D. Kakiashvili

A New and Highly Prognostic System to Discern T1 Bladder Cancer Substage

BACKGROUND Management of T1 bladder cancer (BCa) is controversial. OBJECTIVE Evaluate the impact of substage on the clinical outcome of T1 BCa. DESIGN, SETTING, AND PARTICIPANTS The T1 diagnosis of 134 first-diagnosis BCa patients from two university hospitals was confirmed. For the T1 substage, we used a new system that discerns T1-microinvasive (T1m) and T1-extensive-invasive (T1e) tumors. We then determined the invasion of the muscularis mucosae-vascular plexus (MM-VP): T1a (invasion above the MM-VP), T1b (invasion in the MM-VP), or T1c (invasion beyond the MM-VP). If the MM-VP was not present at the invasion front, the case was assigned to T1a or T1c. All patients were initially managed conservatively (with bacillus Calmette-Guérin). MEASUREMENTS Multivariable analyses for progression and disease-specific survival (DSS). RESULTS AND LIMITATIONS Median follow-up was 6.4 yr (interquartile range: 3.3-9.2 yr). Progression to ≥ T2 was observed in 40 patients (30%), and 19 patients (14%) died of BCa. The MM-VP was not present at the invasion front in 50 patients (37%). T1 substage was as follows: 40 T1m and 94 T1e; 81 T1a, 18 T1b, and 35 T1c. In multivariable analyses, substage (T1m/T1e) was significant for progression (p=0.001) and DSS (p=0.032), whereas substage according to T1a/T1b/T1c was not significant. Female gender (p=0.006) and carcinoma in situ (p=0.034) were also significant predictors of progression. The main limitation to the study is absence of a repeat transurethral resection. CONCLUSIONS Substage according to the new system (T1m and T1e) was user-friendly, possible in 100% of cases, and very predictive of T1 BCa behavior. Future studies may ultimately lead to the incorporation of this new substaging system in the TNM classification system for urinary BCa.

Non–Risk-Adapted Surveillance in Clinical Stage I Nonseminomatous Germ Cell Tumors: The Princess Margaret Hospital’s Experience

BACKGROUND Since 1981 Princess Margaret Hospital has used initial active surveillance (AS) with delayed treatment at relapse as the preferred management for all patients with clinical stage I nonseminomatous germ cell tumors (NSGCT). OBJECTIVE Our aim was to report our overall AS experience and compare outcomes over different periods using this non-risk-adapted approach. DESIGN, SETTING, AND PARTICIPANTS Three hundred and seventy-one patients with stage I NSGCT were managed by AS from 1981 to 2005. For analysis by time period, patients were divided into two cohorts by diagnosis date: initial cohort, 1981-1992 (n=157), and recent cohort, 1993-2005 (n=214). INTERVENTION Patients were followed at regular intervals, and treatment was only given for relapse. MEASUREMENTS Recurrence rates, time to relapse, risk factors for recurrence, disease-specific survival, and overall survival were determined. RESULTS AND LIMITATIONS With a median follow-up of 6.3 yr, 104 patients (28%) relapsed: 53 of 157 (33.8%) in the initial group and 51 of 214 (23.8%) in the recent group. Median time to relapse was 7 mo. Lymphovascular invasion (p<0.0001) and pure embryonal carcinoma (p=0.02) were independent predictors of recurrence; 125 patients (33.7%) were designated as high risk based on the presence of one or both factors. In the initial cohort, 66 of 157 patients (42.0%) were high risk and 36 of 66 patients (54.5%) relapsed versus 17 of 91 low-risk patients (18.7%) (p<0.0001). In the recent cohort, 59 of 214 patients (27.6%) were high risk and 29 of 59 had a recurrence (49.2%) versus 22 of 155 low-risk patients (14.2%) (p<0.0001). Three patients (0.8%) died from testis cancer. The estimated 5-yr disease-specific survival was 99.3% in the initial group and 98.9% in the recent one. CONCLUSIONS Non-risk-adapted surveillance is an effective, simple strategy for the management of all stage I NSGCT.

Surveillance in stage I nonseminomatous germ cell tumours of the testis

Germ cell tumours (GCTs) are the most common malignancy in men aged 15–34 years; it is estimated that 8090 men will be diagnosed with and 380 men will die from GCTs in 2008 in the USA [1]. In the UK, there were 2109 new cases of GCT diagnosed in 2005 and 78 deaths from testicular cancer in 2006 [2,3]. There is a geographical variation in the incidence of GCT. Within the European Union there is about a five-fold variation in incidence between countries with the highest and lowest rates. For example, Denmark, Germany and Austria report age-standardized rates of ≈ 10 per 100 000, while Lithuania, Estonia, Spain and Latvia have agestandardized rates of ≈ 2 per 100 000 [4]. More than half of GCTs present with clinical stage (CS) I disease, defined as those with the tumour markers α -fetoprotein, hCG and lactate dehydrogenase that are or become normal after orchidectomy with no evidence of metastatic disease on imaging studies. A third of nonseminoma GCTs (NSGCT) and 70–80% of seminomas present as CS I [5,6]. With appropriate therapy, the cure rate of patients with CS I NSGCT should be close to 100% [7–10].

Long-term prognostic value of the combination of EORTC risk group calculator and molecular markers in non-muscle-invasive bladder cancer patients treated with intravesical Bacille Calmette-Guérin

Background and Objectives: 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-Guérin (BCG) therapy. Materials and Methods: 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. Results: 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). Conclusion: 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.

299 ANDROGEN RECEPTOR (AR) AND BLADDER CANCER: A LARGE BI-INSTITUTIONAL STUDY ON 473 PATIENTS

S143 only in the Triton-insoluble fraction. Under non-reducing conditions, PRDX 1 and 6 were found as bands of high molecular weight (>170 kDa) in spermatozoa incubated with 0.35-5 mM H2O2 (strong oxidative stress). PRDX 6 became a strong single band due to a mild oxidative stress (0.05 mM H2O2, a condition that promotes sperm capacitation). H2O2 (0.35-5 mM) caused a decrease of the signal for PRDX 4 and 5 compared to non-treated cells. Conclusion: PRDXs are present in human spermatozoa and differentially modified by oxidative stress. These results suggest a role of PRDXs as antioxidants and as potential modulators of H2O2 action in human spermatozoa.