- Email: [email protected]
Bladder Cancer: A 26-Year Review
Vol. 101, Apr. Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1969 by The Williams & Wilkins Co.
BLADDER CANCER: A 26-YEAR REVIEW CLAIRE. COX, ALEXANDERS. CASS
AND
WILLIAM H. BOYCE
From the Division of Urology, Deparlment of Surgery, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina
Retrospective patient surveys, regardless of several well recognized limitations, continue to function as a valuable means of communication within the health-science disciplines. With regard to vesical carcinoma, many excellent reviews have been published and, in general, represent either a review of institutional or individual experience with the disease during a time interval or a review emphasizing certain etiologic, diagnostic or therapeutic aspects of the bladder cancer. 1- 12 This paper presents an additional review of vesical carcinoma and is unique only in Accepted for publication May 15, 1968. Supported in part by the United States Public Health Service, grant CA 07375. Request for reprints: Bowman Gray School of Medicine, Winston-Salem, North Carolina 27013 (C.E.C.). 1 Kretschmer, H. L.: Cancer of the bladder. A study based on 902 epithelial tumors of the bladder in the Carcinoma Registry of the American Urological Association. J. Urol., 31: 423, 1934. 2 Deming, C. L.: The biological behavior of transitional cell papilloma of the bladder. J. Urol., 63: 815, 1950. 3 Flocks R. H.: Treatment of patients with carcinoma of the bladder. J.A.M.A., 145: 295, 1951. 4 Milner, W. A.: The role of conservative surgery in the treatment of bladder tumours. Brit. J. Urol.,
26: 375, 1954. 5 Dean, A. L., Mostofi, F. K., Thomson, R. V. and Clark, M. L.: A restudy of the first fourteen hundred tumors of the bladder tumor registry, Armed Forces Institute of Pathology. J. U rol., 71:
571, 1954.
6 Melicow, M. M.: Tumors of the urinary bladder: a clinico-pathological analysis of over 2500 specimens and biopsies. J. Urol., 74: 498, 1955. 7 Wall ace, D. M.: Tumours of the Bladder. London: E. & S. Livingstone, Ltd., vol. 2, 1959. 8 Rubin, P.: The impact of supervol tage irradiation on the treatment of bladder carcinoma. J. Urol., 86: 82, 1961. 9 Whitmore, W. F., Jr. and Marshall, V. F.: Radical total cystectomy for cancer of the bladder: 230 consecutive cases five years later. J. Urol.,
87: 853, 1962. 10 Del Regato, J. A. and Chahbazian, C. M.: Radiotherapy for transitional-cell carcinoma of the urinary bladder with cobalt 60. Radiology, 87:
1053, 1966. 11 Buschke, F. and Jack, G.: Twenty-five years' experience with supervoltage therapy in the treatment of transitional cell carcinoma of the bladder. Amer. J. Roentgen., 99: 387, 1967. 12 Cordonnier, J. J.: Cystectomy for carcinoma of the bladder. J. Urol., 99: 172, 1968.
550
that it represents the entire experience of one institution with bladder cancer. Since the establishment of the Bowman Gray School of Medicine in 1941, through 1966, 371 patients with vesical carcinoma were admitted to its hospital facility, the North Carolina Baptist Hospital. During this 26-year period an average of 14.3 patients with bladder cancer (lowest, 0 in 1941 and highest, 26 in 1957) were admitted yearly to this institution. As the average patient admission rate during this period was 11,248 per year, 0.13 per cent of all admissions were for bladder carcinoma. This figure compares favorably to the recent Professional Activity Study (PAS) 13 in which 0.19 per cent of more than 5 million hospital admissions were for bladder carcinoma. On the other hand, it is somewhat less than the incidence of 0.4 per cent of hospital admissions as reported by Flocks in an earlier survey. 14 Study population. The physical characteristics of the patient group under study are not unlike those of other reported surveys. The base population of the referral area is quite stable with few transients and is primarily rural. The principal industries within the referral area are related to tobacco, textiles and furniture manufacture. The predominate nationalities are Scottish, English and German. Unfortunately, sufficient data were not available in regard to the incidence of tobacco usage. Of the 371 patient charts reviewed, 173 failed to record an occupation and 11 listed "no occupation". Of the remaining 187 patients, 33 were housewives, 31 farmers, 16 employed in textile mills, 8 furniture plant employees and the remainder employed in a variety of occupations. The number of patients employed in processing of tobacco or petroleum products or in producing textiles or furniture did not seem inconsistent with the available industrial facilities. 13 Clarke, B. G., Mielke, R. and Leighton, E.: Urology in hospitals of the United States and Canada, 1963 and 1964: report of a statistical study. J. Urol., 96: 417, 1966. 14 Flocks, R. H.: Carcinoma of the bladder, Canad. Med. Ass. J., 55: 348, 1946.
BLADDER CANCER:
Of the 371 patients in this review, 69 (] 8.6 per cent) had undergone significant treatment for their bladder carcinoma before admission to our institution. As prior therapy seemingly would further reduce the value of a retro~pective review, these 69 patients, unless otherwise noted, will be excluded from all further data presented in this paper. The remaining 302 patients were all initially diagnosed and primarily treated at this institution. As of July 1967, the status of these 302 patients admitted during this 26-year period (1941 through 1966) was as follows: 79 were alive 9,5 were untraced 57 were dead due to canc~r 29 were dead fr~rn other causes and 42 ' were dead from unknown reasons (table 1). Patient characteristics. There were 216 male and 86 female patients in the group. The most common age group was the sixth decade but a significant number (13.9 per cent) were less than 50 years of age (table 2). Only 6 patients were asymptomatic (tumor found incidentally) and gross hematuria was present history in 252 (83 per cent) of the patients (table 2). Of interest was the large number of patients (113) in whom a time interval in excess of 6 TABLE
1, Current slal'll8, 302 bladder cancer
patients, 1941-1966
Alive Lost to followup Dead From cancer Not from canecr 1Tnknown canse TABLJ,
No.
%,
79 95 128
26 3] 42
57 (44. 5%)
2!) (22.G%) 42 C:l2. Ci'/r,)
2. Age al cliagno.si.s and syn1,plon1s, 302
bladder cance,· patients Age
<50
50-60 60-70 70-80 >80
Xo, Cases
42 66 96 79 19
Symptoms
No. Cases
Jiematmia Dysnria Back pain Suprapubic pain Other symptoms Xo symptoms
252 115
23 19 59 6
26- YEAR TMJLE
REVIEW
3. Duration of .symptoms before admi.,sion
Duration of Symptoms (mos.)
