Data may squelch concerns over statins' effects on bacillus Calmette-Guerin

San Francisco-Statin drugs appear to have no effect on intravesical bacillus Calmette-Guérin (BCG) treatment outcomes in patients with non-muscle invasive bladder cancer, according to a recent retrospective study among Veterans Affairs patients in St. Louis.

Statins, which are used widely to treat cardiovascular disease, have been the subject of conflicting evidence concerning their effect on bladder cancer treatment, noted first author Ted Skolarus, MD, former chief resident at Washington University, St. Louis, working with Robert L. Grubb III, MD, and colleagues.

Evidence began accumulating with a brief 2007 report that statins may attenuate the effect of BCG (N Engl J Med 2007; 355:2705-7). Several large epidemiologic studies have produced conflicting results on possible chemoprotective effects from statins on prostate, bladder, lung, and colorectal cancers, Dr. Skolarus reminded the American College of Surgeons Clinical Congress in San Francisco.

In the case of bladder cancer, theory suggests that statins may attenuate the T-cell response stimulated by intravesical BCG immunotherapy. BCG decreases recurrence and progression of bladder cancer by inducing nonspecific cystitis through multiple pathways that are mediated by TH1 cells. Dr. Skolarus, now a urologic oncology fellow at the University of Michigan, Ann Arbor, led one of the first trials designed specifically to examine a possible association between statin use and intravesical BCG outcomes in VA patients with non-muscle-invasive bladder cancer.

A pilot retrospective study followed 91 patients with a diagnosis of bladder cancer or carcinoma in situ who received intravesical BCG therapy. Patients had to receive at least three BCG treatments and could be taking any statin during the intravesical treatment period.

"The patents were all male and mostly smokers, as you would expect in an older VA population," Dr. Skolarus said.

The mean patient age was 68.5 years and mean follow-up was 5.1 years. Patients had a mean of 1.5 courses of BCG and 47% were taking statins. About 60% of patients had low-grade tumors and 40% had high-grade tumors.

Researchers looked at tumor progression events, total recurrences, cancer-specific survival, and overall survival. There were no significant differences between patients taking statins and those not taking statins in age at presentation, smoking status, total initial cholesterol count, follow-up, or outcomes.

Patients taking statins had higher mortality from bladder cancer than the non-statin cohort (27.3% vs. 12.5%), and men not taking statins had a higher overall mortality than the statin cohort (34% vs. 25.6%). Neither difference was statistically significant.

"Overall, we did not see any [BCG] treatment outcome associated with statin use," Dr. Skolarus said. "There is no current evidence that we should stop statin treatment during BCG therapy."

This is not a definitive study, Dr. Skolarus noted. The sample size is small, and retrospective data are less compelling than prospective results. Disease severity could also affect the results since low-grade bladder cancer is less responsive to BCG than high-grade disease is.

"The use of statins during BCG therapy has been a controversial topic," said discussant Badrinath R. Konety, MD, associate professor and vice chair of urology and epidemiology and biostatistics, University of California, San Francisco. "The biology makes sense. But the data here are not strong."

Dr. Konety noted that the study design, requiring only three courses of BCG therapy, muddies the conclusion. Three courses of BCG do not produce a reliable change in outcome compared to the standard six courses of therapy. There were also no data on specific statin agents or adherence to statin therapy.

"We need a broader perspective before we make a definitive decision on the issue," he said.

While the differences did not reach statistical significance, the numerical values were large and troublesome.

Dr. Skolarus said he agreed. He added that a subgroup analysis of patients with high-grade tumors is planned. A second trial with a larger patient population has already been proposed.