Associates in Urology: Introduction

BCG and the treatment of Superficial Bladder Cancer:

What Patients and Doctors Should Know

Dr. Eric K. Seaman, MD

Bladder cancer will account for 12,500 deaths in the US this year. Most patients with bladder cancer will have either gross or microscopic hematuria at the time of presentation. The most common form of bladder cancer is transitional cell carcinoma or TCC. TCC is more common in males than females by a 3:1 ratio. Males older than 50 years of age with a history of tobacco use and hematuria are at a significantly increased risk for bladder cancer.

Extent of Expansion
Superficial bladder cancer is restricted to the bladder lining or mucosa. It includes both papillary tumors and carcinoma in situ. Invasive cancer is defined as extending through the mucosa into the muscle.

Superficial tumors are present in the majority of cases of TCC at initial presentation. These lesions may be treated endoscopically (using a cystoscope through the urethra) by transurethral resection (TUR) where the tumor is scooped out and the base cauterized. Additional biopsies of the bladder may also be taken.

Recurrence
The tumors may recur. From 60-90% of patients will have a recurrence if treated by TUR alone. In addition, a certain number of superficial tumors will progress to muscle invasive disease. The risk of progression or recurrence correlates with 5 factors: 1) The number of tumors 2) The size 3) Recurrence at first follow up cystoscopy 4) The tumor grade (grade refers to how primitive cells appear to the pathologist 5) the presence of Carcinoma in situ.

Before intravesical therapy was ilable, radical cystectomy (surgical removal of the entire bladder) was the most common treatment for recurrent superficial bladder cancer, especially for CIS.

Bacillus Calmette-Guerin
Bacillus Calmette-Guerin is a suspension of live attenuated bacteria. BCG was initially used as a tuberculosis vaccine. It was first used to treat bladder cancer in 1976. It causes a nonspecific immune reaction within the bladder allowing the cells of the lining to be shed, particularly rapidly dividing cells such as cancer.

How is BCG given?
We usually wait until 2 weeks after TUR to begin treatment. The BCG is placed into the bladder through a catheter once a week for 6 weeks. The patient is instructed to retain the BCG for 2 hours, and then void into a receptacle with dilute chlorine bleach. About 4 weeks later, we perform a cystoscopy, possibly with random bladder biopsies, to evaluate the response.

About 70% of patients respond to BCG. Some physicians also recommend maintenance therapy to responders which consists of 3 weekly instillations at 3 months, 6 months and every 6 months there after for a 3 year duration.

Patients who respond need to be followed with serial cystoscopy every 3 months for 2 years, then every 6 months for 2 years, then every year. Urine cytology is also performed.

What are the side effects of BCG?
The most common side effects include irritative voiding symptoms (90%), hematuria (40%) and flu like symptoms with low grade fever (30%). High fever and sepsis are rare complications (less than 3%) and are treated aggressively with anti-tuberculosis medications.

What if BCG doesn't work?
A second course of BCG will cause a response in 40 % of non-responders. People who fail BCG may be successfully treated with intravesical mitomycin C or alpha interferon.