We very much appreciate the letter to the editor by Wendy Demark-Wahnefried comparing and contrasting our respective pre-prostatectomy weight loss intervention trials [1, 2]. Due to the overlap in the publications, we did not have access to their trial results when we wrote our manuscript. While our study found no significant difference in the prostate cancer epithelium Ki67 index in the radical prostatectomy tissue in the weight loss (WL) intervention compared to control (WL 6.7 ± 5.1, control 5.8 ± 3.0), Demark-Wahnefried et al. found higher Ki67 staining in the WL: 5.0 (2.5; 10.0) vs, control: 0 (0.0; 2.5) group [2]. In addition, they observed an increase in Ki67 staining from biopsy tissue to surgery in patients experiencing weight loss, but not in controls. They also noted upregulation of genes associated with transcription, proliferation, migration, and invasion in a subset of patients. Noteworthy is that our intervention resulted in significant between group differences in weight loss, whereas this was not the case in the Demark-Wahnefried et al. trial. In both of our trials, the Ki-67 index was a secondary endpoint. Demark-Wahnefried et al. commented that they disagreed with our statement that studies incorporating more intensive weight loss over a longer time period are warranted, and they suggested further studies should examine the optimal rate of weight loss and role of physical activity influencing tumor biology.
In our view, the preclinical studies on caloric restriction, combined with the data on obesity and prostate cancer aggressiveness continue to support weight loss intervention trials. Given that our two trials were both short-term biomarker based studies examining secondary and exploratory endpoints, we would exercise caution in concluding that intensive weight loss may be harmful to our prostate cancer patients. We wholeheartedly agree with Demark-Wahnefried et al. that future studies are warranted, and we support a full range of interventions. Other experimental designs of great interest will be studying dietary interventions in men with prostate cancer on active surveillance receiving serial same-site prostate biopsies using fusion biopsy units with advanced technology. We are conducting a trial, using this experimental design, comparing a fish oil supplemented diet to a control group (NCT02176902). We would expect longer-term trials to yield highly useful information as we move forward in this important field of study. The study team of Demark-Wahnefried has pioneered the field of nutritional approaches for cancer, and continues to be on the forefront. We very much appreciate their interest in and comments regarding our article.
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