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T1 transitional cell carcinoma of the bladder
W.A. See / Urologic Oncology: Seminars and Original Investigations 22 (2004) 265–274
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such, a daily multidose vitamin, while providing uncertain value as it relates to bladder tumor recurrence, is a low risk activity that allows the patient to “participate” in their own health care. doi:10.1016/j.urolonc.2004.03.007 William A. See, M.D.
Efficacy of office fulguration for recurrent low-grade papillary bladder tumors less than 0.5 cm. Donat SM, North A, Dalbagni G, Herr HW, Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY. J Urol 2004;171:636 –9 Purpose: Recurrent superficial papillary bladder tumors are most commonly treated with transurethral resection with the patient under anesthesia. We report our experience with office fulguration of small, recurrent, low grade papillary tumors using flexible cystodiathermy. Materials and Methods: We conducted a prospective single institution analysis of 267 consecutive patients with superficial bladder cancer undergoing routine bladder cancer surveillance between January 1998 and December 2001. Cytological and histological recurrences were recorded. Selection criteria for office fulguration were less than five low-grade appearing papillary tumors, tumor size less than 0.5 cm, negative urine cytology and patient desire. All patients completed initial treatment (transurethral resection, partial cystectomy and/or intravesical therapy) and a minimum of 6 months on surveillance without recurrence (median 11.57 months). Results: Flexible cystodiathermy for small, low grade, recurrent papillary tumors was efficacious and well tolerated. Of the 123 patients 46% experienced 1 or more tumor recurrences (range 1 to 11) in a median follow-up of 2.6 years. Of these 123, 74 (60%) underwent office cystodiathermy. No difference was seen in disease specific survival (P ⫽ 0.1633) or disease progression (P ⫽ 0.860). When stratified by risk of recurrence 202 of 267 patients at high risk (76%) with low grade papillary recurrence had similar rates of progression to patients at low risk (P ⫽ 0.9025). Median time from diagnosis was 6.84 years, and time from last tumor was 20.4 months. Conclusions: Office cystodiathermy of small, low-grade papillary recurrence is safe and efficacious in properly selected patients. This change in practice can potentially improve patient quality of life and have a major economic impact on health care.
Commentary For patients with low grade, low stage (TA Grade I or PUNLMP [Papillary Urothelial Neoplasm of Low Malignant Potential]) the burden of therapy can literally be worse than the disease process itself. The natural history of this disease is such that the majority of patients will suffer recurrences subsequent to treatment of their index lesion. Not only does this necessitate cystoscopic monitoring of the lower urinary tract at regular intervals, but, in addition, the recurrent tumors obviously need treatment. Modifications in management, which decrease the burden of therapy without compromising outcome, are of value in this setting. The manuscript by Donat et al. formally reports on a practice which I suspect is used by the majority of urologists. Rather than subject patients with small volume, historically low grade, low stage, tumor recurrences to the morbidity associated with an anesthetic, these lesions can be safely and effectively treated in an office-based setting. The algorithm presented by the authors is quite reasonable based upon their experience. Regarding the authors’ treatment algorithm there are several subtle details that merit comment. The first relates to the role of urinary cytology. The authors appropriately note that if fulguration is performed on the same day as the diagnostic procedure the results of cytology are not available and require subsequent assessment. Depending upon institutional expertise it may be of value to work with your cytopathologist in an effort to discriminate cytology that is suspicious for high-grade urothelium malignancy from that in which a low grade papillary neoplasm cannot be excluded. The point is that when cytopathologists use the term “suspicious” it may have a number of meanings, and from a treatment planning perspective it is of value to know whether the pathologist is concerned with a high-grade lesion or is simply commenting upon the already established presence of a low-grade papillary neoplasm. An additional issue relates to the use of intravesical lidocaine as a topical anesthetic. Although debate exists regarding its efficacy, our practice has been to schedule patients for this procedure, have them return to clinic when their cytology is available, and instill topical lidocaine into their bladder via catheter for 15 minutes before performance of the procedure. This approach obviates the concern related to the need to follow-up a cytology result, and in our hands provides a low morbidity procedure that is well tolerated by patients. doi:10.1016/j.urolonc.2004.03.008 William A. See, M.D.