>To. Patients
G8
1-3 3-6 >6 Unknown BUN elevated Ureteral obstrnction
7G
34 113
(37%)
11
64/232* (28%) 47/287* (17%)
* Number of patients at risk. months existed from the appearance of symptoms until the time of admission (table 3). It was considered that this rather long delay in seeking medical attention by 37 per cent of the might potentially explain the high incidence of azotemia (28 per cent) and obstructive urographic changes (17 per cent) noted in this series 3). However, a relationship between this in admission and obstructive disease did not exist, Likewise, a comparison of the tumor stage and grade with length of history did not suggest that a longer history is associated with a more malig .. nant tumor. Equally evident was a total lack of correlation between length of symptoms and survival. Similar findings were noted in a review of 1,420 cases of this disease. 15 Unassociated disease was present to a variable extent in 102 patients. As urinary tract cytology was unsatisfactory at this institution during most of the survey years, sufficient data are not avail-able for analysis. In addition, although himanual examination was usually performed, the results were not sufficiently recorded to allow comment upon the findings. Urinary infection. Of particular interest to us was the incidence of urinary tract infection m this series. Excluding those patients admitted prior to 1957 (due to inadequate 174 patients were at risk for analysis in regard to urinarv infection. Results were unavailable on 2.5 patients, but of the remaining 149, fi2 .G per cent) had a positive* urine culture at the time of admission to the hospital. All cultures were obtained prior to or at the time of initial instrumentation at our institution. It is to determine the exact number of these who had been subjected to prior catheterizntion 1a Pa,yne, P,: Sex, age, history, tumor type and survivaL In: Tumours of the Bladder.. Edited D. i\!L Wallace, London: K & S. Livingstone chap. 19 p.285, voL 2, 1959, * 10,000 or more bacteria per milliliter of urine.
552
COX, CASS AND BOYCE
TABLE 4. Urinary infection in 1,000 consecutive patients and 62 patients infected secondary to bladder cancer Patients with Various U rologic Bladder Patients, No.(%)
E.coli Aerobacter-klebsiella Intermediate coliforms Proteus mirabilis Indole pos. proteus Pseudomonas Enterococcus Staphylococcus
No.
Cell type: Transitional Squamous Adeno. Not listed Tumor grade:
Carcinoma, No.(%)
376 (37 .6) 172 (17.2) 82 (8.2)
11 (17.7) 7 (11.3) 5 (8)
108 45 114 57 46
4 3 4 21 7
(10.8) (4.5) (11.4) (5.7) (4.6)
TABLE 5. Bladder cancer lesions, 302 cases
1 2 3 4
(6.6) (5) (6.6) (33. 9) (11.3)
Not listed Tumor stage: 0
Total
1,000
A B, B2 C D1 D2 Not listed
62
or instrumentation. But if a maximum estimate of 15 per cent had been instrumented prior to admission, and this had resulted in continuing infection in all (which is possible but doubtful), this would still be inconsistent with the 42 per cent infection rate as noted at the initial admiRsion to our institution. A more likely explanation for this high infection rate is the effect of vesical neoplasia on local bladder defense mechanisms (and possibly systemic defenses as well). This lends support to our previous observations that the principal determinate of infection is the condition of the host and not the availability of bacteria. 16 , 17 Noteworthy also is the bacterial species recovered from these patients (table 4). A comparison of the infecting organisms obtained from these patients with positive cultures from 1,000 consecutive urologic patients with urinary infection reveals several differences (table 4). Most apparent is the substantial increase in enterococcal infections among patients with vesical cancer. This fastidious organism rarely infects individuals without gross urinary tract disease and resultant reduced host resistance. It is not inconceivable that the frequency of hematuria associated with vesical neoplasia is increased by the occurrence of secondary bacterial invasion. Furthermore, as post-therapy (operative or irradiation) morbidity is often 16 Cox, C. E. and Hinman, F., Jr.: Experiments with induced bacteriuria, vesical emptying and bacterial growth on the mechanism of bladder . defense to infection. J. Urol., 86: 739, 1961. 11 Cox, C. E. and Hinman, F., Jr.: Reten!10n catheterization and the bladder defense mechamsm. J.A.M.A., 191: 171, 1965.
Patients
(%)
253 (85) 28 (9) 7 (2) 14 106 109 54 24 9
(35) (36) (18) (8)
121 47 53 22 28 8 6 17
(40) (16) (18) (7) (9) (3) (2)
exaggerated by urinary infection, the need for proper antimicrobial therapy cannot be overemphasized. Tumor characteristics. Tumor location within the bladder was generally consistent with the observations of other investigators. Thirteen per cent of the lesions were located on the bladder dome, 26 per cent on the base, 44 per cent on the lateral walls and 17 per cent were in multiple locations. Forty-two per cent of the lesions were papillary, 53 per cent were solid and 5 per cent were described as an ulceration. Tumor cell type is listed in table 5 and indicates the usual preponderance of transitional cell carcinoma. The small numbers of patients with squamous and adenocarcinomas preclude separate analysis of their course. Tumor grade and stage18 are also listed in table 5 and the distribution of these groups is in accord with most other series. Of 106 grade 1 lesions, all but 5 were stage O or A. Likewise, of 109 grade 2 lesions all but 12 were stage O or A tumors. Conversely, of 78 grade 3 and grade 4 lesions all except 9 were stage B1 or deeper. Due to the consistency of these findino·s b , the relatively small numbers of high grade, 1s Jewett, H. J. and Strong, G .. H.: Infiltrating carcinoma of the bladder: relat10n _of . depth of penetration of the bladder wall to mc1dence of local extension and metastases. J. Urol., 55: 366,
1946.
BLADDER CANCJ;;R: 26-YEAR REVIK\V
low stage le.simrn aml of low grade, high stage lesions were not analyzed independently. However, our im]lres~ion was that high grade O and A lesions were more aggressive and low grade B and C lesions les~ malignant than their more common counterparts. Treatm.ent. Initial treatment in this series of 302 patients ,rns transnrethral resection in 181 (59.9 per cent), partial cystectomy in 59 (19.5 per cent), total cystectomy in 31 (10.2 per cent), cystostorny and fulguration in 13 (4.3 per cent), and other procedures in 18 (5.9 per cent) of the patients (table 6). Radiotherapy, postoperatively in all but 5 instances, was administered as an adjuvant to 89 of the above initial treatment procedures. Ninety-two of the 302 patients ,-vere service and the remaining 210 were under the care of 5 staff pli:,,sicians. Deaths, classified as postoperative, occurred in only 11 (3.6 per cent) of the patients. As of July 1967, 26 per cent of the ua1,1e11c~ ,rnre ;31 per cent untraced (although many were at risk for several years prior to becoming untraced) and 42 per cent were per cent) were dead. Of the 128 deaths, 57 due to vesical carcinoma, 29 (22.6 per cent) were known to be from other causes and 42 (32.6 per cent) were from unknown causes (table I). Therapy, sub~equent to the initial treatment, was required for 104 of the 302 (table 7). These 104 patients underwent a total of 372 treatment procedures. For example, 72 of the patient8 undergoing subsequent transurethral resection received this procedure an average of 2.7 times. Likewise 49 received subsequent iutenrnl or external irradiation on 82 occasions. Survival. Table~ 8 through 12 reveal survival data in relation to tumor stage. This method was TABLlc
