Serenoa repens, lycopene and selenium versus tamsulosin for the treatment of LUTS/BPH. An Italian multicenter double-blinded randomized study between single or combination therapy (PROCOMB trial).

BACKGROUND: Phytotherapy has been used to treat patients with lower urinary tract symptoms (LUTS). We evaluated the efficacy and tolerability of combination therapy between Serenoa Repens (SeR), Lycopene (Ly), and Selenium (Se) + tamsulosin versus single therapies. METHODS: PROCOMB trial (ISRCTN78639965) was a randomized double-blinded, double-dummy multicenter study of 225 patients between 55 and 80 years old, PSA ≤ 4 ng/ml, IPSS ≥12, prostate volume ≤60 cc, Qmax ≤15 ml/sec, postvoid residual urine (PVR) <150 ml. Participants were randomized group A (SeR-Se-Ly), group B (tamsulosin 0.4 mg), group C (SeR-Se-Ly + tamsulosin 0.4 mg). The primary endpoints of the study were the reduction of IPSS, PVR, and increase of Qmax in group C versus monotherapy groups. RESULTS: The decrease for combination therapy was significantly greater versus group A (P < 0.05) and group B (P < 0.01) for IPSS and versus group A (P < 0.01) for PVR from baseline to 6 months. A greater decrease in IPSS was observed for Group C versus group A (P < 0.01) and increase in Qmax versus group B (P < 0.01), from 6 months to 12 months. At one year, the changes of IPSS and Qmax were greater for Group C versus monotherapies (each comparison <0.05). The proportions of men with a decrease of at least three points (each comparison P < 0.05) and decrease of 25% for IPSS (each comparison P < 0.01) were greater for Group C. CONCLUSION: SeR-Se-Ly + tamsulosin therapy is more effective than single therapies in improving IPSS and increasing Qmax in patients with LUTS.

Medial tunica degeneration of the ascending aortic wall is associated with specific microRNA changes in bicuspid aortic valve disease.

Ascending aortic diameter is not an accurate parameter for surgical indication in patients with bicuspid aortic valve (BAV). Thus, the present study aimed to identify specific microRNAs (miRNAs/miRs) and their expression levels in aortic wall aneurysm associated with BAV according to severity of medial degeneration and to elucidate the association between the tissue expression levels of the miRNAs with their expression in plasma. Aortic wall and blood specimens were obtained from 38 patients: 12 controls and 26 patients with BAV with ascending aortic aneurysm. Of the patients with BAV, 19 had cusp fusions of right and left, 5 of right and non­coronary, and 2 of left and non­coronary. Two groups of patients were identified according to the grade of medial degeneration (MD): Low­grade D group (LGMD) and high­grade MD group (HGMD). Expression level of miR­122, miR­130, miR­718 and miR­486 were validated by reverse transcription­quantitative PCR in plasma and tissue samples. MD grade was found to be independent from the BAV phenotype. The HGD group showed increased expression levels of MMP­9 and MMP­2, and an increase in the number of apoptotic cells. Tissue expression levels of miR­718 and miR­122 were lower in the LGMD and HGD groups compared with expression in the control group; the HGD group showed increased levels of miR­486. Plasma expression levels of miR­122 were decreased in the LGMD and HGD groups, and miR­718 was only reduced in the HGD group. On the contrary, expression of miR­486 was increased in the LGMD and HGD groups. The data suggested that miR­486 may be considered as a non­invasive biomarker of aortic wall degeneration. Dysregulation of this putative biomarker may be associated with high risk of dissection and rupture in patients with BAV.

