Printer Friendly

The optimal management of T1 high-grade bladder cancer.

Author(s): Kenneth G. Nepple, MD, Michael A. O'Donnell, MD

Introduction

Approximately 70% of all newly diagnosed bladder tumours are non-muscle invasive bladder cancers (NMIBC), including stage Ta, stage T1 and carcinoma in situ (CIS). Non-muscle invasive bladder cancers exist on a continuum of risk in patients with T1 high-grade (T1Hg) bladder cancer at the aggressive end of the spectrum. Following transurethral resection alone, T1Hg bladder cancer has a 69% to 80% recurrence rate and a 33% to 48% chance of progression to muscle-invasive disease.[sup.1]-[sup.4] This review provides insight into the optimal management of T1Hg bladder cancer.

Initial resection

Optimal management of T1Hg bladder cancer begins with complete initial transurethral resection of the bladder tumour (TURBT). A rectal or bimanual exam under anaesthesia is recommended on presentation of TURBT to evaluate any local extension. Following initial TURBT, attempts should be made to provide complete tumour resection including muscle in the specimen. To avoid perforation, you must follow the contour of the bladder. Anaesthetic paralysis or obturator nerve block while resecting an area near the obturator nerve may be helpful in preventing adductor contraction and potential bladder perforation. Sending separate pathology specimens from the superficial tumour and deeper bites of the muscle may assist pathologists in accurately staging the depth of invasion. An immediate postoperative dose of intravesical chemotherapy (mitomycin 40 mg in 40 cc water) has been reported to decrease the frequency of recurrence in low- and high-risk patients by 39% in a meta-analysis of 7 randomized trials that included 1476 patients.[sup.5] Even among patients scheduled to receive bacillus Calmette-Guerin (BCG) vaccine, there may be some benefit to a single dose of perioperative chemotherapy; this approach, however, remains controversial.[sup.6,7]

Pathology

T1 bladder cancer represents 5% to 20% of NMIBC[sup.3,8,9] and is defined as an invasion into the lamina propria without invasion into the muscularis propria. The 2004 World Health Organization pathology guidelines recommend a conversion from the previous classification of grade G1, G2 or G3 to that of low- or high-grade papillary urothelial carcinoma.[sup.10] Pathology reports should identify whether muscle tissue is present in the resected specimen. One study described that a pathology report of a repeat resection of T1 disease found the incidence of understaging was only 14% when muscle tissue was present compared to 49% when muscle tissue was absent in the initial specimen.[sup.11] It is recommended that pathologists report the extensiveness of T1 disease since some studies have reported that focal lamina propria invasion may present fewer risks than extensive involvement.[sup.12] While understaging remains problematic, overstaging of T1 disease in pathology reports has been described; about 25% to 35% of cases were found to be stage Ta disease when reviewed by a second pathologist.[sup.6,13,14] This is significant to the discussion of cystectomy for treatment of stage T1 disease.

Repeat resection

Understaging is significant in patients with a recent diagnosis of T1Hg bladder cancer. The standard of care has progressed to mandatory second resection (restaging TURBT) in cases of T1Hg bladder cancer. The recommended timeframe for repeat resection is about 4 weeks for patients with T1Hg bladder cancer. At time of re-resection, 45% to 76% of patients demonstrate residual bladder cancer and 29% to 40% are upstaged to muscle-invasive disease.[sup.10,15,16] One study of patients with stage T1 disease that underwent immediate cystectomy following repeat TURBT found that 2 of the 15 patients (13%) had muscle-invasive disease.[sup.17] Repeat resection may also provide prognostic information. In one study, patients diagnosed with less than T1 disease had a progression rate of 14% while those with residual T1 disease had a 76% progression rate following repeat resection.[sup.11] Repeat resection also improves the efficacy of intravesical therapy.[sup.18,19]

Even when no residual disease is visible at repeat resection, the prior resection base should be biopsied. Although not mentioned in the guidelines by the European Urology Association, American Urological Association or even the National Comprehensive Cancer Network, random bladder biopsies can be performed in other portions of the bladder to assess for concomitant CIS. The bladder biopsy is particularly useful in the event of positive cytology.[sup.20] One study reported the only precystectomy prognostic predictor of recurrence was the presence of concomitant CIS.[sup.21] The actual therapeutic benefit of regimented random biopsies during restaging TURBT is, however, probably minimal because these patients should be considered high risk by that point and the presence of CIS would not alter management of the disease.

