Primary Superficial Bladder Cancer Research Articles

Metastatic seminoma in a 77-year-old man with a regressed primary tumour and concurrent high-grade superficial bladder cancer

Metastatic seminoma in a 77-year-old man with a regressed primary tumour and concurrent high-grade superficial bladder cancer

Expression of aquaporins 3 in low grade risk of recurrence primary bladder cancer.

Bladder cancer (BC) is one of the most frequent malignancy of the urinary tract. Recent studies demonstrated the role of aquaporins urothelial tumor cells (AQPs) as potential prognostic factor for tumor progression and invasion. In this study we investigated the AQP3 expression levels inside primary superficial (pTa) low grade bladder cancer, correlating with pathological parameters and clinical outcomes. We retrospectively analyzed tumor samples of 66 patients with diagnosis of superficial urothelial (pTa) bladder cancer between 1997 and 2007. All patients underwent transurethral bladder resection (TURB) and immediate single instillation of mitomycin C. All tumors samples were blindly reviewed by two expert anatomopathologists and only pTa low grade urothelial bladder cancer were included. Cancer recurrence was defined as the detection of bladder lesions during follow-up cystoscopy. AQP3-immunoreactive areas detected at immunohistochemical analysis were classified as AQP3 positive. Of these 60.6% of patients was detected as negative for AQP3 expression. Forty-two patients develop cancer recurrence during follow-up with a mean progression free survival of 16.44 months. The absence of reaction for AQP3 was observed 56% (9/16) tumor grading G1 and 62% (31/50) tumor grading G2. No correlation was observed with sexual gender, grading of tumor differentiation, and recurrence of cancer disease. Kaplan-Meier curves of disease-free survival (DFS) showed a significant separation (p = 0.028) between patients AQP3-positive and AQP3-negative. It was observed a mean DFS of 23.83 and 14.43 months respectively in absence and presence of AQP3 expression. AQP3 expression is related to disease-free interval (DFI) and the absence of AQP3 expression correlates with a late relapse. The expression of AQP3 does not provide a reproducible quantitative aspect. AQP3 are not suitable to forecast tumor cell behavior but they perform a role as regulator for tumor cell homeostasis and for additional therapeutic developments.

Multiplex Protein Signature for the Detection of Bladder Cancer in Voided Urine Samples

Accurate urine assays for bladder cancer detection would benefit patients and health care systems. Through extensive genomic and proteomic profiling of urine components we previously identified a panel of 8 biomarkers that can facilitate the detection of bladder cancer in voided urine samples. In this study we confirmed this diagnostic molecular signature in a diverse multicenter cohort. We performed a case-control, phase II study in which we analyzed voided urine from 102 subjects with bladder cancer and 206 with varying urological disorders. The urinary concentration of 8 biomarkers (IL-8, MMP-9 and 10, PAI-1, VEGF, ANG, CA9 and APOE) was assessed by enzyme-linked immunosorbent assay. Diagnostic performance of the panel of tested biomarkers was evaluated using ROCs and descriptive statistical values, eg sensitivity and specificity. Seven of the 8 urine biomarkers were increased in subjects with bladder cancer relative to those without bladder cancer. The 7 biomarkers were assessed in a new model, which had an AUROC of 0.88 (95% CI 0.84-0.93), and 74% sensitivity and 90% specificity. In contrast, the sensitivity of voided urine cytology and the UroVysion® cytogenetic test in this cohort was 39% and 54%, respectively. Study limitations include analysis performed on banked urine samples and the lack of voided urine cytology and cytogenetic test data on controls. The study provides further evidence that the reported panel of diagnostic biomarkers can reliably achieve the noninvasive detection of bladder cancer with higher sensitivity than currently available urine based assays.

