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Development of upper tract carcinoma after cystectomy for bladder carcinoma
D E V E L O P M E N T OF UPPER TRACT CARCINOMA AFTER CYSTECTOMY FOR BLADDER CARCINOMA S. BRUCE MALKOWICZ, M.D. DONALD G. SKINNER, M.D. From the Division of Urology, University of Southern California School of Medicine, Los Angeles, California
ABSTRACT--Two hundred twenty patients who underwent a radical cystectomy and en bloc pelvic lymph node dissection with urinary diversion were reviewed to define the incidence of upper tract carcinoma developing after cystectomy. Each patient was followed ?for at least five years or until death. In 5 of 220 (2.4 %) upper tract lesions developed, with a disease-free interval ?from cystectomy of twenty-two to fifty-?four months. All patients died within two to twenty-seven months of diagnosis. Common pathologic ?features included the presence of high-grade multifocal lesions or carcinoma in situ (CIS) in the cystectomy specimen, tumor invasion of the intramural ureter, and positive ?findings on urethrectomy specimens. Although the incidence of this disease process is low, heightened surveillance of the upper urinary tracts would seem appropriate in patients displaying these pathologic features.
The incidence of upper urinary tract carcinoma developing after eysteetomy for bladder cancer has been reported infrequently and ranges from 3.3-85 percent in several series. 1-3 This stands in contrast to the better defined incidence for the development of bladder carcinoma after the treatment for upper tract disease. 4-7 The development of upper tract disease, although infrequent, is usually associated with a poor longterm prognosis. Accordingly, more intensive monitoring of high-risk patients leading to early diagnosis would be beneficial. The purpose of this study, therefore, was to review a well-defined population of patients who had undergone radical eysteetomy for bladder carcinoma and who have been followed for a significant length of time to better delineate the incidence of secondary upper tract disease and identify patient features which would suggest the need for more intensive posteysteetomy monitoring. Material and Methods Between August 1971 and December 1982, 220 patients underwent radical eysteetomy and
20
en bloc pelvic lymph node dissection with formation of an ileal loop urinary diversion for carcinoma of the bladder. Prior to 1980 all surgery was performed at the UCLA Medical Center, while those treated afterward were perf o r m e d at the Hospital of the Good Samaritan/University of Southern California. All patients have been observed for greater than, or equal to, five years, or until death. One hundred seventy-four men and 46 women underwent surgery for a male-to-female ratio of 3.6:1. During this study period, 100 patients underwent a preoperative regimen of short course, high-dose (1,600 rad, 4 days) external beam radiation therapy, while 19.0 underwent e y s t e e t o m y w i t h o u t any p rio r r a d i a t i o n therapy. Bladder and upper tract specimens were staged by the Marshall modification of the Jewett-Strong classification and the UICC classification. Histologie classification revealed 21g patients with transitional cell carcinoma of the bladder and 8 patients with squamous cell carcinoma. Patient follow-up consisted of office examinations with standard laboratory tests every
UROLOGY
/
JULY 1990
/
VOLUME XXXVI, NUMBER I
TABLEI. AGE
SEX DX - ~ C Y S T
Clinical characteristics and pathologic status of patients (all patients are deceased)
HISTOLOGY
(MONTHS)
51
M
PATHOLOGY CLINICAL
60
TCC
T2 GD3 MULTIFOCAL
SITE OF
PATHOLOGIC
P3B GO3 MULTIFOCAL
PATHOLOGY
SURVIVAL A F T E R S E C O N D A R Y LESION
LESION
R RENAL PELVIS
(MO)
P4 G D 3 N+
10
71
M
42
TCC
T1 G D 3 MULr,FOCAL
P4 G D 3
R RENAL P ELM IS
P2 G D 3
20
70
F
38
TCC
