ABSTRACT
To evaluate the long-term prognostic value of the combination of the EORTC risk calculator and proapoptotic, antiapoptotic, proliferation, and invasiveness molecular markers in predicting the outcome of intermediate- and high-risk non-muscle-invasive bladder cancer [NMIBC] treated with intravesical Bacille Calmette-Gurin [BCG] therapy. This study included 42 patients accrued prospectively presenting with intermediate- to high-risk NMIBC [high-grade T1 tumors or multiple rapidly recurrent tumors refractory to intravesical chemotherapy] treated with transurethral resection [TUR] and BCG. TUR samples were analyzed for the molecular markers p53, p21 waf1/cip, Bcl-2, CyclinD1, and metallothionein 9 [MMP9] using immunohistochemistry. Frequency of positivity, measured as a percentage, was assessed alone or in combination with EORTC risk calculator, for interaction with outcome in terms of recurrence and progression using univariate analysis and Kaplan-Meier survival curves. Median follow-up was 88 months [mean, 99; range, 14-212 months]. The overall recurrence rate was 61.9% and progression rate was 21.4%. In univariate analysis, CyclinD1 and EORTC risk groups were significantly associated with recurrence [P value 0.03 and 0.02, respectively], although none of the markers showed a correlation to progression. In combining EORTC risk groups to markers expression status, high-risk group associated with positive MMP9, Bcl-2, CyclinD1, or p21 was significantly correlated to tumor recurrence [log rank P values <0.001, 0.03, 0.02, and 0.006, respectively] and when associated with positive MMP9 or p21, it was significantly correlated to progression [log rank P values 0.01 and 0.04, respectively]. Molecular markers have a long-term prognostic value when combined with EORTC scoring system and they may be used to improve the predictive accuracy of currently existing scoring system. Larger series are needed to confirm these findings
ABSTRACT
Since the introduction of nerve-sparing radical prostatectomy [NSRP], there have been concerns about the increased risks of positive surgical margins [PSM] and biochemical progression [BP]. We examined the relationship of NSRP with PSM and BP using a large, mature dataset. Patients who underwent RP for clinically localized prostate cancer at our center between 1997 and 2008 were identified. Patients who received neoadjuvant therapy were excluded. We examined the relation of NSRP to the rate of PSM and BP in univariate and multivariate analyses adjusting for clinical and pathological variables including age, pretreatment prostate-specific antigen [PSA] levels and doubling time, and pathological stage and grade. In total, 856 patients were included, 70.9% underwent NSRP and 29.1% had non-NSRP. PSM rates were 13.5% in the NSRP group compared to 17.7% in non-NSRP [P=0.11]. In a multivariate analysis, non-NSRP was performed in patients with a higher pathological stage [HR 1.95, 95% CI 1.25-3.04, P=0.003] and a higher baseline PSA level [HR 1.04, 95% CI 1.01-1.08, P=0.005]. With a median follow-up of 41 months, BP-free survival was 88% for non-NSRP compared to 92% for the NSRP group [log rank P=0.018]; this difference was not significant in a multivariate Cox regression analysis [HR 0.54, 95% CI 0.28-1.06, P=0.09]. When used in properly selected patients, NSRP does not seem to increase the risk of PSM and disease progression. The most effective way of resolving this issue is through a randomized clinical trial; however, such a trial is not feasible