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Eating raw cruciferous vegetables may improve outcomes for some bladder cancer patients

Kaiser Permanente study suggests a diet that includes vegetables like broccoli and arugula may reduce recurrence in patients treated with Bacillus Calmette-Guerin

Non-muscle invasive bladder cancer patients whose treatment included the immunotherapy Bacillus Calmette-Guerin (BCG) after surgery were less likely to have their cancer recur if their diet included raw cruciferous vegetables, a new Kaiser Permanente study found.

Marilyn Kwan in blue blouse with black jacket
Marilyn Kwan, PhD

The research, published in the Journal of Urology, analyzed data from patients enrolled in the Bladder Cancer Epidemiology, Wellness, and Lifestyle (Be-Well) Study, one of the largest prospective studies to examine the effects of nutrition, lifestyle, and genetics on bladder cancer survivorship.

“One of the reasons we launched Be-Well was because we were interested in learning if diet, particularly cruciferous vegetables, could affect prognosis in non-muscle invasive bladder cancer, which has a high risk of recurrence — from 50%-70%,” said lead author Marilyn L. Kwan, PhD, a research scientist and cancer epidemiologist at the Kaiser Permanente Division of Research. “It’s gratifying to see that our findings suggest that for these patients, raw cruciferous vegetables could fit into the category of food as medicine.”

The study included 1,158 Be-Well participants. Of these, 448 (40%) were treated with the chemotherapy mitomycin C and 565 (50%) were treated with BCG. Both treatments are liquids that are delivered directly into the bladder through a catheter. Nearly 2 years after completing treatment, 343 (30%) of the patients had a recurrence.

The study found that, overall, mitomycin C was associated with an over 40% lower risk of recurrence, while BCG was associated with about a 30% lower risk of recurrence. Eating 2.4 servings or more a month of raw cruciferous vegetables further reduced recurrence risk in the patients receiving BCG compared with patients who ate less than 2.4 servings per month. These patients had a 44% lower risk of recurrence than those who ate fewer cruciferous vegetables.

Biological connections

Li Tang wearing a red and black scarf and black jacket
Li Tang, MD, PhD

Mitomycin C is a chemotherapy drug that kills cancer cells by inhibiting DNA synthesis. But before that can occur, the drug must be activated by a specific enzyme. BCG is an immunotherapy that activates the immune system. Isothiocyanates (ITCs) are naturally occurring molecules found in cruciferous vegetables. Cruciferous vegetables that contain ITCs increase the enzyme mitomycin C uses; they also enhance the immune system. This led the research team to question whether patients receiving these therapies who ate these vegetables might have a better prognosis.

The Be-Well participants completed a comprehensive dietary survey when they enrolled in the study, shortly after their diagnosis. The survey included questions about the amount they ate of 22 specific cooked or raw cruciferous vegetables as well as 4 condiments that contain ITCs. The researchers used these self-reports to estimate the participants’ ITC intake. Dietary levels were categorized as high or low based on the median level of the group. (A standard serving size is half a cup of non-leafy vegetables and 1 cup of leafy vegetables.) In addition, the patients’ urine was tested for ITC metabolites.

The researchers said there are likely biological reasons why the study found a reduced risk only in the patients treated with BCG. “ITCs show immunomodulatory activities at low dose ranges, which could potentially improve the efficacy of BCG,” said senior author Li Tang, MD, PhD, a molecular epidemiologist at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. “But it takes high doses of ITCs to induce the important part of phase II enzyme activation that makes mitomycin C effective, and, in general, most of the people we studied consumed lower amounts of these vegetables.”

Reina Haque wearing a black shirt and gold hoop earrings.
Riena Haque, PhD, MPH

A prior Be-Well study found that bladder cancer patients with high levels of ITCs had a lower risk of developing multiple recurrences and progression. This is the first study to look at whether ITC intake improved outcomes for patients treated with mitomycin C or BCG.

“Since we measured nutrients from diet questionnaires, our results are based on foods consumed by the patients, and not by supplemental vitamins or pills,” said study co-author Reina Haque, PhD, MPH, a cancer epidemiologist in the Kaiser Permanente Southern California Department of Research & Evaluation. “It’s important for patients and their providers to know that non-pharmaceutical factors such as a good diet can help improve cancer-related outcomes.”

Reducing recurrence risk

David Aaronson in a blue shirt and white doctor's coat.
David Aaronson, MD

About 3 in 4 patients with bladder cancer have non-muscle invasive bladder cancer. These patients have a 5-year survival rate of close to 90%. However, more than half of these patients will have one or more recurrences. Of these, 10% to 20% will have cancers that progress to muscle-invasive cancer.

“Patients are always looking for advice on lifestyle changes they can make to help them deal with their cancer diagnosis,” said David Aaronson, MD, a clinician advisor on the Be-Well Study and a urologist with The Permanente Medical Group. “Our study suggests that this may be a reasonable response to answer those patients’ questions. A clinical trial would be needed to confirm if this is truly the case, but it does seem that eating your vegetables is again looking like good advice.”

The study was funded by the National Cancer Institute.

Co-authors include Valerie S. Lee, MHS, Janise M. Roh, MPH, MSW, Isaac J. Ergas, PhD, Charles P. Quesenberry, PhD, and Lawrence H. Kushi, ScD, of the Division of Research; Zinian Wang, Rachell Pratt, Maciej Goniewicz, PhD, PharmD, and Christine B. Ambrosone, PhD, of the Roswell Park Comprehensive Cancer Center; Kimberly L. Cannavale of the Kaiser Permanente Southern California Department of Research and Evaluation; Ronald K. Loo, MD, of Kaiser Permanente Southern California; David S. Aaronson, MD, of The Permanente Medical Group; and Yuesheng Zhang, MD, PhD, of the Massey Comprehensive Cancer Center.

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About the Kaiser Permanente Division of Research

The Kaiser Permanente Division of Research conducts, publishes and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and society at large. It seeks to understand the determinants of illness and well-being, and to improve the quality and cost-effectiveness of health care. Currently, DOR’s 600-plus staff is working on more than 450 epidemiological and health services research projects. For more information, visit or follow us @KPDOR.

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