Intravesical mitomycin C combined with local microwave hyperthermia in non-muscle-invasive bladder cancer with increased European Organization for Research and Treatment of Cancer (EORTC) score risk of recurrence and progression.

PURPOSE: To assess the activity of intravesical chemotherapy and local microwave hyperthermia (ICLMH) in increasing the disease-free interval (DFI) in patients with non-muscle-invasive bladder cancer (NMIBC) and treatment toxicity. METHODS: Forty-two patients with a diagnosis of high-risk NMIBC, according to the European Organization for Research and Treatment of Cancer (EORTC) criteria, were treated with an intensive schedule of ICLMH using 40 mg mitomycin C. The treatment consisted of 4 weekly sessions, followed by 6 sessions delivered every 2 weeks, and by 4 monthly sessions, for a total of 14 sessions over 8 months. The DFIs before and after treatment were compared in each patient. RESULTS: The schedule was completed as planned by 32 patients (76.2 %). The percentage of disease-free patients the year before study was 14.9 % (95 % CI 5.5-28.8) versus 88.8 % (95 % CI 73.7-94.8) after ICLMH (p < 0.0001). Patient EORTC scores, multifocality, and tumour stage were all associated significantly and independently with a higher risk of recurrence after ICLMH treatment with HR of 41.1 (p = 0.01), 17.7 (p = 0.02), and 8.5 (p = 0.02), respectively. After a median follow-up of 38 months, 24 patients (57.1 %) did not show evidence of disease, whereas 13 patients (30.9 %) underwent disease recurrence and 5 patients (11.9 %) showed also stage progression. Toxicity consisted in grades 1 and 2 frequency, non-infectious cystitis, and haematuria. CONCLUSIONS: ICLMH significantly increases the DFI of NMIBC patients with high EORTC score for recurrence and progression. Toxicity of the intensive treatment schedule was generally mild.

Systemic absorption and pharmacokinetics of single-dose early intravesical mitomycin C after transurethral resection of non-muscle-invasive bladder cancer.

OBJECTIVE: To study the systemic absorption and pharmacokinetics of a single dose of intravesical mitomycin C (MMC) given immediately after transurethral resection of bladder tumor (TURBT). METHODS: Fourteen patients with primary or recurrent non-muscle-invasive bladder cancer were eligible for a single early intravesical instillation of MMC (40 mg in 50 mL distilled water) administered immediately after TURBT. Blood samples were obtained at baseline and at 20, 40, 60 (time of voiding), 90, 120, and 150 minutes after instillation. Concentrations of the drug were determined by validated high-performance liquid chromatography assay. During TURBT, we counted the number of excursions of the resecting loop required to completely eradicate the tumor, including a portion of the underlying muscular wall. TURBTs were categorized as small and large, defined as requiring ≤6 or >6 full excursions of the resecting loop, respectively. RESULTS: Maximal MMC plasma concentrations were reached 40 minutes after instillation. At 150 minutes, only minimal drug plasma levels were detectable in 4 patients. The highest plasma peak was 49.25 ng/mL. In the first samples, at 20 minutes after instillation, the plasma concentration of MMC was significantly correlated with the extent of TURBT (P = .026). Four patients (28.6%) complained of G1 side effects, 3 after a large TURBT and 1 after a small TURBT, and 1 patient had G2 dysuria after a large TURBT. CONCLUSION: Low peak blood levels of MMC are observed after a single-dose intravesical instillation immediately after TURBT, with low systemic and local toxicity. The early absorption rate depends on TURBT extension.

Are referral centers for non-muscle-invasive bladder cancer compliant to EAU guidelines? A report from the vesical antiblastic therapy Italian study.

INTRODUCTION: Adherence to international guidelines is viewed as a prerequisite for optimal medical care delivery. Previously reported surveys for non-muscle-invasive bladder cancer (NMIBC) employed mailed questionnaires to urologists or patients resulting in conflicting degrees of agreement with existing guidelines. In the current study, contemporary information on the management of NMIBC was generated from a sample of italian centers. PATIENTS AND METHODS: Eight Italian referral centers for the treatment of NMIBC were asked to collect information relative to all consecutive patients with a histology-proven NMIBC undergoing a transurethral resection from January 1 to March 31, 2009. The primary study objective was to verify the level of adherence of disease management with European guidelines. RESULTS: 344 patients resulted in being evaluable. 49.2% of high-risk patients underwent a repeat transurethral resection. Bacillus Calmette-Guérin was employed in 35% of cases, while chemotherapy was in 22%. An early single regimen was adopted in 136 patients and only in 1 out of 3 low-risk patients. High-risk NMIBC received bacillus Calmette-Guérin and chemotherapy as first-line therapy in 66 and 12.5% respectively. After 3 months, cystoscopy had been reported for 82.5% of patients with a recurrence rate of 13%. CONCLUSION: Adherence of Italian Institutions to EAU guidelines was optimal when reporting baseline variables. Significant degrees of discrepancy emerged in treatment choices.

Prognostic significance of fluorescent in situ hybridisation in the follow-up of non-muscle-invasive bladder cancer.

AIM: To evaluate the potential contribution of a fluorescent in situ hybridization (FISH) as prognostic indicator of the risk of recurrence or progression in patients undergoing follow-up for non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: A total of 126 consecutive patients with a history of NMIBC being followed-up with urinary cytology and cystoscopy at a referral centre were studied. Patients with carcinoma in situ, or tumour stage higher than pT1 were excluded. A UroVysion FISH kit was used to detect four chromosomal abnormalities, specifically, locus 9p21, Ch 3, 7, and 17. Three FISH patterns were defined: negative; low-risk positive, i.e. positive staining for 9p21 and/or Ch3 abnormalities; and high-risk positive, i.e. positive staining for Ch7 and/or 17. RESULTS: Overall 73 out of 126 patients (57.9%) had a positive urinary FISH test. After a median time of 14 months, 46 FISH-positive patients underwent recurrence (36.5%) and in 15 patients there was progression of disease (11.9%). Among positive patients, the low-risk category was found in 34, and the high-risk in 39. Low-risk FISH-positive patients had a higher rate of recurrence as compared to FISH-negative patients, with a hazard ratio (HR) of 1.6. The recurrence rate was even greater in patients with a high-risk positive test, with an HR of 1.9. The limitation of the study was that the impact of intravesical treatment was not assessed. CONCLUSION: The urinary FISH test can be used as an aid in predicting the risk of recurrence during follow-up of patients with history of NMIBC.