Long-term outcomes of a randomized controlled trial comparing thermochemotherapy with mitomycin-C alone as adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC).

OBJECTIVE: • To present long-term efficacy data of intravesical thermochemotherapy vs chemotherapy alone with mitomycin-C (MMC) randomly administered to patients with non-muscle-invasive bladder cancer (NMIBC) as an adjuvant treatment after complete transurethral resection. PATIENTS AND METHODS: • In all, 83 patients with intermediate-/high-risk NMIBC, following complete transurethral resection, were randomly assigned to receive either intravesical thermochemotherapy by means of Synergo® (Medical Enterprises, Amsterdam, The Netherlands) or intravesical chemotherapy alone, for prophylaxis of tumour recurrence. • Two doses of MMC (20 mg dissolved in 50 mL distilled water administered throughout two consecutive sessions) was used as the chemotherapeutic agent in both arms. • In all, 75 patients completed the original study (35 of 42 in the treatment arm, 40 of 41 in the control arm), whose results at minimum 2-year follow-up have already been published. • Recently, the files of these patients have been updated for long-term outcome definition. Data on general health, follow-up examinations, tumour relapse or progression, and cause of death were collected and analysed. RESULTS: • Updated complete data collection was available for 65/75 (87%) of the original patients. • The median follow-up for tumour-free patients was 91 months. The 10-year disease-free survival rate for thermochemotherapy and chemotherapy alone were 53% and 15%, respectively (P < 0.001). • An intent-to-treat analysis performed to overcome the potential bias introduced by the asymmetrical discontinuation rate still showed a significant advantage of the active treatment over the control treatment. Bladder preservation rates for thermochemotherapy and chemotherapy alone were 86% and 79%, respectively. CONCLUSION: • This is the first analysis of long-term follow-up of patients treated with intravesical thermochemotherapy. The high rate (53%) of patients who were tumour-free 10 years after treatment completion, as well as the high rate (86%) of bladder preservation, confirms the efficacy of this adjuvant approach for NMIBC at long-term follow-up, even in patients with multiple tumours.

Quantitative microscopy of human DNA topoisomerase II-alpha expression in transitional cell carcinoma of the bladder.

OBJECTIVE: To compare the nuclear size of various grades of transitional cell carcinoma (TCC) stained immunohistochemically with the nuclear enzyme topoisomerase II-alpha (topo II-alpha) in bladder urothelial neoplasms. STUDY DESIGN: Histologic sections from 53 consecutive papillary bladder neoplasms were stained immunohistochemically for topo II-alpha expression. There were 18 (33.9%) urothelial neoplasms of low malignant potential (UNLMP), 18 (33.9%) low grade urothelial carcinoma (LGUCa), and 17 (32%) with high grade urothelial carcinoma (HGUCa). The histologic slides were photographed at 400 x magnification and then projected on a screen, and the area with stained nuclei was measured. RESULTS: The cells and nuclei in HGUCa were significantly larger than in LGUCa (P < .05) and UNLMP (P < .01). CONCLUSION: Calculation of the area fraction of nuclei in TCC of the bladder stained with topo II-alpha is an additional method of establishing the grade of these tumors.

Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma.

PURPOSE: To compare the efficacy and local toxicity of the intravesical instillation of a cytostatic drug versus the same cytostatic agent in combination with local hyperthermia as an adjuvant treatment, after complete transurethral resection (TURB) of superficial transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: The study was designed as a prospective, multicentric, randomized trial. Eighty-three patients suffering from primary or recurrent superficial (Ta-T1) TCC of the bladder, after a complete TURB, were randomly assigned to receive intravesical instillations of mitomycin C (MMC) alone, for 41 patients, and MMC in combination with local microwave-induced hyperthermia, for 42 patients. For the combined approach, a new system, Synergo101-1 (Medical Enterprises, Amsterdam, the Netherlands) was used. The effectiveness evaluation end points of the study were evaluation of recurrence-free survival and the estimated probability of recurrence. The safety evaluation end points included subjective and objective side effects and clinical complications. For the efficacy end point, Kaplan-Meier analysis was employed, with the log-rank test for significance. Minimum follow-up time was 24 months. RESULTS: Of the 83 randomly assigned patients, 75 completed the study according to the protocol and had valid cystoscopy results. Survival analysis of the 75 assessable patients demonstrated a highly significant difference in the survival curves in favor of thermochemotherapy. Subjective intolerance and clinical complications were significantly higher but transient and moderate in the combined treatment group. CONCLUSION: In our series, endovesical thermochemotherapy appears to be more effective than standard endovesical chemotherapy as an adjuvant treatment for superficial bladder tumors at 24-month follow-up, despite an increased but acceptable local toxicity.