Indian Journal of Urology Users online:1257  
IJU
Home Current Issue Ahead of print Editorial Board Archives Symposia Guidelines Subscriptions Login 
Print this page  Email this page Small font sizeDefault font sizeIncrease font size


 
ORIGINAL ARTICLE
Year : 2008  |  Volume : 24  |  Issue : 4  |  Page : 494-497
 

Small cell cancer of the bladder: The Leon-Berard cancer centre experience


Medical Oncology, Centre Léon-Bérard, 28, Rue Laennec, Lyon-69373, France

Correspondence Address:
Nabil Ismaili
79, Rue 15, Hay Alamane, Riad 2, Meknes-50000- Morocco

Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-1591.44255

Rights and Permissions

 
   Abstract 

Background: Small cell bladder carcinoma is an uncommon tumor. In this retrospective study we report our experience dealing with this disease at the Leon-Berard Cancer Centre.
Materials and Methods: We retrospectively analyzed various characteristics of small cell bladder carcinoma: patient demographics, histological diagnosis, disease stage, treatment effects and outcome, in 14 non-metastatic small cell bladder carcinoma patients treated at our institution between 1995 and 2006.
Results: The mean age at diagnosis was 60 years (range, 45-77). All patients were male. Seventy-five per cent were smokers. All had locally advanced disease. Ten patients (71.4%) were treated by cystoprostatectomy and bilateral pelvic lymph node resection, one by cystoprostatectomy alone. Two patients received neoadjuvant chemotherapy and four received adjuvant chemotherapy. One patient was treated by radiotherapy with concomitant cisplatin after transurethral resection of bladder tumor (TURBT). One patient refused surgery and was treated by chemotherapy alone. One patient was lost to follow-up after TURBT. After 49-month median follow-up, 12 patients had relapsed. Disease-free survival was 5.7 months. The most frequent sites of relapse were the retroperitoneal lymph node (seven patients) and the liver (three patients). Nine patients died of metastasis. Median overall survival was 29.5 months. Survival probability at two years was 58%. Median overall survival was 34 months in the mixed small carcinoma group, as compared with 9.5 months in the pure small cell carcinoma group (P=0.01). Mean overall survival was 27.2 months for all patients and 38.6 months for patients treated with cystectomy and adjuvant chemotherapy.
Conclusion: To date, the optimal treatment for locally advanced small cell bladder carcinoma is not clear. Cystectomy with neoadjuvant or adjuvant chemotherapy appears as a viable option.


Keywords: Bladder, cancer, small cell


How to cite this article:
Ismaili N, Elkarak F, Heudel PE, Flechon A, Droz JP. Small cell cancer of the bladder: The Leon-Berard cancer centre experience. Indian J Urol 2008;24:494-7

How to cite this URL:
Ismaili N, Elkarak F, Heudel PE, Flechon A, Droz JP. Small cell cancer of the bladder: The Leon-Berard cancer centre experience. Indian J Urol [serial online] 2008 [cited 2019 Jul 17];24:494-7. Available from: http://www.indianjurol.com/text.asp?2008/24/4/494/44255



   Introduction Top


Whereas small cell cancer is a common histological variant accounting for 14% of all primitive cancers arising from the lung, [1] small cell bladder carcinoma is extremely rare and accounts for less than 1% of all cancers arising from the bladder. [2],[3] To our knowledge, only 550 cases have been reported up to 2007. [4],[5],[6],[7],[8],[9],[10] This cancer is one of the rare extra-pulmonary localizations of small cell carcinomas. The first case was described in 1981 by Cramer et al. [11] Small cell bladder carcinomas are neuroendocrine epithelial tumors associated with a more aggressive behavior and poorer prognosis than transitional cell bladder carcinoma, and mostly diagnosed at advanced stages. Because of the rarity of the disease, no standard treatment has yet been proposed. For muscle-invasive disease, cystectomy, either alone or in combination with chemotherapy and/or radiotherapy, may be proposed. We conducted a retrospective analysis of all cases of muscle-invasive non-metastatic bladder cancer treated at the Leon-Berard Cancer Centre over a 12-year period.


   Materials and Methods Top


Identification of patients

We retrospectively searched the files of all patients with locally advanced or metastatic bladder carcinoma treated at the Leon-Berard Cancer Centre between January 1995 and December 2006 to identify patients with small cell disease. Patients were considered to have small cell bladder carcinoma if pathological examination of their tumor revealed the presence of any small cell component.