Patient counselling

Counselling patients with T1Hg bladder cancer on their treatment options (bladder-sparing intravesical therapy versus cystectomy) is an extensive and delicate process. Factoring in risk of recurrence and progression, patient age and medical comorbidities that predict life expectancy and quality of life is one of the most daunting clinical challenges facing urologists.[sup.22] Patients should be thoroughly informed about the risks of progression to muscle-invasive disease or development of metastases. Patients must be instructed that vigilant surveillance of symptoms is imperative when receiving conservative therapy.

The worst scenario for patients with T1Hg bladder cancer is progression to an unresectable or metastatic stage during intravesical therapy. T1Hg bladder cancer progresses to muscle-invasive or metastatic disease at a rate of 30% to 50% after 5 years.[sup.2,23] As a result, some studies advocate initial cystectomy based on the perceived acceptable morbidity and a 5-year disease-specific survival rate of 80% to 90%.[sup.24]-[sup.28]

However, the paucity of effective conservative treatment alternatives for stage T1 disease may be misinterpreted as an immediate mortality risk in patients who continue to exhibit organ-confined disease. As we will discuss later, an initial trial of BCG rather than immediate cystectomy appears justified in almost all initial T1Hg cases without undue risk, since progression within the first six months is rare (less than 4%).[sup.9] As previously discussed, a pathology report that over-stages T1 disease could result in some patients undergoing cystectomy for stage Ta disease. Furthermore, the unconvincing results associated with delayed cystectomy do not account for the successful patients who avoided surgery. The risks associated with over-treatment of 50% to 70% of patients with unnecessary cystectomy appear too great to warrant cystectomy as standard practice; however, the issue remains heavily debated. There are no prospective studies that demonstrate that early cystectomy has a survival benefit[sup.29] and there are obvious quality-of-life issues associated with performing unnecessary cystectomies.

Indications for immediate cystectomy in T1Hg disease do exist. They include extensive unresectable disease, diverticular disease, associated hydronephrosis, lymphovascular invasion, prostatic stromal or ductal involvement or variant histology (squamous cell, adenocarcinoma, micropapillary, small cells that require chemotherapy first). Some patients with T1Hg disease and with no concomitant CIS may be candidates for partial cystectomy. Relative indications for cystectomy include multifocal disease, associated CIS, T1 disease on repeat resection, deep T1 disease abutting the muscle and poor patient compliance. The presence of tumours that are greater than 3 cm, their multifocality and the presence of CIS have been reported as negatively prognostic.[sup.30]

Intravesical immunotherapy

The cornerstone of early conservative treatment of T1Hg bladder cancer is intravesical immunotherapy with BCG. Ideally, intravesical therapy could safely eradicate residual tumour cells and prevent tumour recurrence, thereby averting the serious consequences of progression to muscle invasion or metastatic disease. The BCG vaccine remains the most powerful weapon in the arsenal of topical therapies against bladder cancer and has been the mainstay of adjuvant therapy since its antitumour effects were first described by Morales and colleagues in 1976.[sup.31] Bacille Calmette-Guerin antitumour therapy appears to act via cell-mediated Th1 immune response and local influx of inflammatory cells. Multiple studies of intravesical BCG immunotherapy in T1Hg bladder cancer have reported a disease-specific survival rate of 85% to 90%, a decrease in recurrence rates of 35% to 45% and a progression rate of 15% to 25%. Disease progression with transurethral resection (TUR) alone provides a recurrence rate of 69% to 80% and a 33% to 48% chance of progression (Table 1). Other agents, such as mitomycin, may be appropriate first-line therapy in low- to intermediate-risk patients, but BCG remains the preferred agent for T1Hg disease.