fi. lnilia.l lrcalrn.eni, 302 palicnls No. Patients (%)
T"CR Partial cvstectomy Toh1] cyslectomy Cystotomy and fulgt1ra.tion Urinary diversion Laparotomy only None Radiotherapy only Adjm1ctive rn.diothernpy Chemotherapy only Adjnvant. chemotherapy
181 (59. 9) 59 (19.5)
:n
(10. 2) 13 (4.3)
41
5! G( 3)
89 0
12
(5. g)
T AilLJ£ 7. 'L' reatment with 188 .rn./Jseguenl proccclurns in 104. 7,al·icnl.s
'T-UH,
72
]97
Cystectomy
14 g
16
Partial cystectomy Olhcr surgical procednres
:CJ:3
Radiotherapy Chemotherapy
4D ll 188
JA
372
used as it has been shown that cmndation ot stage and sun·inLI is a satisfaci.ot·y parn.n1,'ter on whid1 to assess prognmis and, in addition, 1s consistent with the recent literature. In this regard it seems prndcut to point out that although statistic,1lly valid differences in sm-Yival can ofk:H be noted from series to series or between sub groups within a given series, these cannot usually be taken as conclusive eYidence that one treatment is superior to another. Thb consideration is especially pertinent in to carcinoma therapy in which thcrnpeutic bias i~ prominent and clifferenc:es in result~ rrn1y, in be due to tumor difference rnther Huw to varin.tions in trcatment.19 - 20 In most instances l, ;:i a11cl 5-)·car sun-ival r:1tns in our ,;eries nre consistent with those of' most other reviews. Clearly there is a prngressive dedine in these crude smvival rates stages J'\.. through C. Of 14 stage D, and D 2 tumors, none smYivcd more than 1 year. 6 of 17 unstagecl turnorn were at risk more than 1 year and of these, only one survived 5 yea1·s. Tables 8 to 12 also iudicate survival witbi11 each stage in relation to the initial procedure. However, as the nurnbern no attempt has been made to as to the superior mode of therapy. Operative procedures. Patients unclergoi ng partial cysteetomy as initial treatrnent arc nul eel in table 13. Eleven of the~e 59 given adjunetive (postoperative) 19 Pa.yne, P., Smithers, D. W. and Walla.c:o, JVI.: Results of treatment. In: Tumours of t.h,-, Bladder. Edi Led by D. M. Vl!rtlfa,cc. London: E & S. Livingstone Ltd., clrnp, :307, vol Hl5D. 20 Greiss., F. C., .Jr., Rhyne, L., .Jr. and F. R.. : The role of statistics in 11 thernpy for gynecologic:11 cancer. Obst. & Gynec, 20: 603, 1965
554
COX, CASS AND BOYCE
and, in addition, some of the patients underwent subsequent operative procedures (excluding cystectomy) as well as subsequent radiation therapy. Table 14 lists all 55 cystectomies
(through 1966) performed at this institution and includes not only those 31 performed as initial treatment but, in addition, 14 carried out as subsequent therapy and 10 performed on patients
TABLE 8. Stage O patients Initial Treatment*
TUR TUR+ IR TUR+ ER PC TC TUR+ C Total
Survival (Years) (alive/at risk)
No. Patients
89 7 8 15 1 1
68/68 5/6 5/6 12/14 1/1 0/0
121
91/95
2
3
61/64 5/6 5/6 8/11 1/1 0/0
50/58 4/6 3/6 4/7 1/1 0/0
80/88
62/78
(95.8%)
4
5
44/55 4/6 3/6 3/7 1/1 0/0
37/52 4/6 3/6 3/6 1/1 0/0
55/75
48/71 (67.6%)
(79.5%)
* IR-internal irradiation; ER-external irradiation; PC-partial cystectomy; TC-total cystectomy; C-chemotherapy. TABLE 9. Stage A patients Initial Treatment*
Survival (Years) (alive/at risk)
No. Patients 2
TUR TUR+ ER TC PC PC+ER C&F PC+ IR TUR+ IR C&F+IR
19 12 1 8 1 2 2 1 1
14/17 8/10 1/1 7/8 1/1 1/2 1/1 0/0 0/1
Total
47
33/41
4
5
7/15 2/9 1/1 3/6 0/0 1/2 1/1 0/0 0/1
7/15 1/9 1/1 3/6 0/0 1/2 1/1 0/0 0/1
3
11/15 6/10 1/1 5/6 0/0 1/2 1/1 0/0 0/1
10/16 3/9 1/1 4/6 0/0 1/2 1/1 0/0 0/1
25/36
20/36
(80.5%)
15/35 (55.5%)
14/35 (40%)
* C & F-cystotomy and fulguration. TABLE 10. Stage B1 patients Initial Treatment
Survival (Years) (alive/at risk)
No. Patients
TUR TUR+ ER PC TUR+ IR C & F + ER PC+ ER TC TC+ ER
16 10 5 4 2 5 7 4
6/13 7/7 3/3 4/4 1/1 1/2 6/6 2/4
Total
53
30/40 (75%)
3
4
5
3/13 5/6 1/3 2/4 1/1 1/2 4/6 2/4
3/13 3/5 1/3 2/5 1/1 1/2 4/6 2/4
1/12 3/5 1/3 2/4 1/1 0/2 4/6 1/4
1/12 2/5 1/3 2/4 0/1 0/2 3/6 1/4
19/39
17/39
13/37 (43.6%)
10/37 (27%)
BLADDER CANCER: 26-YEAR REVIEW
555
TABLE 11. Stage B2 patients Initial Treatment
TUR TUR+ ER TC PC PC+ ER Total
Survival (Years) (alive/at risk)
No. Patients
4 6 4 6 2
1/3 2/3 3/3 4/6 1/1
22
11/16
2
3
4
s
1/3 2/3 1/3 3/5 1/1
1/3 1/2 1/3 2/4 0/1
0/3 0/2 1/3 2/4 0/1
0/3 0/2 1/3 2/4 0/1
8/15
5/13
3/13
3/13 (23%)
(68.7%)
(38.4%)
TABLE 12. Stage C patients Initial Treatment
Survival (Years) (alive/at risk)
No. Patients
TUR TUR+ ER TC PC PC+ ER
2 8 13 4 1
0/1 1/5 7/13 2/4 1/1
Total
28
11/24
2
3
4
0/1 0/5 4/12 1/4 0/1
0/1 0/5 3/12 1/4 0/1
0/1 0/5 2/11 1/4 0/1
0/1 0/5 2/11 1/4 0/1
5/23
4/23
3/22
3/22 (13.2%)
(45.8%)
(17.4%)
TABLE 13. Partial cystectomy results Stage
Survival (Years) (alive/at risk)
No. Patients
D1
17 17 10 8 6 1
14/16 14/16 4/5 5/8 3/6 0/1
Total
59
40/52
0 A
B1 B2 C
2
3
4
5
10/13 11/12 3/5 4/7 1/6 0/1
4/7 8/12 3/5 2/6 1/6 0/1
3/7 8/12 1/5 2/6 1/6 0/1
3/7 8/11 1/5 2/6 1/6 0/1
29/44
18/37
(76.9%)
15/37 (48.6%)
15/36 (41. 7%)
TABLE 14. Total cystectomy results Survival (Years) (alive/at risk) Stage
No. Patients
Sarcoma
3 9 17 8 13 4 1
2/2 6/7 15/16 7/7 6/13 1/4 0/0
Total
55
37/49
0 A
B1 B2 C
D1
(75.5%)
2
3
4
5
2/2 4/7 10/15 4/7 4/12 1/4 0/0
2/2 4/7 8/13 2/5 3/12 1/4 0/0
1/2 3/6 7/12 2/5 2/11 1/4 0/0
1/2 2/5 5/11 2/5 2/11 0/3 0/0
25/47
20/43
16/40 (46.5%)
12/37 (32.4%)
556
COX, CASS AND BOYCE
who had received primary treatment preceding admission to our hospital. Only eight of these 55 patients received adjunctive radiotherapy. Interestingly, survival statistics in this series for partial and total cystectomy are very similar. However, patient and tumor differences, as well as physician bias most likely preclude valid conclusions from this comparison. Understaging. In this series, as in most others since 1950, tumors were staged using Jewett'srs original method as modified by others. In the usual case staging was primarily based upon transurethral biopsy in conjunction with the findings of other ancillary procedures such as the excretory urogram, cystogram or bimanual examination. If open surgical procedures were not carried out, the exact stage often remained unknown. On the other hand, in 40 of the patients, initially staged by the aforementioned parameters, a coincidental open surgical procedure (usually partial or total cystectomy) revealed that a deeper stage in fact existed. Therefore, understaging by transurethral biopsy was noted in 40 of 112 (35.7 per cent) patients who underwent an open surgical procedure during their initial evaluation (table 15). This occurrence of erroneous staging by transurethral methods was also often noted in patients undergoing subsequent transurethral and operative procedures for recurrence of disease. Twenty-five of the 40 patients were understaged as superficial lesions (A and 0) when by surgical biopsy they were noted within (or beyond) the musculature. This type of understaging by transurethral resection may result in a delay of appropriate operative and or radiotherapeutic measures. On the contrary, understaging as Br or B2, when the lesion is C or D1, may result in overzealous therapy. To overcome these potential problems we have been inclined to place more emphasis on open surgical biopsy and total specimen histology as a means TABLE
15. Tumors underslaged by transiirethral resection, 40 patients
Stage by TUR
No. Patients
0 or A
25
Br B,
13 2
Surgical Stage*
Br
B,
C
Dr
11 0
g
3
2
10
3 2
* Open biopsy, partial or total cystectomy.
