Obesity, Metabolic Health and Prostate Cancer version 1.0
Research type
Research Study
Full title
Obesity, metabolic health and prostate cancer; leveraging radiogenomics data to predict outcomes
IRAS ID
276857
Contact name
Emma H. Allott
Contact email
Sponsor organisation
Queen's University Belfast
Duration of Study in the UK
0 years, 11 months, 31 days
Research summary
Research Summary: Obesity is associated with increased risk of aggressive prostate cancer and higher prostate cancer-specific mortality, however the mechanisms responsible for this link are incompletely understood. Periprostatic adipose tissue (PPAT), a type of visceral fat that surrounds the prostate is proposed to contribute to prostate cancer etiology given its close proximity. Previous studies have demonstrated that elevated PPAT area is associated with higher tumour grade but the association of PPAT with long-term prostate cancer-specific outcomes has not been studied.
This retrospective study will investigate the role of abdominal and periprostatic obesity, and metabolic health in prostate cancer outcomes in men with prostate cancer, treated with radiotherapy at Northern Ireland Cancer Centre between 2005 and 2009. Standard image analysis will be used to quantify subcutaneous and visceral (both abdominal and periprostatic) adipose tissue, waist circumference, and skeletal muscle area and attenuation (muscle density) from radiation planning CT scans. An advanced image analysis method called radiomics will be applied to the PPAT to extract quantitative and qualitative features which may provide additional information on the composition and characteristics of this fat type. We will examine the association of these measures of obesity with clinical tumour characteristics and prostate cancer-specific outcomes such as recurrence-free and metastasis-free survival, and all-cause mortality, overall and stratified by androgen deprivation therapy receipt. Lastly, we will examine the associations between PPAT characteristics (quantity and radiomics features) with tumour gene expression data. Furthermore, bioinformatics analysis of tumour biopsy gene expression will aim to identify novel pathways linking periprostatic obesity to poor prostate cancer outcomes. In future, this could enable identification of individuals with a periprostatic obesity subtype at heightened risk of disease progression using routine CT scans. This could identify patients who may benefit from additional treatment or inform secondary prevention efforts such as dietary or lifestyle interventions.Summary of Results:
Obesity may increase risk of aggressive prostate cancer, and the location of fat within the body may play an important role. We wanted to understand whether the fat that sits around the prostate — known as periprostatic adipose tissue — plays a role in how aggressive prostate cancer becomes. Although earlier studies have suggested a link, they often defined this fat in a variety of different ways and rarely explored how it might influence the biology of the tumour itself. To address this, we measured both the amount and the density of fat inside the pelvis, using scans from 316 men treated with radiation therapy for prostate cancer. We measured the fat immediately surrounding the prostate as well as total amount of fat in the pelvis, and we also assessed waist size and different types of abdominal or trunk fat in a subset of the men. We then examined whether these fat measurements were related to tumour grade, gene activity within the tumour, and long-term outcomes.Our study found that men with a greater overall amount of fat inside the pelvis were more likely to have more aggressive prostate cancer. In addition, fat located closest to the prostate tended to be denser in men with higher grade tumours, suggesting that the quality of the fat, not just the quantity, may matter. Waist size was also linked to more aggressive disease, even though specific types of fat within the abdomen or trunk were not. When we looked at tumour gene expression, we found that men with higher levels of pelvic fat showed increased activity in pathways related to adipocytokine signalling — a way in which fat tissue can communicate with and potentially influence cancer cells. None of the fat measurements predicted prostate cancer outcomes such as recurrence or death from the disease, but men with a higher ratio of organ-associated fat in the trunk had a greater risk of a more premature death.
Overall, our findings suggest that having more fat within the pelvis is associated with more aggressive prostate cancer. The links between PPAT density, tumour grade, and fat related signalling pathways raise the possibility that an increased amount of fat tissue surrounding the prostate may actively contribute to tumour behaviour rather than simply being a bystander.
REC name
West Midlands - South Birmingham Research Ethics Committee
REC reference
20/WM/0060
Date of REC Opinion
17 Feb 2020
REC opinion
Favourable Opinion