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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 5  |  Page : 881-885
Management of superficial bladder carcinoma: Time to rethink the treatment strategies in the era of orthotopic neo-bladder


Department of Urology, Banaras Hindu University, Institute of Medical Sciences, Varanasi, India

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Date of Web Publication31-Aug-2010
 

   Abstract 

The objective of this study was to evaluate the recurrence and progression, on long-term follow-up, of patients with superficial bladder cancer managed with bladder sparing approach. A total of 48 patients with superficial bladder cancer, initially treated with bladder sparing approach between 1990 and 1992, were available for long-term follow-up ranging bet­ween 10 and 15 years; the remaining patients were lost to follow-up. All patients had undergone transurethral resection and adjuvant intravesical therapy. Recurrence was treated with resection and adjuvant therapy or radical cystectomy in cases of progression. Out of 48 study subjects, 11 had T1G1, 23 had T1G2 and 14 had T1G3 tumor. In the T1G1 group, 45.5% had recurrence. Four had single recurrence managed successfully with TURBT and intravesical therapy. One had multiple recurrences and underwent radiotherapy after the fifth recurrence. In the T1G2 group, 82.6% had recurrence and majority (60.8%) had multiple recurrences. Out of 14 cases with multiple recurrences, eight patients ultimately progressed to invasive bladder carcinoma and underwent radical cystectomy. Majority of these underwent ileal conduit because ileal neo­bladder could not be created due to severe fibrosis. All 14 patients with T1G3 had recurrence, of whom three (21.4%) had single recurrence. Out of the 11 other patients (78.6%) who had multiple recurrences, nine developed invasive bladder carcinoma and underwent radical cystectomy. Orthotopic neo-bladder could be performed only in one patient and the remaining had ileal conduit or Mainz pouch. We conclude that in the era of orthotopic neo-bladder offering good quality of life, radical cystectomy should be considered at the earliest opportunity in patients with aggressive superficial bladder cancer.

How to cite this article:
Singh PB, Kumar A, Das SK, Pandey AK, Sharma GK, Samir Swain HB, Trivedi S, Dwivedi US. Management of superficial bladder carcinoma: Time to rethink the treatment strategies in the era of orthotopic neo-bladder. Saudi J Kidney Dis Transpl 2010;21:881-5

How to cite this URL:
Singh PB, Kumar A, Das SK, Pandey AK, Sharma GK, Samir Swain HB, Trivedi S, Dwivedi US. Management of superficial bladder carcinoma: Time to rethink the treatment strategies in the era of orthotopic neo-bladder. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2019 Aug 24];21:881-5. Available from: http://www.sjkdt.org/text.asp?2010/21/5/881/68885

   Introduction Top


Bladder carcinoma is one of the most co­mmon urological malignancies faced by the urologist. More than 70% of bladder carcino­mas are non-invasive (stage pTa) or lamina propria-invasive at the time of initial diagnosis (stage pT1). [1] Transurethral resection of bladder tumors (TURBT), with or without adjuvant therapy (intravesical chemotherapy or immu­notherapy), is the treatment of choice in these patients. [2] The principle aim of therapy is bla­dder conservation since urinary diversion in the form of ileal conduit or continent diversion with stoma is usually not acceptable to the masses. In spite of all possible efforts, 20 to 80% of all non-invasive carcinomas progress to invasion. [3] Biological markers to identify tumors with aggressive behavior have not been standardized yet. Adjuvant immunotherapy or chemotherapy only delays the recurrence but does not stop the progression. [4] In this retro­spective analysis, we are presenting our expe­rience on 48 patients with superficial bladder cancer, who were initially treated with bladder sparing approach, and their outcome on follow­up ranging from 10 to 15 years.


   Material and Methods Top


Out of 61 patients with superficial bladder cancer initially treated with bladder sparing approach from 1990 to 1992, 48 patients had follow-up ranging between 10 and 15 years; they were analyzed in the present retrospective study. The demographics of the study patients are shown in [Table 1]. All patients underwent thorough evaluation including routine hemo­gram, blood biochemistry, urinary cytology, ultrasonography, cystoscopy, bimanual exami­nation and transurethral resection of the tumor (TURBT). Of the 48 study patients, 11 had T1G1, 23 had T1G2 and the remaining 14 had T1G3 bladder tumor. As per our policy, all tumors with G2 and above received one course of BCG instillation in the dose of 120 mg/ week for six weeks. Routinely, we were not giving maintenance BCG therapy. If the pa­tient had recurrence, another course of induc­tion therapy was given after resection of the recurrence. Out of the 11 T1G1 bladder tu­mors, three had multiple tumors and received intravesical BCG therapy. The remaining pa­tients with G2 and G3 grades received BCG therapy. None of the patients included in the present study received intravesical mitomycin therapy at the time of TURBT. Currently, we are instilling one dose of mitomycin within six hours of TURBT. All patients were followed­up by urine cytology, ultrasound examination and cystoscopy at three months interval in the first year, six monthly for the next two years, and yearly thereafter or, if symptoms reappeared.
Table 1 :Demographic characteristics of the study patients.