Frn. ~- Full thickness surgical biopsy of papillary les10n, stage 0.
Frn. 2. Total specimen technique; note extension into perivesical tissue, stage C. TUR biopsy recorded as stage Br (same patient as figure 3, B). of more accurately delineating the true extent of the lesion (figs. 1 and 2) .21 This approach to staging of vesical cancer will formulate the basis of a subsequent report. In addition, since 1965 we have been using triple contrast vesical arteriography as a means of pre-therapy assessment of stage (fig. 3). Using this procedure in some 25 cases we have noted a 95 per cent correlation be,r Mills, R. and Perez-Mesa, C.: Giant histological sections. Visual/Sonic Medicine, 3: 12, 1968.
BLADDER CANCER: 26-YEAR REVIKW
FIG. 3, A, normal triple contrast vesical arteriogram; note uterine arteries. R, vesical demonstrates stage C lesion (same patient as figure 2). Not,c abnormal vascularit.y extending perivesical tissues.
T,\HLE
Hi. Rewrrence of cancer within the bladder,
97 patient8
T.UJLE
17. Cornplication.s following 55 palien/.s
No. Stage of
Patients
No. Recurrences
Initial Lesion
\Vith Recurrence
(ave.)
A or 0
69
B, B,
lG 8 4
]80 (2. 6) 31 (1. 9)
31
11 (1.3) 4 (1)
ll 4
C
Recurrence (B1 or>)
I
cysiectorny,
P t Lon°·· . Ao. Postop. I · os 0 1ften~ Patients Deaths, ~~tign1; .Cor:npli···
I
'II
I
26
tween the arteriographic and the surgical stage. The procedure has been most impressive in its demonstration of minimal musculature invasion and also in defining the extent of extravesical extension. This material will also be reported as a separate communication. Recurrence. In this recurrence of cancer within the bladder occurred in 97 patients who did not initially have: .l) a total cystectomy, 2) tumor stage greater than C or 3) gross residual tumor following the initial surgical procedure. Therefore, 97 of 230 patients (42.2 per cent) so qualifying had at least one recurrence of bladder cancer (table 16). This rate would, of course, be .somewhat higher if D lesions and incompletely extirpated D and C lesions were included. Recurrence of B and C lesions most often indicated advanced disease followed shortly by death. On the other hand, recurrence of O and A lesions provided a distinct therapeutic challenge. Sixty-nine patients with lesions initially stage 0 or A had 180 recurrences (average 2.G, range 1 to 15) of bladder cancer. ;'Jot only did these recur-
-----;-1~1
0/2 Cutaneons nreteros- tomy i I U reterosigmoidos25 I 3/25 j 8/2.S tomy i I I 28 ! 1/28 I :3/28 Ureteroileostomy
:ca Lions
j
J/2
-
7 /14
2/H
rences require frequent surgical and attendant morbidity; most strikingly, iu 2fi (37.7 per cent) patients the recurrences become more malignant as evidenced by muscle invasion and higher tumor grade (table IG). COMMENTS
This review of 371 bladder cancer admitted to the Bowman Gray School of J\iedicine from 1941 through 1966 represents the entire institutional experience with this disease. The percentage of patienb admitted with vesical carcinoma was consistent with the ,,pparent national average. 13 The study population and patient characteristics do not reveal any unusu:l.l features except that by removing all treated for bladder cancer prior to relatively homogeneous group of ;302 mained for analysis. A. high rate of urinary infertion was noted and we believe this is due to local and turnc)r
558
COX, CASS AND BOYCE
effects which render host defenses incompetent. that a more aggressive therapeutic approach is This high infection rate undoubtedly contributes probably indicated for those patients with initial to an increased incidence of post-therapy mor- A lesions or for patients with O lesions demonbidity; and therefore, intensive antimicrobial strating a recurrence with submucosal involvetherapy is recommended. ment. Tumor characteristics, location, growth patThe data are insufficient to substantiate tern, cellular type, grade and stage were gen- superiority of any one form of treatment within erally consistent with most other series. Seventy- any stage. Although the results of cystectomy in one per cent of the lesions were grade 1 or 2 and our series (32.4 per cent 5-year survival) are 56 per cent were superficial to the vesical muscula- similar to other series, several features should ture. Initial treatment of these lesions was highly be noted. During this 26-year period patient variable, primarily due to the 26-year duration selection for cystectomy was often delayed for of the survey. various reasons, not the least of which was underCrude survival rates, calculated within each staging by transurethral biopsy. For this reason tumor stage, are again in accord with most other we are now more aggressive with diagnostic proreports15 except in regard to our group of A and 0 cedures designed to accurately assess tumor stage. patients. Most investigators have grouped O and These procedures are principally surgical biopsy A lesions together as "mucosal-well differenwhen doubt exists and "triple contrast vesical tiated" and have noted an approximate 50 per arteriography". In addition, early in the series, per cent 5-year crude survival for this group. However, a finer distinction between these lesions postoperative complications following ureterohas revealed, in our series, a 67.6 per cent 5-year sigmoidostomy were considerable (table 17) . survival for patients with O lesions and a 40 per Conversely, the reduced morbidity and mortality cent survival for those with submucosal involve- following ureteroileal anastomosis will result in a ment (stage A). This finding has suggested to us greater number of at risk patients for analysis.