A randomized controlled trial of short-term vs. long-term prophylactic intravesical instillation chemotherapy for recurrence after transurethral resection of Ta/T1 transitional cell carcinoma of the bladder. Koga H, Kuroiwa K, Yamaguchi A, Osada Y, Tsuneyoshi M, Naito S, Department of Urology, Graduate School of Medicine, Kyushu University, Japan. J Urol 2004;171:153–7 Purpose: In a prospective randomized controlled study, we investigated the optimal schedule for intravesical instillation of epirubicin for maximizing its effect on prophylaxis and disease progression after transurethral resection of newly diagnosed Ta/T1 bladder cancer. Materials and Methods: The patients were instilled with epirubicin (30 mg/30 mL in normal saline) within 24 hours after transurethral resection and then randomized into two groups after a definite histopathological diagnosis of Ta/T1 bladder cancer. One group of 77 patients
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W.A. See / Urologic Oncology: Seminars and Original Investigations 22 (2004) 265–274
received 19 intravesical instillations of epirubicin in the year after transurethral resection (Group 1). The second group of 73 patients received nine intravesical instillations of epirubicin during the 3 months after transurethral resection (Group 2). Nonrecurrence rates and toxicity were compared. Results: In the follow-up period, 10 Group 1 patients (13.0%) and 23 Group 2 patients (31.5%) had recurrent disease. The 3-year nonrecurrence rate was 85.2% in Group 1, whereas it was 63.9% in Group 2. The nonrecurrence rate of Group 1 was significantly higher than that of Group 2 throughout the observation period (P ⫽ 0.005). The incidence and severity of toxicity were not significantly different between the two groups. Conclusions: Our study indicates that long-term instillation of epirubicin is more effective than short-term instillation in preventing recurrence after transurethral resection of Ta/T1 bladder cancer.
Commentary The timing and duration of adjuvant intravesical therapies, administered in an effort to prevent the recurrence of nonmuscle invasive bladder tumors, are important variables in determining treatment efficacy. The report by Koga et al. presents data to suggest that long-term instillation of an intravesical therapeutic agent provides greater recurrence prevention benefit than instillation of shorter duration. A growing body of both clinical and basic scientific literature suggests that the etiology of bladder tumor recurrence is multifactoral. Mechanisms contributing to the high rate of bladder tumor recurrence include tumor implantation, field change disease, incomplete resection, and the presence of sub-clinical lesions at the time of the initial treatment. The challenge inherent in attempting to define an optimal adjuvant treatment strategy is to delineate an approach that effectively addresses all of these issues. At present this “ideal” treatment strategy is undefined. However, elements critical to such a regime are established. Several recent publications have demonstrated that immediate perioperative instillation of chemotherapeutic agents is more effective than the delayed administration of multiple intravesical doses. The benefit associated with this strategy is felt to accrue as a consequence of providing an unfavorable milieu for the implantation and subsequent out-growth of tumors seeded at the time of transurethral resection. If “neoplastic infection” is in any way analogous to bacterial wound infections, then the timing of anti-neoplastic administration is critical to efficacy. Unfortunately, in this trial perioperative chemoprophylaxis was defined as any time within the first 24 hours following transurethral tumor resection. Only 16 of 171 enrolled patients had their first intravesical installation in the immediate perioperative setting. Consequently, the conclusion that I would draw from this manuscript is that in the absence of optimal perioperative chemotherapy, administration of a protracted course of therapy is more effective than a shorter course. doi:10.1016/j.urolonc.2004.03.009 William A. See, M.D.