A 1-year maintenance after early adjuvant intravesical chemotherapy has a limited efficacy in preventing recurrence of intermediate risk non-muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the efficacy of 1-year maintenance after a 6-week cycle of early intravesical chemotherapy, as the role of maintenance in intravesical chemotherapy is debated. PATIENTS AND METHODS: Between May 2002 and August 2003, 577 patients with non-muscle-invasive bladder cancer (NMI-BC) underwent transurethral resection (TUR) and early intravesical chemotherapy (epirubicin, 80 mg/50 mL). They were randomized between a 6-week induction cycle and the induction cycle plus maintenance with 10 monthly instillations. In all, 95 patients with T1G3, Tis or single and primary Ta-T1 G1-G2 tumours were excluded; 482 patients at intermediate risk of recurrence continued the study. All patients had cytology and cystoscopy at 3-monthly intervals for the first 2-years and 6-monthly thereafter. RESULTS: The tumours' characteristics were equally distributed between the two arms. Treatment interruption for toxicity was required in 39 patients. One death due to toxicity of early instillation occurred. The median follow-up was 48 months. Ten patients (2.5%) progressed and 117 patients (29.6%) recurred. No statistically significant difference in the recurrence-free rate (RFS) was detected between the two arms (P = 0.43). An advantage in favour of the maintenance arm was evident only at 18 months after TUR (P = 0.03). A trend for a higher benefit from maintenance in primary and multiple tumours was detected. CONCLUSIONS: In patients with intermediate risk NMI-BC treated by TUR and early adjuvant chemotherapy, adding a maintenance regimen with monthly instillations for 1 year is of limited efficacy in preventing recurrence.

Oral chemotherapy in hormone-refractory prostate carcinoma patients unwilling to be admitted to hospital.

OBJECTIVES: To investigate the safety and efficacy in terms of PSA response of a low-dose oral combination of estramustine phosphate (EMP) and etoposide (VP16) in hormone- refractory prostate cancer (HRPC) patients. Well-tolerated outpatient chemotherapy regimens for patients unfit and/or unwilling to be admitted to hospital are needed. METHODS: Fifty-six HRPC patients with metastatic disease (median age 75 years) were randomized between arm A (daily oral EMP 10 mg/kg, in 3 doses) and arm B (28-day cycle with low-dose EMP 3 mg/kg once daily plus VP16 25 mg/m(2) once daily on days 1 through 14). Baseline characteristics between the two groups were similar. LHRH therapy was maintained. Anti- androgen was stopped 1 month before entry. RESULTS: The low-dose combination was better tolerated, with a significant advantage in terms of time to treatment interruption for any reason (p = 0.01) or toxicity (6 vs. 12 months, p = 0.02). A trend in favour of arm B was evident in terms of PSA reduction (41.4 vs. 15%), performance status and pain improvement. Hospital admission due to toxicity was never required for arm B patients and there were no treatment-related deaths. CONCLUSIONS: Low-dose oral combination of EMP and VP16 might represent a treatment option for patients unfit for i.v. chemotherapy. This regimen requires minimal toxicity monitoring when administered at home for prolonged periods.

Cigarette smoking and drinking water source: correlation with clinical features and pathology of superficial bladder carcinoma.

OBJECTIVE: Water source and cigarette smoking are related to clinical characteristics and pathology of superficial transitional cell carcinoma of the bladder. METHODS: Tumor number, dimension, G-grade, T-stage, recurrences, cigarette smoking and water supply were recorded in patients harboring Ta-T1 G1-3 transitional cell carcinoma of the bladder. RESULTS: Of 577 patients, 61% had multiple and 36% recurrent tumors. Two hundred and forty-one patients (42%) were current smokers and 188 (33%) were former smokers. Bottled water was the only drinkable source for 249 (45%) patients, municipal water supply for 177 (32%), artesian wells for 38 (7%), spring water for 7 (1%) and mixed source for 89 (16%). By adopting a cut-off of 30 years of smoking, patients affected by recurrent tumors varied from 22 to 43% (p = 0.0001). T1 tumors were more frequent in patients drinking nonbottled water (p = 0.03). Nonbottled supply was more frequent in never smokers (p = 0.015) and could represent a weak risk factor not detectable in smokers. CONCLUSIONS: Cigarette smoking correlates with the number of recurrences. T1 tumors were statistically more frequent in patients taking nonbottled drinking water. Chlorinated water supply was more frequent among patients who did not present cigarette smoking as a risk factor.

Is PSA density still useful in diagnosing prostate cancer?