THE JOURNAL OF UROLOGY
Copyright© 1969 by The Williams & Wilkins Co.
BLADDER CANCER: A 26-YEAR REVIEW CLAIRE. COX, ALEXANDERS. CASS
AND
WILLIAM H. BOYCE
From the Division of Urology, Deparlment of Surgery, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina
Retrospective patient surveys, regardless of several well recognized limitations, continue to function as a valuable means of communication within the health-science disciplines. With regard to vesical carcinoma, many excellent reviews have been published and, in general, represent either a review of institutional or individual experience with the disease during a time interval or a review emphasizing certain etiologic, diagnostic or therapeutic aspects of the bladder cancer. 1- 12 This paper presents an additional review of vesical carcinoma and is unique only in Accepted for publication May 15, 1968. Supported in part by the United States Public Health Service, grant CA 07375. Request for reprints: Bowman Gray School of Medicine, Winston-Salem, North Carolina 27013 (C.E.C.). 1 Kretschmer, H. L.: Cancer of the bladder. A study based on 902 epithelial tumors of the bladder in the Carcinoma Registry of the American Urological Association. J. Urol., 31: 423, 1934. 2 Deming, C. L.: The biological behavior of transitional cell papilloma of the bladder. J. Urol., 63: 815, 1950. 3 Flocks R. H.: Treatment of patients with carcinoma of the bladder. J.A.M.A., 145: 295, 1951. 4 Milner, W. A.: The role of conservative surgery in the treatment of bladder tumours. Brit. J. Urol.,
26: 375, 1954. 5 Dean, A. L., Mostofi, F. K., Thomson, R. V. and Clark, M. L.: A restudy of the first fourteen hundred tumors of the bladder tumor registry, Armed Forces Institute of Pathology. J. U rol., 71:
571, 1954.
6 Melicow, M. M.: Tumors of the urinary bladder: a clinico-pathological analysis of over 2500 specimens and biopsies. J. Urol., 74: 498, 1955. 7 Wall ace, D. M.: Tumours of the Bladder. London: E. & S. Livingstone, Ltd., vol. 2, 1959. 8 Rubin, P.: The impact of supervol tage irradiation on the treatment of bladder carcinoma. J. Urol., 86: 82, 1961. 9 Whitmore, W. F., Jr. and Marshall, V. F.: Radical total cystectomy for cancer of the bladder: 230 consecutive cases five years later. J. Urol.,
87: 853, 1962. 10 Del Regato, J. A. and Chahbazian, C. M.: Radiotherapy for transitional-cell carcinoma of the urinary bladder with cobalt 60. Radiology, 87:
1053, 1966. 11 Buschke, F. and Jack, G.: Twenty-five years' experience with supervoltage therapy in the treatment of transitional cell carcinoma of the bladder. Amer. J. Roentgen., 99: 387, 1967. 12 Cordonnier, J. J.: Cystectomy for carcinoma of the bladder. J. Urol., 99: 172, 1968.
550
that it represents the entire experience of one institution with bladder cancer. Since the establishment of the Bowman Gray School of Medicine in 1941, through 1966, 371 patients with vesical carcinoma were admitted to its hospital facility, the North Carolina Baptist Hospital. During this 26-year period an average of 14.3 patients with bladder cancer (lowest, 0 in 1941 and highest, 26 in 1957) were admitted yearly to this institution. As the average patient admission rate during this period was 11,248 per year, 0.13 per cent of all admissions were for bladder carcinoma. This figure compares favorably to the recent Professional Activity Study (PAS) 13 in which 0.19 per cent of more than 5 million hospital admissions were for bladder carcinoma. On the other hand, it is somewhat less than the incidence of 0.4 per cent of hospital admissions as reported by Flocks in an earlier survey. 14 Study population. The physical characteristics of the patient group under study are not unlike those of other reported surveys. The base population of the referral area is quite stable with few transients and is primarily rural. The principal industries within the referral area are related to tobacco, textiles and furniture manufacture. The predominate nationalities are Scottish, English and German. Unfortunately, sufficient data were not available in regard to the incidence of tobacco usage. Of the 371 patient charts reviewed, 173 failed to record an occupation and 11 listed "no occupation". Of the remaining 187 patients, 33 were housewives, 31 farmers, 16 employed in textile mills, 8 furniture plant employees and the remainder employed in a variety of occupations. The number of patients employed in processing of tobacco or petroleum products or in producing textiles or furniture did not seem inconsistent with the available industrial facilities. 13 Clarke, B. G., Mielke, R. and Leighton, E.: Urology in hospitals of the United States and Canada, 1963 and 1964: report of a statistical study. J. Urol., 96: 417, 1966. 14 Flocks, R. H.: Carcinoma of the bladder, Canad. Med. Ass. J., 55: 348, 1946.
BLADDER CANCER:
Of the 371 patients in this review, 69 (] 8.6 per cent) had undergone significant treatment for their bladder carcinoma before admission to our institution. As prior therapy seemingly would further reduce the value of a retro~pective review, these 69 patients, unless otherwise noted, will be excluded from all further data presented in this paper. The remaining 302 patients were all initially diagnosed and primarily treated at this institution. As of July 1967, the status of these 302 patients admitted during this 26-year period (1941 through 1966) was as follows: 79 were alive 9,5 were untraced 57 were dead due to canc~r 29 were dead fr~rn other causes and 42 ' were dead from unknown reasons (table 1). Patient characteristics. There were 216 male and 86 female patients in the group. The most common age group was the sixth decade but a significant number (13.9 per cent) were less than 50 years of age (table 2). Only 6 patients were asymptomatic (tumor found incidentally) and gross hematuria was present history in 252 (83 per cent) of the patients (table 2). Of interest was the large number of patients (113) in whom a time interval in excess of 6 TABLE
1, Current slal'll8, 302 bladder cancer
patients, 1941-1966
Alive Lost to followup Dead From cancer Not from canecr 1Tnknown canse TABLJ,
No.
%,
79 95 128
26 3] 42
57 (44. 5%)
2!) (22.G%) 42 C:l2. Ci'/r,)
2. Age al cliagno.si.s and syn1,plon1s, 302
bladder cance,· patients Age
<50
50-60 60-70 70-80 >80
Xo, Cases
42 66 96 79 19
Symptoms
No. Cases
Jiematmia Dysnria Back pain Suprapubic pain Other symptoms Xo symptoms
252 115
23 19 59 6
26- YEAR TMJLE
REVIEW
3. Duration of .symptoms before admi.,sion
Duration of Symptoms (mos.)
