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Management of the Urethra in Men Undergoing Radical Cystectomy for Bladder Cancer
0022-534 7/84/1312-0267$02.00/0 THE JOURNAL OF UROLOGY
Vol. 131, Febn1ary
Copyright© 1984 by The Williams & Wilkins Co.
Printed in U.S.A.
MANAGEMENT OF THE URETHRA IN MEN UNDERGOING RADICAL CYSTECTOMY FOR BLADDER CANCER AUGUST ZABBO
JAMES E. MONTIE
AND
From the Department of Urology, The C/,eveland Clinic Foundation, Cleveland, Ohio
ABSTRACT
The records of 119 men who had undergone radical cystectomy for cancer of the bladder were reviewed for involvement of the urethra at the time of cystectomy and for later recurrence of urethral tumor. Urethral recurrences contributed significantly to the over-all pelvic recurrence rate and were associated with a uniformly poor prognosis. Prophylactic urethrectomy is indicated when pathologic examination reveals multifocal tumors, concurrent upper tract tumors, diffuse carcinoma in situ, involvement of the trigone or prostatic urethra, or positive urethral margin on frozen section. Those patients not undergoing urethrectomy should be followed with periodic urethral wash cytology. The multifocal potential of transitional cell carcinoma is well recognized, the mucosa at risk extending from the caliceal system of the kidney to the urethral meatus. Whether these different foci are the result of tumor seeding from a primary neoplasm, with resultant daughter colonies, or the response of the urothelium to continued contact with a carcinogenic agent, it is important to recognize the potential for recurrent tumors in a patient who has undergone radical cystectomy. The upper tracts and urethral mucosa must be monitored for the reappearance of tumor after radical cystectomy. We present our recent experience with urethral tumors in men who have undergone cystectomy. The indications for prophylactic urethrectomy are reviewed and a plan for surveillance of the urethra in patients who have not undergone prophylactic urethrectomy is described. METHODS
Between 1960 and 1979, 119 men underwent radical cystectomy for bladder cancer. The case records of these patients were reviewed with respect to involvement of the urethra by transitional cell carcinoma at the time of cystectomy, or recurrence of the transitional cell carcinoma in the urethra. Followup data were available for all patients. RESULTS
Of the patients in this series 11 (9 per cent) had undergone prophylactic urethrectomy. Pathologic examination of the urethral specimens from 2 patients revealed unsuspected invasive transitional cell carcinoma and both died of the disease <5 years postoperatively. Two patients had unsuspected carcinoma in situ: 1 died 7 months later, whereas 1 is alive with metastatic disease 6 years after cystectomy. Of the 7 patients with no urethral cancer 5 were free of disease 2 to 5 years after cystourethrectomy, 1 is dead of disease and 1 is alive with known metastatic disease. Pathologically, the disease was stage PO in 8 patients, Pl in 29, P2 in 30, P3 in 25 and PIS in 27. Of these 119 patients 7 (1 with stage Pl, 1 with P2 and 5 with PIS disease) had urethral recurrences 1 to 5 years after the original cystectomy (see table). Two of these patients had had prior urethrectomy by the method described by Whitmore and Mount, 1 and presented later with distal urethral (meatal) recurrences. Both patients still are alive but have inguinal nodal metastases. The remaining 5 patients with urethral recurrence died of disease <4 years after the recurrence was discovered. Accepted for publication September 2, 1983. The opinions expressed herein are not necessarily those of the United States Air Force.
