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Non-Invasive Carcinoma of the Bladder
Vol. 107, March Printed in U.S.A.
THE JouRNAL OF UROLOGY
Copyright © 1972 by The Williams & Wilkins Co.
NON-INVASIVE CARCINOMA OF THE BLADDER EDWIN M. MEARES, JR. From the Division of Urology, Department of Surgery, Stanford University School of Medicine, Stanford, California
Regardless of the therapeutic modality used, the 5-year survival of patients with non-invasive transitional cell carcinoma of the bladder ranges from 40 to 63 per cent in several reported series.1- 5 Barnes reported a 63 per cent 5-year survival among 233 patients treated exclusively by transurethral resection.1 Cordonnier reported a 54 per cent 5-year survival among 54 patients treated by total cystectomy and ileal conduit urinary diversion. 2 Caldwell reported a 60 per cent 5-year survival among 23 patients managed by supravoltage radiotherapy. 3 Because most investigators do not differentiate deaths of carcinoma and deaths of unrelated causes, information regarding tumor mortality is largely absent. Our impression has been that therapy for non-invasive bladder carcinoma (Jewett's stage O and stage A 6) is more successful than the survival figures imply. For this reason we reviewed all cases of non-invasive transitional cell carcinoma of the bladder that were treated at the Veterans Administration Hospital in Palo Alto, California during the past 10 years. MATERIALS AND METHODS
Between July 1, 1960 and June 30, 1970, 58 patients were admitted to the hospital for treatment of non-invasive (Jewett's stage O and stage A) transitional cell carcinoma of the bladder. Hospital charts and all pertinent information regarding these patients were reviewed. Followup was excellent. Gaps in information were filled by extensive recall of patients and contact with other physicians and hospitals that may have participated in the management of the patients. No patient was lost to followup. RESULTS
The age of the patients at the time of initial diagnosis ranged from 18 to 93 years; the median age was 67 years. Followed for a median of 4.5 years, 24 patients (41 per cent) had no recurrent tumors. The Accepted for publication March 19, 1971. Barnes, R. W., Bergman, R. T., Hadley, H. L. and Love, D.: Control of bladder tumors by endoscopic surgery. J. Urol., 97: 864, 1967. 2 Cordonnier, J. J.: Cystectomy for carcinoma of the bladder. J. Urol., 99: 172, 1968. 3 Caldwell, W. L., Bagshaw, M. A. and Kaplan, H. S.: Efficiency of linear accelerator x-ray therapv in cancer of the bladder. J. Urol., 97: 294, 1967. 4 Cox, C. E., Cass, A. S. and Boyce, W. H.: Bladder cancer: a 26-year review. J. Urol., 101: 550, 1969. 5 Maltry, E., Jr.: Carcinoma of the bladder. J. Urol., 99: 165, 1968. 6 Jewett, H. J. and Strong, G. H.: Infiltrating carcinoma of the bladder: relation of depth of penetration of the bladder wall to incidence of local extension and metastases. J. Urol., 55: 366, 1946. 1
remaining 34 patients experienced 166 recurrences (one or more tumors per recurrence). The average recurrence rate for this group was 4.9 per patient. Multiple recurrent, non-invasive tumors occurred in 14 patients (24 per cent). Two patients eventually had multiple papi.llomas of the urethra and required urethrectomy. Two patients had lower ureteral papillary tumors and required nephroureterectomy. Bladder muscular invasion eventually occurred in 8 patients (14 per cent). These patients were included in the over-all survival data. Table 1 denotes the therapeutic modalities used in the management of these 58 patients. Thirty-nine patients were managed exclusively by transurethral resection. One patient also had nephroureterectomy for a low grade papillary tumor of the right lower ureter and was without disease 10 years later. Six patients who had multiple, recurrent, noninvasive carcinomas underwent total cystectomy and ileal conduit urinary diversion: 3 patients were without disease 5 years later (1 patient also had left nephroureterectomy for a low grade papillary tumor of the lower ureter prior to cystectomy), 1 patient was alive 1 month later without disease, 1 patient was alive 6 years later with bony metastasis (he had subsequently undergone total urethrectomy for papillomas of the urethra) and 1 patient died 1.