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Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma
W.A. See / Urologic Oncology: Seminars and Original Investigations 22 (2004) 265–274
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The historic stage and grade categorization system of nonmuscle invasive bladder tumors, while being complex in that it contained at least seven stage/grade combinations, was quite clinically useful. The 1998 revision by the World Health Organization has attempted to simplify this system through the use of a high vs. low grading system (eliminating Grade II) and the definition of a new category titled “Papillary urothelial neoplasm of low malignant potential (PUNLMP).” The manuscript by Fujii et al. reports on the natural history of this newly defined pathologic entity. Their data shows that, similar to the historic Ta Grade I category, patients with PUNLMP have a high rate of recurrence but a very low rate of tumor progression or death from disease. While reassuring that the actual tumor biology is consistent with the implications inherent in the name, one has to wonder what additional value from a patient management perspective has been derived from this new categorization. As is the case for low-grade Ta lesions, these patients will continue to require long-term follow-up to monitor for tumor recurrence, and ultimately a small number will progress to more aggressive disease. doi:10.1016/j.urolonc.2004.03.010 William A. See, M.D.
Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma. Colombo R, Da Pozzo LF, Salonia A, Rigatti P, Leib Z, Baniel J, Caldarera E, Pavone-Macaluso M, Department of Urology, University Vita-Salute, San Raffaele Hospital, Milan, Italy. J Clin Oncol 2003;21:4270 – 6 Purpose: To compare the efficacy and local toxicity of the intravesical instillation of a cytostatic drug vs. 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.
Commentary The manuscript by Columbo et al. reports on the efficacy of intravesical “thermo-chemotherapy” in preventing tumor recurrence compared to intravesical chemotherapy alone. This prospective randomized trial used an innovative technique to take advantage of the known synergy between hyperthermia and chemotherapy. Using a transurethrally delivered microwave antenna/Foley catheter coupled with temperature monitoring probes, the authors delivered hyperthermia simultaneously with the intravesical installation of Mitomycin C. The results demonstrate a significant difference in tumor recurrence rates between their two groups of patients. Minor concerns regarding this manuscript relate to the relatively low (20 mg in 20 mL) total dose of Mitomycin employed and the carefully selected nature of their patient population. Nonetheless, the results in their treatment arm are substantially better than other trials to date employing either chemo or immuno-therapeutic agents alone. Although these efficacy results are certainly intriguing, the value of this approach also needs to be considered in the context of its toxicity and burden of therapy. While clearly more involved than a course of intravesical chemotherapy, administration was achieved without anesthetic and would appear to be associated with both patient acceptance and compliance. Of slightly more concern was the incidence of severe side effects in the combined treatment modality group. Twenty-nine percent of patients treated with the combined modality experienced toxicity categorized as severe vs. 2% in the mitomycin C monotherapy arm. This degree of toxicity may limit the utility of the approach in low-risk patients. Nonetheless, the efficacy results are such that this approach warrants further evaluation for patients refractory to other treatment modalities or at significant risk for tumor progression. doi:10.1016/j.urolonc.2004.03.011 William A. See, M.D.
271
The historic stage and grade categorization system of nonmuscle invasive bladder tumors, while being complex in that it contained at least seven stage/grade combinations, was quite clinically useful. The 1998 revision by the World Health Organization has attempted to simplify this system through the use of a high vs. low grading system (eliminating Grade II) and the definition of a new category titled “Papillary urothelial neoplasm of low malignant potential (PUNLMP).” The manuscript by Fujii et al. reports on the natural history of this newly defined pathologic entity. Their data shows that, similar to the historic Ta Grade I category, patients with PUNLMP have a high rate of recurrence but a very low rate of tumor progression or death from disease. While reassuring that the actual tumor biology is consistent with the implications inherent in the name, one has to wonder what additional value from a patient management perspective has been derived from this new categorization. As is the case for low-grade Ta lesions, these patients will continue to require long-term follow-up to monitor for tumor recurrence, and ultimately a small number will progress to more aggressive disease. doi:10.1016/j.urolonc.2004.03.010 William A. See, M.D.
Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma. Colombo R, Da Pozzo LF, Salonia A, Rigatti P, Leib Z, Baniel J, Caldarera E, Pavone-Macaluso M, Department of Urology, University Vita-Salute, San Raffaele Hospital, Milan, Italy. J Clin Oncol 2003;21:4270 – 6 Purpose: To compare the efficacy and local toxicity of the intravesical instillation of a cytostatic drug vs. 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.
Commentary The manuscript by Columbo et al. reports on the efficacy of intravesical “thermo-chemotherapy” in preventing tumor recurrence compared to intravesical chemotherapy alone. This prospective randomized trial used an innovative technique to take advantage of the known synergy between hyperthermia and chemotherapy. Using a transurethrally delivered microwave antenna/Foley catheter coupled with temperature monitoring probes, the authors delivered hyperthermia simultaneously with the intravesical installation of Mitomycin C. The results demonstrate a significant difference in tumor recurrence rates between their two groups of patients. Minor concerns regarding this manuscript relate to the relatively low (20 mg in 20 mL) total dose of Mitomycin employed and the carefully selected nature of their patient population. Nonetheless, the results in their treatment arm are substantially better than other trials to date employing either chemo or immuno-therapeutic agents alone. Although these efficacy results are certainly intriguing, the value of this approach also needs to be considered in the context of its toxicity and burden of therapy. While clearly more involved than a course of intravesical chemotherapy, administration was achieved without anesthetic and would appear to be associated with both patient acceptance and compliance. Of slightly more concern was the incidence of severe side effects in the combined treatment modality group. Twenty-nine percent of patients treated with the combined modality experienced toxicity categorized as severe vs. 2% in the mitomycin C monotherapy arm. This degree of toxicity may limit the utility of the approach in low-risk patients. Nonetheless, the efficacy results are such that this approach warrants further evaluation for patients refractory to other treatment modalities or at significant risk for tumor progression. doi:10.1016/j.urolonc.2004.03.011 William A. See, M.D.