The pelvic recurrence rate in this series of 119 patients was 15 per cent. Pelvic recurrences were defined as disease in the pelvis that became evident by physical examination or radiologic study. Thus, urethral recurrences accounted for approximately a third of the total pelvic recurrences. DISCUSSION
The reported involvement of the urethra with transitiona) cell carcinoma in patients with bladder cancer varies. In a review of the records of 1,307 patients with bladder cancer Ashworth found a 4.1 per cent rate of urethral involvement. 2 In an autopsy review Gowing reported urethral involvement in 18 per cent of the patients who died of bladder cancer. 3 Invariably, reports of urethral recurrence of bladder tumor after radical cystectomy have been associated with a poor prognosis. Hendry and associates reported 4 anterior urethral recurrences after cystectomy, all with fatal results. 4 Cordonnier and Spjut reported urethral recurrence after cystectomy in 7 patients (4 per cent): 5 died of disease shortly after discovery of the urethral tumor and 2 had only a short followup. 5 PooleWilson and Barnard reported a 12 per cent urethral recurrence rate after cystectomy, all with a fatal result. 6 In the largest series reported Schellhammer and Whitmore noted a 7 per cent recurrence rate for urethral tumors, with 21 of their 24 patients dead or having known metastatic disease. 7 The ominous nature of urethral recurrence may be related to the microscopic anatomy of the urethra. The sole barrier between the vascular spaces of the corpus spongiosum and the urethral mucosa is the lamina propria of the urethra. There is Data on 7 patients with urethral recurrences Pt.
Interval to Urethral Recurrence
Pathologic Stage*
Grade
Results After Urethrectomy
(yrs.) LT JV
4
PISNxMo PISNxMo
III IV
Dead of disease, 4 yrs. Dead of disease, 8
EG PR HE
2 2 1 (no urethrectomy)
PISNlMo PlNxMo P2NoMo
III
Dead of disease, 3 yrs. Dead of disease, 1 yr. Dead of disease, 2
JDt
5
PISNxMo
II
DJt
2
PISNxMo
II
4
mos.
II
III
mos.
Alive, pos. inguinal metastases Alive, pos. inguinal metastases
* Nx~formal lymphadenectomy was not done. t Patient underwent subtotal urethrectomy with late recurrence at urethral meatus.
267
268
ZABBO AND MONTIE
no thick muscle, as in the bladder, affording a potential barrier to spread of the tumor. It is difficult to separate urethral recurrence from other poor prognostic factors relating to the primary tumor of the bladder in patients dying of urethral recurrence. Perhaps urethral recurrence is just an expression of the aggressive nature of the primary tumor. Even if a prophylactic urethrectomy had been done the outcome still might be poor. In 10 cases of urethral recurrences Faysal attributed only 1 death directly to the recurrence itself. 8 However, it must be noted that the average followup was short and several of the survivors had tumors only at the carcinoma in situ stage. In support of the notion that urethral recurrence is the source of further metastatic spread is the frequent finding of an extended interval free of disease after cystectomy, with rapid progression of the disease after the urethral recurrence is manifest. Specifically in this series failure to control urethral disease was the likely cause of relapse and ultimate death in 6 patients (see table). Our series agrees generally with others stating that asymptomatic urethral recurrence implies a poor prognosis. Therefore, several investigators have advised routine prophylactic urethrectomy. In view of the low incidence of recurrence, we are reluctant to recommend routine extension of an already difficult procedure by an additional interval to accomplish a 1stage cystourethrectomy.9 It has been reported that urethral recurrences are more likely in certain clinical situations and that it probably is best to remove the urethra at the time of cystectomy. 4 •5 • 6 • 10• 11 These situations include 1) multifocal tumors, 2) a history of concurrent tumors in the upper urinary tract, 3) diffuse carcinoma in situ, 4) involvement of the prostatic urethra or trigone with tumor at the time of cystectomy and 5) positive urethral margin on frozen section. In our series 5 of the 7 patients with urethral recurrence had carcinoma in situ diffusely in the bladder. We believe that the urethral recurrence is the probable cause of death in these patients and prophylactic urethrectomy may have avoided this occurrence. Based on the aforementioned studies in our experience, 2 specific management practices appear reasonable. First, prophylactic urethrectomy should be performed for the aforementioned specific indications. One-stage cystourethrectomy in continuity is the most desirable procedure and is a necessity if urethral involvement is clinically evident. A prophylactic urethrectomy can be done with the cystectomy either in continuity or by dividing the membranous urethra and using a 2team approach for the ileal conduit and the urethrectomy. Alternatively, if at the time of operation it is believed best that urethrectomy not be included it can be done as a delayed procedure in 4 to 6 weeks. An important point to recognize is that the urethra must be excised totally. In 1970 Whitmore and Mount described a method of urethrectomy that involved transection of the urethra just proximal to the fossa navicularis. 