\.'2 years later of an enterocolic fistula and pelvic abscess with no metastasis at autopsy. One patient who had total cystectomy with ureterosigmoidostomy and subsequent bilateral cutaneous ureterostomy eventually underwent total urethrectomy for papillomas of the urethra. This patient died of widespread metastases 5 years following cystectomy. Two patients had partial cystectomy: 1 was alive without disease 10 years later and 1 was killed in an accident 2½ years later with no carcinoma at autopsy. Of 2 patients who received 7,000 rads of radiotherapy via the linear accelerator for multiple, recurrent, non-invasive carcinoma, 1 patient was without disease 7 years later and 1 patient died 5 years later with a sterile bladder but widespread metastases. Eight patients (14 per cent) eventually had invasion of the muscular wall of the bladder. The interval from the initial diagnosis of non-invasive carcinoma to the eventual appearance of invasive carcinoma ranged from 1 to 9 years; the median interval was 3 years. Six of the 8 received subsequent radiotherapy, 1 patient underwent bilateral cutaneous ureterostomy plus radiotherapy and 1 patient received ileal conduit urinary diversion and died of a myocardial infarction prior to cystectomy. All 8 394
NON-INVASIVE CARCINOMA OF BLADDER
were dead within 17 months. Six of these 8 had metastasis at the time of death. Regardless of the 20 patients died within 10 years of u1is;;11v~,c the over-all survival was 66 per cent. For more accurate tion of the survival data the annual n<>1rfo<>ntQ accumulative survival was noted With this method the absolute n,>.,'M>ntQ determined patients who survived who were at risk
TABLE
395
l. Therapeutic modalities used
f->WVLC,;.LV0
Patients with non-invasive carcinoma: TUR only TUR, total cystectomy, ilea! conduit TUR, total cystectomy, ureterosigmoidostomy. subsequent cutaneous ureterostomy TUR, partial cystectomy TUR, radiotherapy Patients vdth invasive carcinoma: TUR, radiotherapy TUR, cutaneous ureterostomy, radiotherapy TUR, ilea! conduit
39
Total
mulative the absolute percentage of survival for This prevents skewing of the survival patients who have been at risk for a mm1mum time. The survival of the 58 was 76 per cent; survival was 37 per cent (table 2). group (39 patients), the accumulative 5-year was 80 per cent; too few pa GlCl.HS were at risk for wc,,u,,u,;e,, evaluation of (table 3). Postmortem examinations were obtained on 15 of 20 JJa,,,c.,,uo who died. Of the 8 who died in the group, 6 had nACl-r~A,CTOm examinations. None these pa1c1e1ns residual vesical carcinoma and only one had metastasis. The 2 tients who did not have had evidence of metastasis. Of the 20 who 1
ever
unrelated causes bladder carcinoma or metastatic disease. died of metastatic disease without invasion of the bladder musculature. DISCUSSION
This review impression that the outlook with non-invasive transitional cell carcinoma of the bladder is more favorable than many serief; Since this tumor most often occurs in the sixth seventh decades of accurate survival information demands that deaths related to the carcinoma be differentiated from deaths cuvm,~s,u 20 per of carcinoma of the bladdeL Six of 7
Bowles, W. T. and for carcinoma of
.58
TABLE
Pts.
Yrs.
0 to 1 to 2 to 3 to 4 to 5 to 6 to 7 to 8 to 9 to
2. Over-all 10-year accumulative survival
I 2 3 4 5 6 7 8 9 10
Dead
58 52 48
43 33 28 20 18 11 10
TABLE
Alive
57 3 6 I
51 45 37 32
a
27 20
0
15 11
4
6
% Survival
98 98 94 86 97 96
100 83
98 96 90 78 76 73
73
100
61 61
60
37
3. Survival of TUR-only group Dead
Alive
% Survival
39 33 29 26 20 15
97 97
1 2 l 0
38 32 28 24 19 15
11
0
11
9 4
1 0
8 4
Yrs.
Pts. at Risk
0 to l l to 2 2 to 3 3 to 4 4 to 5 5 to 6 6 to 7 7 to 8 8 to 9 9 to 10
2
97
92 95 100 100 89 100 67
97 94 91 84 80 80 80 71 47
9 patients ultimately had invasive bladder carcinoma
and vco,,uua,u died of metastasis. The 5-year survival figures in Barnes' TUB.only series1 and those herein are better than the 5-year survival of those patient.s who had total cystectomy and ileal conduit diversion in Cordonnier's series. 2 'thennore, 41 per cent of our patients (followed a median 4.5 had a single tumor without recurrence. The obvious conclusion is that one should pursue a conservative approach initially in the m:1rn1g,,m,ent of non-invasive carcinoma of the bladder.
