Effect of Supplemental Omega-3 Fatty Acids in Patients with Superficial Bladder Cancer After Transurethral Resection: A Randomized Trial

P.I.: Satia, Jessie A Department: Nutrition and Epidemiology Title: Effect of Supplemental Omega-3 Fatty Acids in Patients with Superficial Bladder Cancer After Transurethral Resection: A Randomized Trial

Bladder cancer is one of the most common malignancies in the United States (U.S.), with an estimated 68,810 new cases expected to be diagnosed in 2008. Of these new cases, approximately 80% will be tumors confined to the epithelium or submucosa "so called" "superficial tumors". These patients with lower grade disease are watched conservatively with transurethral endoscopic resection (TURBT) as the standard initial management of superficial surveillance, followed by cystoscopic bladder examinations and no adjuvant treatment. Under such a treatment plan (representing the standard of care in the U.S.), low risk patients still have a recurrence risk of approximately 60% - albeit only a 5-10% risk of progression and many patients have frequent recurrences, which adversely affects overall health and quality of life. Additional or adjuvant therapeutic or disease management options in this low risk group to reduce the risk of recurrence, and thereby minimize additional TURBTs and the associated morbidities, are urgently needed - particularly agents which are simple, safe, and easily administered, and do not require intervention (e.g., chemotherapy or immunotherapy). Such agents would represent a significant advancement in the treatment of superficial bladder cancer and a significant improvement in the quality of life for many of these patients.

Studies suggest a strong environmental component to bladder cancer risk, e.g.,, cigarette smoking is one of the strongest risk factors and physical inactivity and obesity are also associated with elevated risk. However, relatively few studies have evaluated whether dietary components impact bladder cancer risk. Inflammation has been implicated in the etiology of bladder cancer; therefore, it is plausible that dietary factors that lower inflammation may potentially reduce bladder cancer risk, and perhaps the risk of recurrence. Omega-3 fatty acids are one such possible dietary factor.

This proposed study is a placebo-controlled randomized clinical trial that aims to evaluate whether dietary supplementation of two doses of omega-3 fatty acids (1800 mg and 3600 mg daily) for 9 months can reduce one-year (post-intervention) recurrence rates in patients with low risk, superficial bladder cancer after TURBT. We would recruit 120 patients with low grade superficial bladder cancer and randomly assign them to three groups (n=40/group): omega-3 fatty acids (1800mg daily), omega-3 fatty acids (3600mg daily), or placebo for a period of 9 months. Efficacy of the omega-3 fatty acid supplementation will be determined by comparing the one-year recurrence rates in the treated groups to 1) the placebo group, and 2) the well-accepted historical recurrence rate of 60%. Omega-3 fatty acids are a particularly attractive option because they are generally considered safe, are part of the usual diet, and are potentially mechanistically linked to bladder cancer through inflammation.

To our knowledge, this would be the first dietary intervention trial conducted in bladder cancer patients. It will inform on the feasibility, safety, and potential efficacy of a chemoprevention trial with a dietary agent (omega-3 fatty acids) in patients with low grade, low risk bladder cancer who have no good therapeutic options to manage their disease. In addition, the study will advance understanding of how omega-3 fatty acids might modulate or mediate important physiological parameters and immunohistochemical markers in bladder cancer patients, and may provide useful information regarding the potential of these markers as surrogate endpoints for bladder cancer patients. It would also potentially expose other opportunities for dietary and other health behavior interventions in these patients. In summary, this proposed study could contribute to establishing non-toxic, non-intensive, safe dietary treatment strategies for patients with low risk bladder cancer, forestall the need for repeat surgery, and improve quality of life.