- Email: [email protected]
Variations in reconstruction after radical cystectomy
272
H.B. Grossman / Urologic Oncology: Seminars and Original Investigations 25 (2007) 271–280
Commentary Apaziquone is a derivative of mitomycin and, like mitomycin, requires cellular activation to become cytotoxic. This new drug was tested using a marker lesion strategy. This methodology, although rarely used in the United States, is an effective way of evaluating a new drug for intravesical activity. Tumors ranged from Ta, grade 1 to T1, grade 3. Complete response, defined as complete disappearance of the marker lesion, was achieved in 67%. This is a good result with a marker lesion study. Toxicity was generally mild and similar to that seen with other intravesical chemotherapeutic agents. Unfortunately, tumor grade and stage did not detail responses. Larger clinical trials are needed to evaluate the potential clinical use of this drug. doi:10.1016/j.urolonc.2007.03.001 H. Barton Grossman, M.D. The effect of ofloxacin on bacillus calmette-guerin induced toxicity in patients with superficial bladder cancer: results of a randomized, prospective, double-blind, placebo controlled, multicenter study. Colombel M, Saint F, Chopin D, Malavaud B, Nicolas L, Rischmann P, Service d’Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot, Universite Claude Bernard, 5, France. J Urol 2006;176:935–9 Purpose: We determined whether prophylaxis with ofloxacin could decrease the toxicity of bacillus Calmette-Guerin for transitional cell carcinoma of the bladder. We also investigated the impact of ofloxacin on bacillus Calmette-Guerin antitumor efficacy. Materials and Methods: In this randomized, double-blind, multicenter study 115 patients with primary or recurrent superficial bladder cancer (Ta/T1, CIS, G1-G3) and no prior bacillus Calmette-Guerin treatment were randomized to induction treatment with intravesical bacillus Calmette-Guerin (6 plus 3 instillations) plus 200 mg ofloxacin in group 1 or plus placebo in group 2. Adverse events were assessed using a detailed grid of classification for bacillus Calmette-Guerin related adverse events. Mean patient age ⫹/⫺ SD was 65.6 ⫹/⫺ 10.4 years in the 57 group 1 patients and 65.7 ⫹/⫺ 8.7 years in the 58 in group 2. Median followup was 369 and 374 days in groups 1 and 2, respectively. Results: Ofloxacin significantly decreased by 18.5% the incidence of class II or higher moderate and severe adverse events between instillations 4 and 6. The percent of class III adverse events was significantly decreased by ofloxacin between instillations 1 and 9. Although ofloxacin decreased adverse events involving the lower urinary tract, it did not prevent class I adverse events. Compliance with full bacillus Calmette-Guerin treatment was also improved. Of patients in group 1, 80.7% received 9 instillations compared with 65.5% in group 2 (P ⫽ 0.092). At 12 months recurrence and progression rates in group 1 and 2 were 12.7% and 17.2%, and 5.5% and 1.7%, respectively. Conclusions: Prophylactic ofloxacin decreased the incidence of moderate to severe adverse events associated with bacillus CalmetteGuerin intravesical therapy, particularly class III events, which are primarily associated with patient dropout. Compliance with induction and maintenance therapy may be improved by adjuvant ofloxacin therapy. However, long-term comparative studies with other preventive strategies must be done to confirm these initial findings with compliance and recurrence-free survival as the primary end points.
Commentary Although bacillus Calmette-Guérin (BCG) has been used extensively for intravesical therapy of bladder cancer, the optimal method of delivering this drug remains to be defined. While effective, BCG is known to cause local toxicity. Ofloxacin has tuberculostatic properties and was tested in a randomized study of 115 patients, who were going to receive BCG for 6 weeks followed by 6 weeks off drug and then another 3 weeks of BCG. Toxicity was significantly decreased in the patients randomized to receive ofloxacin. At 1 year, recurrence rates were lower in the patients treated with ofloxacin, but the progression rates were higher. These differences were not significant. Larger studies and long-term follow-up are needed to ensure that the efficacy of BCG is not impaired. Another simple strategy for treating toxicity from intravesical BCG is to lower the dose when significant symptoms develop in patients. doi:10.1016/j.urolonc.2007.03.004 H. Barton Grossman, M.D. Variations in reconstruction after radical cystectomy. Gore JL, Saigal CS, Hanley JM, Schonlau M, Litwin MS, Urologic Diseases in America Project, Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA. Cancer 2006;107:729 –37 Background: Most urologists specializing in the management of patients with bladder cancer consider continent urinary diversion the reconstructive technique that affords the best quality of life after radical cystectomy. The authors sought to evaluate factors that predict reconstructive technique after radical cystectomy. Methods: Using linked data from Medicare and the National Cancer Institute’s (NCI) Surveillance, Epidemiology, and End Results (SEER) program, 3611 subjects were identified who underwent radical cystectomy for bladder cancer between 1992 and 2000. Multivariate logistic regression was used to identify factors independently associated with utilization of continent reconstruction after radical cystectomy, incorporating patient and provider variables. Results: In multivariate analysis, the likelihood of continent diversion was inversely associated with older age (odds ratio [OR] ⬍ or ⫽
H.B. Grossman / Urologic Oncology: Seminars and Original Investigations 25 (2007) 271–280
273
0.68, P ⬍ .002), African American race (OR 0.43, P ⫽ .003), and higher comorbidity index (OR 0.71, P ⫽ .03), and directly associated with male sex (OR 1.45, P ⫽ .002), higher education level (OR 1.54, P ⫽ .03), and year of surgery (OR ⬎ or ⫽ 1.56, P ⬍ .001 for all year categories vs. 1992–1994). Treatment at academic (OR 1.43, P ⫽ .003) and NCI-designated cancer centers (OR 5.50, P ⬍ .001) and by high-volume providers (OR 1.49, P ⬍ .001) was independently associated with continent reconstruction. Conclusions: Disparities in the utilization of continent urinary diversion after radical cystectomy suggest that demographic, socioeconomic, provider-based, and clinical variables predict the likelihood that those undergoing radical cystectomy will receive continent reconstruction. Regionalization of bladder cancer care may ameliorate many of the disparities noted but must be balanced against the risk imposed by a delay in care.
