Weight Loss, Pathological Changes, and Inflammatory Effects from a Short-Term Ketogenic Diet in Overweight and Obese Men with Untreated Prostate Cancer on Active Surveillance.

Background and aims: Active Surveillance (AS) is a favored strategy for the management of indolent prostate cancers (PCs). Overweight and obese men harbor an increased risk of cancer progression during AS. We aim to prospectively evaluate the feasibility and outcomes of a ketogenic diet (KD) weight-loss intervention in overweight men with PC.

Materials and methods: Men with PC and a BMI > 25 kg/m² undergoing AS were placed on an 8-week ad libitum KD program before a scheduled surveillance biopsy to assess the impact on clinical grade group (CGG). Blood ketone levels were tracked to ensure compliance. BMI, PSA, and inflammatory marker data (TNF-α, TNFR1, TNFR2, sICAM-1, sVCAM-1, IL-6, IL1-RA, CRP, and SAA) were collected before and after the KD intervention. A Shapiro-Wilk test was performed to assess the normality of all continuous study variables. Paired t-tests and Wilcoxon rank sum tests were utilized to compare normally and non-normally distributed study outcomes, respectively.

Results: Ten AS patients aged 62.1 (±5.4) years were enrolled with an average BMI of 31.7 kg/m² (±11.8). Post-KD intervention mean blood ketone levels were 0.32 (±0.12) mmol/L with a mean BMI reduction of 7.4% (p < 0.0003). There were no meaningful changes in PSA or inflammatory biomarkers (p > 0.05). Nine patients completed re-biopsy following a KD with four patients showing no evidence of cancer; one downgraded to a lower CGG; two had unchanged CGG scores; and two had higher CGG scores compared to baseline.

Conclusions: Short-term KD interventions for BMI reduction are feasible in men undergoing AS for PC and may result in favorable pathological effects without inflammatory marker changes. Larger studies with longer follow-up are needed to explore whether KD-induced weight loss can improve clinical outcomes with AS in PC.