TUR versus a nonchemotherapy control group (58% versus 97% recurrence, respectively). It is unlikely that a single intravesical dose of thiotepa would alter the.
Intravesical Chemotherapy of Superficial Bladder Cancer B. L. Lum Northern California Oncology Group, Palo Alto, CA, USA
Introduction Bladder cancer accounts for 4.4% of the new cases of cancer diagnosed each year in the United States. It was estimated in 1982 that 37,100 new cases of bladder cancer would be seen, with 27,000 cases appearing in males and 10,100 in females [4]. This sex-related dominance is probably a reflection of the preponderance of industrial· exposure to chemical carcinogens and cigarette smoking in the male population [21, 22,25,85,92, 106, 169]. These statistics do not include carcinoma in situ. It was also estimated in 1982 that 10,600 deaths would result from bladder cancer [4]. This is a 6% increase in the incidence of bladder cancer and a 3% increase in bladder cancer deaths from 1980 estimates [5]. Histologically, these tumors arise from the bladder epithelium, with transitional cell carcinoma accounting for approximately 90% of the cases, squamous cell carcinomas for 8%, and adenocarcinomas for the remaining 2% [129]. Of these newly diagnosed cases, 75%-85% of patients initially present with superficial (localized) tumors [5]; that is, tumors which would fall into the Jewett-Strong-Marshall classification of stage 0 or A tumors and would be classified at _pathologic stage Pa, PIS, or PI in the TNM system [76,99,141,172] (Table 1). These tumors either show no evidence of invasion (0) or invasion of the lamina propria but not the superficial muscle (A). This includes the group of patients with carcinoma in Table 1. Staging for bladder cancer Extent of disease
Jewett-StrongMarshall
VICC (T or P)
Carcinoma in situ Papilloma Invasion not beyond lamina propria Invasion into superficial muscle Invasion into deep muscle Invasion into perivesival fat Invasion into adjacent organs or Invasion into regional lymph nodes Invasion into extrapelvic lymph nodes or Distant metastasis
o o
A Bl B2 C
Tis, No, Mo Ta, No, Mo Tl, No, Mo TI, No, Mo n, No, Mo n, No, Mo
Dl
T4, N±
D2
T4, N+M±
T, clinical stage; P, pathologic stage; Dl, lymph node metastasis below level of the aortic bifurcation; D2, lymph node metastasis above the level of the aortic bifurcation Recent Results in Cancer Research. Vol. 85
© Springer-Verlag Berlin· Heidelberg 1983
4
B. L. Lum
situ. Of the remaining patients, 10% are found to have regional (infiltrative) disease and 5% present with distant disease. Because of the preponderance of transitional cell carcinoma in cancers of the bladder and the poor prognosis for patients with squamous cell carcinomas of the bladder, or adenocarcinomas of the bladder, subsequent discussion will be limited to the transitional cell type [2, 55, 72, 77, 140, 188]. Factors That Int1uence the Natural and Therapeutic History of Superficial Bladder Cancer
The natural and therapeutic histories of the bladder tumors overlap. There are no purely observational series reported in the literature; however, the natural history of the disease may be judged to some extent through the surgical series [187], which have been described extensively in the literature, and to some extent, through the literature concerning intravesival chemotherapy. It is important to realize that these tumors constitute a spectrum of tumors with disparate biologic behavior and dissimilar survival rates. Overall, if one examines the 5-year survival of patients with superficial bladder cancers treated with transurethral resection (TUR) alone, one observes 5-year survival rates of approximately 70% in patients with clinical stage 0 tumors [30], 43%-77% inpatients with stage A disease [9, 30, 51, 98, 107, 128], and approximately 60% in patients with stage B1 neoplasms [9, 107, 128]. One must keep in mind that these series are quite heterogeneous as far as the influence of the other factors mentioned below that influence survival. This data, approximate as it may be, does express that these tumors, although confined to the category of superficial tumors of the bladder mucosa, do have a small but measurable potential for causing cancer-related deaths. Any attempt to unterstand the natural and therapeutic history of superficial bladder tumors must take into account categorizations of the tumor other than clinical stage. These include factors such as grade, multicentricity (polychronotopicity), the variable nature of carcinoma in situ, as well as other factors related to new occurrences, such as tumor implantation. The incidence of tumor recurrence following initial therapy for superficial bladder tumors ranges from 40% to 85% [3, 8, 55, 91, 93, 140, 143, 173, 188]. Most occur within 6-12months. This variation inreported recurrence rates is probably a reflection of the factors mentioned above. Utz and associates [173] reported an 82% recurrence rate within 1 year of initial therapy in 62 patients with carcinoma in situ of the bladder. Lerman et al. [91] revealed an overall recurrence rate of 47% in patients with bladder papillomas. However, it was noted that that if the initial lesions was unifocal, there was recurrence in only 31% of the patients, wereas if the initial presentation was one of multiple papillomas, the recurrence rate was 66%. In contrast, Loening and associates found an overall 12 month recurrence rate of 57% in 153 follow-up patients. These investigators reported that the initial size, grade, or number of tumors did not significantly influence the 12-month recurrence. Of the study patients recurring, 85% did so within 12 months of study entry [93]. Some recurrences have been noted to occur at a higher stage and/or grade and may recur temporally and . spatially as multiple tumors [3, 91, 143, 179]. Since the vast majority of patients who develop superficial bladder cancer do so between the ages of 50-70 years of age [33], _survival is often a difficult endpoint in the evaluation of these patients, since deaths due to current illness make up a substantial portion of any survival. Failure of the local treatment of superficial bladder cancer may be best defined by the development of
30a 7.8 25
85 50 53 64
TIS, Atypia Tl A O-Bl Ta-T2
100 126 129 167 64 292 315
Greene et al. 1973 O'Flynn et al. 1975 Althausen et al. 1976 Williams et al. 1977 Barnes et al. 1977 MacKenzie et al. 1981 Lutzeyer et al. 1982
a
TIS only = 83% S, single; M, multiple
10.0
54 66 (M) 31 (S) 73
Ta Ta T1 T1
6.6 9.5
7.3
207 125
69
T1
Ta
109 86
Invasion %
Denning 1950 Nichols and Marshall 1956 Pyrah et al. 1964 Lerman et al. 1970
Recurrence %
Number of patients
Author
Stage reported
Table 2. Recurrence, invasion, and survival in superficial bladder cancer
3 years 3-5 years
7.6 years
Mean time to invasion
18 months 97 (Ta Grade I) 92 (Tl Grade I)
80 62 100 72 73
88
84
5-year survival %
[55] [128] [3] [188] [9] [96] [95]
[143] [91]
[34] [122]
Reference no.
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