Stage I Bladder Cancer
Current Clinical Trials
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence 1 for more
information.)
Stage I bladder cancer is defined by the following TNM classification:
Patients with stage I bladder tumors can be cured by a variety of treatments, even
though the tendency for new tumor formation is high. In a series of patients
with Ta or T1 tumors who were followed for a minimum of 20 years or until
death, the risk of bladder recurrence following initial resection was 80%.[1]
Patients at greatest risk of recurrent disease are those whose tumors are
large, poorly differentiated, multiple, or associated with nuclear p53
overexpression.[2] In addition, patients with carcinoma in situ (Tis) or
dysplasia of grossly uninvolved bladder epithelium are at greater risk of
recurrence and progression.[1,3,4]
Transurethral resection (TUR) and fulguration are the most common and
conservative forms of management. Careful surveillance of subsequent bladder
tumor progression is important. One retrospective series addressed the value
of performing a second TUR within 2 to 6 weeks of the first.[5][Level of evidence: 3iiDiv] A second TUR performed on 58 patients with T1 disease found
that 14 patients (24%) had residual (T1) disease and 16 patients (28%) had
muscle invasion (T2). Such information may change the definitive management
options in these individuals. Patients who require more aggressive forms of
treatment are those with extensive multifocal recurrent disease and/or other
unfavorable prognostic features. Segmental cystectomy is applicable to only a
small minority of patients because of the tendency of bladder carcinoma to
involve multiple regions of the bladder mucosa and to occur in areas that
cannot be segmentally resected.
Intravesical therapy with thiotepa, mitomycin, doxorubicin, or bacillus Calmette Guérin (BCG) is most often used in patients with multiple tumors or
recurrent tumors or as a prophylactic measure in high-risk patients after TUR.
Administration of intravesical BCG combined with subcutaneous BCG following TUR
was compared with TUR alone in patients with Ta and T1 lesions. Treatment with
BCG delayed progression to muscle-invasive and/or metastatic disease, improved
bladder preservation, and decreased the risk of death from bladder cancer.[6]
Another randomized study in patients with superficial bladder cancer also
reports a decrease in tumor recurrence in patients given intravesical and
percutaneous BCG compared with controls.[7] Two nonconsecutive 6-week courses
with BCG may be necessary to obtain optimal response.[8] Patients with a T1
tumor at the 3-month evaluation after a 6-week course of BCG and patients with
Tis that persists after a second 6-week BCG course have a high likelihood of
developing muscle-invasive disease and should be considered for
cystectomy.[8-10] A randomized study that compared intravesical and
subcutaneous BCG to intravesical doxorubicin showed better response rates and
freedom from recurrence with the BCG regimen for recurrent papillary tumors as
well as for Tis.[11] Preliminary results of one study have shown a possible
survival benefit with maintenance BCG after a 6-week induction course.[12]
Another study that compared alternating mitomycin and BCG with BCG alone, both
given for 24 months, found that the efficacy was equal, but that the side
effects of the combined regimen were slightly less.[13][Level of evidence: 1iiDiii] A similar trial comparing sequential mitomycin and BCG to mitomycin
alone also found no major differences in toxic effects or efficacy.[14][Level of evidence: 1iiDiii] A randomized trial from the Swedish-Norwegian Bladder
Cancer Group compared 2 years of intravesical treatment with mitomycin C versus
BCG for patients at high risk for recurrence or progression. At 5 years, a
significant improvement was noted in disease-free survival with BCG (P = .04);
however, no difference was observed in tumor progression or overall survival
between the two arms.[15]
Standard treatment options:
- TUR with fulguration.[16,17]
- TUR with fulguration followed by intravesical BCG.[6,7,9,10,13]
- TUR with fulguration followed by intravesical chemotherapy.[3,13]
- Segmental cystectomy (rarely indicated).[16]
- Radical cystectomy in selected patients with extensive or refractory
superficial tumor.[18]
- Interstitial implantation of radioisotopes with or without external-beam
radiation therapy.[19,20]
Treatment options under clinical evaluation:
- Use of chemoprevention agents after treatment to prevent recurrence.[21]
- Intravesical therapies.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I bladder cancer 2. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site 3.
References
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Holmäng S, Hedelin H, Anderström C, et al.: The relationship among multiple recurrences, progression and prognosis of patients with stages Ta and T1 transitional cell cancer of the bladder followed for at least 20 years. J Urol 153 (6): 1823-6; discussion 1826-7, 1995.
[PUBMED Abstract]
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Smits G, Schaafsma E, Kiemeney L, et al.: Microstaging of pT1 transitional cell carcinoma of the bladder: identification of subgroups with distinct risks of progression. Urology 52 (6): 1009-13; discussion 1013-4, 1998.