Data collection and follow-up

Patient medical records were retrospectively searched for demographics, clinical stage, histological findings, treatment and outcome. Radiological, pathological and surgical reports were reviewed to determine the stage of the disease at the time of cystectomy by using the 2002 TNM classification for genitourinary tumors. [12] Data about treatment, notably surgery, chemotherapy and radiotherapy, were extracted from patient medical records. The date and site of recurrence and, if applicable, the date and cause of death were also considered.

Statistical analysis

Overall survival and recurrence-free survival were analyzed statistically in all patients. Overall survival was calculated from the date of diagnosis to the date of death or to the date of last follow-up. Time to recurrence was calculated from the date of surgery to the date of first documented relapse or to the date of last follow-up. We retrospectively compared disease-free survival and overall survival between the pure small cell carcinoma group (n=5) and mixed small cell carcinoma group (n=9). The Kaplan-Meier method was used to calculate median time to recurrence and median overall survival. The log-rank test was used to evaluate the differences between the groups.


   Results Top


Between 1995 and 2006, 911 patients with locally advanced or metastatic bladder cancer were treated at the Lιon-Bιrard Cancer Centre. Only 17 patients had small cell histology, of whom 14 had muscle-invasive non-metastatic disease. [Table 1] summarizes the characteristics and clinico-pathological findings of these 14 patients. Mean age at diagnosis was 60 years (range, 45-77 years). All patients were male. Seventy-five per cent of the patients were smokers. Nine patients had both transitional cell and small cell histology, while five had exclusive small cell histology. All patients had a locally advanced T2 disease on transurethral resection of the bladder tumor (TURBT). Four patients had clinical stage II, five had clinical stage III and five had clinical stage IV with no distant metastasis at initial staging. Ten patients (71.4%) were treated by cystoprostatectomy and bilateral pelvic lymph node resection, one by cystoprostatectomy alone. Two patients received neoadjuvant chemotherapy and four received adjuvant chemotherapy. Chemotherapy was a combination of etoposide and cisplatin. One patient was treated by radiotherapy with concomitant cisplatin after TURBT. One was treated by chemotherapy alone because he refused surgery. Finally, one patient was lost to follow-up after TURBT.

After 49-month median follow-up, 12 patients had relapsed. Median disease-free survival was 5.7 months [Figure 1]. The most frequent sites of relapse were the retroperitoneal lymph nodes (seven patients) and the liver (three patients) [Table 2]. Nine patients died of metastatic disease. Median overall survival was 29.5 months [Figure 2]. Survival probability at two years was 58%. The median duration of disease-free survival was 8.6 months in the mixed small cell carcinoma group, as compared with 3.7 months in the pure small cell carcinoma group (P = 0.3) [Figure 3]. The median duration of survival was 34 months in the mixed small cell carcinoma group, as compared with 9.5 months in the pure small cell carcinoma group (P = 0.01) [Figure 4]. Mean overall survival was 27.2 months for the whole group of patients and 38.6 months for patients treated with cystectomy and adjuvant chemotherapy. The survival of the patient treated by chemotherapy alone was 9.2 months. The mean survival of the five patients treated by surgery alone was 22.5 months. Two patients are still alive. All the five patients have received the chemotherapy after progression. The patients treated by concurrent chemoradiotherapy were still alive without disease after 49.7 months.


   Discussion Top


Small cell bladder carcinoma was initially described in 1981 by Cramer et al. [11] On histology, the small cell component appears as small cells with scant cytoplasm, ill-defined cell borders, finely granular nuclear chromatin, and reduced or absent nucleoli. Cells are round or oval, and the mitotic count is high. Immunostaining analysis shows that cells express markers of neuroendocrine differentiation, including chromogranin A, neuron-specific enolase, neural adhesion molecule and synaptophysin.

