Darvinio Melloni

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

Study Type – Therapy (RCT)
Level of Evidence 1b

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.

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/m2 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.

Prevention of topic toxicity of BCG with single-dose prulifloxacin. Preliminary results of a randomized pilot study

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.

Treatment of severe post-prostatectomy stress urinary incontinence using advance sling

Severe stress urinary incontinence (SUI) is usually treated by the implant of artificial sphincter positioned around bulbar urethra. AdVance sling is a functional, non-obstructive, anti-incontinence device that showed good results especially for mild and moderate SUI. We present our experience with AdVance sling in 7 patients with severe SUI unfit for artificial sphincter. Our results, after a follow-up of more than 6 months, showed a continence rate of 28% and an improvement rate of 43%, while 2 patients did not show any benefit. The success of AdVance sling depends on the integrity of urethral sphincter and can be applied also in selected cases for the treatment of severe post-prostatectomy stress urinary incontinence.

EFFICACY OF ONE-YEAR MAINTENANCE IN EARLY ADJUVANT CHEMOTHERAPY FOR INTERMEDIATE RISK NON-MUSCLE- INVASIVE BLADDER CANCER. RESULTS AT 24 MONTHS OF A RANDOMIZED TRIAL

1704 EFFICACY OF ONE-YEAR MAINTENANCE IN EARLY ADJUVANT CHEMOTHERAPY FOR INTERMEDIATE RISK NON-MUSCLEINVASIVE BLADDER CANCER. RESULTS AT 24 MONTHS OF A RANDOMIZED TRIAL Vincenzo Serretta*, Vincenzo Altieri, Giuseppe Morgia, Darvinio Melloni, Maria Karidi, Pasquale Annese, Giuseppe Carrieri, Maurizio Cacciatore, Nino Dispensa, Alessandra Di Lallo, Giovanni Ruggiero, Federico Nicolosi, Mauro Iadevaia, Francesco Vacirca, Francesco Paolo Selvaggi, Rosalinda Allegro. Palermo, Italy, Napoli, Italy, Messina, Italy, Matera, Italy, Foggia, Italy, Partinico (PA), Italy, Campobasso, Italy, Telese Terme (BN), Italy, Catania, Italy, Maddaloni (CE), Italy, Caltanissetta, Italy, and Bari, Italy. INTRODUCTION AND OBJECTIVE: The clinical value of early intravesical adjuvant chemotherapy after TUR of intermediate risk nonmuscle-invasive bladder cancer (NMI TCCB) is well established. On the other hand, the optimal schedule regimen and the role of maintenance are still debated. The aim of the present study was to evaluate the effectiveness of one-year maintenance schedule in patients submitted to TUR plus adjuvant early intravesical chemotherapy for intermediate risk NMI TCCB. METHODS: Between May 2002 and August 2003, 577 patients, were recruited. All patients underwent TUR and early (within 6 hours) intravesical chemotherapy with epirubicin at the dose of 80 mg diluted in 60 ml of saline solution. When histology was available, 95 patients were excluded from the study since they were harbouring T1G3, Tis or single and primary Ta G1-G2 tumors. Four hundred eighty-two