Bacillus Calmette-Guerin therapy is typically administered 3 to 4 weeks following repeat tumour resection with an induction course of 6 weekly treatments. Dosage, timing and duration of intravesical treatment were based on prior study regimens that were initially and arbitrarily developed but appeared to be effective.[sup.31] Bacille Calmette-Guerin therapy was avoided in the presence of gross hematuria, urinary tract infection and in the presence of catheter trauma because of the inherent risks of BCG dissemination. Restaging was performed as discussed below. Administration of maintenance intravesical BCG therapy is essential. In a randomized study, Lamm and colleagues reported a complete response in 87% of patients who received maintenance intravesical BCG therapy compared to 57% in the group without maintenance.[sup.32] The maintenance therapy regimen was initiated at 3 months after induction and administered at 3, 6, 12, 18, 24, 30 and 36 months. A meta-analysis reported that administration of BCG decreased the risk of progression to 9.8% compared to 13.8% in the control group, but only when accompanied with maintenance BCG therapy.[sup.33] There are limitations to BCG therapy since about 20% of patients are BCG intolerant and unable to complete maintenance therapy because of unpleasant local side effects.[sup.34] Decreasing the BCG dose can enable therapy to continue in many of these cases.

Initial results on the administration of electromotive mitomycin C, which applies an intravesical electrical current, have been reported. A randomized study of BCG alone versus sequential BCG plus electromotive mitomycin C in patients with T1 bladder cancer found lower recurrence, progression and disease-specific mortality in patients who received electromotive mitomycin C.[sup.35] However, further data are required before electromotive mitomycin C can be fully endorsed.

Restaging

A dedicated plan is essential for early reassessment after therapy. To reduce the risk of missing a high-grade recurrence after an initial induction course of BCG, restaging should be performed under aesthesia in all T1Hg bladder cancer patients after immunotherapy. In patients who had not received prior intravenous contrast imaging, a computed tomography (CT) urogram should be performed to evaluate filling defects. Operative restaging included evaluation of both the bladder and upper tracts. The bladder should be inspected and 5 random bladder biopsies taken in a stellate manner (trigone, base, dome and both lateral side walls) in addition to biopsies of suspicious areas. In cases of positive cytology without apparent bladder lesion, the upper tracts should be evaluated with urethral washings and retrograde pyelograms since CIS may not be evident on contrast imaging or even ureteroscopy. An important component of a complete evaluation is to obtain a separately labelled biopsy from the prostatic urethra since it can represent a sanctuary site for urothelial carcinoma. Other studies do not advocate the need for bladder biopsies under anaesthesia but instead recommend cystoscopy combined with cytology.[sup.36]

Surveillance cystoscopy

Patients with a history of T1Hg bladder cancer require close surveillance cystoscopy: typically every 3 months for 2 years from the time of the index tumour, then every 6 months for 2 years in recurrence-free patients. Most tumour recurrences occur within the first year. Cytology in combination with cystoscopy is a valuable tool for following T1Hg bladder cancer and, in this setting, demonstrates a sensitivity and specificity of 50% to 60%.[sup.36] Abnormal cytology in the absence of a bladder lesion requires a re-evaluation as previously described. Other tests, such as florescence in situ hybridization, have shown promise but require further study.[sup.37]

Recurrent disease

In patients with high-risk NMIBC, there is a consistent 30% to 35% initial treatment failure rate and about 50% of patients relapse at 5 years after treatment.[sup.32,33,38] Beyond 5 years, a consistent but slower failure rate of 4% has been observed and nearly 90% recur by 15 years.[sup.39] When patients proceed to a second course of BCG, long-term success rates average 35% (range 20% to 51%).[sup.40] It is important to note that the sooner the relapse, the more likely the disease will be life-threatening.[sup.39] In cases of recurrent T1Hg bladder cancer, radical cystectomy is strongly recommended. A recent multicentre review of cystectomy patients with T1Hg bladder cancer, before the era of standard re-resection, reported positive nodes in 18% of patients with a subsequent disease recurrence rate of 29% and a bladder cancer mortality rate of 19%.[sup.21] The only predictor of precystectomy recurrence and survival was the presence of CIS, not the incidence of prior intravesical therapy or time from TUR to cystectomy.