>To. Patients
G8
1-3 3-6 >6 Unknown BUN elevated Ureteral obstrnction
7G
34 113
(37%)
11
64/232* (28%) 47/287* (17%)
* Number of patients at risk. months existed from the appearance of symptoms until the time of admission (table 3). It was considered that this rather long delay in seeking medical attention by 37 per cent of the might potentially explain the high incidence of azotemia (28 per cent) and obstructive urographic changes (17 per cent) noted in this series 3). However, a relationship between this in admission and obstructive disease did not exist, Likewise, a comparison of the tumor stage and grade with length of history did not suggest that a longer history is associated with a more malig .. nant tumor. Equally evident was a total lack of correlation between length of symptoms and survival. Similar findings were noted in a review of 1,420 cases of this disease. 15 Unassociated disease was present to a variable extent in 102 patients. As urinary tract cytology was unsatisfactory at this institution during most of the survey years, sufficient data are not avail-able for analysis. In addition, although himanual examination was usually performed, the results were not sufficiently recorded to allow comment upon the findings. Urinary infection. Of particular interest to us was the incidence of urinary tract infection m this series. Excluding those patients admitted prior to 1957 (due to inadequate 174 patients were at risk for analysis in regard to urinarv infection. Results were unavailable on 2.5 patients, but of the remaining 149, fi2 .G per cent) had a positive* urine culture at the time of admission to the hospital. All cultures were obtained prior to or at the time of initial instrumentation at our institution. It is to determine the exact number of these who had been subjected to prior catheterizntion 1a Pa,yne, P,: Sex, age, history, tumor type and survivaL In: Tumours of the Bladder.. Edited D. i\!L Wallace, London: K & S. Livingstone chap. 19 p.285, voL 2, 1959, * 10,000 or more bacteria per milliliter of urine.
552
COX, CASS AND BOYCE
TABLE 4. Urinary infection in 1,000 consecutive patients and 62 patients infected secondary to bladder cancer Patients with Various U rologic Bladder Patients, No.(%)
E.coli Aerobacter-klebsiella Intermediate coliforms Proteus mirabilis Indole pos. proteus Pseudomonas Enterococcus Staphylococcus
No.
Cell type: Transitional Squamous Adeno. Not listed Tumor grade:
Carcinoma, No.(%)
376 (37 .6) 172 (17.2) 82 (8.2)
11 (17.7) 7 (11.3) 5 (8)
108 45 114 57 46
4 3 4 21 7
(10.8) (4.5) (11.4) (5.7) (4.6)
TABLE 5. Bladder cancer lesions, 302 cases
1 2 3 4
(6.6) (5) (6.6) (33. 9) (11.3)
Not listed Tumor stage: 0
Total
1,000
A B, B2 C D1 D2 Not listed
62
or instrumentation. But if a maximum estimate of 15 per cent had been instrumented prior to admission, and this had resulted in continuing infection in all (which is possible but doubtful), this would still be inconsistent with the 42 per cent infection rate as noted at the initial admiRsion to our institution. A more likely explanation for this high infection rate is the effect of vesical neoplasia on local bladder defense mechanisms (and possibly systemic defenses as well). This lends support to our previous observations that the principal determinate of infection is the condition of the host and not the availability of bacteria. 16 , 17 Noteworthy also is the bacterial species recovered from these patients (table 4). A comparison of the infecting organisms obtained from these patients with positive cultures from 1,000 consecutive urologic patients with urinary infection reveals several differences (table 4). Most apparent is the substantial increase in enterococcal infections among patients with vesical cancer. This fastidious organism rarely infects individuals without gross urinary tract disease and resultant reduced host resistance. It is not inconceivable that the frequency of hematuria associated with vesical neoplasia is increased by the occurrence of secondary bacterial invasion. Furthermore, as post-therapy (operative or irradiation) morbidity is often 16 Cox, C. E. and Hinman, F., Jr.: Experiments with induced bacteriuria, vesical emptying and bacterial growth on the mechanism of bladder . defense to infection. J. Urol., 86: 739, 1961. 11 Cox, C. E. and Hinman, F., Jr.: Reten!10n catheterization and the bladder defense mechamsm. J.A.M.A., 191: 171, 1965.
Patients
(%)
253 (85) 28 (9) 7 (2) 14 106 109 54 24 9
(35) (36) (18) (8)
121 47 53 22 28 8 6 17
(40) (16) (18) (7) (9) (3) (2)
exaggerated by urinary infection, the need for proper antimicrobial therapy cannot be overemphasized. Tumor characteristics. Tumor location within the bladder was generally consistent with the observations of other investigators. Thirteen per cent of the lesions were located on the bladder dome, 26 per cent on the base, 44 per cent on the lateral walls and 17 per cent were in multiple locations. Forty-two per cent of the lesions were papillary, 53 per cent were solid and 5 per cent were described as an ulceration. Tumor cell type is listed in table 5 and indicates the usual preponderance of transitional cell carcinoma. The small numbers of patients with squamous and adenocarcinomas preclude separate analysis of their course. Tumor grade and stage18 are also listed in table 5 and the distribution of these groups is in accord with most other series. Of 106 grade 1 lesions, all but 5 were stage O or A. Likewise, of 109 grade 2 lesions all but 12 were stage O or A tumors. Conversely, of 78 grade 3 and grade 4 lesions all except 9 were stage B1 or deeper. Due to the consistency of these findino·s b , the relatively small numbers of high grade, 1s Jewett, H. J. and Strong, G .. H.: Infiltrating carcinoma of the bladder: relat10n _of . depth of penetration of the bladder wall to mc1dence of local extension and metastases. J. Urol., 55: 366,
1946.
BLADDER CANCJ;;R: 26-YEAR REVIK\V
low stage le.simrn aml of low grade, high stage lesions were not analyzed independently. However, our im]lres~ion was that high grade O and A lesions were more aggressive and low grade B and C lesions les~ malignant than their more common counterparts. Treatm.ent. Initial treatment in this series of 302 patients ,rns transnrethral resection in 181 (59.9 per cent), partial cystectomy in 59 (19.5 per cent), total cystectomy in 31 (10.2 per cent), cystostorny and fulguration in 13 (4.3 per cent), and other procedures in 18 (5.9 per cent) of the patients (table 6). Radiotherapy, postoperatively in all but 5 instances, was administered as an adjuvant to 89 of the above initial treatment procedures. Ninety-two of the 302 patients ,-vere service and the remaining 210 were under the care of 5 staff pli:,,sicians. Deaths, classified as postoperative, occurred in only 11 (3.6 per cent) of the patients. As of July 1967, 26 per cent of the ua1,1e11c~ ,rnre ;31 per cent untraced (although many were at risk for several years prior to becoming untraced) and 42 per cent were per cent) were dead. Of the 128 deaths, 57 due to vesical carcinoma, 29 (22.6 per cent) were known to be from other causes and 42 (32.6 per cent) were from unknown causes (table I). Therapy, sub~equent to the initial treatment, was required for 104 of the 302 (table 7). These 104 patients underwent a total of 372 treatment procedures. For example, 72 of the patient8 undergoing subsequent transurethral resection received this procedure an average of 2.7 times. Likewise 49 received subsequent iutenrnl or external irradiation on 82 occasions. Survival. Table~ 8 through 12 reveal survival data in relation to tumor stage. This method was TABLlc
