Non-bilharzial squamous cell carcinoma is the most prevalent epithelial neoplasm of the bladder after urothelial carcinoma, accounting approximately for 3–5% of bladder tumors in Western countries [1]. It is associated with chronic irritation of the bladder. In contrast to transitional cell carcinoma, NBSCC of the bladder is characterized by a lower frequency of distant metastases. The patients die usually after locoregional recurrence [1][2][3]. Due to the rarity of this entity, prospective studies are necessary to codify the optimal management of this disease. In the present study, we retrospectively reviewed our experience with non-bilharzial squamous cell carcinoma of bladder within a period of five years.

A retrospective study was conducted in radiotherapy and oncology department of Ibn Rochd hospital during a five-year study period between January 2008 and December 2012. Diagnosis was established on biopsy in all the patients. Staging was performed on the basis of the TNM criteria. None of the patients suffered from schistosomiasis. We included only pure NBSCC. For the identified cases, clinical history, treatment, histology, and postoperative follow-up were recorded. Each patient had a preoperative metastatic workup that included blood tests, computed tomography (CT) scan of the chest, abdomen and pelvis, and bone scan.

Between January 2008 and December 2012, seven cases of NBSCC of the bladder were diagnosed on endoscopic biopsy specimen out of 935 patients with bladder cancer with frequency of 1.7%. The characteristics of our patients are summarized in Table 1.

The age range was between 40 and 76 years and the average age at diagnosis was 58 years. In our collective, a male predominance was observed including five males and two females. The duration of symptoms ranged from six months to two years and the average time of consultation was one year. Among the patients presented with hematuria, there were four patients who suffered from pelvic pain and three patients had urinary frequency and urinary discharge. Five patients reported significant weight loss. All the patients underwent cystoscopy with biopsy and resection. The diagnosis was carried out at an advanced stage in all patients. Two patients had distant metastasis at presentation. One patient had pulmonary metastasis and the other patient had bone metastasis. Three patients had pelvic lymph node involvement. Radical cystectomy was the chosen treatment in three cases. Adjuvant chemotherapy was administered in the three patients using gemcitabine/cisplatine in two cases and methotrexate/cisplatin in one case. Two patients inoperable had received an exclusive combined radio-chemotherapy with cisplatin weekly and pelvic irradiation of 60 Gy. The other two patients had received best supportive care. With a median follow-up period of 25 months, three patients had died from NBSCC of the bladder, two of them were metastatic. Three other patients had local recurrence, two of them were treated by chemoradiation and just one patient was treated by surgery.

Non-bilharzial SCC and bilharzial SCC of the bladder are two entities that differ in incidence, epidemiology, and natural history [1]. The risk factors of non-schistosoma related squamous cell carcinoma are various. The most relevant common factor appears to be some form of chronic bladder irritation. This condition occur in patients with chronic inflammatory disorders of the bladder, persistent calculi, chronic cystitis, and bladder diverticula, cyclophosphamide treatment, intravesical Bacillus Calmette-Guérin (BCG). In the United States, patients with spinal cord injury represent the largest group of patients affected by NBSCC. The black race is also considered a risk factor for some authors [2] [3]. The relation between SCC and smoking is not clear [2] [3].

Pure SCC of the bladder must be distinguished from urothelial carcinoma with squamous differentiation. In our study, we included only pure NBSCC of the bladder. Superficial tumors are almost never seen; because most of patients present with locally advanced disease. Clinical presentation and tumor location are similar to the other histological gender.

Treatment of NBSCC of the bladder has been controversial, because patients are usually given the diagnosis of NBSCC at an advanced stage. Options include surgical resection, chemotherapy and radiotherapy [1].

Radical cystectomy remains the mainstay of therapy for pure NBSCC of the bladder [4]. The role of radical cystectomy as the key therapeutic approach for bladder SCC has been previously shown by Richie et al., who documented a five-year survival of 48% among patients treated with cystectomy and lymphadenectomy [5].

