Page 57 - CUA 2020_Onco_Prostate

Moderated Posters 10: Prostate Cancer II

SOC group was identified from the pan-Canadian Prostate Cancer Risk Conclusions: This is the largest report on real-world use of degarelix in
Stratification (ProCaRS) database treated between 1994 and 2008. Men PCa patients. Current use of degarelix in clinical practice provides optimal
were matched using propensity score-based pre-radiation characteristics: T control in PCa patients.
age, prostate-specific antigen (PSA), Gleason score, T-stage, and ADT
use. Primary endpoints were overall survival (OS) and cancer-specific MP-10.12
survival (CSS).
Results: A total of 982 men developed biochemical failure in the SOC Development of a panel of circulating DNA methylation
group; 186 men were treated with sCT and 113 men with sHIFU. Median biomarkers predictive of treatment response in castration-
followup from radiation treatment was 11.6, 25.1, and 14.3 years fol- resistant prostate cancer 3 4 5
1,2
lowing external beam radiation therapy (EBRT), sCT, and sHIFU, respec- Madonna Peter , Misha Bilenky , Ruth Isserlin , Aaron Hansen , Gary
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5,6
1,2,8
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tively. In the first comparison, the propensity-matched cohorts consisted Bader , Martin Hirst , Anthony Joshua , Neil E. Fleshner , Bharati Bapat
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of 196 EBRT vs. 98 sCT. Prostate cancer-specific deaths occurred in 24 Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto,
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of 80 deaths in the sCT group and 49 of 78 deaths in the SOC group. ON, Canada; Department of Laboratory Medicine and Pathobiology,
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Propensity-matched analysis showed significant benefit in CSS (p<0.001) University of Toronto, Toronto, ON, Canada; Canada’s Michael
and OS (p<0.001) favoring sCT. In the second comparison, the propensity- Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC,
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matched cohort consisted of 177 SOC vs. 59 sHIFU. There were 52 Canada; Terrence Donnelly Centre for Cellular and Biomolecular
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deaths (31 prostate cancer) for SOC vs. 18 deaths (nine prostate cancer) Research, University of Toronto, Toronto, ON, Canada; Division of
for sHIFU. There were no significant differences in CSS or OS, likely Medical Oncology and Hematology, Princess Margaret Cancer Centre,
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attributed to shorter followup of sHIFU cohort. Toronto, ON, Canada; Department of Medical Oncology, Kinghorn
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Conclusions: In select men with radio-recurrent prostate cancer, further Cancer Centre, Darlinghurst, Australia; Departments of Surgery and
local treatment may lead to benefits in CSS and OS. Careful patient selec- Surgical Oncology, Division of Urology, University Health Network,
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tion remains critical in the decision-making process of salvage therapy. Toronto, ON, Canada; Department of Pathology, University Health
Network, Toronto, ON, Canada
Introduction: Androgen-targeting agents continue to be a major therapeu-
MP-10.11 tic avenue for castration-resistant prostate cancer (CRPC). However, de
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Real-world testosterone suppression outcomes in a Canadian novo or therapy-driven resistance is inevitable, especially among those
population of prostate cancer patients treated with degarelix patients that develop neuroendocrine-CRPC (NE-CRPC). Biomarkers
Miran Kenk , Virna Cepero , Lorne E. Aaron , Bobby Shayegan , Richard that identify this subgroup upfront are needed to guide optimal therapy
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Sioufi , Anil Kapoor , Victor Mak , Zeid Mohamedali , Jeffrey M. Spodek , sequences. Circulating cell-free DNA (cfDNA) can harbor tumor-derived
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Paul Jr. Ouellette , Neil T. Dwyer , George Vrabec , Lee M. Jonat , Sergio mutations (i.e., androgen receptor) associated with treatment resistance.
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Dalla Nora , Neil E. Fleshner 1 Beyond genomic aberrations, changes in DNA methylation are also a
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1 Surgical Oncology, Princess Margaret Cancer Centre, University major hallmark of prostate cancer. In this study, we assessed genome-
Health Network, Toronto, ON, Canada; Ferring Pharmaceuticals, North wide changes in the cfDNA methylome to identify markers of treatment
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York, ON, Canada; Service d’ Urologie, Hôpital Charles LeMoyne, response.