fi. lnilia.l lrcalrn.eni, 302 palicnls No. Patients (%)
T"CR Partial cvstectomy Toh1] cyslectomy Cystotomy and fulgt1ra.tion Urinary diversion Laparotomy only None Radiotherapy only Adjm1ctive rn.diothernpy Chemotherapy only Adjnvant. chemotherapy
181 (59. 9) 59 (19.5)
:n
(10. 2) 13 (4.3)
41
5! G( 3)
89 0
12
(5. g)
T AilLJ£ 7. 'L' reatment with 188 .rn./Jseguenl proccclurns in 104. 7,al·icnl.s
'T-UH,
72
]97
Cystectomy
14 g
16
Partial cystectomy Olhcr surgical procednres
:CJ:3
Radiotherapy Chemotherapy
4D ll 188
JA
372
used as it has been shown that cmndation ot stage and sun·inLI is a satisfaci.ot·y parn.n1,'ter on whid1 to assess prognmis and, in addition, 1s consistent with the recent literature. In this regard it seems prndcut to point out that although statistic,1lly valid differences in sm-Yival can ofk:H be noted from series to series or between sub groups within a given series, these cannot usually be taken as conclusive eYidence that one treatment is superior to another. Thb consideration is especially pertinent in to carcinoma therapy in which thcrnpeutic bias i~ prominent and clifferenc:es in result~ rrn1y, in be due to tumor difference rnther Huw to varin.tions in trcatment.19 - 20 In most instances l, ;:i a11cl 5-)·car sun-ival r:1tns in our ,;eries nre consistent with those of' most other reviews. Clearly there is a prngressive dedine in these crude smvival rates stages J'\.. through C. Of 14 stage D, and D 2 tumors, none smYivcd more than 1 year. 6 of 17 unstagecl turnorn were at risk more than 1 year and of these, only one survived 5 yea1·s. Tables 8 to 12 also iudicate survival witbi11 each stage in relation to the initial procedure. However, as the nurnbern no attempt has been made to as to the superior mode of therapy. Operative procedures. Patients unclergoi ng partial cysteetomy as initial treatrnent arc nul eel in table 13. Eleven of the~e 59 given adjunetive (postoperative) 19 Pa.yne, P., Smithers, D. W. and Walla.c:o, JVI.: Results of treatment. In: Tumours of t.h,-, Bladder. Edi Led by D. M. Vl!rtlfa,cc. London: E & S. Livingstone Ltd., clrnp, :307, vol Hl5D. 20 Greiss., F. C., .Jr., Rhyne, L., .Jr. and F. R.. : The role of statistics in 11 thernpy for gynecologic:11 cancer. Obst. & Gynec, 20: 603, 1965
554
COX, CASS AND BOYCE
and, in addition, some of the patients underwent subsequent operative procedures (excluding cystectomy) as well as subsequent radiation therapy. Table 14 lists all 55 cystectomies
(through 1966) performed at this institution and includes not only those 31 performed as initial treatment but, in addition, 14 carried out as subsequent therapy and 10 performed on patients
TABLE 8. Stage O patients Initial Treatment*
TUR TUR+ IR TUR+ ER PC TC TUR+ C Total
Survival (Years) (alive/at risk)
No. Patients
89 7 8 15 1 1
68/68 5/6 5/6 12/14 1/1 0/0
121
91/95
2
3
61/64 5/6 5/6 8/11 1/1 0/0
50/58 4/6 3/6 4/7 1/1 0/0
80/88
62/78
(95.8%)
4
5
44/55 4/6 3/6 3/7 1/1 0/0
37/52 4/6 3/6 3/6 1/1 0/0
55/75
48/71 (67.6%)
(79.5%)
* IR-internal irradiation; ER-external irradiation; PC-partial cystectomy; TC-total cystectomy; C-chemotherapy. TABLE 9. Stage A patients Initial Treatment*
Survival (Years) (alive/at risk)
No. Patients 2
TUR TUR+ ER TC PC PC+ER C&F PC+ IR TUR+ IR C&F+IR
19 12 1 8 1 2 2 1 1
14/17 8/10 1/1 7/8 1/1 1/2 1/1 0/0 0/1
Total
47
33/41
4
5
7/15 2/9 1/1 3/6 0/0 1/2 1/1 0/0 0/1
7/15 1/9 1/1 3/6 0/0 1/2 1/1 0/0 0/1
3
11/15 6/10 1/1 5/6 0/0 1/2 1/1 0/0 0/1
10/16 3/9 1/1 4/6 0/0 1/2 1/1 0/0 0/1
25/36
20/36
(80.5%)
15/35 (55.5%)
14/35 (40%)
* C & F-cystotomy and fulguration. TABLE 10. Stage B1 patients Initial Treatment
Survival (Years) (alive/at risk)
No. Patients
TUR TUR+ ER PC TUR+ IR C & F + ER PC+ ER TC TC+ ER
16 10 5 4 2 5 7 4
6/13 7/7 3/3 4/4 1/1 1/2 6/6 2/4
Total
53
30/40 (75%)
3
4
5
3/13 5/6 1/3 2/4 1/1 1/2 4/6 2/4
3/13 3/5 1/3 2/5 1/1 1/2 4/6 2/4
1/12 3/5 1/3 2/4 1/1 0/2 4/6 1/4
1/12 2/5 1/3 2/4 0/1 0/2 3/6 1/4
19/39
17/39
13/37 (43.6%)
10/37 (27%)
BLADDER CANCER: 26-YEAR REVIEW
555
TABLE 11. Stage B2 patients Initial Treatment
TUR TUR+ ER TC PC PC+ ER Total
Survival (Years) (alive/at risk)
No. Patients
4 6 4 6 2
1/3 2/3 3/3 4/6 1/1
22
11/16
2
3
4
s
1/3 2/3 1/3 3/5 1/1
1/3 1/2 1/3 2/4 0/1
0/3 0/2 1/3 2/4 0/1
0/3 0/2 1/3 2/4 0/1
8/15
5/13
3/13
3/13 (23%)
(68.7%)
(38.4%)
TABLE 12. Stage C patients Initial Treatment
Survival (Years) (alive/at risk)
No. Patients
TUR TUR+ ER TC PC PC+ ER
2 8 13 4 1
0/1 1/5 7/13 2/4 1/1
Total
28
11/24
2
3
4
0/1 0/5 4/12 1/4 0/1
0/1 0/5 3/12 1/4 0/1
0/1 0/5 2/11 1/4 0/1
0/1 0/5 2/11 1/4 0/1
5/23
4/23
3/22
3/22 (13.2%)
(45.8%)
(17.4%)
TABLE 13. Partial cystectomy results Stage
Survival (Years) (alive/at risk)
No. Patients
D1
17 17 10 8 6 1
14/16 14/16 4/5 5/8 3/6 0/1
Total
59
40/52
0 A
B1 B2 C
2
3
4
5
10/13 11/12 3/5 4/7 1/6 0/1
4/7 8/12 3/5 2/6 1/6 0/1
3/7 8/12 1/5 2/6 1/6 0/1
3/7 8/11 1/5 2/6 1/6 0/1
29/44
18/37
(76.9%)
15/37 (48.6%)
15/36 (41. 7%)
TABLE 14. Total cystectomy results Survival (Years) (alive/at risk) Stage
No. Patients
Sarcoma
3 9 17 8 13 4 1
2/2 6/7 15/16 7/7 6/13 1/4 0/0
Total
55
37/49
0 A
B1 B2 C
D1
(75.5%)
2
3
4
5
2/2 4/7 10/15 4/7 4/12 1/4 0/0
2/2 4/7 8/13 2/5 3/12 1/4 0/0
1/2 3/6 7/12 2/5 2/11 1/4 0/0
1/2 2/5 5/11 2/5 2/11 0/3 0/0
25/47
20/43
16/40 (46.5%)
12/37 (32.4%)
556
COX, CASS AND BOYCE
who had received primary treatment preceding admission to our hospital. Only eight of these 55 patients received adjunctive radiotherapy. Interestingly, survival statistics in this series for partial and total cystectomy are very similar. However, patient and tumor differences, as well as physician bias most likely preclude valid conclusions from this comparison. Understaging. In this series, as in most others since 1950, tumors were staged using Jewett'srs original method as modified by others. In the usual case staging was primarily based upon transurethral biopsy in conjunction with the findings of other ancillary procedures such as the excretory urogram, cystogram or bimanual examination. If open surgical procedures were not carried out, the exact stage often remained unknown. On the other hand, in 40 of the patients, initially staged by the aforementioned parameters, a coincidental open surgical procedure (usually partial or total cystectomy) revealed that a deeper stage in fact existed. Therefore, understaging by transurethral biopsy was noted in 40 of 112 (35.7 per cent) patients who underwent an open surgical procedure during their initial evaluation (table 15). This occurrence of erroneous staging by transurethral methods was also often noted in patients undergoing subsequent transurethral and operative procedures for recurrence of disease. Twenty-five of the 40 patients were understaged as superficial lesions (A and 0) when by surgical biopsy they were noted within (or beyond) the musculature. This type of understaging by transurethral resection may result in a delay of appropriate operative and or radiotherapeutic measures. On the contrary, understaging as Br or B2, when the lesion is C or D1, may result in overzealous therapy. To overcome these potential problems we have been inclined to place more emphasis on open surgical biopsy and total specimen histology as a means TABLE
15. Tumors underslaged by transiirethral resection, 40 patients
Stage by TUR
No. Patients
0 or A
25
Br B,
13 2
Surgical Stage*
Br
B,
C
Dr
11 0
g
3
2
10
3 2
* Open biopsy, partial or total cystectomy.