Frequency of Tumor Recurrence: A Strong Predictor of Stage Progression in Initially Diagnosed Nonmuscle Invasive Bladder Cancer

Patients with nonmuscle invasive bladder cancer usually experience multiple instances of tumor recurrence until stage progression occurs. However, it has not yet been fully evaluated whether the timing and/or pattern of tumor recurrence could affect subsequent stage progression. We examined whether the frequency of tumor recurrence provides additional predictive information concerning stage progression. A total of 484 patients with initially diagnosed nonmuscle invasive bladder cancer were identified between 1985 and 2006 at our institution. Median followup was 7.2 years. Frequency of tumor recurrence was analyzed to determine if it affected subsequent stage progression. Of these patients 40 (8.3%) experienced stage progression during followup. Using Kaplan-Meier analysis subsequent stage progression could be most strongly predicted in patients with a recurrence rate of 1 or more per year during the first 2 years, although similar results were observed for various cutoff periods and recurrence rates. The 10-year progression-free survival rate was 58.0% in patients with a recurrence rate of 1 or more per year and 93.3% in their counterparts (p <0.001). Multivariate analysis demonstrated that the appearance of tumor grade 3 (p = 0.027, risk ratio 2.36), carcinoma in situ (p = 0.045, risk ratio 2.44) and a recurrence rate of 1 or more per year during the first 2 years (p <0.001, risk ratio 7.40) were independent risk factors for subsequent stage progression. Frequency of tumor recurrence is a strong predictor of subsequent stage progression in patients initially diagnosed with nonmuscle invasive bladder cancer. More appropriate followup and aggressive treatment due to a higher malignant potential for stage progression might be recommended in patients with a recurrence rate of 1 or more per year during the first 2 years.

Should Patients With Primary Upper Urinary Tract Cancer Receive Prophylactic Intravesical Chemotherapy After Nephroureterectomy?

We assessed the efficacy of prophylactic intravesical chemotherapy for primary upper urinary tract urothelial cancer after nephroureterectomy during long-term followup. From January 1985 to June 2007, 196 patients with primary upper urinary tract urothelial cancer were included in this study. Patients were divided into group 1-31 who received intravesical epirubicin instillation, group 2-27 who received intravesical mitomycin C instillation and group 3-138 who did not receive prophylactic instillation after nephroureterectomy. We compared the bladder tumor recurrence rate, number of recurrence episodes, time to first bladder tumor recurrence, tumor type, percent of patients with cystectomy and percent who died of urothelial cancer, and the recurrence-free survival rate. Of the 196 patients 73 had subsequent bladder recurrence at a mean followup of 55.6 months. There were no significant differences in recurrence type, mean number of bladder tumor recurrences, percent of patients with cystectomy and the cancer specific survival rate. The bladder recurrence rate was lower in group 1 and 2 than in group 3. Mean time to first bladder tumor recurrence was longer in groups 1 and 2. Kaplan-Meier curves of recurrence-free survival rates were significantly increased in groups 1 and 2. Intravesical instillation of epirubicin or mitomycin C appears to be well tolerated and effective for preventing bladder recurrence and prolonging time to first bladder recurrence. Patients should receive prophylactic intravesical chemotherapy after nephroureterectomy.

Distinctive Expression Pattern of ErbB Family Receptors Signifies an Aggressive Variant of Bladder Cancer

Expression of various members of the ErbB family (epidermal growth factor receptor/ErbB-1, ErbB-2, ErbB-3 and ErbB-4) is associated with disease stage and survival in patients with urothelial carcinoma. We examined the correlation of ErbB family receptor expression with the progression of urothelial carcinoma and survival. A urothelial carcinoma tissue array was constructed from 248 archival paraffin blocks and quality control studies were ascertained. The tissue microarray was stained for epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4, and analyzed using an automated reader. Patient data included grade, stage, growth pattern, recurrence and survival. Kaplan-Meier estimates of 5-year overall and recurrence-free survival were 58% and 27%, respectively. Patients with high grade, invasive or nonpapillary disease had a worse prognosis than patients with low grade, superficial or papillary disease (p <0.0001). High epidermal growth factor receptor or low ErbB-4 expression was associated with nonpapillary, high grade and invasive tumors as well as with significantly shorter recurrence-free and overall survival (p <0.002, 0.028 and 0.047, respectively). Levels of ErbB-2 and ErbB-3 expression were not associated with overall or recurrence-free survival. The expression profiles of ErbB-4 and epidermal growth factor receptor are prognostic in urothelial carcinoma. They may help in selecting patients at high risk with bladder cancer for more aggressive therapy.

