Page 15 - CUA2019 Abstracts - Oncology-Prostate

Poster session 10: Prostate Cancer II

MP-10.10 also determined the effect of autophagy over-activation (rapamycin) and
Relationship between metabolic syndrome, physical activity, and inhibition (bafilomycin A1 and CRISPR Atg5/16L1) on the survival of PCa
prostate-specific antigen levels, prostate volume, and subsequent cells to olaparib.
cancer in men at high risk of prostate cancer with a first negative Results: Our results show that PC3 and DU145 have a higher basal level
prostate biopsy of autophagy compare to other cell lines. The double-tagged LC3 cells
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Jonathan Fadel , Pierre Douville , Laurence Bettan , Alain Bergeron , show that olaparib increases the autophagic flux in PC3 only. These cells
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Hélène Hovington , François Meyer , Isabelle Bairati, Fred Saad , Armen are more resistant to olaparib. Rapamycin reduces sensitivity to PARPi
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G. Aprikian , Michel Carmel , Vincent Fradet , BIOCaPPE Network , for all cell lines. We observed a modification of PC3 and DU145 cells
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Yves Fradet 1 morphology after PARPi treatments.
1 CHU de Québec Research Centre, Université Laval, Québec City, QC, Conclusions: The autophagic flux seems to play in the development
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Canada; CHUM Research Centre (CRCHUM), Université de Montréal, of resistance. We will intend to determine how this resistance is reg-
Montréal, QC, Canada; Research Institute of McGill Hospital Centre, ulated. We will measure the role of senescence in the sensitivity to
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McGill University, Montréal, QC, Canada; CHU de Sherbrooke Research PARPi. Understanding the role of autophagy in PCa progression may
Centre, Université de Sherbrooke, Sherbrooke, QC, Canada lead to strategies to inhibit this resistance mechanism. Combinations of
Introduction: Growing data show an association between metabolic syn- autophagy inhibitors with PARPi may increase the durability of response
drome and prostate cancer. The aims of this study were to evaluate the and further improve outcomes of patients with aggressive PCa.
relationship between metabolic syndrome and physical activity on pros-
tate volume, prostate-specific antigen (PSA) levels, and the occurrence MP-10.13
of prostate cancer on subsequent biopsy in men with a recent negative Liquid biopsy in prostate cancer: Novel predictive test for
first prostate biopsy. screening and treatment response
Methods: We recruited prospectively, in a multicentre, observational Michael A. Di Lena , Christopher R. Mueller , D. Robert Siemens 1
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study, a cohort of 669 men at high risk of prostate cancer, who under- 1 Urology, Queen’s University, Kingston, ON, Canada
went a first prostate biopsy with a negative result. Evaluation of metabolic Introduction: The use of prostate-specific antigen (PSA) as a screening tool
syndrome was established with at least three criteria from the following: has grown increasingly controversial, secondary to poor test characteris-
waist circumference above 102 cm, low high-density lipoprotein (HDL) tics. There is a need for a better prostate cancer detection tool, one that is
cholesterol level, and medication taken to treat high blood pressure, dys- able to differentiate aggressive from indolent cancers and that has some
lipidemia, and diabetes. Physical activity was evaluated with the Godin predictive value. Research is looking into methylation profiles of urologic
Leisure-Time Exercise questionnaire and data collected from biobanked tumours in hopes that identification can assist in cancer prognosis, diag-
blood samples, medical questionnaires, prostate ultrasound, and biopsy nosis, and treatment. This information can be obtained non-invasively
results. from patients’ serum as part of a “liquid biopsy.” This study looks at DNA
Results: A total of 143 patients presented a metabolic syndrome (21.38%). methylation patterns as gathered from blood samples in men with prostate
Spearman correlation, Box plot, Chi-square, and Kruskal-Wallis non- cancer and assesses its ability to replace PSA for primary screening, for
parametric tests were used for analysis. Results showed no association active surveillance, and for management of men on androgen-depravation
between physical activity and/or metabolic syndrome with PSA levels therapy (ADT).