Primary small cell carcinoma of the bladder is a rare disease that accounts for less than 1% of all bladder cancers. [2],[3] The relatively high incidence of 1.8% reported here might reflect a bias due to the fact that our centre mostly recruits patients with metastatic bladder cancer. We found that most small cell bladder cancers (64%) were admixed with transitional cell carcinoma. Other teams have shown a higher incidence of pure small cell carcinoma. [10]

Because small cell bladder carcinoma is rare, and in the absence of randomized controlled trials, there is no standard treatment for muscle-invasive non-metastatic disease. In a multi-institutional review of 64 patients, a multivariate analysis has indicated that neither chemotherapy, nor radiation, nor surgery has any impact on overall survival.[7] The poor prognosis of patients treated by radical cystoprostatectomy alone reported by Sved et al., [8] supports the use of combination modality treatments. In our series, the mean survival of the five patients treated by surgery alone was 22.5 months. A retrospective study of 46 patients treated at the M. D. Anderson Cancer Centre has reported a five-year survival of 78% for patients receiving neoadjuvant chemotherapy followed by cystectomy, versus 36% for patients undergoing cystectomy alone. [9] In the Mayo Clinic Study, the authors have proposed radical cystectomy for patients with locally advanced disease and adjuvant treatment for patients with Stage III and VI (M0) disease.[10] The results obtained in our series are in concordance with these previous results and show a 38.6-month mean survival for patients treated with radical cystectomy and adjuvant chemotherapy. The protocol of chemotherapy recommended by the M. D. Anderson Cancer Center was the associations used in the neuroendocrine tumors for both pure small cell carcinoma and mixed small cell carcinoma of the bladder. [13] Bastus et al., have reported on a series of five patients with locally advanced disease treated with sequential chemoradiotherapy. Four patients have had long-term disease-free survival and overall survival. [14] In another study, the authors have expressed a realistic optimism and acknowledged a potential for long-term survival in patients with limited stage small cell cancer of the bladder treated with a combination of chemotherapy and local radiotherapy; the actuarial survival rate was 70% at two years and 44% at five years. [15] In our series, the patient treated with concurrent chemoradiotherapy was still alive without disease after 49.7 months. The most common site of relapse in our study was the retroperitoneal lymph nodes (50% of the patients), suggesting that retroperitoneal lymph node irradiation after radical cystectomy might possibly improve disease-free survival. Of the five patients with retroperitoneal lymph node disease, three relapsed in the retroperitoneum, one in the retroperitoneum and the liver, and one in the lung. Finally, we found that pure small cell carcinoma has poorer outcome than mixed small cell carcinoma of the bladder. The median duration of survival was 34 months in the mixed small cell carcinoma group, as compared with 9.5 months in the pure small cell carcinoma group (P=0.01) [Figure 4]. In one series, mixed histologies tended to do better than pure neuroendocrine tumors, although this did not attain statistical significance (P=0.064). [16]


   Conclusion Top


In the absence of prospective study, the best treatment for small cell bladder cancer cannot be established for certain. From our study and from the literature, it appears that combined treatment is necessary for achieving long-term recurrence-free and overall survival. Cystectomy with neoadjuvant or adjuvant chemotherapy appears to be a logical option. The association of chemotherapy and radiotherapy should also be considered. In addition, the pure small cell carcinoma appears to have poorer outcome than the mixed small cell carcinoma of the bladder.