Patients with a diagnosis of less than stage T1 who do not respond favourably to BCG therapy may be candidates for salvage intravesical therapy. A multicentre trial of patients with recurrent T1 and lack of response to BCG therapy and treated with reduced-dose BCG plus interferon-alpha (50 million units) reported a disease-free rate of 45% at 24 months.[sup.41] Study subjects received BCG combined with interferon-alpha for salvage (and induction) based on in vitro evidence that this combination may have a synergistic effect on immune response. Other combinations of intravesical agents are currently being evaluated.[sup.42,43]

Some patients that are candidates for cystectomy are not suitable for radical surgery because of the presence of comorbid medical illnesses or because they refuse surgery even after extended discussion of the risks. In these circumstances, alternative strategies are available but with a guarded success rate. These strategies include further salvage intravesical therapy, combination aggressive TURBT and chemotherapy or radiation. Limited studies show varying results.[sup.44]-[sup.47]

Disease outside the bladder

Patients with T1Hg bladder cancer are also at risk of developing tumours at sites outside the bladder vault. In patients with accompanying multifocal CIS, urothelial carcinoma outside the bladder in sites such as the upper tracts and prostatic urethra may occur in 10% to 20% of cases.[sup.1,48] Upper tract abnormalities are identified as a filling defect on delayed images of a CT urogram or intravenous pyelogram. The upper tracts and prostatic urethra should also be examined when voided or when bladder-wash cytology is positive for high-grade urothelial cancer. Evaluation of abnormal cytology should be performed similarly to the restaging process previously described. Monitoring of the upper tract in patients with a history of T1Hg bladder cancer is recommended at least once every 1 to 2 years.

Conclusion

Stage T1Hg bladder cancer should be considered an aggressive and potentially lethal disease. The importance of initial re-resection to identify unrecognized muscle-invasive disease is significant. Most patients with high-risk disease are candidates for initial bladder salvage with intravesical BCG, a procedure with a high survival rate; however, failure of the procedure may result in a guarded prognosis. Even with apparent success, patients must be informed of the risks of disease progression to muscle-invasive or metastatic disease and the necessity of vigorous monitoring. Despite optimal management, a significant number of patients will relapse or progress to invasive disease and require cystectomy.

Competing interests: None declared.

This paper has been peer-reviewed.

References

1.. Cookson MS, Herr HW, Zhang ZF, et al. The treated natural history of high risk superficial bladder cancer: 15-year outcome. J Urol 1997;158:62-7.

2.. Heney NM, Ahmed S, Flanagan MJ, et al. IR. Superficial bladder cancer: progression and recurrence. J Urol 1983;130:1083-6.

3.. Jakse G, Loidl W, Seeber G, et al. Stage T1, grade 3 transitional cell carcinoma of the bladder: an unfavorable tumor? J Urol 1987;137:39-43.

4.. Lutzeyer W, Rubben H, Dahm H. Prognostic parameters in superficial bladder cancer: an analysis of 315 cases. J Urol 1982;127:250-2.

5.. Sylvester RJ, Oosterlinck W, van der Meijden AP. A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a meta-analysis of published results of randomized clinical trials. J Urol 2004;171(6Pt1)::2186-90.

6.. Cai T, Nesi G, Tinacci G, et al. Can early single dose instillation of epirubicin improve bacillus Calmette-Guerin efficacy in patients with nonmuscle invasive high risk bladder cancer? Results from a prospective, randomized, double-blind controlled study. J Urol 2008;180:110-5.

7.. Sylvester RJ, Oosterlinck W, O'Donnell. Re: Can early single dose instillation of epirubicin improve bacillus calmetteguerin efficacy in patients with nonmuscle invasive high risk bladder cancer? Results from a prospective, randomized, double-blind controlled study: T. Cai, G. Nesi, G. Tinacci, et al. J Urol 2008;180:110-5J Urol; 2009; 181:410.

8.. Witjes JA, Kiemeney LA, Schaafsma HE, et al. The influence of review pathology on study outcome of a randomized multicentre superficial bladder cancer trial. Members of the Dutch South East Cooperative Urological Group. Br J Urol 1994;73:172-6.

9.. Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J, et al. Primary superficial bladder cancer risk groups according to progression, mortality and recurrence. J Urol 2000;164(3Pt1)::680-4.

10.. EbleJNSauterGEpsteinJI, et al. World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARC Press; 2004.