A Single Instillation of Epirubicin After Transurethral Resection of Bladder Tumors Prevents Only Small Recurrences

We studied whether a single instillation of epirubicin after transurethral bladder tumor resection would influence the interval to and size of the first recurrence. A total of 404 patients from 13 hospitals were randomized to 1 instillation of 50 mg epirubicin or placebo within 6 hours after transurethral resection of bladder tumors. Of 155 evaluable patients in the epirubicin group 79 (51.0%) had recurrence compared to 95 of 152 (62.5%) in the placebo group (p = 0.04). Of the recurrences 63.3% were small (1 to 5 mm). Tumor size was unknown in 5 patients. Of 79 patients with recurrence in the epirubicin arm 33 (42.9%) vs 29 (31.5%) of 95 in the placebo arm had larger (more than 5 mm) first recurrences (p = 0.12). Approximately half of the patients with first recurrences were treated as outpatients and the other half spent a total of 145 days in the hospital with no difference between the groups. We confirmed the results of previous studies showing that 8.5 patients must be treated with a single instillation to prevent 1 recurrence. Furthermore, our data may indicate that only small recurrences are prevented, which could easily be fulgurated using local anesthesia at followup cystoscopy. The benefit of single instillations can be questioned if this finding is confirmed by others.

XIAP as a prognostic marker of early recurrence of nonmuscular invasive bladder cancer

Dysregulation of apoptosis has been implicated not only in carcinogenesis and tumor progression but also in tumor recurrence. We investigated whether the expression of X-linked inhibitor of apoptosis (XIAP) might predict early recurrence in patients with non-muscular invasive bladder cancer. The cohort comprised 176 consecutive patients with primary superficial bladder cancer treated with transurethral resection. Immunohistochemical staining using the standard avidin-biotin-peroxidase technique and RT-PCR were used to detect XIAP protein and mRNA expressions in cancer tissues. The relationship between XIAP expression and clinicopathological characteristics, cancer recurrence were analyzed. XlAP expression was observed in 108 cases (61.4%) and no expression in 68. There was no correlation between XIAP expression rate and the tumor pathological grade, but was an apparent trend toward the increased XIAP levels from well (G1) to poor (G3) differentiated cancer. Eighty-two (46.6%) patients experienced tumor recurrence at a mean of 28.6 months of the follow-up; 66 of them expressed XIAP (61.1%) and 16 were XIAP negative (23.5%). Twelve patients presented with invasive disease at the time of relapse and all of them expressed XIAP. Patients without XIAP expression or with low tumor grades had significantly higher recurrence-free survival than those with XIAP expression (log rank test P = 0.0015) or high tumor grades (log rank test P < 0.001). Multivariate analysis revealed that XIAP expression, tumor grade, and tumor number were independent predictors for the recurrence of non-muscular invasive bladder cancer (P = 0.004, 0.016, and 0.043, respectively). XIAP may be considered as a new independent prognostic marker for early recurrence of non-muscular invasive bladder cancer.