Commentary Evaluation of the Surveillance, Epidemiology, and End Results national cancer registry and Medicare claims for 1992 through 2000 document significant variation in the methods of urinary diversion after radical cystectomy. Older individuals, African-Americans, women, and those with higher comorbidity were significantly less likely to receive a continent diversion. Patients treated at academic centers or by high-volume providers were more likely to have a continent diversion. The rates of continent diversion increased with more recent times. This snapshot shows that continent diversions are being used more frequently than in the past. Whether this trend will persist and decrease the unevenness in the application of continent urinary diversion remains to be seen. doi:10.1016/j.urolonc.2007.03.003 H. Barton Grossman, M.D. Natural history of positive urinary cytology after radical cystectomy. Raj GV, Bochner BH, Serio AM, Vickers A, Donat SM, Herr H, Lin O, Dalbagni G, Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY. J Urol 2006;176:2000 –5 Purpose: The natural history and risk of disease progression in patients with positive urine cytology after radical cystectomy for urothelial carcinoma has not been adequately elucidated. Materials and Methods: An institutional review board approved, retrospective review in patients undergoing radical cystectomy was performed to identify those with positive urinary cytology after radical cystectomy. Cox proportional hazards regression was used to determine factors associated with positive cytology after radical cystectomy and upper tract recurrence after positive cytology. Survival curves and probabilities were examined by Kaplan-Meier analysis. Results: A total of 101 patients with at least a single positive urinary cytology result after radical cystectomy were identified. Ureteral involvement in the radical cystectomy specimen was significantly associated with subsequent positive cytology. At the first positive urinary cytology only 9 of 101 patients (9%) had documented urothelial recurrence but eventually 57 of 101 had radiographic evidence of urothelial recurrence. Median freedom from radiological evidence of urothelial recurrence after positive cytology was 2.1 years and ureteral involvement was associated with a higher likelihood of urothelial recurrence. Despite surgical and chemotherapeutic interventions median survival after urothelial recurrence was 2.1 years. Conclusions: Urine cytology may have a valuable role for detecting upper tract recurrence after radical cystectomy. Most patients with positive cytology after radical cystectomy eventually have radiological evidence of urothelial recurrence. These data may help clarify natural history in patients with positive cytology after radical cystectomy. Additionally, these data indicate the need for diligent evaluation for recurrent disease and potentially the role of early adjuvant therapy in patients with positive cytology after radical cystectomy.
Commentary Patients with bladder cancer are at risk for recurrence in the upper tract. This retrospective review examined the ability of urine cytology to detect upper tract disease after radical cystectomy. Of 1,408 patients who had at least 1 urine cytology after radical cystectomy, 101 (7.2%) had at least 1 positive test. Of them, 40% had a positive cytology within 1 year of the cystectomy. The rates of continent and loop urinary diversions in these patients were almost equal. A history of ureteral involvement was strongly associated with a positive cytology, and positive cytology was predictive of upper tract recurrence. However, only 9% of the patients with a positive cytology were found to have a recurrence at the first positive cytology. The median time to recurrence after positive cytology was 2.1 years. Of the 101 patients with a positive cytology, 57 were found to have recurrent urothelial cancer. Urine cytology can be used to monitor patients after radical cystectomy. Patients with positive cytology after radical cystectomy need careful assessment of their upper tracts and close monitoring for recurrence. doi:10.1016/j.urolonc.2007.03.005 H. Barton Grossman, M.D.