11.. Brauers A, Buettner R, Jakse G. Second resection and prognosis of primary high risk superficial bladder cancer: is cystectomy often too early? J Urol 2001;165:808-10.

12.. Orsola A, Trias I, Raventós CX, et al. Initial high-grade T1 urothelial cell carcinoma: feasibility and prognostic significance of lamina propria invasion microstaging (T1a/b/c) in BCG-treated and BCG-non-treated patients. Eur Urol 2005;48:231-8.

13.. Tosoni I, Wagner U, Sauter G, et al. Clinical significance of interobserver differences in the staging and grading of superficial bladder cancer. BJU Int 2000;85:48-53.

14.. Abel PD, Henderson D, Bennett MK, et al. Differing interpretations by pathologists of the pT category and grade of transitional cell cancer of the bladder. Br J Urol 1988;62:339-42.

15.. Klan R, Loy V, Huland H. Residual tumor discovered in routine second transurethral resection in patients with stage T1 transitional cell carcinoma of the bladder. J Urol 1991;146:316-8.

16.. Herr HW. The value of a second transurethral resection in evaluating patients with bladder tumors. J Urol 1999;162:74-6.

17.. Dalbagni G, Herr HW, Reuter VE. Impact of a second transurethral resection on the staging of T1 bladder cancer. Urology 2002;60:822-4.

18.. Divrik RT, Yildirim U, Zorlu F, et al. The effect of repeat transurethral resection on recurrence and progression rates in patients with T1 tumors of the bladder who received intravesical mitomycin: a prospective, randomized clinical trial. J Urol 2006;175:1641-4.

19.. Herr HW. Restaging transurethral resection of high risk superficial bladder cancer improves the initial response to bacillus Calmette-Guerin therapy. J Urol 2005;174:2134-7.

20.. Hara T, Takahashi M, Gondo T, et al. Risk of concomitant carcinoma in situ determining biopsy candidates among primary non-muscle-invasive bladder cancer patients: retrospective analysis of 173 Japanese cases. Int J Urol 2009;16:293-8.

21.. Gupta A, Lotan Y, Bastian PJ, et al. Bladder Cancer Research Consortium. Outcomes of patients with clinical T1 grade 3 urothelial cell bladder carcinoma treated with radical cystectomy. Urology 2008;71:302-7.

22.. Kulkarni GS, Finelli A, Fleshner NE, et al. Optimal management of high-risk T1G3 bladder cancer: a decision analysis. PLoS Med 2007;4:e284.

23.. Kaubisch S, Lum BL, Reese J, et al. Stage T1 bladder cancer: grade is the primary determinant for risk of muscle invasion. J Urol 1991;146:28-31.

24.. Esrig D, Freeman JA, Stein JP, et al. Early cystectomy for clinical stage T1 transitional cell carcinoma of the bladder. Semin Urol Oncol 1997;15:154-60.

25.. Stockle M, Alken P, Engelmann U, et al. Radical cystectomy--often too late? Eur Urol 1987;13:361-7.

26.. Amling CL, Thrasher JB, Frazier HA, et al. Radical cystectomy for stages Ta, Tis and T1 transitional cell carcinoma of the bladder. J Urol 1994;151:31-6.

27.. Skinner EC. The best treatment for high-grade T1 bladder cancer is cystectomy. Urol Oncol 2007;25:523-5.

28.. Stein JP, Penson DF. Invasive T1 bladder cancer: indications and rationale for radical cystectomy. BJU Int 2008;102:270-5.

29.. Thalmann GN, Markwalder R, Shahin O, et al. Primary T1G3 bladder cancer: organ preserving approach or immediate cystectomy? J Urol 2004;172:70-5.

30.. Denzinger S, Otto W, Fritsche HM, et al. Bladder sparing approach for initial T1G3 bladder cancer: do multifocality, size of tumor or concomitant carcinoma in situ matter? A long-term analysis of 132 patients. Int J Urol 2007;14:995-9.

31.. Morales A, Eidinger D, Bruce AW. Intracavitary bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol 1976;116:180-3.

32.. Lamm DL, Blumenstein BA, Crissman JD, et al. Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J Urol 2000;163:1124-9.