Thymidine phosphorylase expression as a prognostic marker for predicting recurrence in primary superficial bladder cancer

No prognostic marker for predicting recurrence in primary superficial bladder cancer has been established. The aim of this study was to investigate the expression levels of thymidine phosphorylase (TP) by enzyme-linked immunosorbent assay (ELISA) and the immunohistological localization of TP in primary superficial bladder cancer tissue to assess its association with tumor recurrence and stage progression as well as the pathological parameters of the tumor. TP expression in cancer tissues from 77 patients was measured by sandwich-type ELISA. Clinicopathological factors and the clinical prognosis were examined in relation to the expression levels of TP. To clarify the clinicopathological implication of TP localization in primary superficial bladder cancer tissue, the immunohistochemically determined TP expression was assessed for histological grades 1-3. The TP expression in primary superficial bladder cancer significantly increased with the histological grade and stage. The TP expression in patients with a shift to invasive cancer was significantly higher than in those without invasive cancer. Patients with low TP expression had a significant longer postoperative tumor-free period than those with high TP expression (P=0.011). High TP expression was an independent prognostic factor for tumor recurrence (P=0.0441). Strong immunoreactivity for TP was observed in the cytoplasms of tumor cells and vascular endothelial cells. This study suggests that elevated TP expression may be a prognostic marker for predicting recurrence in primary superficial bladder cancer, and that high TP expression may be associated with the marked proliferation of tumor cells and increased vascular endothelial cells, showing strong immunoreactivity for TP.

Multivariate Analysis of Clinical Parameters of Synchronous Primary Superficial Bladder Cancer and Upper Urinary Tract Tumor

Multivariate Analysis of Clinical Parameters of Synchronous Primary Superficial Bladder Cancer and Upper Urinary Tract Tumor

MULTIVARIATE ANALYSIS OF CLINICAL PARAMETERS OF SYNCHRONOUS PRIMARY SUPERFICIAL BLADDER CANCER AND UPPER URINARY TRACT TUMOR

We determined the incidence and characteristic of synchronous upper urinary tract tumors (UUTTs) in patients with primary superficial bladder carcinoma and evaluated the characteristics of bladder tumors related to UUTTs. We performed a retrospective study of 1,529 patients with primary superficial bladder carcinoma who underwent initial examination of the upper urinary tract with excretory urography. Data were analyzed by multivariate analysis using logistic regression. Variables evaluated and related to the incidence of UUTT were multiplicity, carcinoma in situ, bladder tumor size, localization of tumor in the bladder, and tumor grade and stage. A total of 28 patients (1.8%) had simultaneous bladder tumor and UUTT. UUTTs showed no preferred location and 17.9% were multiple. Of UUTTs 46% were invasive and almost 87% were grade 2 or 3. The only significant variable related to UUTT was bladder tumor in the trigone (RR 5.8, 95% IC 2.18 to 15.9, p <0.0005). Of 147 tumors located in the trigone 11 (7.5%) were associated with UUTT, corresponding to 41% of the UUTTs first diagnosed. If multiplicity and tumors in the trigone (551 cases) had been considered, 66.7% of tumors would have been diagnosed. Synchronous UUTT and superficial bladder tumor are uncommon but 46% are invasive. Considering the possible examination of the upper urinary tract only in patients with tumor in the trigone or with multiple bladder tumors 41.4% or 69% of UUTTs, respectively, would have been diagnosed. Patients with tumor in the trigone are at almost 6-fold higher risk for a synchronous tumor in the upper urinary tract.

A SURVEILLANCE SCHEDULE FOR G1Ta BLADDER CANCER ALLOWING EFFICIENT USE OF CHECK CYSTOSCOPY AND SAFE DISCHARGE AT 5 YEARS BASED ON A 25-YEAR PROSPECTIVE DATABASE

In the absence of clear evidence, surveillance of low grade superficial bladder cancer by regular check cystoscopy may continue unnecessarily, or discharge from followup may occur empirically. We review the followup during a prospective 25-year period of patients presenting with G1Ta bladder cancer, and it is this analysis on which we base a safe schedule for discharge. A prospectively kept, computerized record of bladder cancers diagnosed between 1978 and 1985 and subsequently followed up at the Western General Hospital, Edinburgh was reviewed. A total of 115 patients with G1Ta disease were followed for a mean of 19.4 years. Tumor status at 3 months was the strongest prognostic factor for recurrence. Although the absence of tumor at 1 year was also a favorable prognostic sign, it was not for 5 years that the situation entirely stabilized (recurrence developed in 8 of 66 such patients between 1 and 5 years). Of those who did not have recurrence in 5 years, 98.3% patients remained tumor-free for 20 years. In contrast in those with recurrence at 3 months the recurrence rate was much higher. Overall 12% of patients experienced progression, mostly in year 1. None of the 8 who had their first recurrence after year 1 had disease progression. Patients with G1Ta disease who are free of recurrence for 5 years after presentation can be safely discharged. We propose to alter the regime for patients with no recurrence in year 1 and discharge them at 5 years.