1 In 1976 Schellhammer and Whitmore reported 8 cases of urethral meatal recurrence after urethrectomy performed in this manner. 12 We have seen this unfortunate circumstance in 2 of our patients and both probably will die because of incomplete urethrectomy. Thus, a circumscribing incision around the urethral meatus should be made and the glanular urethra should be resected entirely. The second recommendation is that all patients without urethrectomy should be followed with urethral wash cytology every 6 to 12 months. 13 Wolinska and associates described
findings in 65 patients followed with urethral wash cytology. 14 Of their patients 21 of 24 with positive cytology results subsequently were shown to have tumor on urethrectomy (11 of these at the carcinoma in situ stage), whereas ony 1 of 35 had false negative cytology findings. The method for urethral wash cytology is simple. A catheter is inserted into the urethra as far as it can be advanced, 10 to 15 ml. saline are injected and the effluent is collected from around the urethral meatus. The specimen then is processed for cytologic examination. Urethroscopy is more cumbersome and probably is not necessary if urethral wash specimens are obtained. Moreover, if one waits until a lesion becomes either symptomatic or grossly visible the results will be poor. Even though improved survival secondary to implementing urethral wash cytology as a routine method of surveillance has not yet been documented, identification of recurrences in a noninvasive stage should accomplish this. The surveillance probably should continue for the life of the patient since remote recurrences, some as late as 20 years, have been reported. 7 Although the recurrence rate in the urethra after cystectomy for bladder cancer is small (5.9 per cent in our series if the 2 urethral meatal recurrences noted after subtotal urethrectomy are included), the prognosis of this lesion is extremely poor. If effective surgical therapy is to be accomplished urethrectomy must be done when the tumors are at an early stage. We then recommend prophylactic urethrectomy for specific indications and close followup, including urethral wash cytology, of patients who have not undergone urethrectomy. REFERENCES 1. Whitmore, W. F., Jr. and Mount, B. M.: A technique of urethrectomy in the male. Surg., Gynec. & Obst., 131: 303, 1970. 2. Ashworth, A.: Papillomatosis of the urethra. Brit. J. Urol., 28: 3, 1956. 3. Gowing, N. F. C.: Urethral carcinoma associated with cancer of the bladder. Brit. J. Urol., 32: 428, 1960. 4. Hendry, W. F., Gowing, N. F. C. and Wallace, D. M.: Surgical treatment of urethral tumours associated with bladder cancer. Proc. Roy. Soc. Med., 67: 304, 1974. 5. Cordonnier, J. J. and Spjut, H. J.: Urethral occurrence of bladder carcinoma following cystectomy. J. Urol., 87: 398, 1962. 6. Poole-Wilson, D. S. and Barnard, R. J.: Total cystectomy for bladder tumours. Brit. J. Urol., 43: 16, 1971. 7. Schellhammer, P. F. and Whitmore, W. F., Jr.: Transitional cell carcinoma of the urethra in men having cystectomy for bladder cancer. J. Urol., 115: 56, 1967. 8. Faysal, M. H.: Urethrectomy in men with transitional cell carcinoma of bladder. Urology, 16: 23, 1980. 9. Johnson, D. E. and Guinn, G. A.: Surgical management of urethral carcinoma occurring after cystectomy. J. Urol., 103: 314, 1970. 10. Richie, J.P. and Skinner, D. G.: Carcinoma in situ of the urethra associated with bladder carcinoma: the role of urethrectomy. J Urol., 119: 80, 1978. 11. Raz, S., McLorie, G., Johnson, S. and Skinner, D. G.: Management of the urethra in patients undergoing radical cystectomy for bladder carcinoma. J. Urol., 120: 298, 1978. 12. Schellhammer, P. F. and Whitmore, W. F., Jr.: Urethral meatal carcinoma following cystourethrectomy for bladder carcinoma. J. Urol., 115: 61, 1976. 13. Williams, G.: Cytological screening of the urethra. Brit. J. Urol., 40: 703, 1968. 14. Wolinska, W. H., Melamed, M. R., Schellhammer, P. F. and Whitmore, W. F., Jr.: Urethral cytology following cystectomy for bladder carcinoma. Amer. J. Surg. Path., 1: 225, 1977.