33.. Sylvester RJ, van der Meijden AP, Lamm DL. Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol 2002;168:1964-70.

34.. van der Meijden AP, Sylvester RJ, Oosterlinck W, et al. EORTC Genito-Urinary Tract Cancer Group. Maintenance bacillus Calmette-Guerin for Ta T1 bladder tumors is not associated with increased toxicity: results from a European Organisation for Research and Treatment of Cancer Genito-Urinary Group Phase III Trial. Eur Urol 2003;44:429-34.

35.. Di Stasi SM, Giannantoni A, Giurioli A, et al. Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial. Lancet Oncol 2006;7:43-51.

36.. Guy L, Savareux L, Molinie V, et al. Should bladder biopsies be performed routinely after bacillus Calmette-Guerin treatment for high-risk superficial transitional cell cancer of the bladder? Eur Urol 2006;50:516-20.

37.. Lotan Y, Bensalah K, Ruddell T, et al. Prospective Evaluation of the Clinical Usefulness of Reflex Fluorescence In Situ Hybridization Assay in Patients With Atypical Cytology for the Detection of Urothelial Carcinoma of the Bladder. J Urol 2008;179:2164-9.

38.. Nepple KG, Aubert HA, Braasch MR, et al. Combination of BCG and interferon intravesical immunotherapy: an update. World J Urol 2009;27:343-6.

39.. Nadler RB, Catalona WJ, Hudson MA, et al. Durability of the tumor-free response for intravesical bacillus Calmette-Guerin therapy. J Urol 1994;152(2Pt1)::367-73.

40.. O'Donnell MA, Bohle A. Treatment options for BCG failures. World J Urol 2006;24:481-7.

41.. Joudi FN, Smith BJ, O'Donnell MA. Final results from a national multicenter phase II trial of combination bacillus Calmette-Guerin plus interferon alpha-2B for reducing recurrence of superficial bladder cancer. Urol Oncol 2006;24:344-8.

42.. Addeo R, Caraglia M, Bellini S, et al. Randomized Phase III Trial on Gemcitabine Versus Mytomicin in Recurrent Superficial Bladder Cancer: Evaluation of Efficacy and Tolerance. J Clin Oncol 2009Oct19[Epub ahead of print].

43.. Laudano MA, Barlow LJ, Murphy AM, et al. Long-term Clinical Outcomes of a Phase I Trial of Intravesical Docetaxel in the Management of Non-Muscle-Invasive Bladder Cancer Refractory to Standard Intravesical Therapy. Urology 2009Nov 12 [Epub ahead of print].

44.. Quilty PM, Duncan W. Treatment of superficial (T1) tumours of the bladder by radical radiotherapy. Br J Urol 1986;58:147-52.

45.. Shipley WU, Kaufman DS, Zehr E, et al. Selective bladder preservation by combined modality protocol treatment: long-term outcomes of 190 patients with invasive bladder cancer. Urology 2002;60:62-8.

46.. Inoue M, Ishioka J, Fukuda H, et al. Clinical outcome of chemoradiotherapy for T1G3 bladder cancer. Int J Urol 2008;15:747-50.

47.. Weiss C, Wolze C, Engehausen DG, et al. Radiochemotherapy after transurethral resection for high-risk T1 bladder cancer: an alternative to intravesical therapy or early cystectomy? J Clin Oncol 2006;24:2318-24.

48.. Hurle R, Losa A, Manzetti A, et al. Intravesical bacille Calmette-Guerin in Stage T1 grade 3 bladder cancer therapy: a 7-year follow-up. Urology 1999;54:258-63.

49.. Pfister C, Lande P, Herve JM, et al. T1 G3 bladder tumors: the respective role of BCG and cystectomy. Prog Urol 1995;5:231-7.

50.. Mack D, Frick J. Five-year results of a phase II study with low-dose bacille Calmette-Guerin therapy in high-risk superficial bladder cancer. Urology 1995;45:958-61.

51.. Pansadoro V, Emiliozzi P, Defidio L, et al. Bacillus Calmette-Guerin in the treatment of stage T1 grade 3 transitional cell carcinoma of the bladder: long-term results. J Urol 1995;154:2054-8.