Current data on the therapeutic results after external irradiation are poor. Radiotherapy has been used exclusively or as an adjunct to surgery in the neoadjuvant setting [1] [6]. Neo-adjuvant irradiation has been discussed by several authors and small patient series, which reports that patients who were downstaged by neoadjuvant radiation therapy demonstrated durable response to therapy. These results were not confirmed by prospective studies, and the benefit of preoperative radiation to improve local control is still uncertain [7]. We can not assess the impact of this therapeutic approach because none of our patients had received neoadjuvant radiotherapy.

Systemic chemotherapy is not very effective to date because NBSCC is described as a chemotherapy refractory disease and is considerably less responsive to standard chemotherapy regimens used for urothelial carcinoma. The standard chemotherapy regimens seem to have limited impact on the disease because of the relative chemo-resistance of NBSCC [8]. An effective chemotherapy protocol against this disease has not yet been found; however, new protocols using "Gemcitabine - cisplatin" may offer better responses [8] [9]. The role of neoadjuvant or adjuvant chemotherapy in the treatment of patients with pure SCC of the bladder is uncertain. In our study, heterogeneous adjuvant, neoadjuvant chemotherapy and combination radio-chemotherapy regimens were performed because all the patients were received at advanced stages of disease.

Patients with non-schistosomiasis-related SCC of the bladder have an unfavorable prognosis. The natural history of NBSCC of bladder is characterized by locoregional evolution while metastatic extension is rare ranging from 8% to 10%; which strongly distinguished NBSCC from transitional cell tumors. In the absence of effective therapy, locoregional failures of SCC of the bladder will continue to be the primary cause of death in these patients [4]. In our study, we notified more locoregional recurrence in patients treated by chemoradiation more than patients treated by surgery, yet we can't extract conclusions because patients receiving chemoradiation had tumors at advanced stage.

In summary, primary squamous cell carcinoma (SCC) in the non-bilharzial bladder is a rare entity. It has a poor prognosis, and most patients die of locoregional failure. Local control is more important in the treatment approach. Most authors support cystectomy as the most appropriate treatment.

Zineb bouchbika, Nadia benchakroun, Nezha tawfiq

1. Abol-Enein H, Kava BR, Carmack AJ. Nonurothelial cancer of the bladder. Urology 2007 Jan;69(1 Suppl):93–104.   [CrossRef]   [Pubmed]    
2. Bejany DE, Lockhart JL, Rhamy RK. Malignant vesical tumors following spinal cord injury. J Urol 1987 Dec;138(6):1390–2.   [Pubmed]    
3. Cohen SM, Shirai T, Steineck G. Epidemiology and etiology of premalignant and malignant urothelial changes. Scand J Urol Nephrol Suppl 2000;(205):105–15.   [CrossRef]   [Pubmed]    
4. Kassouf W, Spiess PE, Siefker-Radtke A, et al. Outcome and patterns of recurrence of nonbilharzial pure squamous cell carcinoma of the bladder: a contemporary review of The University of Texas M D Anderson Cancer Center experience. Cancer 2007 Aug 15;110(4):764–9.   [CrossRef]   [Pubmed]    
5. Richie JP, Waisman J, Skinner DG, Dretler SP. Squamous carcinoma of the bladder: treatment by radical cystectomy. J Urol 1976 Jun;115(6):670–2.   [Pubmed]    
6. Rundle JS, Hart AJ, McGeorge A, Smith JS, Malcolm AJ, Smith PM. Squamous cell carcinoma of bladder. A review of 114 patients. Br J Urol 1982 Oct;54(5):522–6.   [CrossRef]   [Pubmed]    
7. Swanson DA, Liles A, Zagars GK. Preoperative irradiation and radical cystectomy for stages T2 and T3 squamous cell carcinoma of the bladder. J Urol 1990 Jan;143(1):37–40.   [Pubmed]    
8. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003 Aug 28;349(9):859–66.   [CrossRef]   [Pubmed]    
9. Raghavan D. Progress in the chemotherapy of metastatic cancer of the urinary tract. Cancer 2003 Apr 15;97(8 Suppl):2050–5.   [CrossRef]   [Pubmed]