An extremely low-carbohydrate diet could have a modest effect on slowing tumor growth in men with recurrent prostate cancer in addition to producing significant weight loss, a preliminary study has found.

Findings from the pilot clinical trial, co-led by Cedars-Sinai and Duke University, were published recently in Clinical Cancer Research, a journal of the American Association for Cancer Research. The weight loss finding is notable because numerous studies have linked obesity to more aggressive prostate cancer, the investigators said.

Prostate cancer is the second most common type of cancer in U.S. men and the second-leading cause of cancer deaths in men. The American Cancer Society estimates that about 192,000 new cases will be reported in 2020, and 33,330 deaths will occur.

The clinical trial initially focused on 57 patients who had rising levels of a protein called prostate-specific antigen (PSA) in their blood, an indicator of tumor growth, after being treated with surgery or radiation for localized prostate cancer. One group of patients was randomly assigned to follow an extremely low-carbohydrate diet of equal to or less than 20 grams of carbohydrates per day, and the other group was assigned to make no diet changes. The investigators then measured how quickly the patients' PSA levels rose over six months.

The trial ended early, with 45 patients finishing the study, after interim results suggested it was unlikely to achieve statistical significance for differences in the  rate of PSA rise  between the two groups. However, when they re-examined the data, this time controlling for factors such as the type of prior cancer treatment, baseline PSA,  the rate of PSA rise before the study started and the natural rise in PSA levels caused by weight loss, they noted significant differences.

"Our re-examination showed PSA levels in patients who followed the extremely low carbohydrate diet rose more slowly than did levels in patients who did not follow the diet," said Stephen J. Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle and the Warschaw, Robertson, Law Families Chair in Prostate Cancer at Cedars-Sinai Cancer. "In addition, over six months, men on the low carbohydrate died lost an average of 26 pounds per person compared with one pound weight loss in the control group, without significant adverse effects on prostate cancer growth or overall health."

Freedland is professor of Surgery and the study's first and corresponding author. The senior author was Pao-Hwa Lin, PhD, associate professor of Medicine at Duke University School of Medicine in Durham, North Carolina.

The study's findings are preliminary, Freedland emphasized. "We need to conduct clinical trials with larger numbers of patients over longer periods of time to confirm the value of an extremely low carbohydrate diet in controlling recurrent prostate cancer," he said.

As one step toward that goal, the research team is examining prostate cancer tissues, collected after patients followed a low-carb diet for six months, to understand the effect on tumor biology. "Potentially, diet could be one tool to delay the time until a patient might need to start hormonal therapy," Freedland said.

Conflicts of interest: A.J. Armstrong reports receiving other commercial research support from Astellas, Janssen, and Pfizer and speakers bureau honoraria from Dendreon and Bayer. H. Sandler is an employee/paid consultant for Janssen and holds ownership interest (including patents) in Radiogel. No potential conflicts of interest were disclosed by the other authors.

Funding: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number NCI K24 CA160653 and by the Hartford Foundation.

DOI: 10.1158/1078-0432.CCR-19-3873