In a peer-reviewed study believed to be the first of its kind published, a research team led by Johns Hopkins Medicine provides scientific evidence that a healthy diet may reduce the chance of low risk prostate cancer progressing to a more aggressive state in men undergoing active surveillance — a clinical option in which men with lower risk cancer are carefully monitored for progression in lieu of treatments that could have undesired side effects or complications.
The findings are reported today in the journal JAMA Oncology.
"Many men diagnosed with low grade prostate cancer are interested in changes they can make to reduce the risk of their tumor becoming more aggressive, and the role of diet and nutrition is one of the most commonly asked questions," says study co-senior author Bruce Trock, Ph.D. , a professor of urology, epidemiology and oncology at the Johns Hopkins University School of Medicine, and director of the Brady Urological Institute's epidemiology division. "These men are motivated to make changes that may improve their prognosis, which is why we began collecting data on their diets, lifestyles and exposures 20 years ago. Hopefully, these latest findings will enable us to develop some concrete steps they can take to reduce the risk of cancer progression."
When a patient is found after a biopsy to have developed prostate cancer, the sampled cells are assigned to a grade group based on how they look when compared with normal prostate tissue. Grade groups range from 1 to 5, with grade group 1 indicating indolent cancer cells that don't look very different than normal tissue and do not metastasize (spread to other parts of the body).
At the other end of the scale, grade group 5 indicates cancer cells that are quite abnormal in appearance, and can grow and spread throughout the body if untreated. These grade groups are how clinicians classify the cancer's biological aggressiveness.
During active surveillance, biopsies are performed at regular intervals in order to look for change in the prostate cancer that would move it to a higher grade group. This is called grade reclassification. Reclassification often leads to a recommendation for treatment. It also is a common way for researchers to evaluate the effectiveness of therapies and lifestyle modifications.
"While there have been previous research studies looking at diet and its relationship to prostate cancer, we believe that ours is the first to provide statistically significant evidence that a healthy diet is associated with a reduction in risk of prostate cancer progressing to a higher grade group, as shown by a reduction in the percentage of men on active surveillance experiencing grade reclassifications over time," says study co-senior author Christian Pavlovich, M.D. , a professor in urologic oncology at the Johns Hopkins University School of Medicine and director of the Brady Urological Institute's prostate cancer active surveillance program.
In the newly published study, the researchers prospectively evaluated the histories of 886 men (median age at diagnosis: 66) diagnosed with grade group 1 prostate cancer from January 2005 to February 2017, all of whom were in the Johns Hopkins Medicine active surveillance program and whom, at the time of enrollment, completed a validated food frequency survey — the Block 1998 Food Frequency Questionnaire — regarding their usual dietary patterns. Of the participants, 55 were Black (6.2%), 803 (90.6%) were white and 28 (3.2%) identified as other races and ethnicities.
Based on their responses to the questionnaire, a Healthy Eating Index (HEI) score was calculated for each patient. The HEI ranges from 0 to 100.
"The HEI is a validated measure of overall diet quality, quantifying how well an individual's dietary pattern adheres to the recommendations of the U.S. Department of Agriculture's Dietary Guidelines for Americans," says study lead author Zhuo Tony Su, M.D. , a fifth-year resident at the Brady Urological Institute and the Johns Hopkins University School of Medicine. "We looked at each patient's HEI score — as calculated from their dietary information recorded at enrollment in our active surveillance program — and assessed whether men with a higher quality diet were less likely to experience grade reclassification in the years afterward."
Su says the researchers also evaluated the patients using an energy-adjusted HEI (E-HEI) score that takes into account a person's daily caloric intake.
Along with those two metrics, Su says, the researchers calculated scores for each study participant using the Dietary Inflammatory Index (DII) and the energy-adjusted DII (E-DII).
"The DII and E-DII scores assess the inflammatory or anti-inflammatory potential of any diet, so higher scores indicate a diet that may cause more inflammation, which in turn, may contribute to the development and progression of prostate cancer," says Su. "We evaluated whether higher inflammatory potential was associated with increased risk of grade reclassification."
By a follow-up assessment at 6.5 years after diagnosis, 187 men (21%) had been reclassified as grade group 2 or greater, of whom 55 (6%) had extreme grade reclassification to grade group 3 or greater.
"When our team looked at the HEI and E-HEI scores in relation to the grade reclassification rates, we found a statistically significant inverse association between adherence to a high quality diet — as indicated by high HEI and E-HEI scores — and the risk of grade reclassification during active surveillance," says Trock. "In other words, the higher the HEI and E-HEI scores, the more reduced the risk that a low grade prostate cancer had progressed to a higher grade disease that mandated curative treatment."
Pavlovich says for patients adhering to a high quality diet, every increase of 12.5 points in the HEI score was associated with an approximately 15% reduction in reclassification to grade group 2 or greater, and a 30% reduction in reclassification to grade group 3 or greater.
The researchers say their findings also indicate that lower inflammation potential is among several possible risk lowering mechanisms as a result of a higher quality diet. However, they did not find an association between grade reclassification and baseline DII/E-DII scores.
"This lack of association with DII/E-DII may indicate that inflammation plays a role in driving the progression from a healthy prostate to one with cancer," says Trock. "Whereas, in men who already have prostate cancer, the more subtle biological change from a lower to higher grade may reflect other mechanisms potentially influenced by diet."
The researchers report several limitations in their study, including diet data based on patient self-reporting, results subject to potential nonresponse bias (bias occurring when respondents and nonrespondents differ in ways that impact the research, making the sample population less representative of the whole population) and not accounting for dietary changes over time. Additionally, they say the study population — consisting predominantly of white men with grade group 1 disease at diagnosis — may not be generalizable to all patients.
"Our findings-to-date should be helpful for the counseling of men who choose to pursue active surveillance and are motivated to modify their behaviors, including quality of diet," says Pavlovich. "However, to truly validate the association between higher quality diet and reduced risk of prostate cancer progression, future studies with more diverse populations are needed."
Along with Trock, Pavlovich and Su, research team members from Johns Hopkins Medicine are Patricia Landis and Mufaddal Mamawala, M.B.B.S., M.P.H.
Team members from other medical institutions are Claire de la Calle, M.D., from the University of Washington, and three researchers from the University of South Carolina: James Hebert, Sc.D., M.S.P.H.; Nitin Shivappa, Ph.D., M.B.B.S., M.P.H.; and Michael Wirth, Ph.D., M.S.P.H.
The work was supported by the Persky Family Foundation and the Patrick C. Walsh Prostate Cancer Research Fund.
Hebert reports controlling interest in Connecting Health Innovations, a company that has licensed the right to his invention of the Dietary Inflammatory Index from the University of South Carolina to develop computer and smartphone applications for patient counseling and dietary intervention in clinical settings. Su reports receiving a Persky scholarship and a Johns Hopkins urology intramural grant during conduct of this study. Trock reports receiving personal fees for consulting from Emmes and from Myriad Genetics, and grants from MDxHealth outside this study.
No other authors had disclosures to report.
