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A 59-year-old man presents to a hospital in Yokohama, Japan, after being referred by his local medical provider for further workup regarding gross hematuria. He has no other symptoms.

Clinicians perform cystoscopy, followed by CT and MRI scans, which identify a nodular tumor that occupies the patient's bladder -- it is 8 cm in diameter.

Aside from being a tobacco smoker, the patient's medical history is unremarkable. Laboratory tests are performed but fail to identify any abnormalities. The patient undergoes transurethral resection of the bladder tumor, which is sent to histology for analysis.

The pathology report reveals the tumor as the sarcomatoid variant of urothelial carcinoma with a heterologous osteosarcomatous element of osteosarcoma and high-grade spindle cells. The patient refuses to undergo the radical cystectomy proposed by clinicians, opting instead to undergo another transurethral resection of the tumor.

The specimen from the second surgery reveals the same elements, with evidence of invasion to the muscle. Based on these findings, clinicians schedule the patient for two courses of neoadjuvant chemotherapy with gemcitabine (1,000 mg/m² on days 1 and 8) and cisplatin (70 mg/m² on day 2); they recommend that this be followed by a radical cystectomy.

After treatment with neoadjuvant chemotherapy is completed, an abdominal CT scan shows that the patient's pelvic lymph nodes are enlarged on both sides, and his left kidney is swollen with urine build-up. There is no evidence of distant metastasis.

At that point, the patient is unable to undergo radical cystectomy. Six months after his initial consultation, the patient succumbs to cancer of the bladder.

Discussion

Clinicians presenting this of a patient with sarcomatoid-variant bladder carcinoma that progressed rapidly during neoadjuvant chemotherapy noted at the time of publication, in September 2018, that there was little information regarding viable chemotherapy regimens and treatment outcomes for this rare form of urothelial carcinoma.

Sarcomatoid-variant carcinoma, which is comprised of an epithelial component as well as a non-epithelial sarcoma component, is generally found in the bladder. It accounts for less than 1% of all urothelial carcinomas and is associated with a rapid growth rate and tends to present at an , the authors wrote.

In contrast, urinary bladder cancer is one of the most commonly diagnosed malignancies. It presents initially as non-muscle-invasive (pTa or pT1) disease in two-thirds to three-fourths of patients and thus is often treated initially using conservative approaches, case authors noted. However, recurrence is not uncommon and involves grade and/or stage progression in some patients.

In the U.S., the average 5-year survival with bladder cancer is around 77% and is highly dependent on the stage at diagnosis. Metastatic disease, which accounts for only 5% of U.S. cases, has a 5-year survival of around 5%, according to a 2020 review of the .

Authors of that paper noted that tobacco smoking represents the greatest risk factor for the urothelial subtype of bladder cancer, which comprises 90% of all cases -- smoking accounts for 50% to 65% of all bladder cancer cases and increases the risk of the disease threefold.

Sarcomatoid carcinoma is generally a biphasic malignant tumor demonstrating morphological and/or immunohistochemical evidence of epithelial and mesenchymal differentiation, authors observed. The epithelial elements react with cytokeratin or epithelial membranous antigen, whereas the stromal elements react with vimentin, actin, or specific biomarkers, they added.

Expanding Treatment Considerations

Treatment of bladder cancer has evolved somewhat in the 3 years since publication of the case report, with the FDA recently expanding indications for sacituzumab govitecan (Trodelvy) to grant conditional approval for its third-line use in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-containing chemotherapy and a PD-1/L1 inhibitor.

Additionally, following a complete response to in one patient thought to have unresectable sarcomatoid bladder cancer, Johns Hopkins started offering a neoadjuvant multi-agent chemotherapy regimen of cisplatin, gemcitabine, and docetaxel before cystectomy to sarcomatoid bladder cancer patients who were eligible for cisplatin-based chemotherapy.

Nevertheless, as the case authors concluded, sarcomatoid bladder cancer is an aggressive neoplasm with a very poor prognosis compared with other types of tumors.

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