|Year : 2013 | Volume
| Issue : 4 | Page : 571-573
Sarcomatoid variant of urothelial carcinoma of the urinary bladder
Anshuma Bansal, Narendra Kumar, Suresh C Sharma
Department of Radiotherapy, Post Graduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||11-Feb-2014|
Department of Radiotherapy, Post Graduate Institute of Medical Education and Research, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
Sarcomatoid carcinoma of the urinary bladder is a rare presentation. Less than 100 case reports have been published in the literature. It has been considered as an aggressive variant of bladder carcinoma. Though different treatment modalities have been tried in the literature, yet radical cystectomy followed by adjuvant chemotherapy and radiation should be preferred in all patients, in view of high incidence of local and distant metastasis.
Keywords: Bladder carcinoma, sarcomatoid, variant
|How to cite this article:|
Bansal A, Kumar N, Sharma SC. Sarcomatoid variant of urothelial carcinoma of the urinary bladder. J Can Res Ther 2013;9:571-3
| > Introduction|| |
Carcinosarcomas (CS) are rare variant of bladder carcinomas known to have aggressive behavior.  Definitive treatment strategy has not been defined yet, due to the availability of small case series or reports only. This review article focuses on favorable prognostic factors in such patients, the treatment options and its effect on the outcome, so that optimal management can be planned for individual cases.
| > Discussion|| |
CS are biphasic malignant neoplasms with morphological evidence of both epithelial (carcinomatous) and mesenchymal (sarcomatous) differentiation. It is different from sarcomatoid carcinoma (SaC) of the bladder, which is a malignant spindle cell neoplasm, in which epithelial differentiation may be demonstrated by immunohistochemical or ultrastructural studies. However, World Health Organization classification system acknowledges the controversy surrounding the terminology and histogenesis of these lesions and refers to these lesions as SCs. 
Sarcamatoid variant of transitional cell carcinoma (TCC) of the urinary bladder (UB) is a rare variant of UB cancer, which accounts for approximately 0.3% of all urothelial tumors.  A history of radiation and intravesical cyclophosphamide chemotherapy has been associated.
Macroscopically, tumors are often polypoid with large intraluminal masses. The sarcomatous component is usually a high-grade spindle cell neoplasm. The epithelial component can be in the form of TCC, squamous cell carcinoma, adenocarcinoma, small cell carcinoma or overlying carcinoma in situ. The immunohistochemical profile of the sarcomatoid variant of TCC includes positivity for epithelial markers, at least focally, including cytokeratin and epithelial membrane antigen. This distinguishes this entity from pure sarcomas. 
The mean age of presentation is 66 years (50-77). Presentation is similar to urothelial tumors, with hematuria as the usual presenting symptom. These tumors are typically diagnosed at advanced local stage and they often exhibit nodal or distant metastases. The significance of this variant lies in its association with a poor prognosis. 
Pathological stage is the best predictor of survival in sarcomatoid variants.  Good prognostic factors include negative surgical margins and absence of metastatic disease at the initial presentation. At 2-year mortality is almost 70%.
Few cases reports/series have been reported until now. Only one study examining 221 consecutive cases from SEER database has been published.  Appropriate treatment has not yet been defined. However, the aggressive behavior of the tumor precludes radical therapy whenever possible, since adjuvant therapy seems to have little effect. Total cystectomy often followed by radiation therapy and/or chemotherapy seems to be the preferred treatment.
Wright et al. presented a SEER database of patients with SaC, CS and urothelial carcinoma (UC) treated between 1988 and 2003.  It was found that patients with both SaC and CS presented more frequently with locally advanced or metastatic disease. Survival was worse for sarcomatoid variants compared with UC in organ-confined and in metastatic disease. 5 year survival was 17% and 37% in SaC and CS respectively, compared with 47% in UCs.
A variety of treatment modalities have been described, but optimal treatment requires rather a multimodality approach. The effectiveness of different modalities is not known because of varying rates of usage of adjuvant radiation (15-45%) and chemotherapy (5-60%) and varying results of each case.  Transurethral resection and partial cystectomy carry the risk of incomplete tumor resection. Radical cystectomy with pelvic lymphadenectomy is the mainstay of treatment, although patients tend to develop local recurrence after surgery. 
Wang et al. presented SEER databases, which included 221 patients, between 1973 and 2004. Median age of the patients was 75 years (range 41-96).  72.5% had a locally advanced or distant stage. 53.9% patients underwent transurethral resection only, 35.8% had radical or partial cystectomy and 15.8% of patients received surgery followed by radiation therapy. The median overall survival was 14 months (95% confidence interval 7-21 months). Overall 1- 5- and 10-year survival rate were 53.9%, 28.4% and 25.8%. Overall 5-year survival rate after cystectomy was only 20.3%, suggesting a high-risk of early dissemination. Cancer-specific survival was significantly better for those who underwent cystectomy instead of transurethral resection.