OBJECTIVE: To evaluate the concordance between the PSAD (PSA density) values calculated using the actual prostate weight and the PSAD values calculated by using the dimensions of the gland given by the pathologist when freshly excised (volume 1) or using TRUS measures (volume 2). Diagnostic accuracy of PSAD in diagnosing PCa (prostate cancer) was evaluated and compared with accuracy obtained using PSA free/total (FIT). MATERIAL AND METHODS: 102 consecutive patients with PSA included between 2 and 10 ng/mL underwent radical prostatectomy. Indications to perform prostate biopsy were: abnormal digital rectal examination, PSA < or = 2.5 ng/mL, PSA between 2.6 and 4 ng/mL and between 4.1 and 10 ng/mL with PSA F/T (free/total) < or = 15%, < or = 20% and < or = 25%, respectively We compared the PSAD values obtained using the actual prostate weight (PSAD1) vs those calculated using volume 1 (PSAD2) and volume 2 (PASD3). RESULTS: The mean weight of prostate specimen was 55.61 grams, while the estimated mean volumes were 50.02 mL (volume 1) and 48.49 mL (volume 2). A statistically significant difference among actual weight vs volume 1 vs. volume 2 (p < 0.0001) was found. In the patients with PSA ranging from 4.1 to 10 ng/mL a cumulative accuracy of 82.6% was found using a cut-off > 0.10 whereas, with a cut-off > 0.15, a diagnostic accuracy of 36.9% (PSAD1), 58.6% (PSAD2) and 60.8% (PSAD3) was reported. CONCLUSIONS: No concordance between the actual prostate weight and the estimated volume was found; moreover PSAD accuracy was of poor value in diagnosing PCa in comparison with PSA F/T.

Epidermal Growth Factor Receptor (EGFR) Cell Expression During Adjuvant Treatment After Transurethral Resection for Non-Muscle-Invasive Bladder Cancer: A New Potential Tool to Identify Patients at Higher Risk of Disease Progression.

BACKGROUND: The aim of the study was to investigate the feasibility of Epidermal Growth Factor Receptor (EGFR) measurement in bladder washings of patients affected by non-muscle-invasive bladder cancer (NMIBC) and its prognostic role in identifying risk subgroups and predicting disease recurrence and progression. PATIENTS AND METHODS: Patients with NMIBC treated with transurethral resection of bladder tumor (TURBT) from 2012 to 2015 were enrolled. Samples of bladder washings were collected and stored at -80°C until RNA extraction. The cDNA obtained from RNA was used to perform a gene expression analysis by a real time polymerase chain reaction. RESULTS: An adequate cellular pellet was obtained in 50 (86.2%) of 58 patients and in 18 (85.7%) of 21 controls. Patients had a median 2.5-, a 1.6- and a 2.8-fold EGFR expression compared with controls before, during, and after adjuvant treatment, respectively. Patients at higher risk had a significantly higher EGFR expression compared with patients at low and intermediate risk when EGFR was measured during (P = .04) and after (P = .001) adjuvant therapy. At a median follow-up of 35.5 months (interquartile range, 19.0-54.8 months), in the high-risk group, patients with overexpression had a significantly lower recurrence-free survival (27.9% vs. 58%), progression-free survival (75.9% vs. 90.2%), and cancer-specific survival (77.7% vs. 93.3%). At multivariable analysis, EGFR overexpression was an additional independent prognostic factor to the European Organisation for Research and Treatment of Cancer scoring system of disease recurrence (hazard ratio, 1.98; 95% confidence interval, 1.32-2.97) and progression (hazard ratio, 1.84; 95% confidence interval, 1.27-2.65). CONCLUSIONS: EGFR overexpression might represent an additional parameter to the current clinical tools for an individualized risk stratification.

Multiplicity and history have a detrimental effect on survival of patients with T1G3 bladder tumors selected for conservative treatment.