 
   References Top

1.National Cancer Institute, DCCPS SRP, Branch CS. Surveillance, Epidemiology, and End Results (SEER) Program, Public-Use Data (1973-2000). Available from: http://www.seer.cancer.gov. [cited on 2003 Apr], [submitted on 2002 Nov].  Back to cited text no. 1    
2.Holmang S, Borghede G, Johansson SL. Primary small cell carcinoma of the bladder: A report of 25 cases. J Urol 1995;153:1820-2.  Back to cited text no. 2    
3.Blomjous CEM, Vos W, De Voogt HJ, van der Valk P, Meijer CJ. Small cell carcinoma of the urinary bladder: A clinicopathologic, morphologic, immunohistochemical and ultrastructural study of 18 cases. Cancer 1989;64:1347-57.  Back to cited text no. 3    
4.Mangar SA, Logue JP, Shanks JH, Cooper RA, Cowan RA, Wylie JP. Small-cell carcinoma of the urinary bladder: 10-year experience. Clin Oncol (R Coll Radiol) 2004;16:523-7.  Back to cited text no. 4  [PUBMED]  
5.Bex A, Nieuwenhuijzen JA, Kerst M, Pos F, van Boven H, Meinhardt W, et al . Small cell carcinoma of bladder: A single-center prospective study of 25 cases treated in analogy to small cell lung cancer. Urology 2005;65:295-9.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Asmis TR, Reaume MN, Dahrouge S, Malone S. Genitourinary small cell carcinoma: A retrospective review of treatment and survival patterns at The Ottawa Hospital Regional Cancer Center. BJU Int 2006;97:711-5.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Cheng L, Pan CX, Yang WJ, Lopez-Beltran A, MacLennan GT, Haiqun L, et al . Small cell carcinoma of the urinary bladder: Aclinicopathologic analysis of 64 patients. Cancer 2004;101:957-62.  Back to cited text no. 7    
8.Sved P, Gomez P, Manoharan M, Civantos F, Soloway MS. Small cell carcinoma of the bladder. BJU Int 2004;94:12-7.   Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Siefker-Radtke AO, Dinney CP, Abrahams NA, Moran C, Shen Y, Pisters LL, et al . Evidence supporting preoperative chemotherapy for small cell carcinoma of the bladder: A retrospective review of the MD Anderson cancer experience. J Urol 2004;172:481-4.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Choong NW, Fernando Quevedo J, Kaur JS. Small cell carcinoma of the urinary bladder. Cancer 2005;103:1172-8  Back to cited text no. 10    
11.Cramer SF, Aikawa M, Cebelin M. Neurosecretory granules in small cell invasive carcinoma of the urinary bladder. Cancer 1981;41:724.   Back to cited text no. 11    
12.Greene FL, Page DL, Fleming ID. AJCC cancer staging manual, 6 th ed. New York: Springer-Verglag; 2002.   Back to cited text no. 12    
13.Black PC, Brown GA, Dinney CP. The impact of variant histology on the outcome of bladder cancer treated with curative intent. Urol Oncol 2008.  Back to cited text no. 13    
14.Bastus R, Caballero JM, Gonzalez G, Borrat P, Casalots J, Gomez de Sequra G. Small cell carcinoma of the urinary bladder treated with chemotherapy and radiotherapy: Results in five cases. Eur Urol 1999;35:323-6.  Back to cited text no. 14    
15.Lohrisch C, Murray N, Pickles T. Small cell carcinoma of the bladder: Long term outcome with integrated chemoradiation. Cancer 1999;86:2346-52.  Back to cited text no. 15    
16.Quek ML, Nichols PW, Yamzon J, Daneshmand S, Miranda G, Cai J, et al . Radical cystectomy for primary neuroendocrine tumors of the bladder: The university of southern California experience. J Urol 2005;174:93-6.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]