H.B. Grossman / Urologic Oncology: Seminars and Original Investigations 25 (2007) 271–280
Commentary Apaziquone is a derivative of mitomycin and, like mitomycin, requires cellular activation to become cytotoxic. This new drug was tested using a marker lesion strategy. This methodology, although rarely used in the United States, is an effective way of evaluating a new drug for intravesical activity. Tumors ranged from Ta, grade 1 to T1, grade 3. Complete response, defined as complete disappearance of the marker lesion, was achieved in 67%. This is a good result with a marker lesion study. Toxicity was generally mild and similar to that seen with other intravesical chemotherapeutic agents. Unfortunately, tumor grade and stage did not detail responses. Larger clinical trials are needed to evaluate the potential clinical use of this drug. doi:10.1016/j.urolonc.2007.03.001 H. Barton Grossman, M.D. The effect of ofloxacin on bacillus calmette-guerin induced toxicity in patients with superficial bladder cancer: results of a randomized, prospective, double-blind, placebo controlled, multicenter study. Colombel M, Saint F, Chopin D, Malavaud B, Nicolas L, Rischmann P, Service d’Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot, Universite Claude Bernard, 5, France. J Urol 2006;176:935–9 Purpose: We determined whether prophylaxis with ofloxacin could decrease the toxicity of bacillus Calmette-Guerin for transitional cell carcinoma of the bladder. We also investigated the impact of ofloxacin on bacillus Calmette-Guerin antitumor efficacy. Materials and Methods: In this randomized, double-blind, multicenter study 115 patients with primary or recurrent superficial bladder cancer (Ta/T1, CIS, G1-G3) and no prior bacillus Calmette-Guerin treatment were randomized to induction treatment with intravesical bacillus Calmette-Guerin (6 plus 3 instillations) plus 200 mg ofloxacin in group 1 or plus placebo in group 2. Adverse events were assessed using a detailed grid of classification for bacillus Calmette-Guerin related adverse events. Mean patient age ⫹/⫺ SD was 65.6 ⫹/⫺ 10.4 years in the 57 group 1 patients and 65.7 ⫹/⫺ 8.7 years in the 58 in group 2. Median followup was 369 and 374 days in groups 1 and 2, respectively. Results: Ofloxacin significantly decreased by 18.5% the incidence of class II or higher moderate and severe adverse events between instillations 4 and 6. The percent of class III adverse events was significantly decreased by ofloxacin between instillations 1 and 9. Although ofloxacin decreased adverse events involving the lower urinary tract, it did not prevent class I adverse events. Compliance with full bacillus Calmette-Guerin treatment was also improved. Of patients in group 1, 80.7% received 9 instillations compared with 65.5% in group 2 (P ⫽ 0.092). At 12 months recurrence and progression rates in group 1 and 2 were 12.7% and 17.2%, and 5.5% and 1.7%, respectively. Conclusions: Prophylactic ofloxacin decreased the incidence of moderate to severe adverse events associated with bacillus CalmetteGuerin intravesical therapy, particularly class III events, which are primarily associated with patient dropout. Compliance with induction and maintenance therapy may be improved by adjuvant ofloxacin therapy. However, long-term comparative studies with other preventive strategies must be done to confirm these initial findings with compliance and recurrence-free survival as the primary end points.
Commentary Although bacillus Calmette-Guérin (BCG) has been used extensively for intravesical therapy of bladder cancer, the optimal method of delivering this drug remains to be defined. While effective, BCG is known to cause local toxicity. Ofloxacin has tuberculostatic properties and was tested in a randomized study of 115 patients, who were going to receive BCG for 6 weeks followed by 6 weeks off drug and then another 3 weeks of BCG. Toxicity was significantly decreased in the patients randomized to receive ofloxacin. At 1 year, recurrence rates were lower in the patients treated with ofloxacin, but the progression rates were higher. These differences were not significant. Larger studies and long-term follow-up are needed to ensure that the efficacy of BCG is not impaired. Another simple strategy for treating toxicity from intravesical BCG is to lower the dose when significant symptoms develop in patients. doi:10.1016/j.urolonc.2007.03.004 H. Barton Grossman, M.D. Variations in reconstruction after radical cystectomy. Gore JL, Saigal CS, Hanley JM, Schonlau M, Litwin MS, Urologic Diseases in America Project, Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA. Cancer 2006;107:729 –37 Background: Most urologists specializing in the management of patients with bladder cancer consider continent urinary diversion the reconstructive technique that affords the best quality of life after radical cystectomy. The authors sought to evaluate factors that predict reconstructive technique after radical cystectomy. Methods: Using linked data from Medicare and the National Cancer Institute’s (NCI) Surveillance, Epidemiology, and End Results (SEER) program, 3611 subjects were identified who underwent radical cystectomy for bladder cancer between 1992 and 2000. Multivariate logistic regression was used to identify factors independently associated with utilization of continent reconstruction after radical cystectomy, incorporating patient and provider variables. Results: In multivariate analysis, the likelihood of continent diversion was inversely associated with older age (odds ratio [OR] ⬍ or ⫽
H.B. Grossman / Urologic Oncology: Seminars and Original Investigations 25 (2007) 271–280
273
0.68, P ⬍ .002), African American race (OR 0.43, P ⫽ .003), and higher comorbidity index (OR 0.71, P ⫽ .03), and directly associated with male sex (OR 1.45, P ⫽ .002), higher education level (OR 1.54, P ⫽ .03), and year of surgery (OR ⬎ or ⫽ 1.56, P ⬍ .001 for all year categories vs. 1992–1994). Treatment at academic (OR 1.43, P ⫽ .003) and NCI-designated cancer centers (OR 5.50, P ⬍ .001) and by high-volume providers (OR 1.49, P ⬍ .001) was independently associated with continent reconstruction. Conclusions: Disparities in the utilization of continent urinary diversion after radical cystectomy suggest that demographic, socioeconomic, provider-based, and clinical variables predict the likelihood that those undergoing radical cystectomy will receive continent reconstruction. Regionalization of bladder cancer care may ameliorate many of the disparities noted but must be balanced against the risk imposed by a delay in care.
