.0%–95.0%; NMP22 BladderChek (Matritech), 49.5%–65.0% and 40.0%–89.8%;ImmunoCyt/uCyt+ (DiagnoCure), 63.3%–84.9% and 62.0%–78.1%; ImmunoCyt/uCyt+ and cytology, 81.0%–89.3% and 61.0%–77.7%; and UroVysion (Abbott Molecular)/florescence in situ hybridization, 68.6%–100% and 65.0%–96.0%.Conclusion: We find that no currently available bladder cancer urinary marker is sensitive enough to eliminate the need for cystoscopy. In addition, cytology remains integral to the detection of occult cancer. However, owing to their relatively high sensitivities, these markers may be used to extend the period between cystoscopies in the surveillance of patients with transitional cell carcinoma. Further study is required to determine which markers, alone or in panel, would best accomplish this.

NMP22 is predictive of recurrence in high-risk superficial bladder cancer patients

“…If tumour recurrence is detected during follow-up, the protocol is reset and patients will have to undergo surveillance every 3 months. 13 Although NMP22 has been approved for use in the detection of initial and recurrent bladder tumours, it has not been widely adopted. However, our data suggest that patients with high-risk superficial UCB who are NMP22 positive with negative cystoscopies are even more likely to recur than patients who are NMP22 negative.…”

Microdevices for Non-Invasive Detection of Bladder Cancer

“…For biomarkers that are typically present in the urine of healthy individuals and have elevated levels in bladder cancer patients, somewhat arbitrary choices of cut-off concentrations can lead to stark differences in medical decision-making. But on the other hand, allowing flexibility in the selection of cut-off values to account for different patient populations and medical practitioners inhibits the ability to accurately compare research results and evaluate device efficacy [117,118]. Variations in cut-off concentrations may drive potentially conflicting conclusions on the ability of a given device to accurately identify individuals with bladder cancer.…”

Disease map-based biomarker selection and pre-validation for bladder cancer diagnostic

“…Furthermore, it is a costly and invasive procedure which is unpleasant for patients, and carries an additional 10% risk of developing urinary tract infection (Budman et al, 2008;Shariat et al, 2008). Urine cytology has a higher specificity, ranging from 85 to 100%, but lacks sensitivity (13-75%), especially when it comes to the detection of low-grade tumors (van Rhijn et al, 2005).…”