PURPOSE: In the absence of Tis tumor we assessed whether history and multiplicity have a detrimental effect on conservative treatment in carefully selected patients with T1G3 bladder carcinoma. MATERIALS AND METHODS: Between January 1976 and December 1999, 165 select patients with T1G3 bladder tumors were conservatively treated with transurethral resection plus adjuvant intravesical therapy. Patients with concomitant or previous Tis, previous T1G3, tumor size greater than 3 cm and more than 3 lesions were excluded from analysis. Repeat transurethral resection was not routinely performed. However, cytology had to be negative for atypia before the start of adjuvant intravesical therapy. RESULTS: Recurrence-free survival at 1, 3 and 5 years was 71.8%, 55.6% and 45%, respectively. Of the cases 14 (8.4%) progressed with a median progression-free survival of 149 months. A total of 23 patients (14%) died. The 5-year recurrence-free survival rate was 52%, 34% and 15% in cases of single and/or primary, multiple and recurrent tumors, respectively. Median overall survival was 144 months. The 5-year disease-free overall survival rate was 85%, 83%, 79% and 69% in cases of primary, single, multiple and recurrent tumors, respectively. An intact bladder was maintained in 137 patients (83%) with a mean disease-free overall survival of 102.7 months. Patients with recurrent and/or multiple T1G3 tumors showed worse survival (p = 0.0021 and 0.0142, respectively). CONCLUSIONS: History and multiplicity are relevant predictors of survival even in highly selected patients with TIG3 bladder tumors that are conservatively treated.

Intravesical chemotherapy for intermediate risk non-muscle invasive bladder cancer recurring after a first cycle of intravesical adjuvant therapy.

CONTEXT: The therapeutic strategy in intermediate risk (IR) non-muscle invasive bladder cancer (NMIBC) recurring after intravesical therapy (IT) is not well defined. Most patients are usually retreated by Bacillus Calmette-Guerin (BCG). AIMS: To evaluate the efficacy of intravesical chemotherapy (ICH) given at recurrence after the first cycle of ICH in IR-NMIBC recurring 6 months or later. SETTINGS AND DESIGN: Retrospective analysis of the efficacy of ICH given after previous IT. MATERIALS AND METHODS: The clinical files of IR-NMIBC patients recurring later than 6 months after transurethral resection (TUR) and IT and retreated by IT were reviewed. The patients should be at intermediate risk both initially and at the first recurrence. BCG should have been given at full dose. Cytology and cystoscopy were performed 3 monthly for 2 years and then 6 monthly. STATISTICAL ANALYSIS: The RFS was estimated by the Kaplan-Meier method and the differences between treatment groups were compared by log-rank test. Mann Whitney U-test was used to compare the parameters' distribution for median time to recurrence. Multivariate Cox proportional hazards models were used. RESULTS: The study included 179 patients. The first IT was ICH in 146 (81.6%) and BCG in 33 (18.4%), re-IT was ICH in 112 (62.6%) and BCG in 67 (37.4%) patients. Median time to recurrence was 18 and 16 months after first and second IT (P = 0.32). At 3 years, 24 (35.8%) and 49 (43.8%) patients recurred after BCG and ICH, respectively (P = 0.90). No difference in RFS was found between BCG and ICH given after a first cycle of ICH (P = 0.23). CONCLUSIONS: Re-treatment with ICH could represent a legitimate option to BCG in patients harboring IR-NMIBC recurring after TUR and previous ICH. Prospective trials are needed.

Correlation between GP-170 expression, prognosis, and chemoresistance of superficial bladder carcinoma.

PURPOSE: To study GP-170 in superficial bladder cancer at initial diagnosis and at recurrence and to evaluate if intravesical chemoprophylaxis modifies the expression of GP-170 in tumor recurrences. MATERIALS AND METHODS: GP-170 was retrospectively assessed in 160 patients affected by primary superficial transitional cell carcinoma of the bladder and followed for up to 10 years. Eighty-four patients (52.5%) recurred after transurethral resection (TUR). Adjuvant intravesical chemotherapy after TUR was adopted in 52 patients. The correlations between GP-170 and G-grade, T-category, risk of recurrence and of progression, and adoption of adjuvant intravesical chemotherapy were investigated. The correlations between variations in grade and stage at recurrence and modifications in GP-170 expression were also studied. RESULTS: No significant correlation between GP-170 expression and G-grade and T-category was found. A significant correlation was detected between GP-170 expression and recurrence ( P=0.0383). It showed a biphasic pattern, i.e., tumors that did not express GP-170 had a higher recurrence rate, but high GP-170 levels were also associated with an increasing risk of recurrence. Intravesical chemotherapy did not induce significative variations in GP-170 expression. No correlation was found between progression and GP-170. CONCLUSION: GP-170 seems to be an independent prognostic factor for recurrence in superficial bladder tumors. A negative GP-170 pattern and high levels of GP-170 are associated with an increasing risk of recurrence but have no impact upon progression. In our experience, GP-170 is neither induced nor modified by intravesical chemotherapy, although it might represent a factor of chemoresistance when strongly expressed.