Vol. 131, Febn1ary
Copyright© 1984 by The Williams & Wilkins Co.
Printed in U.S.A.
MANAGEMENT OF THE URETHRA IN MEN UNDERGOING RADICAL CYSTECTOMY FOR BLADDER CANCER AUGUST ZABBO
JAMES E. MONTIE
AND
From the Department of Urology, The C/,eveland Clinic Foundation, Cleveland, Ohio
ABSTRACT
The records of 119 men who had undergone radical cystectomy for cancer of the bladder were reviewed for involvement of the urethra at the time of cystectomy and for later recurrence of urethral tumor. Urethral recurrences contributed significantly to the over-all pelvic recurrence rate and were associated with a uniformly poor prognosis. Prophylactic urethrectomy is indicated when pathologic examination reveals multifocal tumors, concurrent upper tract tumors, diffuse carcinoma in situ, involvement of the trigone or prostatic urethra, or positive urethral margin on frozen section. Those patients not undergoing urethrectomy should be followed with periodic urethral wash cytology. The multifocal potential of transitional cell carcinoma is well recognized, the mucosa at risk extending from the caliceal system of the kidney to the urethral meatus. Whether these different foci are the result of tumor seeding from a primary neoplasm, with resultant daughter colonies, or the response of the urothelium to continued contact with a carcinogenic agent, it is important to recognize the potential for recurrent tumors in a patient who has undergone radical cystectomy. The upper tracts and urethral mucosa must be monitored for the reappearance of tumor after radical cystectomy. We present our recent experience with urethral tumors in men who have undergone cystectomy. The indications for prophylactic urethrectomy are reviewed and a plan for surveillance of the urethra in patients who have not undergone prophylactic urethrectomy is described. METHODS
Between 1960 and 1979, 119 men underwent radical cystectomy for bladder cancer. The case records of these patients were reviewed with respect to involvement of the urethra by transitional cell carcinoma at the time of cystectomy, or recurrence of the transitional cell carcinoma in the urethra. Followup data were available for all patients. RESULTS
Of the patients in this series 11 (9 per cent) had undergone prophylactic urethrectomy. Pathologic examination of the urethral specimens from 2 patients revealed unsuspected invasive transitional cell carcinoma and both died of the disease <5 years postoperatively. Two patients had unsuspected carcinoma in situ: 1 died 7 months later, whereas 1 is alive with metastatic disease 6 years after cystectomy. Of the 7 patients with no urethral cancer 5 were free of disease 2 to 5 years after cystourethrectomy, 1 is dead of disease and 1 is alive with known metastatic disease. Pathologically, the disease was stage PO in 8 patients, Pl in 29, P2 in 30, P3 in 25 and PIS in 27. Of these 119 patients 7 (1 with stage Pl, 1 with P2 and 5 with PIS disease) had urethral recurrences 1 to 5 years after the original cystectomy (see table). Two of these patients had had prior urethrectomy by the method described by Whitmore and Mount, 1 and presented later with distal urethral (meatal) recurrences. Both patients still are alive but have inguinal nodal metastases. The remaining 5 patients with urethral recurrence died of disease <4 years after the recurrence was discovered. Accepted for publication September 2, 1983. The opinions expressed herein are not necessarily those of the United States Air Force.
The pelvic recurrence rate in this series of 119 patients was 15 per cent. Pelvic recurrences were defined as disease in the pelvis that became evident by physical examination or radiologic study. Thus, urethral recurrences accounted for approximately a third of the total pelvic recurrences. DISCUSSION
The reported involvement of the urethra with transitiona) cell carcinoma in patients with bladder cancer varies. In a review of the records of 1,307 patients with bladder cancer Ashworth found a 4.1 per cent rate of urethral involvement. 2 In an autopsy review Gowing reported urethral involvement in 18 per cent of the patients who died of bladder cancer. 3 Invariably, reports of urethral recurrence of bladder tumor after radical cystectomy have been associated with a poor prognosis. Hendry and associates reported 4 anterior urethral recurrences after cystectomy, all with fatal results. 4 Cordonnier and Spjut reported urethral recurrence after cystectomy in 7 patients (4 per cent): 5 died of disease shortly after discovery of the urethral tumor and 2 had only a short followup. 5 PooleWilson and Barnard reported a 12 per cent urethral recurrence rate after cystectomy, all with a fatal result. 6 In the largest series reported Schellhammer and Whitmore noted a 7 per cent recurrence rate for urethral tumors, with 21 of their 24 patients dead or having known metastatic disease. 7 The ominous nature of urethral recurrence may be related to the microscopic anatomy of the urethra. The sole barrier between the vascular spaces of the corpus spongiosum and the urethral mucosa is the lamina propria of the urethra. There is Data on 7 patients with urethral recurrences Pt.