This article has been cited by
1 A clinical review of small-cell carcinoma of the urinary bladder
Thota, S. and Kistangari, G. and Daw, H. and Spiro, T.
Clinical Genitourinary Cancer. 2013; 11(2): 73-77
[Pubmed]
2 Management of small cell carcinoma of the bladder: Consensus guidelines from the Canadian Association of Genitourinary Medical Oncologists (CAGMO)
Moretto, P. and Wood, L. and Emmenegger, U. and Blais, N. and Mukherjee, S.D. and Winquist, E. and Belanger, E.C. and MacRae, R. and Balogh, A. and Cagiannos, I. and Kassouf, W. and Black, P. and Czaykowski, P. and Gingerich, J. and North, S. and Ernst, S. and Richter, S. and Sridhar, S. and Reaume, M.N. and Soulieres, D. and Eisen, A. and Canil, C.M.
Journal of the Canadian Urological Association. 2013; 7(2): E44-E56
[Pubmed]
3 Small cell carcinoma of the urinary bladder diverticulum: A case report and review of the literature
Dong, W.X. and Ping, Y.X. and Liang, W.C. and Jian, L.Z. and Lin, Z.J.
Journal of Cancer Research and Therapeutics. 2013; 9(1): 151-153
[Pubmed]
4 A Clinical Review of Small-Cell Carcinoma of the Urinary Bladder
Swapna Thota,Gaurav Kistangari,Hamed Daw,Timothy Spiro
Clinical Genitourinary Cancer. 2013; 11(2): 73
[Pubmed] | [DOI]
5 Cancer de vessie inhabituel : carcinome neuroendocrine à petites cellules pur de la vessie : à propos d’une observation et revue de la littérature
A. Kassogué,M. F. Tazi,A. Diarra,A. Bennani,A. Amarti,M. J. Fassi,M. H. Farih
Journal Africain du Cancer / African Journal of Cancer. 2013; 5(4): 216
[Pubmed] | [DOI]
6 Carcinome neuroendocrine à petites cellules de la vessie : une entité anatomoclinique rare et agressive
A. Elktaibi,A. Nasri,M. Oukabli,Z. Bernoussi,A. Al Bouzidi,N. Mahassini
Journal Africain du Cancer / African Journal of Cancer. 2013; 5(4): 237
[Pubmed] | [DOI]
7 Neuroendocrine carcinoma of the urinary bladder: a retrospective study of CT findings
Andrew C. Boyer,S. Zafar Jafri,S. Mohammad A. Jafri,Mitual B. Amin
Abdominal Imaging. 2013; 38(4): 870
[Pubmed] | [DOI]
8 Optimal management of extra-pulmonary small cell carcinoma and the role of prophylactic cranial irradiation
N. Ismaili
Strahlentherapie und Onkologie. 2012;
[VIEW] | [DOI]
9 Primary Small Cell Carcinoma of the Urinary Bladder - Mini-review of the Literature
Sarabjeet Chhabra,Padmaraj Hegde,Paras Singhal
Asian Pacific Journal of Cancer Prevention. 2012; 13(8): 3549
[Pubmed] | [DOI]
10 Primary small cell carcinoma of the urinary bladder-Minireview of the literature
Chhabra, S. and Hegde, P. and Singhal, P.
Asian Pacific Journal of Cancer Prevention. 2012; 13(8): 3549-3553
[Pubmed]
11 Clinical and pathologic characteristics of small cell neuroendocrine carcinoma of urinary tract
Guo, A.-T. and Chen, W. and Wei, L.-X.
Chinese Journal of Pathology. 2012; 41(11): 747-751
[Pubmed]
12 Small cell neuroendocrine carcinoma of the bladder: A case report and review of the literature [Carcinome neuroendocrine à petites cellules de la vessie: à propos dæune observation et revue de littérature]
Chekrine, T. and De Bari, B. and Cassier, P. and Kulisa, M. and Chapet, O. and Mornex, F.
Cancer/Radiotherapie. 2011; 15(3): 250-253
[Pubmed]
13 Multidisciplinary approach in the treatment of patients with small cell bladder carcinoma
L.T. Macedo, J. Ribeiro, G. Curigliano, L. Fumagalli, M. Locatelli, J.B.C. Carvalheira, A. Quintela, S. Bertelli, O. De Cobelli
European Journal of Surgical Oncology (EJSO). 2011;
[VIEW] | [DOI]
14 Carcinome neuroendocrine à petites cellules de la vessie : à propos d’une observation et revue de littérature
T. Chekrine, B. De Bari, P. Cassier, M. Kulisa, O. Chapet, F. Mornex
Cancer/Radiothérapie. 2011; 15(3): 250
[VIEW] | [DOI]
15 A rare bladder cancer - small cell carcinoma: review and update
Nabil Ismaili
Orphanet Journal of Rare Diseases. 2011; 6(1): 75
[VIEW] | [DOI]
16 Small cell carcinoma of the genitourinary system [Genitoüriner sistemin küçük hücreli karsinomu]
Kotb, A.F. and Ismail, A.M.
Turk Uroloji Dergisi. 2010; 36(4): 344-349
[Pubmed]
17 Outcome of recurrent and metastatic small cell carcinoma of the bladder
Ismaili, N., Heudel, P.E., Elkarak, F., Kaikani, W., Bajard, A., Ismaili, M., Errihani, H., (...), Flechon, A.
BMC Urology. 2009; 9(1): 4
[Pubmed]
18 Small cell cancer of the bladder: Pathology, diagnosis, treatment and prognosis
Ismaili, N., Arifi, S., Flechon, A., El Mesbahi, O., Blay, J.-Y., Droz, J.-P., Errihani, H.
Bulletin du Cancer. 2009; 96(6): E30-E44
[Pubmed]
19 Small cell carcinoma of the urinary bladder: A case report and review of the literature
Ismaili, N., Ghanem, S., Mellas, N., Afqir, S., Taleb, M., Amrani, M., Gamra, L., Errihani, H.
Journal of Cancer Research and Therapeutics. 2009; 5(2): 133-136
[Pubmed]



 

Top
Print this article  Email this article
Previous article Next article

    

 
   Search
 
   Next article
   Previous article 
   Table of Contents
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (162 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
    Introduction
    Materials and Me...
    Results
    Discussion
    Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed10038    
    Printed137    
    Emailed5    
    PDF Downloaded255    
    Comments [Add]    
    Cited by others 19    

Recommend this journal

HEALTHWARE INDIA