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Longueuil, QC, Canada; Institute of Urology, Juravinski Cancer Centre, Methods: We collected 45 blood samples from 16 metastatic (m) CRPC
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Hamilton, ON, Canada; Hôpital Anna Laberge, Châteauguay, QC, patients receiving either enzalutamide or abiraterone acetate. We ana-
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Canada; Department of Surgery, Mackenzie Health, Richmond Hill, lyzed sequentially collected plasma cfDNA samples, from prior to treat-
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ON, Canada; Department of Urological Sciences, University of British ment initiation (baseline), 12 weeks during treatment, and upon clinical
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Columbia, Port Alberni, BC, Canada; Scarborough Health Network, progression. We used methylated cfDNA immunoprecipitation sequenc-
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Scarborough, ON, Canada; Centre de recherche TheraDev, Granby, QC, ing (cfMeDIP-seq) and developed a novel analysis pipeline that identifies
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Canada; The Moncton Hospital, Moncton, NB, Canada; Abbotsford changes in methylation between treatment visits.
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Regional Hospital and Cancer Centre, Abbotsford, ON, Canada; Royal Results: Overall, cfDNA harbors changes in well-established prostate
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Inland Hospital, Kamloops, BC, Canada cancer methylation markers and alterations in key pathways, such as Wnt
Acknowledgements: We gratefully acknowledge doctors, nurses and clini- and neuronal development. Patients that maintained methylation changes
cal personnel from all centers participating in this program; also Dan Toma from baseline to week 12 and until progression tended to have a longer
(Pharmec) for data collection and processing time to clinical progression (TTP). Importantly, we observed that markers
Introduction: Testosterone (T) control is key for advanced prostate cancer associated with NE-CRPC could be detected prior to initiating treatment
(PCa) patients. Data suggest that lower T levels correlate with better out- and were correlated with a faster TTP. Currently, we are developing a
comes. While the traditional target is T ≤1.7 nmol/L, data support a cutoff targeted panel to further validate these candidate markers.
of T ≤0.7 nmol/L. Degarelix showed fast and sustained T suppression in Conclusions: This study highlights the potential of monitoring the cfDNA
clinical studies. However, little data are available from its real-world methylome during therapy in mCRPC. Our findings also suggest that
use. Here, we report T suppression outcomes in a prospective cohort of detection of NE-CRPC-associated methylation signatures in earlier stages
Canadian patients. of treatment may serve as predictive markers.
Methods: A prospective survey-based program assessing real-world use of References
degarelix was conducted in 88 centers across Canada from April 2016 to 1. Saad F, Aprikian A, Finelli A, et al. 2019 Canadian Urological
April 2019. Aggregate data were collected monthly, at treatment initiation Association (CUA)-Canadian Uro Oncology Group (CUOG) guide-
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>0.7 to ≤1.7 nmol/L, T >1.7 nmol/L. Can Urol Assoc J 2019;13:307-14. https://doi.org/10.5489/cuaj.6136
Results: Data from 1340 initial and 17321 followup visits were collected. 2. Vandekerkhove G, Chi KN, Wyatt AW. Clinical utility of emerg-
At degarelix initiation, 72% of patients were ≥70 years; 58% were newly ing liquid biomarkers in advanced prostate cancer. Cancer
diagnosed, 20% had prostate-specific antigen (PSA) rise after failure Genet 2018;228-229:151-8. https://doi.org/10.1016/j.cancer-
of local therapy, 13% had PSA rise on luteinizing hormone releasing gen.2017.08.003
hormone agonist, and 9% were reported as other/unknown; 46% were 3. Massie CE, Mills IG, Lynch AG. The importance of DNA methyla-
metastatic. During followup, 10 656 T measurements were obtained on tion in prostate cancer development. J Steroid Biochem Mol Biol
degarelix. Of these, 99% had T ≤1.7 nmol/L, including 81% with T ≤0.7 2017;166:1-15. https://doi.org/10.1016/j.jsbmb.2016.04.009
nmol/L; 0.9% had T >1.7 nmol/L. Of 3095 T measurements on degarelix
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CUAJ • June 2020 • Volume 14, Issue 6(Suppl2) S141