Dietary changes may slow prostate cancer growth during active surveillance
Key takeaways:
- A diet with reduced omega-6 and increased omega-3 fatty acids could slow progression of prostate cancer.
- The dietary change included the addition of fish oil supplements.
A dietary change that included a decrease in dietary omega-6 and an increase in omega-3 fatty acids could reduce prostate cancer progression among men undergoing active surveillance, according to results of a randomized phase 2 trial.
Men who lowered their omega-6 intake and increased omega-3, aided with fish oil supplements, had decreased expression of a biomarker linked to disease progression. Those who did not make dietary changes had increased expression of that biomarker.
William J. Aronson, MD, professor in the department of urology at David Geffen School of Medicine at UCLA, summarized his reaction to the results in one word.
“Elation,” Aronson told Healio. “I personally speak with over 100 patients with a new diagnosis of prostate cancer every year. We go through what type of prostate cancer they have, what they can expect, what the options are — whether they be active surveillance or treatments. Nearly every patient that I talk with, and nearly every family member, looks at me and asks the same question: What can they do for themselves? Is there anything they can change in their diet? I think when clinicians are handed that question, they can draw back on this study as an important finding.”
Background
Approximately 30% of men undergoing active surveillance for prostate cancer ultimately require surgery or radiation within 5 years of diagnosis.
For more than 30 years, Aronson and colleagues have researched ways to delay progression through dietary changes.
Their initial research showed corn oil caused human prostate cancer progression in mouse models. Typical American diets are high in corn oil, sunflower oil and safflower oil, which have high amounts of omega-6 and can be found in fried foods, mayonnaise, tortilla chips and bottled salad dressing.
“We are just inundating ourselves with omega-6,” Aronson said.
Researchers conducted another study where they raised omega-3, commonly found in fish, and lowered omega-6. The diet reduced cancer growth in animal models. Likewise, in a randomized study involving men who had surgery planned to remove their prostate cancer, a low omega-6 diet with fish oil showed inhibition of Ki-67, a biomarker associated with an increased risk for prostate cancer progression and metastasis.
Methods
Aronson and colleagues conducted the CAPFISH-3 trial to further their research.
The open-label study included 100 men (mean age, 64.2 years; range, 46-83; 85% white) undergoing active surveillance for prostate cancer. All men had Gleason scores equal to or less than 3 + 4 and a PSA equal to or less than 25.
Researchers randomly assigned men to one of two groups. Those in the intervention arm underwent monthly dietary counseling and received instruction to reduce their intake of foods with omega-6 fats and increase intake of fish providing omega-3s. They also were provided fish oil supplements.
Men in the control arm did not make any changes to their diet.
Researchers evaluated diets through food journals, with assessments performed every 3 months for the intervention group and every 6 months for the control group.
Change in Ki-67 index from baseline to 1-year after the dietary intervention served as the primary endpoint. Pathologic features of the cancer — such as tumor grade group and maximum length, Decipher 22-gene classifier score, PSA, testosterone, lipids and cytokines — served as secondary endpoints.
Results and next steps
Over 12 months, men in the intervention group significantly lowered the amount of omega-6 (14.1 g vs. 9.2 g; P < .001) and the ratio of omega-6 to omega-3 (8.7 to 5.7 without fish oil; P = .017; 8.7 to 2.2 with fish oil) in their diets. Results showed no reduction among men in the control group.
Men who lowered their omega-6 and increased their omega-3 had a 15% decrease in Ki-67 from baseline to 1 year (1.34% to 1.14%). The control group had a 24% increase in their Ki-67 (1.23% vs. 1.52%).
Of the 50 men in the intervention group, four stopped the diet due to adverse events from the fish oil supplement. One participant had grade 2 constipation, bloating and flatulence, and another had grade 2 diarrhea, eructation and gastrointestinal discomfort.
Researchers did not observe any differences in tumor grade, tumor length, Decipher 22 score, testosterone or PSA in the intervention group.
However, they did see a significant decrease in triglyceride levels as well as in cytokine macrophage colony-stimulating factor-1.
“Our study was not powered for these secondary endpoints,” Aronson said.
Long-term phase 3 trials are needed to evaluate how the diet affects these other endpoints.
Aronson and colleagues have already begun work investigating the mechanisms behind the Ki-67 reduction.
Aronson said he is “super interested” in how the dietary changes and fish oil supplements impact men with advanced prostate cancers.
“Advanced prostate cancer does not have an intense T-cell infiltration,” Aronson said. “What you do see filling up the prostate cancer metastasis is M2 macrophages. M2 macrophages help with normal tissue healing. For a number of cancers, the cancers recruit the patient’s macrophages into the cancer itself, and then the cancer converts the macrophage to an M2 macrophage, which can help promote the cancer’s progression and spread.
"If you look at metastases in a patient with prostate cancer, there’s a large number of these M2 macrophages in there, and we’ve actually found that when you raise the omega-3 level and lower the omega-6 level, there is inhibition of M2 macrophages,” he added.
Aronson emphasized taking supplements like fish oil without lowering omega-6 and raising omega-3 have not yielded any substantial results in men with prostate cancer.
“It’s remarkable how patients, once they have that diagnosis of cancer, are able to change their diet and lifestyle,” Aronson said. “It is dramatic across all socioeconomic statuses. I do think our study is going to remain an important finding over time.”
For more information:
William J. Aronson, MD, can be reached at waronson@ucla.edu.
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