[PUBMED Abstract]
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Igawa M, Urakami S, Shirakawa H, et al.: Intravesical instillation of epirubicin: effect on tumour recurrence in patients with dysplastic epithelium after transurethral resection of superficial bladder tumour. Br J Urol 77 (3): 358-62, 1996.
[PUBMED Abstract]
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Lacombe L, Dalbagni G, Zhang ZF, et al.: Overexpression of p53 protein in a high-risk population of patients with superficial bladder cancer before and after bacillus Calmette-Guérin therapy: correlation to clinical outcome. J Clin Oncol 14 (10): 2646-52, 1996.
[PUBMED Abstract]
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Herr HW: The value of a second transurethral resection in evaluating patients with bladder tumors. J Urol 162 (1): 74-6, 1999.
[PUBMED Abstract]
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Herr HW, Schwalb DM, Zhang ZF, et al.: Intravesical bacillus Calmette-Guérin therapy prevents tumor progression and death from superficial bladder cancer: ten-year follow-up of a prospective randomized trial. J Clin Oncol 13 (6): 1404-8, 1995.
[PUBMED Abstract]
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Sarosdy MF, Lamm DL: Long-term results of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer. J Urol 142 (3): 719-22, 1989.
[PUBMED Abstract]
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Coplen DE, Marcus MD, Myers JA, et al.: Long-term followup of patients treated with 1 or 2, 6-week courses of intravesical bacillus Calmette-Guerin: analysis of possible predictors of response free of tumor. J Urol 144 (3): 652-7, 1990.
[PUBMED Abstract]
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Catalona WJ, Hudson MA, Gillen DP, et al.: Risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer. J Urol 137 (2): 220-4, 1987.
[PUBMED Abstract]
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Herr HW: Progression of stage T1 bladder tumors after intravesical bacillus Calmette-Guerin. J Urol 145 (1): 40-3; discussion 43-4, 1991.
[PUBMED Abstract]
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Lamm DL, Blumenstein BA, Crawford ED, et al.: A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder. N Engl J Med 325 (17): 1205-9, 1991.
[PUBMED Abstract]
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Lamm DL, Crawford ED, Blumenstein B, et al.: Maintenance BCG immunotherapy of superficial bladder cancer: a randomized prospective Southwest Oncology Group study. [Abstract] Proceedings of the American Society of Clinical Oncology 11: A-627, 203, 1992.
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Rintala E, Jauhiainen K, Kaasinen E, et al.: Alternating mitomycin C and bacillus Calmette-Guerin instillation prophylaxis for recurrent papillary (stages Ta to T1) superficial bladder cancer. Finnbladder Group. J Urol 156 (1): 56-9; discussion 59-60, 1996.
[PUBMED Abstract]
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Witjes JA, Caris CT, Mungan NA, et al.: Results of a randomized phase III trial of sequential intravesical therapy with mitomycin C and bacillus Calmette-Guerin versus mitomycin C alone in patients with superficial bladder cancer. J Urol 160 (5): 1668-71; discussion 1671-2, 1998.
[PUBMED Abstract]
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Malmström PU, Wijkström H, Lundholm C, et al.: 5-year followup of a randomized prospective study comparing mitomycin C and bacillus Calmette-Guerin in patients with superficial bladder carcinoma. Swedish-Norwegian Bladder Cancer Study Group. J Urol 161 (4): 1124-7, 1999.
[PUBMED Abstract]
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Soloway MS: The management of superficial bladder cancer. In: Javadpour N, ed.: Principles and Management of Urologic Cancer. 2nd ed. Baltimore, Md: Williams and Wilkins, 1983, pp 446-467.
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Herr HW, Reuter VE: Evaluation of new resectoscope loop for transurethral resection of bladder tumors. J Urol 159 (6): 2067-8, 1998.
[PUBMED Abstract]
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Amling CL, Thrasher JB, Frazier HA, et al.: Radical cystectomy for stages Ta, Tis and T1 transitional cell carcinoma of the bladder. J Urol 151 (1): 31-5; discussion 35-6, 1994.
[PUBMED Abstract]
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Goffinet DR, Schneider MJ, Glatstein EJ, et al.: Bladder cancer: results of radiation therapy in 384 patients. Radiology 117 (1): 149-53, 1975.
[PUBMED Abstract]
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van der Werf-Messing B, Hop WC: Carcinoma of the urinary bladder (category T1NxM0) treated either by radium implant or by transurethral resection only. Int J Radiat Oncol Biol Phys 7 (3): 299-303, 1981.
[PUBMED Abstract]
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Lamm DL, Riggs DR, Shriver JS, et al.: Megadose vitamins in bladder cancer: a double-blind clinical trial. J Urol 151 (1): 21-6, 1994.
[PUBMED Abstract]
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