APOPTOSIS AND CHEMOTHERAPY FOR BLADDER CANCER

We discuss the role of apoptosis, that is gene directed self-destruction of a cell, in the response of bladder transitional cell carcinoma cells to chemotherapy. A directed MEDLINE literature search of apoptosis, bladder cancer and chemotherapy was performed to extract relevant information for review. The characteristics of apoptotic cells were defined and the methods in common use to detect these traits is described. The role of the key mediators of the apoptotic process in bladder cancer is discussed in the context of chemosensitivity and disease stage. The importance of the apoptosis induction after chemotherapy is highlighted. On stimulus by appropriate external or internal signals a cell may alter the expression of genes encoding for proteins associated with the apoptotic process. The development of apoptosis depends on the balance between pro-apoptotic and anti-apoptotic proteins. Key alterations in genes and proteins related to apoptosis within bladder cancer result in a shift away from the default state of apoptosis toward a cell with increased survival properties that is chemoresistant. Much current research in bladder cancer is aimed at restoring chemosensitivity by shifting the cell toward a pro-apoptotic phenotype. Successful translation of this work into clinical practice may improve survival in patients in whom prognosis is currently poor.

Clinical study of G3 superficial bladder cancer without concomitant CIS treated with conservative therapy.

The treatment for superficial G3 transitional cell carcinoma (TCC) of the urinary bladder remains controversial. It is important to reveal the clinical features of superficial G3 bladder cancer that can be treated conservatively. A total of 39 patients with primary superficial bladder cancer (Ta, T1) with G3 components but without concomitant carcinoma in situ (CIS), who had been treated initially with transurethral resection (TUR), were retrospectively analyzed for factors related to tumor recurrence, progression and survival. The patients were 34 males and five females whose age ranged from 49 to 85 years (average, 68 years). Initial tumor stages were Ta in one patient and T1 in 38. Initial treatments were TUR alone in 18 patients and TUR with adjuvant therapy (intravesical chemotherapy or BCG therapy) in 21. Factors examined included age, gender, morphology, size and number of tumors and adjuvant therapies. Follow-up periods were 3-138 months (median, 37 months). Tumor recurrence, progression and cancer death were observed in 23, seven and four cases, respectively. The 5-year progression-free rate (75%) and survival rate (83%) in 39 patients with G3 did not show a statistically significant difference from those of the 109 patients with G1 or the 187 patients with G2 superficial bladder cancer who were treated with TUR initially. Only the rate of recurrence of patients with G3 was significantly higher than that of patients with G2 or G1. Adjuvant therapies reduced the recurrence rate of the patients with G3. Only tumor morphology, papillary or non-papillary, affected both the progression-free rate and the survival rate of patients with G3. There were no statistically significant differences associated with other factors. The results suggest that superficial G3 bladder cancer could be treated with TUR initially, especially for papillary tumors.

