Individual risk assessment in bladder cancer patients based on a multi-marker panel.
OBJECTIVE
To investigate whether a combined application of urine cytology (CYT) and molecular markers for bladder cancer (BC) can predict tumor aggressiveness.


METHODS
The study comprised 2,113 patients who underwent urethrocystoscopy and transurethral resection of the bladder. CYT, fluorescence in situ hybridization (FISH), immunocytology (uCyt+) and nuclear matrix protein 22 test (NMP22-ELISA) were performed. Results of the individual tests and of a multi-marker panel were correlated with pT-stages and tumor grades.


RESULTS
Five hundred and two of 2,113 (23.8 %) patients had BC. False-negative test rates of CYT (p < 0.001), FISH (p = 0.01) and NMP22-ELISA (p = 0.05) were lower in patients with muscle-invasive BC compared with patients with non-muscle-invasive BC. Furthermore, false-negative rates of CYT (p < 0.001), FISH (p = 0.0002) and NMP22-ELISA (p < 0.001) were lower in patients with G3/CIS compared with patients with G1-G2 BC. In patients with evidence of tumor in urethrocystoscopy, the presence of simultaneously positive CYT and NMP22 was associated with a 20-fold risk for G3/CIS (p < 0.0001).


CONCLUSIONS
This is the first study investigating the combined use of four urine markers in addition to cystoscopy to predict tumor aggressiveness. Our results indicate that combined application of urine markers as an adjunct to cystoscopy may facilitate identification of patients harboring high-grade tumors.
Department of Urology, University Hospital Tuebingen, Tuebingen, Germany.
Tilman
T
Todenhöfer
Jörg
J
Hennenlotter
Stefan
S
Aufderklamm
Ursula
U
Kühs
Georgios
G
Gakis
Miriam
M
Germann
Arnulf
A
Stenzl
Christian
C
Schwentner
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000652:urine*; D015653:Cystectomy / Q000379:methods; D003558:Cystoscopy; D004797:Enzyme-Linked Immunosorbent Assay; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D016017:Odds Ratio; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000601:surgery / Q000652:urine*
D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C100379:nuclear matrix protein 22