T2TIS GD3
P3A GD4
R URETER
P2 G D 3
2
N÷
68
M
1
5 I
F
9
TCC SOUAMOUS
T2TIS GD3
P2 PIS
R RENAL PELVIS
P4 G D 3 N+
27
T2 GD3
P3B
R RENAL
P2
10
N÷
three to four months for the first three years, every six months for the fourth and fifth years, and yearly examinations thereafter. Intravenous urograms were performed at six-month initervals during the first postoperative year, and intravenous urograms and/or loopograms were performed yearly thereafter, unless abnormal findings indicated the need for more frequent iexaminations. Urinary cytology was obtained ~for patients who displayed abnormalities on raiidiographie studies, and adjunctive studies such as computerized tomography (CT) scans or ra~ionuelide seans were performed to delineate ~uggestive findings, or in eases where patients displayed severe contrast media sensitivity. Results Upper urinary tract tumors developed after eystectomy in 5 of the 210 patients (2.4 % ). One patient had squamous cell primary tumor with a squamous cell upper tract recurrence, but the i:!i~emainder of the primary and secondary tumors were transitional cell carcinoma. All re)urrences were diagnosed by intravenous urog}aphy or loopogram and c o n f i r m e d with ipdsitive urine cytology. ~ii~ Only 1 patient (pt. 3) had undergone the ~igh-dose, short-course, preoperative radiation therapy regimen. Another patient (pt. 2) had Received 4,400 rad of external beam radiation i'cystotomy and fulguration for multifocal T1 disease one year prior to cystectomy, while the remaining 3 patients received no preoperative therapy. Adjuvant systemic chemotherapy was iadministered to 1 patient (pt. 1) after cystectomy (cisplatin 100mg/m 2 x 3 courses) and to 1 p a t i e n t (pt. 4) after n e p h r o u r e t e r e c t o m y (CISCA x 3). Table I displays the pertinent data concerning the patients with secondary upper tract dis-
UROLOGY
/ JULY 1990 /
VOLUME XXXVI, NUMBER 1
PELVIS
ease. There were 3 men and 2 women between fifty-one and seventy-one years of age. Clinical and pathologic staging revealed multifocal disease and/or carcinoma in situ (CIS) in all patients with transitional cell carcinoma. Pathologie staging revealed muscle-invasive disease in all instances with 2 of 5 patients exhibiting node-positive disease. The disease-free interval from cysteetomy ranged from twenty-two to fifty-four months, and all secondary lesions were unilateral and occurred in the right renal pelvis in 4 of 5 cases. The upper tract recurrences were of high grade and high stage, and time from secondary lesion to death in all 5 patients ranged from two to twenty-seven months. On review of the ureteral pathology, it was noted that the distal ureters in all eases were normal or displayed mild atypia. In eontrast, the intravesical ureter displayed tumor extension in 3 of 5 patients. Additionally, all male subjects prior to the development of upper tract disease underwent a urethreetomy (1 primary, 2 delayed), and all specimens displayed transitional cell carcinoma, CIS, or urothelial atypia. Comment The nature and incidence of secondary carcinomas of the urothelial tract after primary treatment for upper tract disease has been welldocumented, 4-7 yet the incidence of upper tract tumors after initial treatment for lower tract disease has been addressed less often. 1-3,s The 220 patients in this review, followed for at least five years or until death, provides an adequate sample of patients on which to comment. The 5/220 (2.4%) incidence of secondary upper tract carcinomas is slightly lower than that previously reported and is even less if only transitional cell carcinoma is considered (4/212, 21