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   Results Top


In the group with T1G1 bladder tumor [Table 2], five (45.5%) out of 11 had recurrence in the follow-up period ranging from two years to ten years. Out of these five patients, three had previously received BCG instillation (for mul­tiple tumors) after the TURBT. All five patients underwent transurethral resection of the recurrent tumor followed by BCG instillation. Histopathology showed low grade tumor involving lamina propria only (T1G1) in all patients. Four out of these five patients were free of recurrence during subsequent follow-up. One patient had multiple recurrences and has undergone TURBT five times during followup of 12 years. This patient also received radiotherapy since he was not suitable for radical surgery at the time of fifth recurrence. He still remains on follow-up.

In 23 patients with T1G2, 19 (82.6%) had recurrence and majority (60.8%) had multiple recurrences in the follow-up period ranging from two to nine years. Recurrence was treated with TURBT followed by BCG instillation with or without intravesical interferon therapy. Five patients could afford interferon and in these patients 80 mg of BCG and ten million units of interferon were instilled weekly for six weeks. It was again repeated if they had further recurrence. Out of 14 cases with multiple recurrences, eight patients ultimately progressed to invasive bladder carcinoma and underwent radical cystectomy. The majority required an ileal conduit because ileal neo-bladder could not be made due to severe fibrosis resulting from multiple resections [Table 3].
Table 2 :Recurrences and progression in the follow-up period of each group.

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Table 3 :Management of patients with recurrences.

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All 14 patients with T1G3 had recurrence. Three (21.4%) had single recurrence and are still on follow-up. Of the 11 patients (78.6%) who had multiple recurrences, nine developed invasive bladder carcinoma in the second or third recurrence with in a follow-up period of three years and underwent radical cystectomy. Orthotopic neo-bladder could be performed only in one patient and the remaining had ileal conduit or Mainz pouch [Table 3].


   Discussion Top


Superficial bladder carcinoma is a non-invasive tumor and it was thought that the majority do not progress to invasion or recurrence. However, long-term follow-up data of these cases are available which confirm that more than 30% either progress to invasion or have recurrence. [5] All these tumors were initially treated with bladder preservation regimen by TURBT, with or without adjuvant therapy. Patients as well as surgeons were not in favor of aggressive approach because of added morbidity and mortality of cystectomy as well as non-availability of an ideal diversion techniques. Majority of the patients used to undergo ileal conduit after radical cystectomy, although patients were not prepared mentally and socially to have an appliance life-long, which would affect the quality of their lives.

In our study, out of 48 patients presenting with superficial bladder carcinoma, 25 (52%) had multiple recurrences and 17 (35.4%) required radical cystectomy. Patients treated with BCG and interferon α2b instillation, [6] also progressed to invasion. In an extensive follow-up study by Cookson MS et al, [7] 15-years followup revealed progression of disease in 53% and cystectomy was required in 36% of the cases. These findings are similar to our findings where 35% patients required cystectomy.

Today, management of bladder carcinoma is not only aimed to achieve cancer free survival but also to have good quality of life. With the introduction of orthotopic neo-bladder, which offers excellent quality of life and minimum morbidity and mortality of radical cystectomy, acceptability of surgery has increased. In the era of orthotopic neo-bladder, introspection is required in the management of superficial bladder carcinoma in light of cancer cure, morbidity and quality of life. The principal author of this paper has personal experience of more than 126 ileal neo-bladder with follow-up of more than 15 years. The quality of life and overall morbidity in patients who primarily underwent radical cystectomy and ileal neobladder is much better than those who have undergone multiple TURBTs, with or without adjuvant therapy, and had progression to invasion. [8],[9] Also, biological markers predicting invasion has not been standardized to modify treatment strategies in superficial bladder carcinoma although markers like over expression of P53 in tissue as well as serum correlated with invasion. [10],[11]