Commentary Evaluation of the Surveillance, Epidemiology, and End Results national cancer registry and Medicare claims for 1992 through 2000 document significant variation in the methods of urinary diversion after radical cystectomy. Older individuals, African-Americans, women, and those with higher comorbidity were significantly less likely to receive a continent diversion. Patients treated at academic centers or by high-volume providers were more likely to have a continent diversion. The rates of continent diversion increased with more recent times. This snapshot shows that continent diversions are being used more frequently than in the past. Whether this trend will persist and decrease the unevenness in the application of continent urinary diversion remains to be seen. doi:10.1016/j.urolonc.2007.03.003 H. Barton Grossman, M.D. Natural history of positive urinary cytology after radical cystectomy. Raj GV, Bochner BH, Serio AM, Vickers A, Donat SM, Herr H, Lin O, Dalbagni G, Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY. J Urol 2006;176:2000 –5 Purpose: The natural history and risk of disease progression in patients with positive urine cytology after radical cystectomy for urothelial carcinoma has not been adequately elucidated. Materials and Methods: An institutional review board approved, retrospective review in patients undergoing radical cystectomy was performed to identify those with positive urinary cytology after radical cystectomy. Cox proportional hazards regression was used to determine factors associated with positive cytology after radical cystectomy and upper tract recurrence after positive cytology. Survival curves and probabilities were examined by Kaplan-Meier analysis. Results: A total of 101 patients with at least a single positive urinary cytology result after radical cystectomy were identified. Ureteral involvement in the radical cystectomy specimen was significantly associated with subsequent positive cytology. At the first positive urinary cytology only 9 of 101 patients (9%) had documented urothelial recurrence but eventually 57 of 101 had radiographic evidence of urothelial recurrence. Median freedom from radiological evidence of urothelial recurrence after positive cytology was 2.1 years and ureteral involvement was associated with a higher likelihood of urothelial recurrence. Despite surgical and chemotherapeutic interventions median survival after urothelial recurrence was 2.1 years. Conclusions: Urine cytology may have a valuable role for detecting upper tract recurrence after radical cystectomy. Most patients with positive cytology after radical cystectomy eventually have radiological evidence of urothelial recurrence. These data may help clarify natural history in patients with positive cytology after radical cystectomy. Additionally, these data indicate the need for diligent evaluation for recurrent disease and potentially the role of early adjuvant therapy in patients with positive cytology after radical cystectomy.
Commentary Patients with bladder cancer are at risk for recurrence in the upper tract. This retrospective review examined the ability of urine cytology to detect upper tract disease after radical cystectomy. Of 1,408 patients who had at least 1 urine cytology after radical cystectomy, 101 (7.2%) had at least 1 positive test. Of them, 40% had a positive cytology within 1 year of the cystectomy. The rates of continent and loop urinary diversions in these patients were almost equal. A history of ureteral involvement was strongly associated with a positive cytology, and positive cytology was predictive of upper tract recurrence. However, only 9% of the patients with a positive cytology were found to have a recurrence at the first positive cytology. The median time to recurrence after positive cytology was 2.1 years. Of the 101 patients with a positive cytology, 57 were found to have recurrent urothelial cancer. Urine cytology can be used to monitor patients after radical cystectomy. Patients with positive cytology after radical cystectomy need careful assessment of their upper tracts and close monitoring for recurrence. doi:10.1016/j.urolonc.2007.03.005 H. Barton Grossman, M.D.