1.9%). Still, those affected patients share specific attributes previously reported for such individuals with secondary upper traet tumors. 1 All patients with transitional cell carcinoma displayed multifoeal disease and/or careinoma in situ in their clinical or pathologic staging. Additionally, the cystectomy specimen displayed tumor extension to the intramural ureter in 3 of 5 eases. Interestingly all 3 males in this series underwent a urethreetomy and each had pathologic findings. This corroborates previous work in which patients with positive findings on urethrectomy (primary or delayed) had a higher incidenee of secondary upper tract lesions (22-84 % ) compared with the overall ineidence (4 %) for the cystectomy series reported. 2 Specific recommendations regarding postcystectomy follow-up cannot be categorically stated from the findings in this patient population, yet the aforementioned data and that from other studies suggest certain patient characteristics which indicate the greater potential for a secondary upper urinary tract lesion. These include high tumor grade, multifocality, carcinoma in situ, tumor invasion of the intravesical ureters, and pathology demonstrated in a urethrectomy specimen. Any surveillanee schedule should include routine urine cytology in association with intravenous urography and retrograde eonduit studies. 9 Since a delayed diagnosis of an upper tract lesion is associated with a poor long-term
22
prognosis, any abnormalities detected by such a surveillanee scheme would require vigorous elucidation. A reasonable schedule in higher risk patients may consist of yearly intravenous urograms and loopograms with semiannual urine eytologies. Alterations in such a sehedule would be predicated on the perceived risk of the patient, but surveillanee should be maintained indefinitely, since the latency for the development of seeondary upper tract lesions has an upper limit greater than seven years. Los Angeles, California 90035 (DIt. SKINNER) Referenees 1. Zinke H, Garbeff PJ, and Beahrs JR: Upper urinary tract transitional eell eaneer after radieal eystectomy for bladder caneer, J Urol 13I: 50 (i984). 2. Sehellhammer PF, and Whitmore WF Jr: Transitional celF carcinoma of the urethra in men having eystectomy for bladder eaneer, J Urol 115:56 (1976). 3. Mufti GR, Grove JRW, and Riddle PR: Nephroureterectomy after radical eystectomy, JUrot 139:588 (1988). 4. Grabstald H, Whitmore WF, and Melamed M: Renal pelvid: tumors, JAMA 218:845 (1971). 5. Williams CB, and Mitchell JP: Careinoma of the renal pelvis: a review of 4a eases, Br J Urol 45:370 (1973). 6. Williams CB, and Mitehell JP: Carcinoma of the ureter: a review of 54 cases, Br J Urol 45:377 (1973). 7. Kakizoe T, et ah Transitional cell eareinoma of the bladder;~ in patients with renal pelvic and ureteral eaneer, J Urol 124: 17!
(1%0).
8. Walzer Y, and $oloway MS: Shouldthe follow-up ofpatients~ with bladder cancer include routine excretory urogram? J Urol~ 130:672 (1988). 9. Zinke H, et al: Significance of urinary cytology in the earl~ detection of transitional cell carcinoma of the upper urinary tracti~ J Urol 116:781 (1976).
UROLOGY
/ JULY 1990
/
VOLUME XXXVI, NUMBER:!
ABSTRACT--Two hundred twenty patients who underwent a radical cystectomy and en bloc pelvic lymph node dissection with urinary diversion were reviewed to define the incidence of upper tract carcinoma developing after cystectomy. Each patient was followed ?for at least five years or until death. In 5 of 220 (2.4 %) upper tract lesions developed, with a disease-free interval ?from cystectomy of twenty-two to fifty-?four months. All patients died within two to twenty-seven months of diagnosis. Common pathologic ?features included the presence of high-grade multifocal lesions or carcinoma in situ (CIS) in the cystectomy specimen, tumor invasion of the intramural ureter, and positive ?findings on urethrectomy specimens. Although the incidence of this disease process is low, heightened surveillance of the upper urinary tracts would seem appropriate in patients displaying these pathologic features.