Interval to Urethral Recurrence
Pathologic Stage*
Grade
Results After Urethrectomy
(yrs.) LT JV
4
PISNxMo PISNxMo
III IV
Dead of disease, 4 yrs. Dead of disease, 8
EG PR HE
2 2 1 (no urethrectomy)
PISNlMo PlNxMo P2NoMo
III
Dead of disease, 3 yrs. Dead of disease, 1 yr. Dead of disease, 2
JDt
5
PISNxMo
II
DJt
2
PISNxMo
II
4
mos.
II
III
mos.
Alive, pos. inguinal metastases Alive, pos. inguinal metastases
* Nx~formal lymphadenectomy was not done. t Patient underwent subtotal urethrectomy with late recurrence at urethral meatus.
267
268
ZABBO AND MONTIE
no thick muscle, as in the bladder, affording a potential barrier to spread of the tumor. It is difficult to separate urethral recurrence from other poor prognostic factors relating to the primary tumor of the bladder in patients dying of urethral recurrence. Perhaps urethral recurrence is just an expression of the aggressive nature of the primary tumor. Even if a prophylactic urethrectomy had been done the outcome still might be poor. In 10 cases of urethral recurrences Faysal attributed only 1 death directly to the recurrence itself. 8 However, it must be noted that the average followup was short and several of the survivors had tumors only at the carcinoma in situ stage. In support of the notion that urethral recurrence is the source of further metastatic spread is the frequent finding of an extended interval free of disease after cystectomy, with rapid progression of the disease after the urethral recurrence is manifest. Specifically in this series failure to control urethral disease was the likely cause of relapse and ultimate death in 6 patients (see table). Our series agrees generally with others stating that asymptomatic urethral recurrence implies a poor prognosis. Therefore, several investigators have advised routine prophylactic urethrectomy. In view of the low incidence of recurrence, we are reluctant to recommend routine extension of an already difficult procedure by an additional interval to accomplish a 1stage cystourethrectomy.9 It has been reported that urethral recurrences are more likely in certain clinical situations and that it probably is best to remove the urethra at the time of cystectomy. 4 •5 • 6 • 10• 11 These situations include 1) multifocal tumors, 2) a history of concurrent tumors in the upper urinary tract, 3) diffuse carcinoma in situ, 4) involvement of the prostatic urethra or trigone with tumor at the time of cystectomy and 5) positive urethral margin on frozen section. In our series 5 of the 7 patients with urethral recurrence had carcinoma in situ diffusely in the bladder. We believe that the urethral recurrence is the probable cause of death in these patients and prophylactic urethrectomy may have avoided this occurrence. Based on the aforementioned studies in our experience, 2 specific management practices appear reasonable. First, prophylactic urethrectomy should be performed for the aforementioned specific indications. One-stage cystourethrectomy in continuity is the most desirable procedure and is a necessity if urethral involvement is clinically evident. A prophylactic urethrectomy can be done with the cystectomy either in continuity or by dividing the membranous urethra and using a 2team approach for the ileal conduit and the urethrectomy. Alternatively, if at the time of operation it is believed best that urethrectomy not be included it can be done as a delayed procedure in 4 to 6 weeks. An important point to recognize is that the urethra must be excised totally. In 1970 Whitmore and Mount described a method of urethrectomy that involved transection of the urethra just proximal to the fossa navicularis. 1 In 1976 Schellhammer and Whitmore reported 8 cases of urethral meatal recurrence after urethrectomy performed in this manner. 12 We have seen this unfortunate circumstance in 2 of our patients and both probably will die because of incomplete urethrectomy. Thus, a circumscribing incision around the urethral meatus should be made and the glanular urethra should be resected entirely. The second recommendation is that all patients without urethrectomy should be followed with urethral wash cytology every 6 to 12 months. 13 Wolinska and associates described