Wang et al. in a single institute study retrospectively reviewed 14 patients of sarcomatoid bladder cancer between 1997 and 2011.  85% had muscle invasive disease and 50% were Stage IV carcinoma. Nearly, 71% patients underwent cystectomy. At a median follow-up of 7 months (range 1.3-112), 35.7% patients have died in last follow-up. 2-year survival was 53.5%. Three patients with long-term survival were reported.
The rationale for the use of adjuvant chemotherapy in this variant is the aggressive nature of the disease. Probability of metastasis is high (50-70%). The combination of gemcitabine and cisplatin is an effective and well-tolerated chemotherapy regimen for the treatment of advanced UC. However, no data are available regarding its use in bladder CS. The use of this chemotherapy regimen in sarcomatoid variants was first reported by Froehner in a single case of metastatic (pulmonary) SC showing durable, complete local and pulmonary remission, but, the pathological stage, was not reported (pTxNxM1) in this study and hence no conclusion can therefore be drawn. 
Another regimen was used by García Gonzαlez e al. in a 26-year-old Stage III sarcomatoid bladder carcinoma (T3aN0M0), who was treated with partial cystectomy followed by four cycles of adjuvant chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin.  Patient was disease free at 1 year follow-up.
Damiano et al. reported a case of 73-year-old man who underwent radical cystoprostatectomy and urinary diversion.  On histological examination, it came out to be SC (pT4N0M0). Gemcitabine 1250 mg/m 2 on day 1 and 8 and Cisplatin 80 mg/m 2 on day 1 every 21 days for a total of four courses were given. At 2-year follow-up, the patient is alive and free from disease, with an excellent quality-of-life and normal urinary tract function. The study concluded that the favorable outcome of the case may be explained by patient's good performance status, the absence of nodal and metastatic involvement and delivery of chemotherapeutic agents at the full dose.
Nomikos et al. reported a case of 32-year-old woman with neurogenic bladder due to spina bifida diagnosed with sarcomatoid UC of the bladder (stage pT3aN0M0).  Treatment included radical cystectomy with ileal conduit diversion and adjuvant chemotherapy with four cycles of gemcitabine and carboplatin. No evidence of disease disease at was found 3 year follow-up.
Role of adjuvant radiation in SC can be justified on the basis of high chances of local invasion and pelvic lymph node metastasis, known with this variant. Adjuvant radiotherapy to the dose of 50-60 Gy, along with the various combinations of chemotherapy has been used in certain case reports, but has yielded inconsistent results. No definite effect of adjuvant radiation on local control can be concluded in view of limited case studies and high disease specific mortality. However, since this is a TCC variant, in which there is established role of concurrent chemoradiation, there adjuvant radiation should always be considered in such cases. Some definite indications of adjuvant radiation are high grade disease, extravesical spread, margin positivity, lymph node positivity and lymphovascular emboli present.
Onal et al. reported a case of 55-year-old female patient with SC, who underwent total cystectomy with lymph node dissection and total abdominal hysterectomy and bilateral salpingo-oophorectomy.  Histopathology report and immunohistochemistry correlates with SC and tumor infiltrating all layers of the bladder wall. The patient was treated with 3D conformal radiotherapy with a total dose of 59.4 Gy with 1.8 Gy fractional daily doses. Patient was alive without any local recurrence and distant metastasis 10 months after surgery.
In locally advanced unresectable disease and metastatic disease, role of neoadjuvant chemotherapy (NACT) has been defined in a limited number of studies, which have shown preliminary promise worthy of further investigation.
Spiess et al. (1980-2005) in his study took 18 patients with primary sarcoma and 17 with SC.  All SC patients received NACT followed by salvage surgery (41%) and TUR (35%). The NACT regimen selected consisted of cisplatin, gemcitabine and ifosfamide in four patients, ifosfamide and adriamycin in two; methotrexate, vinblastine, adriamycin and cisplatin in one patient. The disease-specific mortality rate of patients with SC was 65%, with an additional two patients who were alive with persistent disease.
Antonelli et al. reported a case of 34-year-old male bladder SC with lymphnodal, hepatic and lung metastasis.  He was given NACT with adriamycin, vinblastine and ifosfamide, radical surgery and adjuvant chemotherapy with the same drugs. Complete remission as confirmed by computed tomography, vesical biopsies during chemotherapy and by the findings detected on the surgical specimen. Follow-up is negative for relapses at 72 months. The case presented is remarkable due to the young age of the patient but, overall, for the complete and durable regression of the disease achieved by applying a chemotherapy scheme commonly adopted to treat pure sarcomatous mesenchymal neoplasms.
| > Conclusion|| |
In SCs, treatment paradigms, from other tumors with similar characteristics should be considered. Radical cystectomy followed by adjuvant chemotherapy and radiation should be preferred in all patients, in view of high incidence of local and distant metastasis. Emphasis on early detection is needed to improve the outcome for patients with this malignancy. Further multicentric research is necessary to establish adequate treatment recommendations.
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