Page 14 - CUA2019 Abstracts - Oncology-Prostate

2019 CUA Abstracts

MP-10.7 standardized uptake value (SUVmax) between patients with PI likely
Leisure-time physical activity and circulating insulin-like benign, suspicious for CaP, having no PSA testing, and CaP. Only 40.1%
growth factor-1 level in men at high-risk of prostate cancer: of patients underwent PSA testing within six months of PI identification,
The BIOCaPPE-GRéPEC study although 64.1% eventually underwent PSA testing or obtained a tissue
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Lamoussa Diabate , Laurence Bettan , Molière Nguile-Makao , Hélène diagnosis. Six patients underwent a dedicated prostate multiparametric
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Hovington , Pierre Julien , Fred Saad , Michel Carmel , Armen Aprikian , magnetic resonance imaging (mpMRI), of which one identified Gleason
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BIOCaPPE Network 1,2,3,4 , Yves Fradet , Vincent Fradet 1 3+4 CaP. Twenty-seven (79.4%) of the patients diagnosed with CaP had
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1 CHU de Québec Research Centre–Université Laval, Québec City, QC, intermediate-risk, high-risk, or metastatic disease. Many patients with a
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Canada; CHUM Research Centre, Montréal, QC, Canada; CHUS PI were diagnosed with CaP within one year of the FDG PET; however,
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Research Centre, Sherbrooke, QC, Canada; CUSM Research Institute, 15 (44.1%) patients had delayed PSA testing and subsequently a delayed
Montréal, QC, Canada diagnosis of CaP.
Introduction: In Canada, 58 men are diagnosed with prostate cancer Conclusions: A FDG PET PI may represent clinically significant CaP. We
(PCa) every day. Physical activity is associated, at least in part, with PCa recommend patients with a PI be referred for urological assessment, allow-
risk in this population. The preventive role of physical activity remains ing for timely investigation if indicated.
to be clarified but likely implies modulation of biomarkers that could be Reference
used to risk-stratify PCa. We believe that physical activity is associated 1. Sone Y, Sobajima A, Kawachi T, et al. Ability of 18-fludeoxyglucose
with circulating insulin-like growth factor-1 (IGF-1) level, which in turn, positron emission tomography/CT to detect incidental cancer. Br J
may influence the risk of PCa. In this study, we aimed at assessing the Radiol 2014;87:20140030-7. https://doi.org/10.1259/bjr.20140030
relationship between leisure-time physical activity (LTPA) and IGF-1 level
in men at high risk of developing PCa. MP-10.9
Methods: Study participants are men at high risk of PCa currently enrolled Prostate cancer-derived anti-GRP78 autoantibodies compromise
in a prospective, multicentre clinical trial (BIOCaPPE_GRéPEC trial). This the blood-brain barrier and accelerate atherosclerosis progression
trial aims at evaluating the role of environmental exposures on PCa devel- in vivo
opment. At study baseline, LTPA score was calculated using the validated Ali Al-Hashimi , Kevin Won , Richard Austin , Bobby Shayegan 1
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Godin Leisure-Time Exercise Questionnaire. This LTPA score was used to 1 Department of Surgery and Medicine, McMaster University, Hamilton,
categorize participants into active or inactive groups. IGF-1 level was also ON, Canada
collected at study baseline. The association between LTPA score and IGF-1 Introduction: Pathological conditions of prostate cancer (PCa) drive the
level was assessed using multivariate linear regression. translocation of the endoplasmic reticulum-resident chaperone, GRP78,
Results: The mean age of the first 1067 participants was 63 years old to the cell surface (cs), where it acts as an antigenic protein with signal-
(±7) and the mean circulating IGF-1 level was 110 ng/mL (±30). Most ing properties. In PCa, csGRP78 drives the production of anti-GRP78
participants were active (n=743, 69.6%). The multivariable model was autoantibodies (AutoAbs) that engage csGRP78 and promote PCa sur-
adjusted for confounding factors (age, alcohol, body mass index, waist cir- vival/progression. New studies now demonstrate csGRP78 expression on
cumference, self-rated health, education level, marital status) and showed endothelial cells (EC) that line the arterial vasculature and the blood-brain
that inactive participants had a higher IGF-1 level compared to active barrier (BBB), suggesting that these AutoAbs can affect other systems in
participants (β=-4.73, I 95% confidence interval -8.86;-0.60; p=0.02). the body. The engagement of anti-GRP78 AutoAbs to csGRP78 on EC
Conclusions: LTPA was inversely associated with circulating IGF-1 level can contribute to EC dysfunction that can promote atherosclerosis and
among men at high risk of PCa. Our data support IGF-1 level as a putative compromise the integrity of the BBB.
