Background: This study investigated whether a point-of-care proteomic test (NMP22® BladderChek® Test) in combination with cystoscopy could enhance detection of bladder cancer in diagnosis and surveillance patients.
Methods: Twenty-three academic, private practice and veterans hospitals in 10 states prospectively enrolled 1,331 patients at risk for bladder cancer and 668 patients with a history of bladder cancer. Patients provided a voided urine sample for analysis of NMP22 antigen and cytology prior to cystoscopy. Cytology was performed per the standard protocol of the facility and testing for the NMP22 marker was done in a blinded manner.
Results: Among the 1,331 patients screened, 79 had pathologically confirmed transitional cell carcinomas. Cystoscopy alone detected 86% (68/79) of the cancers, while the combination of cystoscopy with the NMP22 assay detected significantly more of the malignancies, 94% (74/79) (p=0.014). The NMP22 test was positive in 91% (10/11) of muscle invasive cancers, compared to 55% (6/11) by cystoscopy and 20% (2/10) by cytology. The NMP22 assay detected 79% (21/27) of the grade 3 cancers compared to 39% (10/26) with cytology. The point-of-care test was positive for 6 cancers not seen during initial cystoscopy: bladder Tis, T2, T3; ureter T2; renal pelvis T1, T3.
Among the 668 patients undergoing surveillance, 103 had recurrent tumors. Cystoscopy alone detected 91% (94/103) of the cancers, while the combination of cystoscopy with the NMP22 assay detected 99% (102/103) (p=0.005). For muscle invasive cancers, sensitivity of the point-of-care test combined with cystoscopy was 91% (10/11), compared to 64% (7/11) for cystoscopy alone. The NMP22 assay detected 8 out of 9 cancers that were not visualized during initial cystoscopy, of which 7 were high grade. The positive predictive value of the NMP22 assay and cytology were equivalent at 41%, but the NMP22 test had better negative predictive value at 91% than cytology did at 86% (p= 0.012) due to fewer false positives.
Conclusions: Combined with cystoscopy, the noninvasive point-of-care assay for elevated urinary NMP22 antigen significantly improves detection of transitional cell carcinoma with test results available during the patient visit. The test is CLIA waived, can be performed in any physician’s office, and is half the cost of voided cytology.