and prostate volume. However, prostate volume was significantly higher Methods: Blood samples were collected from 20 men with prostate cancer
with increasing age, body weight, and body mass index (p<0.0001). We on ADT treatment at a single academic centre. Ten of these men had stable
observed 52 new cancer patients over two years’ followup and no changes PSA on ADT and 10 had PSA progression on ADT. DNA methylation of
were noticed in relation to the level of physical activity and metabolic the patients’ serum was assessed at 27 specific gene loci. Relevant patient
syndrome. However, PSA levels were slightly higher at initial evaluation demographics were obtained and correlated with the circulating DNA
for patients who developed cancer (p=0.0323). analysis. Assay performance was characterized using area under the curve
Conclusions: We found a significant and strong relationship between age, (AUC) analysis for overall sensitivity, specificity, and likelihood ratio.
obesity, and prostate volume. However, metabolic syndrome criteria and Results: Twenty male patients were included in this study, half of whom
physical activity didn’t show any relationship with prostate volume and whose PSA remained stable on ADT and half who were progressing on
PSA levels. PSA level at first biopsy shows an increased risk of cancer on ADT. A total of 27 gene sites were analyzed to assess for specific methyla-
subsequent biopsies despite the limited number of events so far. tion patterns. Overall, the test was shown to have excellent performance
as a predictor of PSA progression on ADT, with an AUC of 0.9821, a
MP-10.11 sensitivity of 100%, and a specificity of 85%. This index was not found
Impact of autophagy in the development of PARP inhibitor to be correlated with PSA levels or PSA doubling times as would be
resistance in prostate cancer expected for an independent marker.
Maxime Cahuzac 1,2,3 , Benjamin Péant , Anne-Marie Mes-Masson 1,2,3 , Conclusions: These results demonstrate the ability of methylation markers
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Fred Saad 2,3,4 . to provide deep insight into prostate cancer development and produce
1 Biologie Moléculaire, Université de Montréal, Montréal, QC, Canada; diagnostic and prognostic information that would be vital for manage-
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2 Institut du Cancer de Montréal, Montréal, QC, Canada; Centre de ment of the disease.
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Recherche du CHUM, Montréal, QC, Canada; Chirurgie, Université de
Montréal, Montréal, QC, Canada MP-10.14
Introduction: Prostate cancer (PCa) is the most frequently diagnosed can- Early oncological and functional outcomes of magnetic
cer in North American men. Over time, one in four men develop a resis- resonance-guided focal high-intensity focused ultrasound for
tance against actual compound, making it difficult to treat. Recently, new intermediate-risk prostate cancer
therapies like PARP inhibitors (PARPi) have been tested in clinic for PCa. Nathan Perlis , Guan Hee Tan , Antonio Finelli , Eugen Hlasney , Robert
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Several studies show that they ameliorate life expectancy but resistance Hamilton , Alexandre Zlotta , Girish S. Kulkarni , Kateri Corr , Rosanna
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can appear. Autophagy is knows to induce resistance to different treat- Chan , Stuart McCluskey , Walter Kucharczyk , Sangeet Ghai 2
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ments in cancers. Actually, no studies have yet shown the link between 1 Division of Urology, University Health Network, Toronto, ON, Canada;
autophagy and PARPi resistance in PCa. The goal of this project is to 2 Joint Department of Medical Imaging, University Health Network,
determine if autophagy can promote resistance to PARPi in PCa cell lines. Toronto, ON, Canada; Department of Anesthesia and Pain Management,
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Methods: Autophagy has been measured in different PCa cell lines University Health Network, Toronto, ON, Canada
(LNCaP, 22Rv1, PC3, and DU145), after treatment with PARPi (olaparib) Introduction: Focal ablation with high intensity focused ultrasound (HIFU)
by Western blot. To confirm our results, we established LC3 double-tagged reduces complications with promising oncological results. Magnetic reso-
cell lines and observed autophagy using confocal microscopy. We have nance image (MRI)-guided HIFU (MRgFUS) using MR-thermometry allows
CUAJ • June 2019 • Volume 13, Issue 6(Suppl5) S151