Cigarette smoking status at diagnosis and recurrence in intermediate-risk non-muscle-invasive bladder carcinoma.

OBJECTIVE: To study the effect of smoking status at diagnosis on recurrence in intermediate-risk non-muscle-invasive bladder carcinoma treated by transurethral resection (TUR) of the bladder and early intravesical chemotherapy. METHODS: Tumor characteristics and smoking status were recorded in 395 patients entered in a randomized multicenter trial comparing 2 different schedules of early intravesical chemotherapy. All patients received intravesical epirubicin (80 mg/50 mL) within 6 hours after TUR, followed by 5 more weekly instillations with (arm B) or without (arm A) monthly instillations for 1 year. Smoking habit was investigated at diagnosis through a structured questionnaire. Multivariate statistical analysis was performed to study the recurrence-free survival (RFS) and the recurrence-free rate (RFR) in relation to smoking status. RESULTS: Ninety-seven (24.6%) patients never smoked and 298 (75.4%) were smokers. At a median follow-up of 48 months, 117 patients (29.6%) recurred, 63 in arm A and 54 in arm B (P = .43). Ten patients (2.5%) progressed. The 3-year RFS, RFR, and median time to first recurrence of smokers and patients who never smoked were 64.0% and 71.3% (P = .08), 69.1% and 74.2% (P = .16), and 13.6 and 14.2 months (P = .27), respectively. The multivariate analysis identified previous history (P = .01) and smoking status (P = .04) as the main prognostic factors for recurrence in these patients. No difference in recurrence risk at 3 years was detected between current and former smokers. CONCLUSION: In intermediate-risk non-muscle-invasive bladder carcinoma treated by early intravesical chemotherapy, smoking status influences significantly the 3-year RFS. No difference was detected between current and former smokers.

A randomized trial comparing tamoxifen therapy vs. tamoxifen prophylaxis in bicalutamide-induced gynecomastia.

BACKGROUND: Tamoxifen (TAM) has been shown to be active against the bicalutamide-induced breast events (BEs) gynecomastia, and breast pain in patients with prostate cancer (PC). Optimal doses and schedules are not yet established. Debate still exists about whether prophylaxis with TAM is more effective than treatment of BEs when diagnosed. The results of a randomized study comparing TAM prophylaxis vs. TAM therapy are presented. METHODS: One hundred seventy-six patients with prostate cancer (PC) who were candidates for bicalutamide monotherapy were randomized to receive TAM 20 mg daily orally within 1 month from the onset of BEs (arm A) vs. TAM 10 mg daily starting simultaneously with bicalutamide (arm B). TAM was administered for up to 1 year. BEs were evaluated by a self-administered visual analogue scale. Neither ultrasonography nor calipers were used to measure the degree of gynecomastia. RESULTS: In arm A, BEs showed a prevalence, increasing with time up to 78.3%. After therapy with TAM they persisted in 27.7% of cases. Two patients (3%) interrupted TAM therapy because of dizziness, and 3 patients (4%) interrupted bicalutamide therapy because of painful gynecomastia. In arm B, the prevalence of BEs was 35% after 12 months of therapy. The difference in BEs between the 2 arms was statistically significant (P < .0001). The differences in prevalence of gynecomastia and breast pain between the 2 arms both favored TAM prophylaxis (P < .0001 and P < .001, respectively). Up to 35% of patients had BEs of low intensity, never requiring bicalutamide withdrawal. Two patients (3%) interrupted the treatment because of gastrointestinal intolerance. No difference emerged between the 2 arms in terms of prostate-specific antigen (PSA) response, plasma testosterone levels, and tumor progression. CONCLUSION: Bicalutamide-induced BEs can be prevented to a significant degree by prophylaxis with TAM 10 mg/day or effectively treated with TAM therapy 20 mg/day. Persisting BEs are of higher intensity after therapy than after prophylaxis.