findings in 65 patients followed with urethral wash cytology. 14 Of their patients 21 of 24 with positive cytology results subsequently were shown to have tumor on urethrectomy (11 of these at the carcinoma in situ stage), whereas ony 1 of 35 had false negative cytology findings. The method for urethral wash cytology is simple. A catheter is inserted into the urethra as far as it can be advanced, 10 to 15 ml. saline are injected and the effluent is collected from around the urethral meatus. The specimen then is processed for cytologic examination. Urethroscopy is more cumbersome and probably is not necessary if urethral wash specimens are obtained. Moreover, if one waits until a lesion becomes either symptomatic or grossly visible the results will be poor. Even though improved survival secondary to implementing urethral wash cytology as a routine method of surveillance has not yet been documented, identification of recurrences in a noninvasive stage should accomplish this. The surveillance probably should continue for the life of the patient since remote recurrences, some as late as 20 years, have been reported. 7 Although the recurrence rate in the urethra after cystectomy for bladder cancer is small (5.9 per cent in our series if the 2 urethral meatal recurrences noted after subtotal urethrectomy are included), the prognosis of this lesion is extremely poor. If effective surgical therapy is to be accomplished urethrectomy must be done when the tumors are at an early stage. We then recommend prophylactic urethrectomy for specific indications and close followup, including urethral wash cytology, of patients who have not undergone urethrectomy. REFERENCES 1. Whitmore, W. F., Jr. and Mount, B. M.: A technique of urethrectomy in the male. Surg., Gynec. & Obst., 131: 303, 1970. 2. Ashworth, A.: Papillomatosis of the urethra. Brit. J. Urol., 28: 3, 1956. 3. Gowing, N. F. C.: Urethral carcinoma associated with cancer of the bladder. Brit. J. Urol., 32: 428, 1960. 4. Hendry, W. F., Gowing, N. F. C. and Wallace, D. M.: Surgical treatment of urethral tumours associated with bladder cancer. Proc. Roy. Soc. Med., 67: 304, 1974. 5. Cordonnier, J. J. and Spjut, H. J.: Urethral occurrence of bladder carcinoma following cystectomy. J. Urol., 87: 398, 1962. 6. Poole-Wilson, D. S. and Barnard, R. J.: Total cystectomy for bladder tumours. Brit. J. Urol., 43: 16, 1971. 7. Schellhammer, P. F. and Whitmore, W. F., Jr.: Transitional cell carcinoma of the urethra in men having cystectomy for bladder cancer. J. Urol., 115: 56, 1967. 8. Faysal, M. H.: Urethrectomy in men with transitional cell carcinoma of bladder. Urology, 16: 23, 1980. 9. Johnson, D. E. and Guinn, G. A.: Surgical management of urethral carcinoma occurring after cystectomy. J. Urol., 103: 314, 1970. 10. Richie, J.P. and Skinner, D. G.: Carcinoma in situ of the urethra associated with bladder carcinoma: the role of urethrectomy. J Urol., 119: 80, 1978. 11. Raz, S., McLorie, G., Johnson, S. and Skinner, D. G.: Management of the urethra in patients undergoing radical cystectomy for bladder carcinoma. J. Urol., 120: 298, 1978. 12. Schellhammer, P. F. and Whitmore, W. F., Jr.: Urethral meatal carcinoma following cystourethrectomy for bladder carcinoma. J. Urol., 115: 61, 1976. 13. Williams, G.: Cytological screening of the urethra. Brit. J. Urol., 40: 703, 1968. 14. Wolinska, W. H., Melamed, M. R., Schellhammer, P. F. and Whitmore, W. F., Jr.: Urethral cytology following cystectomy for bladder carcinoma. Amer. J. Surg. Path., 1: 225, 1977.