Stage 0 Bladder Cancer
Stage 0 bladder cancer is defined by the following TNM classifications:
- Ta, N0, M0
- Tis, N0, M0
Patients with stage 0 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 cancer recurrence following initial resection was 80%. Patients at greatest risk of recurrent disease are those whose tumors are large, poorly differentiated, multiple, or associated with nuclear p53 overexpression. 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]
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.[Level of evidence: 3iiDiv] A second TUR performed on 38 patients with Tis or Ta disease found that nine patients (24%) had lamina propria invasion (T1) and three patients (8%) 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 plus 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.[5,6]
A randomized study of patients with superficial bladder cancer also reported a decrease in tumor recurrence in patients given intravesical and percutaneous BCG compared with controls. Two nonconsecutive 6-week treatment courses with BCG may be necessary to obtain optimal response. 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]
Another randomized study that compared intravesical and subcutaneous BCG with intravesical doxorubicin showed better response rates and freedom from recurrence with the BCG regimen for recurrent papillary tumors as well as for Tis. A randomized trial from the Swedish-Norwegian Bladder Cancer Group compared 2 years of intravesical treatment with mitomycin C versus BCG. No difference was observed in tumor progression or overall survival (OS) between the two arms at 5 years.[Level of evidence: 1iiDii] Although BCG may not prolong OS for Tis disease, it appears to afford complete response rates of about 70%, thereby decreasing the need for salvage cystectomy.
Studies show that intravesical BCG delays tumor recurrence and tumor progression.[6,14] Preliminary results from a prospective randomized trial suggest that maintenance BCG, when given to patients who are disease-free after a 6-week induction course, improves survival. One study that compared mitomycin with interferon-α-2b showed an improved outcome with mitomycin, even though interferon was better tolerated.
Standard treatment options:
- TUR with fulguration.
- TUR with fulguration followed by intravesical BCG. BCG is the treatment of choice for Tis.[5,7,9,13,14]
- TUR with fulguration followed by intravesical chemotherapy.[2,11,17]
- Segmental cystectomy (rarely indicated).
- Radical cystectomy in selected patients with extensive or refractory superficial tumor.[17,18]
Treatment options under clinical evaluation:
- Photodynamic therapy after intravenous hematoporphyrin derivative appears capable of completely eradicating tumors in 50% of the treated patients who were in a small study with minimal follow-up. Further evaluation of this technique is needed.
- Intravesical interferon-alpha-2a has shown activity against papillary tumors and Tis both as primary treatment and as secondary treatment after failure of other intravesical agents.
- Use of chemoprevention agents after treatment to prevent recurrence.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 bladder cancer. 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.References
- 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]
- 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]
- 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]
- Herr HW: The value of a second transurethral resection in evaluating patients with bladder tumors. J Urol 162 (1): 74-6, 1999. [PUBMED Abstract]
- 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]
- Lamm DL, Griffith JG: Intravesical therapy: does it affect the natural history of superficial bladder cancer? Semin Urol 10 (1): 39-44, 1992. [PUBMED Abstract]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- De Jager R, Guinan P, Lamm D, et al.: Long-term complete remission in bladder carcinoma in situ with intravesical TICE bacillus Calmette Guerin. Overview analysis of six phase II clinical trials. Urology 38 (6): 507-13, 1991. [PUBMED Abstract]
- Herr HW, Wartinger DD, Fair WR, et al.: Bacillus Calmette-Guerin therapy for superficial bladder cancer: a 10-year followup. J Urol 147 (4): 1020-3, 1992. [PUBMED Abstract]
- 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.
- Boccardo F, Cannata D, Rubagotti A, et al.: Prophylaxis of superficial bladder cancer with mitomycin or interferon alfa-2b: results of a multicentric Italian study. J Clin Oncol 12 (1): 7-13, 1994. [PUBMED Abstract]
- 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.
- 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]
- Prout GR Jr, Lin CW, Benson R Jr, et al.: Photodynamic therapy with hematoporphyrin derivative in the treatment of superficial transitional-cell carcinoma of the bladder. N Engl J Med 317 (20): 1251-5, 1987. [PUBMED Abstract]
- Torti FM, Shortliffe LD, Williams RD, et al.: Alpha-interferon in superficial bladder cancer: a Northern California Oncology Group Study. J Clin Oncol 6 (3): 476-83, 1988. [PUBMED Abstract]
- 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]