Prognostic effect of DNA aneuploidy from bladder washings in superficial bladder cancer.
BACKGROUND
Superficial (papillary) bladder cancer is associated with progression and death from muscle-invasive bladder cancer, but no reliable predictors of the outcomes have been identified.


METHODS
We analyzed the long-term prognostic effect of DNA flow cytometry in bladder washings from 93 subjects with previously resected T(a) and T(1) bladder tumors who participated in a chemoprevention trial of the synthetic retinoid fenretinide. Kaplan-Meier analysis and Cox regression were used to determine the prognostic effect of DNA aneuploidy on cancer progression and mortality in conjunction with conventional clinical factors after a median of 11.5 years (interquartile range, 9.5-11.7 years).


RESULTS
Overall, 58 of 93 (62%) specimens were DNA aneuploid at baseline. Progression-free survival was significantly shorter in subjects with stage T(1) [hazard ratio (HR), 31.6; 95% confidence interval (95% CI), 2.6-386.1; P < 0.001] and in subjects with baseline DNA aneuploid washing (HR, 10.5; 95% CI, 1.1-126.1; P = 0.03). The risk of death was also greater for stage T(1) tumors (HR, 2.6; 95% CI, 1.04-6.7; P = 0.04). DNA aneuploidy was a significant prognostic factor also for overall survival (HR, 2.8; 95% CI, 1.0-9.0; P = 0.05). Fenretinide treatment had no significant effect on cancer progression and death.


CONCLUSIONS
DNA aneuploidy in washings from endoscopically normal bladder is a significant predictor of progression and death in addition to tumor stage. This biomarker may help to identify and monitor a high-risk group who may benefit from a chemoprevention intervention.
Puntoni
Matteo
M
Division of Medical Oncology, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128 Genoa, Italy.
Zanardi
Silvia
S
Branchi
Daniela
D
Bruno
Silvia
S
Curotto
Antonio
A
Varaldo
Marco
M
Bruzzi
Paolo
P
Decensi
Andrea
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000032:analysis* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D017313:Fenretinide / Q000627:therapeutic use; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000517:prevention & control
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D017313:Fenretinide