What is Small Cell Bladder Cancer?

Small cell bladder cancer is officially known as small cell carcinoma of the bladder (SCCB) or as a poorly differentiated neuroendocrine carcinoma of the bladder.¹ It is a rare epithelial tumor, accounting for less than 1% of all bladder cancers. It affects men 5 times more often than women and based on a literature review it appears that first diagnosis is made at a mean age of 67.¹

Most bladder cancer diagnoses are transitional cell carcinoma (TCC) which starts in urothelial cells that line the bladder. This is different from SCCB, which is a much more aggressive disease. SCCB cancer cells have a can be hard to identify early and thus more difficult to treat. SCCB has no known cause or pathogenesis (the reasons for the development of a disease), is thought to be highly metastatic, and most often diagnosed at advanced stage.¹

Diagnosing small cell bladder cancer

Symptoms of SCCB are similar to those of TCC. The diagnostic process begins with pathological examinations of cells sometimes from cystoscopy or transurethral resection of the bladder tumor (TURBT). Primary SCCB requires a differential diagnosis generally based on ruling out other forms of cancer, including:¹

• Invasion of the bladder by small cell carcinoma of the prostate
• Metastatic small cell carcinoma from elsewhere in the body, usually the lung
• Primary lymphomas of the bladder

Small cell carcinoma of the bladder is often identified when combined with those characteristics, and other histological forms of bladder cancer like TCC, adenocarcinoma and squamous cell carcinoma. SCCB has been compared, from a pathological standpoint, to small cell lung cancer (SCLC) which has informed the treatment approaches.¹ Yet retrospective reviews suggest that SCCB exhibits different tumor biology and clinical behavior compared to SCLC which would result in different combinations of treatment protocols to address different cellular compositions.²

History of small cell bladder cancer

SCCB was first described in literature in 1981, making it a relatively recent form of cancer. In a period of over 30 years, fewer than 1000 cases have been diagnosed and reported. An aggressive cancer, at the time of diagnosis more than 90% are classified to be Stage II or beyond, with 50% being at Stage III or IV.¹

SCCB is thought to be of a multipotent origin.¹ That means certain kinds of organ-specific cells have the ability to differentiate into specialized cell types that cause cancer.

Treatment for small cell bladder cancer

There is no standard treatment for SCCB because its incidence is so scarce. Treatment is most commonly multimodality, a combination of therapies including chemotherapy, radiation therapy, and surgery, as considered appropriate for each case.² More than half of those with SCCB have surgery, a radical resection, which is the removal of blood supply, lymph nodes and sometimes adjacent structures of a diseased organ or tumor. Considered major surgery, it is associated with improved survival outcomes. Another treatment option is a combination of chemotherapy and radiation therapy.

Yet surgery is not a cure. Based on a study from the MD Anderson Cancer Center in Texas, survival outcomes were further improved for those who received neoadjuvant chemotherapy (chemo before surgery), as compared with those who did not.

Considered a chemosensitive condition, SCCB is responsive to chemotherapy. Chemo is either used to shrink the tumor prior to surgery or as adjuvant treatment after surgery. The benefits of chemotherapy prior to surgery include the early treatment of micrometastatic disease and using a systemic approach that may be better tolerated with less toxicity. Successful tumor shrinkage may result in the downstaging of the tumor allowing for easier surgery.

Treatment recommendations for SCCB are that neoadjuvant chemotherapy should be the first-line approach for cases that are candidates for surgery.^1,2