Perioperative Single Dose Instillation of Epirubicin or Interferon-α After Transurethral Resection for The Prophylaxis of Primary Superficial Bladder Cancer Recurrence: A Prospective Randomized Multicenter Study—Finnbladder III Long-Term Results

We evaluated the long-term efficacy of a single dose of interferon or epirubicin administered immediately after transurethral resection compared with transurethral resection alone for primary superficial bladder cancer recurrence. A total of 200 patients with primary superficial stages Ta to T1, grades 1 to 3 bladder cancer were randomized into 3 treatment groups, including transurethral resection alone, transurethral resection plus 50 milliunits interferon-alpha2b and transurethral resection plus 100 mg. epirubicin. The primary end point was time to first recurrence. At a median followup of 72 months we observed a sustained effect of a single epirubicin instillation compared with other treatments. To date only 46% of the patients in group 3 have experienced recurrence in contrast to 73% and 68% in groups 1 and 2, respectively (p = 0.002). At 72 months the Kaplan-Meier disease-free estimates were 24%, 31% and 51% in groups 1 to 3, respectively (p = 0.002). The Cox multivariate model revealed a more than 2-fold relative risk of recurrence in group 1 versus group 3 (p <0.001). Other significant variables predicting recurrence were grade and the number of tumors. A single perioperative instillation of 100 mg. epirubicin causes a significant and sustained decrease in primary superficial bladder cancer recurrence, whereas a single dose of 50 milliunits interferon-alpha2b is ineffective for prophylaxis.

Perioperative Single Dose Instillation of Epirubicin or Interferon-?? After Transurethral Resection for The Prophylaxis of Primary Superficial Bladder Cancer Recurrence: A Prospective Randomized Multicenter Study???Finnbladder III Long-Term Results

Perioperative Single Dose Instillation of Epirubicin or Interferon-?? After Transurethral Resection for The Prophylaxis of Primary Superficial Bladder Cancer Recurrence: A Prospective Randomized Multicenter Study???Finnbladder III Long-Term Results

Transurethral Resection For Bladder Cancer Using 5-Aminolevulinic Acid Induced Fluorescence Endoscopy Versus White Light Endoscopy

Endoscopy done under fluorescence induced by 5-aminolevulinic acid has proved to be a procedure with high sensitivity for detecting transitional cell carcinoma of the bladder. In this multicenter, parallel group, phase III study we compared 5-aminolevulinic acid fluorescence endoscopy guided transurethral bladder resection with transurethral bladder resection done using only white light endoscopy. The proportion of tumor-free resected cases in the 2 groups was evaluated. After patient stratification according to participating centers and European Organization for the Research and Treatment of Cancer risk score 65 and 64 were randomized to the 5-aminolevulinic acid fluorescence and white light endoscopy groups, respectively. Residual tumor was evaluated in the 2 groups by repeat transurethral resection 10 to 14 days later. Analysis was performed according to the intent to treat principle with all patients randomized, followed by per protocol analysis. Intent to treat analysis revealed that in the white light endoscopy group 40.6% of cases were resected tumor-free at primary resection, whereas with 5-aminolevulinic acid fluorescence endoscopy guided transurethral resection 61.5% were resected tumor-free (p <0014). On protocol analysis 46.9% patients in the white light and 67.3% in the 5-aminolevulinic acid fluorescence endoscopy groups were resected tumor-free (p <0.031). No difference was noted in the 2 groups in regard to side effects or laboratory findings. The risk of residual tumor after transurethral resection of transitional cell carcinoma is significantly decreased by 5-aminolevulinic acid fluorescence endoscopy.

The significance of random bladder biopsies in superficial bladder cancer.

Today, there is no consensus about taking random bladder biopsies during transurethral resection of superficial bladder tumors for staging and to determine the urothelial abnormalities like dysplasia and carcinoma in situ. The aim of our study was to evaluate the results and indications of random bladder biopsies for primary superficial bladder cancer. Random bladder biopsies were taken from 84 patients with primary superficial bladder cancer after transurethral resection. 40 patients had Ta and 44 had T1 tumor. The random biopsies were taken from right and left bladder walls, anterior and posterior walls, dome, trigone and prostatic urethra. The incidence of urothelial abnormalities were evaluated according to the stage and grade of the tumor. None of the patients had carcinoma in situ or dysplasia with Ta tumor. In T1 group, 4 patients (9.1%) had carcinoma in situ and 3 patients (6.8%) had dysplasia. There was a statistically significant difference with regard to urothelial abnormalities between groups Ta and T1. The same difference was also seen between low and high grade tumors. In our study, only 7/84 (8.3%) of patients with primary superficial bladder cancer had urothelial abnormalities like carcinoma in situ or dysplasia. All of these pathologies were seen in T1 tumors. According to our results, we believe that random biopsies are not useful in superficial bladder cancers to detect urothelial abnormalities and also do not help for the planning of further treatment.