THE JouRNAL OF UROLOGY
Copyright © 1972 by The Williams & Wilkins Co.
NON-INVASIVE CARCINOMA OF THE BLADDER EDWIN M. MEARES, JR. From the Division of Urology, Department of Surgery, Stanford University School of Medicine, Stanford, California
Regardless of the therapeutic modality used, the 5-year survival of patients with non-invasive transitional cell carcinoma of the bladder ranges from 40 to 63 per cent in several reported series.1- 5 Barnes reported a 63 per cent 5-year survival among 233 patients treated exclusively by transurethral resection.1 Cordonnier reported a 54 per cent 5-year survival among 54 patients treated by total cystectomy and ileal conduit urinary diversion. 2 Caldwell reported a 60 per cent 5-year survival among 23 patients managed by supravoltage radiotherapy. 3 Because most investigators do not differentiate deaths of carcinoma and deaths of unrelated causes, information regarding tumor mortality is largely absent. Our impression has been that therapy for non-invasive bladder carcinoma (Jewett's stage O and stage A 6) is more successful than the survival figures imply. For this reason we reviewed all cases of non-invasive transitional cell carcinoma of the bladder that were treated at the Veterans Administration Hospital in Palo Alto, California during the past 10 years. MATERIALS AND METHODS
Between July 1, 1960 and June 30, 1970, 58 patients were admitted to the hospital for treatment of non-invasive (Jewett's stage O and stage A) transitional cell carcinoma of the bladder. Hospital charts and all pertinent information regarding these patients were reviewed. Followup was excellent. Gaps in information were filled by extensive recall of patients and contact with other physicians and hospitals that may have participated in the management of the patients. No patient was lost to followup. RESULTS
The age of the patients at the time of initial diagnosis ranged from 18 to 93 years; the median age was 67 years. Followed for a median of 4.5 years, 24 patients (41 per cent) had no recurrent tumors. The Accepted for publication March 19, 1971. Barnes, R. W., Bergman, R. T., Hadley, H. L. and Love, D.: Control of bladder tumors by endoscopic surgery. J. Urol., 97: 864, 1967. 2 Cordonnier, J. J.: Cystectomy for carcinoma of the bladder. J. Urol., 99: 172, 1968. 3 Caldwell, W. L., Bagshaw, M. A. and Kaplan, H. S.: Efficiency of linear accelerator x-ray therapv in cancer of the bladder. J. Urol., 97: 294, 1967. 4 Cox, C. E., Cass, A. S. and Boyce, W. H.: Bladder cancer: a 26-year review. J. Urol., 101: 550, 1969. 5 Maltry, E., Jr.: Carcinoma of the bladder. J. Urol., 99: 165, 1968. 6 Jewett, H. J. and Strong, G. H.: Infiltrating carcinoma of the bladder: relation of depth of penetration of the bladder wall to incidence of local extension and metastases. J. Urol., 55: 366, 1946. 1
remaining 34 patients experienced 166 recurrences (one or more tumors per recurrence). The average recurrence rate for this group was 4.9 per patient. Multiple recurrent, non-invasive tumors occurred in 14 patients (24 per cent). Two patients eventually had multiple papi.llomas of the urethra and required urethrectomy. Two patients had lower ureteral papillary tumors and required nephroureterectomy. Bladder muscular invasion eventually occurred in 8 patients (14 per cent). These patients were included in the over-all survival data. Table 1 denotes the therapeutic modalities used in the management of these 58 patients. Thirty-nine patients were managed exclusively by transurethral resection. One patient also had nephroureterectomy for a low grade papillary tumor of the right lower ureter and was without disease 10 years later. Six patients who had multiple, recurrent, noninvasive carcinomas underwent total cystectomy and ileal conduit urinary diversion: 3 patients were without disease 5 years later (1 patient also had left nephroureterectomy for a low grade papillary tumor of the lower ureter prior to cystectomy), 1 patient was alive 1 month later without disease, 1 patient was alive 6 years later with bony metastasis (he had subsequently undergone total urethrectomy for papillomas of the urethra) and 1 patient died 1.