biomarker to stratify PCa development risk and warrant further analyses. Methods: Anti-GRP78 AutoAbs were purified from PCa patients (St.
IGF-1 should also be considered an intermediate factor in epidemiologi- Joseph’s Healthcare Hamilton); human aortic EC and the ApoE mouse
-/-
cal studies. model were used for in vitro and in vivo investigations, respectively. EC
or mice were treated with anti-GRP78 AutoAbs or IgG control (60 μg/
MP-10.8 mL); EC dysfunction was investigated by measuring attachment protein
18-Fluoro-2-deoxy-D-glucose positron emission tomography/ expression in vitro. In vivo evaluation was carried out by studying ath-
computed tomography-detected incidentalomas of the prostate erosclerotic plaque progression (immunohistochemistry; aorta); the BBB
Miles Mannas , Taeweon Lee , Maral Pourghiasian , Don Wilson , Peter integrity was examined using the Evans Blue dye.
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C. Black . Results: Mice injected with anti-GRP78 AutoAbs demonstrated larger
1 Urologic Sciences, University of British Columbia, Vancouver, BC, atherosclerotic plaque volume and hallmarks of a leaky BBB. In terms
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Canada; Functional Imaging, BC Cancer, Vancouver, Canada; Vancouver of a mechanism, in vitro studies demonstrated that treating EC with
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Prostate Centre, Vancouver, BC, Canada anti-GRP78 AutoAbs resulted in activation of the NFκB pathway that led
Introduction: Prostate incidentalomas (PI) are prostatic lesions discovered by to increased expression of attachment proteins. All these effects were
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imaging patients without a known history of prostatic cancer (CaP). Fluoro- reversed by using a recombinant molecule that interferes with the binding
2-deoxy-D-glucose positron emission tomography/computed tomography of the AutoAb to csGRP78.
(FDG PET) is an imaging modality used to diagnose, stage, and assess Conclusions: We have identified anti-GRP78 AutoAb as a driver of EC dys-
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response to treatment for many cancers. FDG PET is not routinely used in function that promotes atherosclerotic plaque progression and damage to the
the diagnosis or management of CaP. We aimed to describe the incidence, BBB. Our results indicate that interfering with anti-GRP78 AutoAb:csGRP78
characteristics, rate of malignancy, and management of PI. complex can reverse the pathological effects of the AutoAbs.
Methods: A retrospective review was conducted of FDG PET performed
on male patients between 2005 and 2017 to identify patients with PI.
Demographic, clinical data, investigations, and management were col-
lected from regional databases and outcomes were assessed.
Results: A total of 31 019 FDG PET scans were performed revealing 309
(1%) patients with a PI. Based on age-standardized prostate-specific anti-
gen (PSA) (<2.5 ng/ml if <50 years, <3.5 ng/ml if 50–59 years, <4.5 ng/
ml if 60–69 years, and <6.5 ng/ml if >70 years) or tissue diagnosis, 130
(42.1%) patients PI were deemed likely benign, 34 (11.0%) suspicious
for CaP, 77 (24.9%) had no PSA testing, and 33 (11.0%) were diag-
nosed with CaP. T-testing showed no differences in age or maximum
S150 CUAJ • June 2019 • Volume 13, Issue 6(Suppl5)