Freeman et al [12] found that pathological upstaging to muscle invasion or metastasis occurred in one-third of highly selected patients with clinically superficial bladder cancer who had undergone radical cystectomy, half of whom had extravesical disease. They concluded that with the option of orthotopic urinary diversion available, radical cystectomy should be considered a viable alternative to continued conservative measures for selected patients with aggressive superficial bladder tumor. May M et al [13] in their retrospective analysis of over 450 patients found that patients with superficial bladder carcinoma with tumor progression to muscle invasion did not have a better prognosis after radical cystectomy than patients presenting initially with muscle-invasive bladder carcinoma. They concluded that survival rates in patients with superficial bladder cancer could only be improved by performing cystectomy at an earlier stage in patients with risk factors for progression. Lee CT et al [14] proved that even stringent surveillance of early stage bladder cancer does not improve the survival rates if high-risk patients of superficial bladder cancer are permitted to progress to muscle invasion. [14] Stockle et al [15] reported a five-year survival rate of 90% for patients who had undergone radical cystectomy at diagnosis which decreased to 62% for patients who had undergone cystectomy after one or more recurrences. Herr HW and Sogani PC [16] found that, for recurrent, high-risk, superficial TCC, early (< 2 years after TUR) cystectomy can improve survival when BCG therapy fails. A 15-year survival in patients who underwent early cystectomy has been reported to be 69%, but drops to 26% if cystectomy is not performed within two years of TUR. Kulkarni GS et al [17] demonstrated that younger patients with highrisk T1G3 bladder had a higher life expectancy and quality adjusted life expectancy with immediate cystectomy. Similarly, Malstrom et al [1] and Anderstrom et al [18] also reported a survival advantage with early cystectomy.

Therefore, the decision to pursue immediate cystectomy versus conservative therapy in patients with superficial bladder cancer should be based on discussions with the patients considering patient age, co-morbid status, and an individual's preference for particular post-cystectomy health states.


   Conclusion Top


Seeing the overall morbidity in management of T1G2 and G3 bladder tumor and good quality of life after radical cystectomy in the era of orthotopic neo-bladder, radical cystectomy should be considered at earliest opportunity when tumor shows aggression in the form of multiplicity or early recurrence.

 
   References Top

1.Malmstrom PU, Busch C, Norlen BJ. Recurrence, progression and survival in bladder cancer. Scand J Urol Nephrol 1987;21:185-95.  Back to cited text no. 1      
2.Divrik RT, Yildrim 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.  Back to cited text no. 2      
3.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;163:1697-201.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Lamm DL, Riggs DR, Traynelis CL et al. Apparent failure of current intravesical chemotherapy prophylaxis to influence the long term course of superficial transitional cell carcinoma of the bladder. J Urol 1995;153:1444-50.  Back to cited text no. 4      
5.Solsona E, Iborra I, Rubio J, et al. The optimum timing of radical cystectomy for patients with recurrent high-risk superficial bladder tumour. BJU Int 2004;94(9):1258-62.  Back to cited text no. 5      
6.Singh GP, Dwivedi US, Singh PB. BCG plus recombinant alfa Interferon 2b in superficial bladder carcinoma. Indian J Urol 2001;17:124-6.  Back to cited text no. 6    Medknow Journal  
7.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.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Singh PB, Saraf SK. Ileal Neobladder: 5 years followup. Indian J Urol 1997;13:75-8.  Back to cited text no. 8      
9.Singh PB, Mahmood M, Tandon V, et al. Ileal Neo-bladder: a decade experience with 'Pouch first and ileal neo-urethra' our modification.Uro Oncol 2004;4(1):35-7.  Back to cited text no. 9      
10.Vibhav M, Singh H, Dwivedi US, et al. Serum p53 and bladder cancer: Can serum p53 be used as tumour marker. Urol Res 2004;32:391-4.  Back to cited text no. 10      
11.Kishore G, Arif H, Dwivedi US, et al. The Correlation of tissue p53 protein over expression and p53 antigen in serum of patients with bladder cancer. Uro Oncol 2003;2:121-8.  Back to cited text no. 11      
12.Freeman JA, Esrig D, Stein JP, et al. Radical cystectomy for high risk patients with superficial bladder cancer in the era of orthotropic urinary diversion. Cancer 2006;76:833-9.  Back to cited text no. 12      
13.May M, Braun KP, Richter W, et al. Radical cystectomy in the treatment of bladder cancer always in due time? Urologe A 2007;46(8): 913-9.  Back to cited text no. 13      
14.Lee CT, Dunn RL, Ingold C, et al. Early-stage bladder cancer surveillance does not improve survival if high-risk patients are permitted to progress to muscle invasion. Urology 2007;69(6):1068-72.  Back to cited text no. 14      
15.Stockle M, Alken P, Engelmann U, et al. Radical cystectomy-often too late? Eur Urol 1987;13:361-7.  Back to cited text no. 15      
16.Herr HW, Sogani PC. Does early cystectomy improve the survival of patients with high risk superficial bladder tumors? J Urol 2001;166:1296-9.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]  
17.Kulkarni GS, Finelli A, Fleshner NE, et al. Optimal management of high-risk T1G3 bladder cancer: A decision analysis. PLoS Med 2007;4:e284.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]  
18.Anderstrom C, Johansson S, Nilsson S. The significance of lamina propria invasion on the prognosis of patients with bladder tumors. J Urol 1980;124:23-36.  Back to cited text no. 18      

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Correspondence Address:
Pratap B Singh
Department of Urology, Banaras Hindu University, Institute of Medical Sciences Varanasi-221 005
India
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PMID: 20814125

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    Tables

  [Table 1], [Table 2], [Table 3]

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