Long-term outcome of bladder papillary urothelial neoplasms of low malignant potential. Fujii Y, Kawakami S, Koga F, Nemoto T, Kihara K, Urology and Reproductive Medicine, and Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. BJU Int 2003;92:559 – 62 Objective: To evaluate the long-term outcome of bladder papillary urothelial neoplasms of low malignant potential (PUNLMP). Patients and Methods: Of 475 consecutive patients with newly diagnosed bladder tumors between 1976 and 1993, 330 (69%) had superficial (Ta and T1) tumors and 53 (11%) were diagnosed as having PUNLMP. Fifty patients (mean age at presentation 57.2 years, range 26-83; male-to-female ratio 6:1) who were followed for ⬎5 years or until they died, were included in the present study. All histological slides were reviewed, and fulfilled the diagnostic criteria of the 1998 World Health Organization/International Society of Urological Pathology classification system. Results: The mean (median, range) follow-up was 11.7 (10.8, 1.3-24.4) years. During the follow-up, 30 patients (60%) had local recurrences. The 2, 5 and 10-year recurrence-free rates were 66%, 51% and 36%, respectively. No patients developed high-grade or muscle-invasive (⬎/⫽ T2) carcinomas, or upper urinary tract tumors, or died from the disease. At the last follow-up, 34 patients (68%) had been disease-free for ⬎5 years. Conclusions: Despite a high recurrence rate, PUNLMP carries a very low malignant potential. We agree with the use of the term ‘papillary urothelial neoplasms of low malignant potential’ instead of ‘superficial bladder carcinoma (cancer)’ for these tumors.
Commentary The pathologic definition of human neoplastic diseases, both in terms of stage and grade, is critical to the appropriate management of the individual patient. Based upon the previously defined natural history of a given tumor stage and grade, clinicians can provide prognostic information and make appropriate therapeutic decisions. Given the importance of clinical grading and staging, it is appropriate that the urologic/oncologic community continually revisit and refine the stage and grade categories used in clinical management. In the ideal setting, stage/grade categorizations provide a system of minimalist complexity resulting in maximal clinical utility.
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such, a daily multidose vitamin, while providing uncertain value as it relates to bladder tumor recurrence, is a low risk activity that allows the patient to “participate” in their own health care. doi:10.1016/j.urolonc.2004.03.007 William A. See, M.D.
Efficacy of office fulguration for recurrent low-grade papillary bladder tumors less than 0.5 cm. Donat SM, North A, Dalbagni G, Herr HW, Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY. J Urol 2004;171:636 –9 Purpose: Recurrent superficial papillary bladder tumors are most commonly treated with transurethral resection with the patient under anesthesia. We report our experience with office fulguration of small, recurrent, low grade papillary tumors using flexible cystodiathermy. Materials and Methods: We conducted a prospective single institution analysis of 267 consecutive patients with superficial bladder cancer undergoing routine bladder cancer surveillance between January 1998 and December 2001. Cytological and histological recurrences were recorded. Selection criteria for office fulguration were less than five low-grade appearing papillary tumors, tumor size less than 0.5 cm, negative urine cytology and patient desire. All patients completed initial treatment (transurethral resection, partial cystectomy and/or intravesical therapy) and a minimum of 6 months on surveillance without recurrence (median 11.57 months). Results: Flexible cystodiathermy for small, low grade, recurrent papillary tumors was efficacious and well tolerated. Of the 123 patients 46% experienced 1 or more tumor recurrences (range 1 to 11) in a median follow-up of 2.6 years. Of these 123, 74 (60%) underwent office cystodiathermy. No difference was seen in disease specific survival (P ⫽ 0.1633) or disease progression (P ⫽ 0.860). When stratified by risk of recurrence 202 of 267 patients at high risk (76%) with low grade papillary recurrence had similar rates of progression to patients at low risk (P ⫽ 0.9025). Median time from diagnosis was 6.84 years, and time from last tumor was 20.4 months. Conclusions: Office cystodiathermy of small, low-grade papillary recurrence is safe and efficacious in properly selected patients. This change in practice can potentially improve patient quality of life and have a major economic impact on health care.
