Bladder cancer is not a homogeneous disease. While urothelial carcinoma is most common, with upwards of 60,000 new cases in the US identified each year, there are several different types of bladder cancer, each with their own unique characteristics and treatment profiles . Additionally, the urothelial histology itself is not monolithic, with several important subhistologies now being identified by expert bladder pathologists. Below is a brief synopsis of several key histologic variants of bladder cancer, and a discussion of how these variants impact treatment decisions.
Part 1 Non-Urothelial Histology
Squamous Cell CarcinomaBackground Highlights: Squamous cell carcinoma (SCC) has historically been associated with the parasite schistosoma hematoebium (see below), and indeed nearly 60% of all bladder cancer patients in parts of the developing world (notably Egypt) have schistosoma induced SCC. In the United States, the disease encompasses about 3% of all bladder cancer, with chronic indwelling catheters and intractable UTIs being the most common inciting causes.
|Lifecycle of the parasite schistosomiasis hematobium which can cause squamous cell cancer of the bladder through chronic irritation. (from http://www.cdc.gov/parasites/schistosomiasis/biology.html)|
Management Notes: SCC, stage for stage, is a more aggressive disease than urothelial cancer . Currently, there is no role for intravesical therapy, or for neoadjuvant chemotherapy, both of which are often utilized for appropriately selected urothelial cancer patients. Some in Egypt have advocated the use of adjuvant radiation therapy after cystectomy based on schistosoma SCC patients, though this remains controversial in the United States .
AdenocarcinomaBackground Highlights: Adenocarcinoma constitutes (AC) constitutes 2% of all bladder malignancies worldwide. The urachus, the embrologic remnant of the allantois that drains the fetal bladder before closing, is involved in 10% of these tumors. Another source is often the colon, whose glandular lining is prone to AC and can advance into the bladder wall.
Management Notes: AC is thought to be more aggressive the urothelial cancer, particularly those with signet ring features. There is no role for intravesical or neoadjuvant therapy. As this is a rare tumor, there is currently no data as to how adjuvant therapy may alter the disease course.
Small Cell CarcinomaBackground Highlights: Small Cell Carcinoma of the bladder is a rare disease affecting 1% of all bladder cancer patients. While genetic analysis have shown a common clonal origin to urothelial carcinoma, small cell is a systemic disease and as such has important differences in management. 
Management Notes: Small Cell Carcinoma is thought to be more aggressive, and immediate chemotherapy is the standard of care, with survival doubling when compared to surgery alone . The current treatment regimen that has undergone rigorous study alternates ifosfamide/doxorubicin and etoposide/cisplatin. This is usually followed by cystectomy, though it is not known whether radiation after chemo provides similar efficacy.
This blog was written by Max Kates, MD, a URO-2 resident at the Brady Urological Institute at Johns Hopkins.
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