[Prevention of topic toxicity of BCG with single-dose prulifloxacin. Preliminary results of a randomized pilot study]. / Prevenzione della tossicità topica del BCG con prulifloxacina in monodose. Risultati preliminari di uno studio pilota randomizzato.

INTRODUCTION: Toxicity is a major problem for patients undergoing intravesical therapy with Bacillus Calmette-Guérin (BCG) for the conservative management of intermediate or high-risk non-muscle invasive bladder cancer (NMI-BC). A prospective pilot trial was designed to evaluate the adoption of a single dose of prulifloxacin to prevent the toxicity of BCG. Treatment tolerability and its possible influence on BCG efficacy have been analyzed. MATERIALS AND METHODS: The study was designed to evaluate the action of prulifloxacin in patients with intermediate or high-risk NMI-BC, undergoing 6-week induction cycle of BCG. Main exclusion criteria were previous intravesical therapy, urinary infection and any other factor that could influence tolerability to BCG intravesical immunotherapy. The patients were randomized to receive BCG alone versus BCG plus prulifloxacin. BCG toxicity and local tolerability were evaluated by self-administered EORTC QLQ-BLS24 questionnaire, and BCG adverse events (AEs) were classified according a four-class classification. The toxicity and tolerability evaluations were performed at baseline, one week after every instillation and one week and one month after the last instillation. Cystoscopy and cytology were performed 3-monthly. Recurrence and progression were recorded. RESULTS: The study included 43 patients receiving 258 instillations of BCG. The patients were randomized to receive BCG alone (Arm A: 132 instillations in 22 patients) versus BCG plus prulifloxacin given as a single oral dose (600 mg) 6 hours after the instillation. An advantage in favor of prulifloxacin prophylaxis emerged, according to EORTC QLQ-BLS24, in overall incidence of nocturnal micturitions (56% vs 28.6%; p=0.001), insomnia (40% vs 14.3%; p=0.002), urgency (70% vs 42.6%; p=0.05), incontinence (44% vs 12.7%; p=0.01) and bothersome events due to intravesical therapy (84% vs 63.5%; p=0.02). Systemic class IIB and III adverse events occurred in only 14.2% and 3.5% of the patients, respectively. No class IV AE was detected. Due to the low incidence no statistically significant difference was evident between the two arms (p=0.6). Three patients of Arm B and 1 patient of Arm A interrupted the treatment, after the 3rd - 4th instillation. Anti-tuberculosis therapy war required for 3 months in only one patient. Three and 2 instillations were postponed for one-(two) week(s) in Arm B and Arm A, respectively. Prulifloxacin, generally well tolerated, was withdrawn in one patient due to skin allergic reaction. Recurrence rate at a mean follow-up of 12 months did not significantly differ between the two arms. CONCLUSIONS: Prulifloxacin decreases the incidence of local symptoms and improves the compliance to BCG intravesical therapy. Due to the low number of events, no evidence emerges in our study about its capability of preventing severe systemic toxicity, although it has proved effective in reducing local symptoms.

Is free/total PSA predictive of pathological stage and Gleason score in patients with prostate cancer and serum PSA

INTRODUCTION: To evaluate whether percent free prostate-specific antigen (%-fPSA) could be predictive of pathological stage and Gleason score in patients with prostate cancer (PCa) and serum PSA of 10 ng/ml or less. MATERIALS AND METHODS: In 100 patients with total PSA7 were compared. RESULTS: 32 patients had an organ-confined and 68 a locally advanced PCa. Median %-fPSA level was 15%; Gleasonscore was <7 in 49 patients, equal to 7 in 40 and >7 in 11. Median %-fPSA levels in PCa with Gleason score7 was 14, 15.5 and 15%, respectively. Multiple logistic regression analysis did not show any correlation between %-fPSA in organ-confined vs. non-organ-confined PCa (p=0.4991) either between Gleason score<7 vs. equal to 7 (p=0.588) or >7 (p=0.547). CONCLUSIONS: %-fPSA cut-off does not seem to be useful for preoperative staging of patients with PCa and serum PSA

Gemcitabine in intravesical treatment of Ta-T1 transitional cell carcinoma of bladder: Phase I-II study on marker lesions.