Commentary For patients with low grade, low stage (TA Grade I or PUNLMP [Papillary Urothelial Neoplasm of Low Malignant Potential]) the burden of therapy can literally be worse than the disease process itself. The natural history of this disease is such that the majority of patients will suffer recurrences subsequent to treatment of their index lesion. Not only does this necessitate cystoscopic monitoring of the lower urinary tract at regular intervals, but, in addition, the recurrent tumors obviously need treatment. Modifications in management, which decrease the burden of therapy without compromising outcome, are of value in this setting. The manuscript by Donat et al. formally reports on a practice which I suspect is used by the majority of urologists. Rather than subject patients with small volume, historically low grade, low stage, tumor recurrences to the morbidity associated with an anesthetic, these lesions can be safely and effectively treated in an office-based setting. The algorithm presented by the authors is quite reasonable based upon their experience. Regarding the authors’ treatment algorithm there are several subtle details that merit comment. The first relates to the role of urinary cytology. The authors appropriately note that if fulguration is performed on the same day as the diagnostic procedure the results of cytology are not available and require subsequent assessment. Depending upon institutional expertise it may be of value to work with your cytopathologist in an effort to discriminate cytology that is suspicious for high-grade urothelium malignancy from that in which a low grade papillary neoplasm cannot be excluded. The point is that when cytopathologists use the term “suspicious” it may have a number of meanings, and from a treatment planning perspective it is of value to know whether the pathologist is concerned with a high-grade lesion or is simply commenting upon the already established presence of a low-grade papillary neoplasm. An additional issue relates to the use of intravesical lidocaine as a topical anesthetic. Although debate exists regarding its efficacy, our practice has been to schedule patients for this procedure, have them return to clinic when their cytology is available, and instill topical lidocaine into their bladder via catheter for 15 minutes before performance of the procedure. This approach obviates the concern related to the need to follow-up a cytology result, and in our hands provides a low morbidity procedure that is well tolerated by patients. doi:10.1016/j.urolonc.2004.03.008 William A. See, M.D.
A randomized controlled trial of short-term vs. long-term prophylactic intravesical instillation chemotherapy for recurrence after transurethral resection of Ta/T1 transitional cell carcinoma of the bladder. Koga H, Kuroiwa K, Yamaguchi A, Osada Y, Tsuneyoshi M, Naito S, Department of Urology, Graduate School of Medicine, Kyushu University, Japan. J Urol 2004;171:153–7 Purpose: In a prospective randomized controlled study, we investigated the optimal schedule for intravesical instillation of epirubicin for maximizing its effect on prophylaxis and disease progression after transurethral resection of newly diagnosed Ta/T1 bladder cancer. Materials and Methods: The patients were instilled with epirubicin (30 mg/30 mL in normal saline) within 24 hours after transurethral resection and then randomized into two groups after a definite histopathological diagnosis of Ta/T1 bladder cancer. One group of 77 patients
270
W.A. See / Urologic Oncology: Seminars and Original Investigations 22 (2004) 265–274
received 19 intravesical instillations of epirubicin in the year after transurethral resection (Group 1). The second group of 73 patients received nine intravesical instillations of epirubicin during the 3 months after transurethral resection (Group 2). Nonrecurrence rates and toxicity were compared. Results: In the follow-up period, 10 Group 1 patients (13.0%) and 23 Group 2 patients (31.5%) had recurrent disease. The 3-year nonrecurrence rate was 85.2% in Group 1, whereas it was 63.9% in Group 2. The nonrecurrence rate of Group 1 was significantly higher than that of Group 2 throughout the observation period (P ⫽ 0.005). The incidence and severity of toxicity were not significantly different between the two groups. Conclusions: Our study indicates that long-term instillation of epirubicin is more effective than short-term instillation in preventing recurrence after transurethral resection of Ta/T1 bladder cancer.