EOSINOPHILIC CYSTITIS IN ADULTS

We describe the largest clinical experience with the diagnosis and management of largely anecdotally reported eosinophilic cystitis. Five women and 12 men 18 to 84 years with proved eosinophilic cystitis were treated in a 23-year period. Some combination of hematuria, irritative voiding, dysuria and suprapubic pain was present in 14 cases (82%). The remaining 3 patients (18%) were asymptomatic and the diagnosis was made by cystoscopy done because of a history of bladder carcinoma. Available data included no peripheral eosinophilia in 10 of 10 patients studied, pyuria in 12 (92%), microhematuria in 11 of 13 (84%), sterile urine in all 17, abnormal urine cytology in 2 of 17 (12%), bilateral hydronephrosis in 1 and a bladder mass or thickening in 2. Cystoscopy showed erythema in all cases and tumor-like lesions or edema in 3 (17.6%). Histological studies revealed eosinophilic cystitis in all 17 patients, while in 1 with no history of bladder carcinoma eosinophilic cystitis coexisted with carcinoma. Two patients were lost to followup and the remaining 15 were followed 1 to 37 months. After biopsy and fulguration of the lesions 10 patients received no further treatment, including 6 with complete symptom resolution and 1 with improvement. The 3 asymptomatic patients with a history of bladder carcinoma remained asymptomatic and disease-free. Another 4 patients underwent medical therapy and improved, of whom 1 had recurrence that was successfully re-treated medically. The remaining patient, who was symptomatic, underwent cystoprostatectomy for end stage bladder disease. Manifestations of eosinophilic cystitis indistinguishably mimic those of other inflammatory and malignant bladder disorders that may precede or coexist with it. The condition usually follows a benign course in most cases but occasionally its relentless progression causes crippling disease.

CD44 standard form expression as a predictor of progression in high risk superficial bladder tumors.

The purpose of this study was to assess the significance of the standard CD44 adhesion molecule expression in predicting progression of high risk superficial bladder carcinoma in the short term. Sixty-six patients (51 males and 15 females, aged 27 to 89 years (mean 64.75 years) with primary superficial transitional cell bladder cancer initially treated with transurethral resection (TURBT) were enrolled in the study. Only pTa/pT1 grade 2 multiple tumors as well as all grade 3 tumors were included in this study. All tumor samples obtained after the resection were immunohistochemically evaluated for the expression of the CD44 standard molecule. Fifty eight patients remained during the follow up period which ranged from 3 to 36 months (mean 11.8 months). Tumor progression in the short term was considered as the critical end point of interest in this study. The prognostic significance of tumor stage, grade, presence of carcinoma-in-situ (CIS) and expression of CD44 in determining the risk for progression, was studied with both univariate (log rank test) and multivariate (Cox proportional hazards) methods of analysis. Kaplan-Meier survival curves indicated that a shorter median progression-free survival is expected for those patients with G3 bladder tumors (p = 0.0055), concomitant CIS (p = 0.0051), and loss of expression of CD44 (p = 0.0015), whereas a similar association with stage was not detected (p = 0.5793). The cox regression multivariate analysis did not yield a significant result for any of the studied parameters therefore no one of the factors taken into account can serve as an independent predictor of progression in superficial bladder cancer in the short term. The immunohistochemically detectable loss of the expression of CD44 standard form from superficial bladder tumor samples may be, complementary to the established prognostic factors, a useful predictor of tumor progression in the short term.