medwireNews: A two-tiered screening approach comprising dipstick testing for hematuria followed by testing for molecular markers of bladder cancer (BCa) may significantly reduce the number of men who are referred for cystoscopy compared with dipstick testing alone, show study findings.
However, the screening program also had a low diagnostic yield in the individuals tested, which included nonselected, asymptomatic European males.
"Although the use of molecular markers reduced the number of cystoscopies performed for microhematuria evaluation, very few urothelial tumors were diagnosed in this protocol (0.23%)," write Monique Roobol (Erasmus University Medical Center, Rotterdam, the Netherlands) and colleagues.
The researchers say, however, that the two-tiered screening approach may still be of value in diagnosing selected, high-risk patients.
In an analysis of the Bladder Cancer Urine Marker Project (BLU-P), the researchers found that of 1747 men who underwent hematuria testing, 1338 (76.6%) tested negative for hematuria, while 409 (23.4%) tested positive, including 203 (49.6%) with trace hematuria and 206 (50.4%) with more significant hematuria.
Of the 409 men who tested positive for hematuria, 385 (94.1%) underwent molecular marker testing, in which 14 (3.6%) tested positive for nuclear matrix protein 22 (NMP22), 33 (8.6%) positive for microsatellite analysis (MA), six (1.6%) positive for fibroblast growth factor receptor 3 (FGFR3), and 40 (10.4%) positive for peaks on multiplex ligation-dependent probe amplification (MLPA).
On the basis of positive hematuria and molecular testing, cystoscopy was recommended for 75 individuals, of whom 71 underwent the procedure.
As reported in European Urology, four BCas and one kidney urothelial tumor were detected through screening.
The team found that for significant hematuria by dipstick testing, the specificity for detecting BCa was 88.4% and the positive predictive value (PPV) was 1.9%.
For any positive molecular test, the specificity was 95.9%, while the PPV was 5.3%. And for the individual tests, the PPV was also poor, at 7.7%, 6.1%, 20.0%, and 2.5% for markers NMP22, MA, FGFR3, and MLPA peaks, respectively.
"An increasing number of new BCa markers have been recently identified, and there is a great need for additional data on the integration of these markers in clinical paradigms," write Roobol et al. "Our study did not find utility in population-based BCa screening through home dipstick testing and molecular markers."
However, the researchers say: "It should be noted that screening for BCa may have different performance characteristics in selected high-risk populations, such as those with aristolochic acid nephropathy or occupational exposures."
Additional research should still therefore be conducted to evaluate the performance of a two-tier screening protocol in selected high-risk individuals, they conclude.