Commentary The timing and duration of adjuvant intravesical therapies, administered in an effort to prevent the recurrence of nonmuscle invasive bladder tumors, are important variables in determining treatment efficacy. The report by Koga et al. presents data to suggest that long-term instillation of an intravesical therapeutic agent provides greater recurrence prevention benefit than instillation of shorter duration. A growing body of both clinical and basic scientific literature suggests that the etiology of bladder tumor recurrence is multifactoral. Mechanisms contributing to the high rate of bladder tumor recurrence include tumor implantation, field change disease, incomplete resection, and the presence of sub-clinical lesions at the time of the initial treatment. The challenge inherent in attempting to define an optimal adjuvant treatment strategy is to delineate an approach that effectively addresses all of these issues. At present this “ideal” treatment strategy is undefined. However, elements critical to such a regime are established. Several recent publications have demonstrated that immediate perioperative instillation of chemotherapeutic agents is more effective than the delayed administration of multiple intravesical doses. The benefit associated with this strategy is felt to accrue as a consequence of providing an unfavorable milieu for the implantation and subsequent out-growth of tumors seeded at the time of transurethral resection. If “neoplastic infection” is in any way analogous to bacterial wound infections, then the timing of anti-neoplastic administration is critical to efficacy. Unfortunately, in this trial perioperative chemoprophylaxis was defined as any time within the first 24 hours following transurethral tumor resection. Only 16 of 171 enrolled patients had their first intravesical installation in the immediate perioperative setting. Consequently, the conclusion that I would draw from this manuscript is that in the absence of optimal perioperative chemotherapy, administration of a protracted course of therapy is more effective than a shorter course. doi:10.1016/j.urolonc.2004.03.009 William A. See, M.D.
Long-term outcome of bladder papillary urothelial neoplasms of low malignant potential. Fujii Y, Kawakami S, Koga F, Nemoto T, Kihara K, Urology and Reproductive Medicine, and Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. BJU Int 2003;92:559 – 62 Objective: To evaluate the long-term outcome of bladder papillary urothelial neoplasms of low malignant potential (PUNLMP). Patients and Methods: Of 475 consecutive patients with newly diagnosed bladder tumors between 1976 and 1993, 330 (69%) had superficial (Ta and T1) tumors and 53 (11%) were diagnosed as having PUNLMP. Fifty patients (mean age at presentation 57.2 years, range 26-83; male-to-female ratio 6:1) who were followed for ⬎5 years or until they died, were included in the present study. All histological slides were reviewed, and fulfilled the diagnostic criteria of the 1998 World Health Organization/International Society of Urological Pathology classification system. Results: The mean (median, range) follow-up was 11.7 (10.8, 1.3-24.4) years. During the follow-up, 30 patients (60%) had local recurrences. The 2, 5 and 10-year recurrence-free rates were 66%, 51% and 36%, respectively. No patients developed high-grade or muscle-invasive (⬎/⫽ T2) carcinomas, or upper urinary tract tumors, or died from the disease. At the last follow-up, 34 patients (68%) had been disease-free for ⬎5 years. Conclusions: Despite a high recurrence rate, PUNLMP carries a very low malignant potential. We agree with the use of the term ‘papillary urothelial neoplasms of low malignant potential’ instead of ‘superficial bladder carcinoma (cancer)’ for these tumors.
Commentary The pathologic definition of human neoplastic diseases, both in terms of stage and grade, is critical to the appropriate management of the individual patient. Based upon the previously defined natural history of a given tumor stage and grade, clinicians can provide prognostic information and make appropriate therapeutic decisions. Given the importance of clinical grading and staging, it is appropriate that the urologic/oncologic community continually revisit and refine the stage and grade categories used in clinical management. In the ideal setting, stage/grade categorizations provide a system of minimalist complexity resulting in maximal clinical utility.