Frn. ~- Full thickness surgical biopsy of papillary les10n, stage 0.
Frn. 2. Total specimen technique; note extension into perivesical tissue, stage C. TUR biopsy recorded as stage Br (same patient as figure 3, B). of more accurately delineating the true extent of the lesion (figs. 1 and 2) .21 This approach to staging of vesical cancer will formulate the basis of a subsequent report. In addition, since 1965 we have been using triple contrast vesical arteriography as a means of pre-therapy assessment of stage (fig. 3). Using this procedure in some 25 cases we have noted a 95 per cent correlation be,r Mills, R. and Perez-Mesa, C.: Giant histological sections. Visual/Sonic Medicine, 3: 12, 1968.
BLADDER CANCER: 26-YEAR REVIKW
FIG. 3, A, normal triple contrast vesical arteriogram; note uterine arteries. R, vesical demonstrates stage C lesion (same patient as figure 2). Not,c abnormal vascularit.y extending perivesical tissues.
T,\HLE
Hi. Rewrrence of cancer within the bladder,
97 patient8
T.UJLE
17. Cornplication.s following 55 palien/.s
No. Stage of
Patients
No. Recurrences
Initial Lesion
\Vith Recurrence
(ave.)
A or 0
69
B, B,
lG 8 4
]80 (2. 6) 31 (1. 9)
31
11 (1.3) 4 (1)
ll 4
C
Recurrence (B1 or>)
I
cysiectorny,
P t Lon°·· . Ao. Postop. I · os 0 1ften~ Patients Deaths, ~~tign1; .Cor:npli···
I
'II
I
26
tween the arteriographic and the surgical stage. The procedure has been most impressive in its demonstration of minimal musculature invasion and also in defining the extent of extravesical extension. This material will also be reported as a separate communication. Recurrence. In this recurrence of cancer within the bladder occurred in 97 patients who did not initially have: .l) a total cystectomy, 2) tumor stage greater than C or 3) gross residual tumor following the initial surgical procedure. Therefore, 97 of 230 patients (42.2 per cent) so qualifying had at least one recurrence of bladder cancer (table 16). This rate would, of course, be .somewhat higher if D lesions and incompletely extirpated D and C lesions were included. Recurrence of B and C lesions most often indicated advanced disease followed shortly by death. On the other hand, recurrence of O and A lesions provided a distinct therapeutic challenge. Sixty-nine patients with lesions initially stage 0 or A had 180 recurrences (average 2.G, range 1 to 15) of bladder cancer. ;'Jot only did these recur-
-----;-1~1
0/2 Cutaneons nreteros- tomy i I U reterosigmoidos25 I 3/25 j 8/2.S tomy i I I 28 ! 1/28 I :3/28 Ureteroileostomy
:ca Lions
j
J/2
-
7 /14
2/H
rences require frequent surgical and attendant morbidity; most strikingly, iu 2fi (37.7 per cent) patients the recurrences become more malignant as evidenced by muscle invasion and higher tumor grade (table IG). COMMENTS
This review of 371 bladder cancer admitted to the Bowman Gray School of J\iedicine from 1941 through 1966 represents the entire institutional experience with this disease. The percentage of patienb admitted with vesical carcinoma was consistent with the ,,pparent national average. 13 The study population and patient characteristics do not reveal any unusu:l.l features except that by removing all treated for bladder cancer prior to relatively homogeneous group of ;302 mained for analysis. A. high rate of urinary infertion was noted and we believe this is due to local and turnc)r
558
COX, CASS AND BOYCE
effects which render host defenses incompetent. that a more aggressive therapeutic approach is This high infection rate undoubtedly contributes probably indicated for those patients with initial to an increased incidence of post-therapy mor- A lesions or for patients with O lesions demonbidity; and therefore, intensive antimicrobial strating a recurrence with submucosal involvetherapy is recommended. ment. Tumor characteristics, location, growth patThe data are insufficient to substantiate tern, cellular type, grade and stage were gen- superiority of any one form of treatment within erally consistent with most other series. Seventy- any stage. Although the results of cystectomy in one per cent of the lesions were grade 1 or 2 and our series (32.4 per cent 5-year survival) are 56 per cent were superficial to the vesical muscula- similar to other series, several features should ture. Initial treatment of these lesions was highly be noted. During this 26-year period patient variable, primarily due to the 26-year duration selection for cystectomy was often delayed for of the survey. various reasons, not the least of which was underCrude survival rates, calculated within each staging by transurethral biopsy. For this reason tumor stage, are again in accord with most other we are now more aggressive with diagnostic proreports15 except in regard to our group of A and 0 cedures designed to accurately assess tumor stage. patients. Most investigators have grouped O and These procedures are principally surgical biopsy A lesions together as "mucosal-well differenwhen doubt exists and "triple contrast vesical tiated" and have noted an approximate 50 per arteriography". In addition, early in the series, per cent 5-year crude survival for this group. However, a finer distinction between these lesions postoperative complications following ureterohas revealed, in our series, a 67.6 per cent 5-year sigmoidostomy were considerable (table 17) . survival for patients with O lesions and a 40 per Conversely, the reduced morbidity and mortality cent survival for those with submucosal involve- following ureteroileal anastomosis will result in a ment (stage A). This finding has suggested to us greater number of at risk patients for analysis.