Bladder cancer (BC) is a common malignancy, with an estimated 429,800 new cases and 165,100 deaths in 2012; worldwide. Urothelial carcinoma is the most common type of BC; it is stratified to non-muscular invasive bladder cancer (NMIBC) and muscular invasive bladder cancer (MIBC). Patients with MIBC have a high risk of disease progression and metastasis and usually, need aggressive treatments; such as radical cystectomy or chemotherapy; whereas NMIBC has a better prognosis and can be treated curatively by transurethral resection of bladder tumor (TUR-BT).
However, NMIBC has a high risk of recurrence and can progress to MIBC. To prevent recurrence and progression, intravesical instillation (IVI) of anthracycline or bacillus Calmette-Guérin (BCG) has administered; but about 50% still recur. As the treatment has not changed for decades, new studies leading to new treatments are to prevent recurrence and progression.
The Androgen receptor
Men tend to diagnosed about four times more often than women; which implies that BC is endocrine-related cancer. Androgen receptor (AR) signaling has suggested having an important role in BC occurrence and progression by previous studies. Thus, in this study, they assessed the correlation between NMIBC recurrence and tumor AR expression in Japanese patients; by quantifying AR mRNA expression with a real-time quantitative polymerase chain reaction (RT-qPCR).
The researcher retrospectively reviewed 53 specimens of non-metastatic NMIBC, with recurrence-free survival (RFS) as the primary endpoint. They used a real-time quantitative polymerase chain reaction to quantify AR mRNA expression. Kaplan–Meier product-limit estimators were used to assess RFS distribution, log-rank tests to analyze differences in RFS between high- and low-risk groups; multivariate analyses of AR mRNA expression and other clinicopathological factors to predict independent factors for RFS.
The high AR mRNA-expressing
The high AR mRNA-expressing group (n = 43) tended to have a longer median RFS (not reached); than did the low-AR group (n = 10; 9.04 months; P = 0.112). Multivariate analysis showed female sex (hazard ratio [HR]: 7.360, 95% CI: 1.649–32.856, P = 0.009), tumor size ≥3 cm (HR: 23.697, 95% CI: 4.383–128.117, P < 0.001) and low AR mRNA expression (HR: 0.202, 95% CI: 0.048–0.841, P = 0.028) to independent predictors of shorter RFS.
The study showed that low AR mRNA expression level is an independent risk factor for RFS in Japanese patients with NMIBC. Further studies are necessary but AR expression might be a new indicator of recurrence of NMIBC. Our study had several limitations. First, it was a retrospective study with relatively few patients and a short follow-up period. Second, CIS was not analyzed in this study.
CIS is an essential risk factor of recurrence and progression in NMIBC, but our study cohort had only two BCs with coexisting CIS. Finally, to verify the role of the AR pathway in NMIBC; not only AR mRNA expression levels but also protein expression levels should investigate in the current study. Future clinical studies would need to estimate an appropriate sample size to include enough of these patients and investigate mRNA; protein expression levels simultaneously.