\.'2 years later of an enterocolic fistula and pelvic abscess with no metastasis at autopsy. One patient who had total cystectomy with ureterosigmoidostomy and subsequent bilateral cutaneous ureterostomy eventually underwent total urethrectomy for papillomas of the urethra. This patient died of widespread metastases 5 years following cystectomy. Two patients had partial cystectomy: 1 was alive without disease 10 years later and 1 was killed in an accident 2½ years later with no carcinoma at autopsy. Of 2 patients who received 7,000 rads of radiotherapy via the linear accelerator for multiple, recurrent, non-invasive carcinoma, 1 patient was without disease 7 years later and 1 patient died 5 years later with a sterile bladder but widespread metastases. Eight patients (14 per cent) eventually had invasion of the muscular wall of the bladder. The interval from the initial diagnosis of non-invasive carcinoma to the eventual appearance of invasive carcinoma ranged from 1 to 9 years; the median interval was 3 years. Six of the 8 received subsequent radiotherapy, 1 patient underwent bilateral cutaneous ureterostomy plus radiotherapy and 1 patient received ileal conduit urinary diversion and died of a myocardial infarction prior to cystectomy. All 8 394
NON-INVASIVE CARCINOMA OF BLADDER
were dead within 17 months. Six of these 8 had metastasis at the time of death. Regardless of the 20 patients died within 10 years of u1is;;11v~,c the over-all survival was 66 per cent. For more accurate tion of the survival data the annual n<>1rfo<>ntQ accumulative survival was noted With this method the absolute n,>.,'M>ntQ determined patients who survived who were at risk
TABLE
395
l. Therapeutic modalities used
f->WVLC,;.LV0
Patients with non-invasive carcinoma: TUR only TUR, total cystectomy, ilea! conduit TUR, total cystectomy, ureterosigmoidostomy. subsequent cutaneous ureterostomy TUR, partial cystectomy TUR, radiotherapy Patients vdth invasive carcinoma: TUR, radiotherapy TUR, cutaneous ureterostomy, radiotherapy TUR, ilea! conduit
39
Total
mulative the absolute percentage of survival for This prevents skewing of the survival patients who have been at risk for a mm1mum time. The survival of the 58 was 76 per cent; survival was 37 per cent (table 2). group (39 patients), the accumulative 5-year was 80 per cent; too few pa GlCl.HS were at risk for wc,,u,,u,;e,, evaluation of (table 3). Postmortem examinations were obtained on 15 of 20 JJa,,,c.,,uo who died. Of the 8 who died in the group, 6 had nACl-r~A,CTOm examinations. None these pa1c1e1ns residual vesical carcinoma and only one had metastasis. The 2 tients who did not have had evidence of metastasis. Of the 20 who 1
ever
unrelated causes bladder carcinoma or metastatic disease. died of metastatic disease without invasion of the bladder musculature. DISCUSSION
This review impression that the outlook with non-invasive transitional cell carcinoma of the bladder is more favorable than many serief; Since this tumor most often occurs in the sixth seventh decades of accurate survival information demands that deaths related to the carcinoma be differentiated from deaths cuvm,~s,u 20 per of carcinoma of the bladdeL Six of 7
Bowles, W. T. and for carcinoma of
.58
TABLE
Pts.
Yrs.
0 to 1 to 2 to 3 to 4 to 5 to 6 to 7 to 8 to 9 to
2. Over-all 10-year accumulative survival
I 2 3 4 5 6 7 8 9 10
Dead
58 52 48
43 33 28 20 18 11 10
TABLE
Alive
57 3 6 I
51 45 37 32
a
27 20
0
15 11
4
6
% Survival
98 98 94 86 97 96
100 83
98 96 90 78 76 73
73
100
61 61
60
37
3. Survival of TUR-only group Dead
Alive
% Survival
39 33 29 26 20 15
97 97
1 2 l 0
38 32 28 24 19 15
11
0
11
9 4
1 0
8 4
Yrs.
Pts. at Risk
0 to l l to 2 2 to 3 3 to 4 4 to 5 5 to 6 6 to 7 7 to 8 8 to 9 9 to 10
2
97
92 95 100 100 89 100 67
97 94 91 84 80 80 80 71 47
9 patients ultimately had invasive bladder carcinoma
and vco,,uua,u died of metastasis. The 5-year survival figures in Barnes' TUB.only series1 and those herein are better than the 5-year survival of those patient.s who had total cystectomy and ileal conduit diversion in Cordonnier's series. 2 'thennore, 41 per cent of our patients (followed a median 4.5 had a single tumor without recurrence. The obvious conclusion is that one should pursue a conservative approach initially in the m:1rn1g,,m,ent of non-invasive carcinoma of the bladder.