52.. Pansadoro V, Emiliozzi P, de Paula F, et al. Long-term follow-up of G3T1 transitional cell carcinoma of the bladder treated with intravesical bacille Calmette-Guerin: 18-year experience. Urology 2002;59:227-31.

53.. Hurle R, Losa A, Ranieri A, et al. Low dose Pasteur bacillus Calmette-Guerin regimen in stage T1, grade 3 bladder cancer therapy. J Urol 1996;156:1602-5.

54.. Lebret T, Gaudez F, Herve JM, et al. Low-dose BCG instillations in the treatment of stage T1 grade 3 bladder tumours: recurrence, progression and success. Eur Urol 1998;34:67-72.

55.. Gohji K, Nomi M, Okamoto M, et al. Conservative therapy for stage T1b, grade 3 transitional cell carcinoma of the bladder. Urology 1999;53:308-13.

56.. Brake M, Loertzer H, Horsch R, et al. Recurrence and progression of stage T1, grade 3 transitional cell carcinoma of the bladder following intravesical immunotherapy with bacillus Calmette-Guerin. J Urol 2000;163:1697-701.

57.. Patard J, Moudouni S, Saint F, et al. the members of the Groupe Necker. Tumor progression and survival in patients with T1G3 bladder tumors: multicentric retrospective study comparing 94 patients treated during 17 years. Urology 2001;58:551-6.

58.. Kulkarni JN, Gupta R. Recurrence and progression in stage T1G3 bladder tumour with intravesical bacille Calmette-Guerin (Danish 1331 strain). BJU Int 2002;90:554-7.

59.. Griffiths TR, Charlton M, Neal DE, et al. Treatment of carcinoma in situ with intravesical bacillus Calmette-Guerin without maintenance. J Urol 2002;167:2408-12.

60.. Bogdanovi J, Marusi G, Djozi J, et al. The management of T1G3 bladder cancer. Urol Int 2002;69:263-5.

61.. Peyromaure M, Guerin F, Amsellem-Ouazana D, et al. Intravesical bacillus Calmette-Guerin therapy for stage T1 grade 3 transitional cell carcinoma of the bladder: recurrence, progression and survival in a study of 57 patients. J Urol 2003;169:2110-2.

62.. Shahin O, Thalmann GN, Rentsch C, et al. A retrospective analysis of 153 patients treated with or without intravesical bacillus Calmette-Guerin for primary stage T1 grade 3 bladder cancer: recurrence, progression and survival. J Urol 2003;169:96-100.

63.. Cheng CW, Chan SF, Chan LW, et al. 15-year experience on intravesical therapy of T1G3 urinary bladder cancer: a conservative approach. Jpn J Clin Oncol 2004;34:202-5.

Table

Table 1: Published results of BCG treatment for T1 G3 bladder cancer [Table omitted]

Author Affiliation(s):

[1] From the University of Iowa Department of Urology, Iowa City, IA

Correspondence: Dr. Michael A. O'Donnell, University of Iowa, Department of Urology, 200 Hawkins Dr., 3 RCP, Iowa City, IA 52242-1089; fax: 319-356-3900; michael-odonnell@uiowa.edu
COPYRIGHT 2009 Canadian Urological Association
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2009 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Review
Author:Nepple, Kenneth G.; O'Donnell, Michael A.
Publication:Canadian Urological Association Journal (CUAJ)
Article Type:Disease/Disorder overview
Geographic Code:1USA
Date:Dec 1, 2009
Words:4950
Previous Article:Chemoprevention in bladder cancer: What's new?
Next Article:Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer.
Topics:


Related Articles
Current concepts in biomarker technology for bladder cancers.
Key issues in bladder cancer management.
Screening for bladder cancer: the best opportunity to reduce mortality.
Chemoprevention in bladder cancer: What's new?
Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer.
The management of BCG failure in non-muscle-invasive bladder cancer: an update.
Personalized medicine in advanced urothelial cancer: when to treat, how to treat and who to treat.
Surveillance strategies after definitive therapy of invasive bladder cancer.
NMP22 is predictive of recurrence in high-risk superficial bladder cancer patients.

Terms of use | Privacy policy | Copyright © 2020 Farlex, Inc. | Feedback | For webmasters