BACKGROUND: Bacillus Calmette-Guérin (BCG) is a standard treatment to reduce tumor recurrence and delay progression of high-risk non-muscle-invasive (NMI) bladder tumors.
However, it is not clear yet which patients are more likely to respond to BCG.
OBJECTIVE: The aim was to evaluate the role of polyamine-modulated factor-1 (PMF-1) methylation in predicting clinical outcome of T1 high-grade (T1HG) bladder tumors treated with BCG.
DESIGN, SETTING, AND PARTICIPANTS: In a retrospective design, PMF-1 methylation was analyzed on tumor specimens belonging to 108 patients with T1HG NMI bladder cancer undergoing BCG treatment. Median follow-up was 77 mo (range: 5-235 mo).
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PMF-1 methylation was assessed by methylation-specific polymerase chain reactions. Recurrence, progression into muscle-invasive tumors, and disease-specific survival rates were analyzed using competing risks regression analysis.
RESULTS AND LIMITATIONS: Among the 108 patients analyzed, 35 had recurring disease (32.4%), 21 progressed (19.4%), and 16 died of disease (14.8%); 71.3% of tumors had PMF-1 methylation. Univariate analyses using cumulative incidence curves revealed that an unmethylated PMF-1 was significantly associated with increased recurrence (p=0.026), progression (p=0.01), and shorter disease-specific survival (log-rank, p=0.03). Multivariate analyses indicated that among sex, age, focality, tumor size, and concomitant carcinoma in situ, only PMF-1 methylation provided significant hazard ratios (HRs) for recurrence of (HR: 2.032; p=0.042), and progression (HR: 2.910; p=0.020). Limitations of the study include its retrospective design, lymphovascular invasion status not available, short maintenance BCG, and that a second transurethral resection was not performed.
CONCLUSIONS: Epigenetic analyses revealed that the methylation status of PMF-1 was associated with the clinical outcome of patients with T1HG tumors undergoing BCG treatment. An unmethylated PMF-1 correlated to recurrence and progression in T1HG disease using univariate and multivariate analyses. Thus, assessing the methylation status of PMF-1 may serve to distinguish patients responding to BCG from those who may require more aggressive therapeutic approaches.
Written by:
Alvarez-Múgica M, Fernández-Gómez JM, Cebrian V, Fresno F, Escaf S, Sánchez-Carbayo M. Are you the author?
Tumor Markers Group, Molecular Pathology Program, Spanish National Cancer Center, Madrid, Spain; Urology Department, Hospital Valle del Nalón, Langreo, Spain.
Reference: Eur Urol. 2012 Jun 5. Epub ahead of print.
doi: 10.1016/j.eururo.2012.05.050
PubMed Abstract
PMID: 22682992
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