OBJECTIVES: To study the ablative activity of intravesical gemcitabine against superficial transitional cell carcinoma of the bladder at different doses and concentrations. METHODS: A total of 27 patients were treated with intravesical gemcitabine after transurethral resection during which one to three papillary marker lesions were left unresected. Starting 14 days after transurethral resection, six instillations of gemcitabine were given at weekly intervals. Gemcitabine, diluted in 50 mL of saline solution and maintained for 2 hours, was given at the dose of 500 mg, 1000 mg, and 2000 mg in groups of 9 patients each. A complete response (CR) was defined as negative cytology, cystoscopy, and biopsy findings. Patients achieving a CR received monthly maintenance for up to 1 year and underwent cytology and cystoscopy at 3-month intervals. RESULTS: Of the 27 patients, 1 was lost to follow-up, and of the remaining 26 patients, 6 (23%) achieved a CR. A CR was achieved in 1 patient (12.5%), 2 patients (22.2%), and 3 patients (33.3%) at a dose of 500, 1000, and 2000 mg, respectively. A partial response was obtained in 2 additional patients (22%) at a dose of 500 and 1000 mg. Bladder Tis was diagnosed in 2 patients with a CR at 3 and 8 months after treatment. The remaining 4 patients were disease free at a follow-up of up to 22 months. Systemic and local tolerability was excellent, and no treatment interruption was required. CONCLUSIONS: Our experience has shown the good tolerability and potential efficacy of intravesical gemcitabine against recurrent transitional cell carcinoma of the bladder. Gemcitabine might be proposed, if our results are confirmed by larger studies, as a second-line therapy in patients who cannot tolerate more aggressive intravesical therapy.

TUR and adjuvant intravesical chemotherapy in T1G3 bladder tumors: recurrence, progression and survival in 137 selected patients followed up to 20 years.

OBJECTIVES: To evaluate a highly selected population of patients affected by T1G3 bladder transitional cell carcinoma (TCCB) treated by transurethral resection (TUR) and adjuvant intravesical chemotherapy. MATERIALS AND METHODS: Between January 1976 and April 1999, 137 patients with T1G3 TCCB were treated by TUR plus intravesical chemotherapy. Particularly, a sequential combination of mitomycin C (MMC) and epirubicin (EPI) was adopted in 91 patients (66.4%). The main exclusion criteria were concomitant or previous Tis, previous T1G3 TCCB, tumor size greater than 3 centimeters and number of tumors more than 3. TUR was repeated if a superficial tumor recurred. Patients went off study if Tis, recurrent T1G3 or invasive tumor were detected during treatment or thereafter. Adjuvant therapy, recurrence and progression were considered in multivariate analysis regarding recurrence, progression and survival respectively. RESULTS: Observation period was up to 240 months with a minimum of 2 years in 112 patients (82%). Seventy patients (51%) recurred. The recurring tumor was again a T1G3 in 22 (16%) patients. Thirteen patients (9.5%) progressed. The 5-year progression-free survival rate was 90%. Median progression-free survival was 149 months. Twenty-two patients (16%) died, 9 (6.6%) of whom due to bladder cancer. Median overall survival was 155 months. The 3- and 5-year disease-free overall survival rates were 89% and 80% respectively. Ten cystectomies (7.3%) were performed. In conclusion, 123 patients (90%) maintained their intact bladder with a mean disease-free overall survival of 104 months. The sequential combination of MMC and EPI adjuvant therapy resulted more effective to be than single drug chemotherapy on recurrence rate (p=0.0021) but had no impact upon progression (p=0.127) and specific survival (p=0.163). Progression (p<0.001) after conservative treatment was the main prognostic factor for survival. CONCLUSION: A conservative approach is an appropriate therapeutic option for the initial management of selected T1G3 bladder tumors.