The incidence of upper urinary tract carcinoma developing after eysteetomy for bladder cancer has been reported infrequently and ranges from 3.3-85 percent in several series. 1-3 This stands in contrast to the better defined incidence for the development of bladder carcinoma after the treatment for upper tract disease. 4-7 The development of upper tract disease, although infrequent, is usually associated with a poor longterm prognosis. Accordingly, more intensive monitoring of high-risk patients leading to early diagnosis would be beneficial. The purpose of this study, therefore, was to review a well-defined population of patients who had undergone radical eysteetomy for bladder carcinoma and who have been followed for a significant length of time to better delineate the incidence of secondary upper tract disease and identify patient features which would suggest the need for more intensive posteysteetomy monitoring. Material and Methods Between August 1971 and December 1982, 220 patients underwent radical eysteetomy and
20
en bloc pelvic lymph node dissection with formation of an ileal loop urinary diversion for carcinoma of the bladder. Prior to 1980 all surgery was performed at the UCLA Medical Center, while those treated afterward were perf o r m e d at the Hospital of the Good Samaritan/University of Southern California. All patients have been observed for greater than, or equal to, five years, or until death. One hundred seventy-four men and 46 women underwent surgery for a male-to-female ratio of 3.6:1. During this study period, 100 patients underwent a preoperative regimen of short course, high-dose (1,600 rad, 4 days) external beam radiation therapy, while 19.0 underwent e y s t e e t o m y w i t h o u t any p rio r r a d i a t i o n therapy. Bladder and upper tract specimens were staged by the Marshall modification of the Jewett-Strong classification and the UICC classification. Histologie classification revealed 21g patients with transitional cell carcinoma of the bladder and 8 patients with squamous cell carcinoma. Patient follow-up consisted of office examinations with standard laboratory tests every
UROLOGY
/
JULY 1990
/
VOLUME XXXVI, NUMBER I
TABLEI. AGE
SEX DX - ~ C Y S T
Clinical characteristics and pathologic status of patients (all patients are deceased)
HISTOLOGY
(MONTHS)
51
M
PATHOLOGY CLINICAL
60
TCC
T2 GD3 MULTIFOCAL
SITE OF
PATHOLOGIC
P3B GO3 MULTIFOCAL
PATHOLOGY
SURVIVAL A F T E R S E C O N D A R Y LESION
LESION
R RENAL PELVIS
(MO)
P4 G D 3 N+
10
71
M
42
TCC
T1 G D 3 MULr,FOCAL
P4 G D 3
R RENAL P ELM IS
P2 G D 3
20
70
F
38
TCC
T2TIS GD3
P3A GD4
R URETER
P2 G D 3
2
N÷
68
M
1
5 I
F
9
TCC SOUAMOUS
T2TIS GD3
P2 PIS
R RENAL PELVIS
P4 G D 3 N+
27
T2 GD3
P3B
R RENAL
P2
10
N÷
three to four months for the first three years, every six months for the fourth and fifth years, and yearly examinations thereafter. Intravenous urograms were performed at six-month initervals during the first postoperative year, and intravenous urograms and/or loopograms were performed yearly thereafter, unless abnormal findings indicated the need for more frequent iexaminations. Urinary cytology was obtained ~for patients who displayed abnormalities on raiidiographie studies, and adjunctive studies such as computerized tomography (CT) scans or ra~ionuelide seans were performed to delineate ~uggestive findings, or in eases where patients displayed severe contrast media sensitivity. Results Upper urinary tract tumors developed after eystectomy in 5 of the 210 patients (2.4 % ). One patient had squamous cell primary tumor with a squamous cell upper tract recurrence, but the i:!i~emainder of the primary and secondary tumors were transitional cell carcinoma. All re)urrences were diagnosed by intravenous urog}aphy or loopogram and c o n f i r m e d with ipdsitive urine cytology. ~ii~ Only 1 patient (pt. 3) had undergone the ~igh-dose, short-course, preoperative radiation therapy regimen. Another patient (pt. 2) had Received 4,400 rad of external beam radiation i'cystotomy and fulguration for multifocal T1 disease one year prior to cystectomy, while the remaining 3 patients received no preoperative therapy. Adjuvant systemic chemotherapy was iadministered to 1 patient (pt. 1) after cystectomy (cisplatin 100mg/m 2 x 3 courses) and to 1 p a t i e n t (pt. 4) after n e p h r o u r e t e r e c t o m y (CISCA x 3). Table I displays the pertinent data concerning the patients with secondary upper tract dis-
UROLOGY
/ JULY 1990 /
VOLUME XXXVI, NUMBER 1
PELVIS
ease. There were 3 men and 2 women between fifty-one and seventy-one years of age. Clinical and pathologic staging revealed multifocal disease and/or carcinoma in situ (CIS) in all patients with transitional cell carcinoma. Pathologie staging revealed muscle-invasive disease in all instances with 2 of 5 patients exhibiting node-positive disease. The disease-free interval from cysteetomy ranged from twenty-two to fifty-four months, and all secondary lesions were unilateral and occurred in the right renal pelvis in 4 of 5 cases. The upper tract recurrences were of high grade and high stage, and time from secondary lesion to death in all 5 patients ranged from two to twenty-seven months. On review of the ureteral pathology, it was noted that the distal ureters in all eases were normal or displayed mild atypia. In eontrast, the intravesical ureter displayed tumor extension in 3 of 5 patients. Additionally, all male subjects prior to the development of upper tract disease underwent a urethreetomy (1 primary, 2 delayed), and all specimens displayed transitional cell carcinoma, CIS, or urothelial atypia. Comment The nature and incidence of secondary carcinomas of the urothelial tract after primary treatment for upper tract disease has been welldocumented, 4-7 yet the incidence of upper tract tumors after initial treatment for lower tract disease has been addressed less often. 1-3,s The 220 patients in this review, followed for at least five years or until death, provides an adequate sample of patients on which to comment. The 5/220 (2.4%) incidence of secondary upper tract carcinomas is slightly lower than that previously reported and is even less if only transitional cell carcinoma is considered (4/212, 21
1.9%). Still, those affected patients share specific attributes previously reported for such individuals with secondary upper traet tumors. 1 All patients with transitional cell carcinoma displayed multifoeal disease and/or careinoma in situ in their clinical or pathologic staging. Additionally, the cystectomy specimen displayed tumor extension to the intramural ureter in 3 of 5 eases. Interestingly all 3 males in this series underwent a urethreetomy and each had pathologic findings. This corroborates previous work in which patients with positive findings on urethrectomy (primary or delayed) had a higher incidenee of secondary upper tract lesions (22-84 % ) compared with the overall ineidence (4 %) for the cystectomy series reported. 2 Specific recommendations regarding postcystectomy follow-up cannot be categorically stated from the findings in this patient population, yet the aforementioned data and that from other studies suggest certain patient characteristics which indicate the greater potential for a secondary upper urinary tract lesion. These include high tumor grade, multifocality, carcinoma in situ, tumor invasion of the intravesical ureters, and pathology demonstrated in a urethrectomy specimen. Any surveillanee schedule should include routine urine cytology in association with intravenous urography and retrograde eonduit studies. 9 Since a delayed diagnosis of an upper tract lesion is associated with a poor long-term
22
prognosis, any abnormalities detected by such a surveillanee scheme would require vigorous elucidation. A reasonable schedule in higher risk patients may consist of yearly intravenous urograms and loopograms with semiannual urine eytologies. Alterations in such a sehedule would be predicated on the perceived risk of the patient, but surveillanee should be maintained indefinitely, since the latency for the development of seeondary upper tract lesions has an upper limit greater than seven years. Los Angeles, California 90035 (DIt. SKINNER) Referenees 1. Zinke H, Garbeff PJ, and Beahrs JR: Upper urinary tract transitional eell eaneer after radieal eystectomy for bladder caneer, J Urol 13I: 50 (i984). 2. Sehellhammer PF, and Whitmore WF Jr: Transitional celF carcinoma of the urethra in men having eystectomy for bladder eaneer, J Urol 115:56 (1976). 3. Mufti GR, Grove JRW, and Riddle PR: Nephroureterectomy after radical eystectomy, JUrot 139:588 (1988). 4. Grabstald H, Whitmore WF, and Melamed M: Renal pelvid: tumors, JAMA 218:845 (1971). 5. Williams CB, and Mitchell JP: Careinoma of the renal pelvis: a review of 4a eases, Br J Urol 45:370 (1973). 6. Williams CB, and Mitehell JP: Carcinoma of the ureter: a review of 54 cases, Br J Urol 45:377 (1973). 7. Kakizoe T, et ah Transitional cell eareinoma of the bladder;~ in patients with renal pelvic and ureteral eaneer, J Urol 124: 17!
(1%0).
8. Walzer Y, and $oloway MS: Shouldthe follow-up ofpatients~ with bladder cancer include routine excretory urogram? J Urol~ 130:672 (1988). 9. Zinke H, et al: Significance of urinary cytology in the earl~ detection of transitional cell carcinoma of the upper urinary tracti~ J Urol 116:781 (1976).
UROLOGY
/ JULY 1990
/
VOLUME XXXVI, NUMBER:!