Global Congress on Prostate Cancer: abstract booklet by mirrorsofmedicine

8th edition

Abstract book VIRTUAL MEETING

10 to 15 October 2020

Live 14 October prosca.org

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ORGANISING COMMITTEE OF THE CONGRESS Amit Bahl, Bristol Haematology & Oncology Centre, Bristol, UK Piotr Chlosta, Jagiellonian University, Krakow, Poland Piotr Milecki, Wielkopolskie Oncology Centre, Poznan, Poland Piet Ost, Ghent University Hospital, Ghent, Belgium Iwona Skoneczna, Saint Elizabeth’s Hospital, Warsaw, Poland Ash Tewari, Icahn School of Medicine at Mount Sinai, New York, USA Bertrand Tombal, University Hospital Saint-Luc, Brussels, Belgium Piotr Wysocki, Jagiellonian University, Krakow, Poland

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ABSTRACTS OF THE GLOBAL CONGRESS ON PROSTATE CANCER, 8TH EDITION VIRTUAL MEETING, 10 TO 15 OCTOBER 2020

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PROSTATE CANCER IN MARONI AREA, FRENCH GUIANA: THE LACK OF ACCESS TO HEALTH FACILITIES PENALIZES PATIENTS

ABIRATERONE ACETATE WITHDRAWAL SYNDROME IN METASTATIC CASTRATIONRESISTANT PROSTATE CANCER (MCRPC)

Jean-Pierre Droz, Medicine, Centre Hospitalier Ouest Guyane, French Guyana Bill Wankpo, French Guyana, CHOG, French Guyana A Mésange X Coulaud

Pedro Miguel Duarte Simões, Medical Oncology Department, Hospital Beatriz Ângelo, Portugal Carlota Sofia Vieira Baptista, Oncologia Médica, Hospital Beatriz Ângelo, Portugal Luísa Leal-Costa, Oncology, Hospital Beatriz Ângelo, Portugal João Paulo Baptista Godinho, Oncology, Hospital Beatriz Ângelo, Portugal Ana Faria Miriam Capoulas José Alberto Teixeira José Luís Passos Coelho

Introduction & objectives: Treatment of prostate cancer in French Guiana is limited by the absence of radiotherapy, the lack of oncology specialists, the distances between the 3 territory hospitals and often the patients’ precarity (neither administrative rights nor health insurance coverage). A urology center is based in Kourou. Maroni area is characterized by cultural diversity, social precarity, proximity of Surinam, presence of illegal gold panning sites. It is 200 and 250 km far from Kourou and Cayenne, respectively.

Introduction & objectives: Abiraterone acetate (AA) has established efficacy in mCRPC. AA withdrawal syndrome (AAWS) is characterized by a temporary decrease in PSA levels after AA cessation, and occurs in 6%-23% of patients, with variable clinical response. Its mechanism and clinical significance are still unclear. We report our center experience with AAWS in patients with mCRPC.

The study objective is to determine whether these factors may influence prostate cancer management in this area. Materials & methods: We reviewed the prospective hospital data base of 459 cancer patients (2015-2019) of whom 56 had prostate cancer. We focused on patients’ characteristics, cancer status and treatment access. We used EXCEL® software functions. The data base was declared according to European GDPR guidelines.

Materials & Methods: This is an observational, retrospective, single-center cohort study of patients with mCRPC treated with AA + prednisolone. Patients with AAWS, defined by any decrease in PSA level after AA discontinuation, were included. Clinical data and survival outcomes were collected from electronic medical records.

Results: Patients: median age 72 (50-94) years; 27 patients were administratively in good standing, 29 had no rights; 25 patients had no health insurance coverage (11 obtained medical aid after 3 months). Thirty-two patients were maroons. PS was 0-1 in 31, 2 in 12, 3-4 in 13 patients. G8 frailty screening test was performed in 23 patients (score less than 15 in 14). Cancer: local disease (≤ T2N0) in 18, regional in 11, metastatic in 27 patients. Gleason score was 6 in 18, 7 in 10, 8 in 6, 9-10 in 10, PIN3 in 2, unknown in 2 patients. Diagnosis was based on abnormal DRE, metastases, and high serum PSA level in 8 patients. Treatment: 3 patients had a prostatectomy, 2 curative and 3 palliative radiotherapy (in main France). Thirty-four patients received ADT (of whom 7 received taxanes), 3 ADT and abiraterone acetate, 5 surgical castration, 14 surveillance, no treatment or palliative management. Follow-up data are not reliable: on 31/12/2019, 23 patients have died (median survival 42 weeks), 28 alive with disease, 5 with non-evolutive disease (median follow-up 31 weeks). We focused analysis on two patients’ groups: patients older than 70 and maroon patients. We did not observe major differences from the whole cohort.

Results: Between January 2013 and July 2020 57 patients with mCRPC were treated with AA. Thirty-eight discontinued AA due to disease progression; 5 had AAWS criteria (13%). At diagnosis the median age of these 5 patients was 76 y (range 61-87) and median PSA was 14.3 (range 9-53); 3 patients already had metastatic disease. All developed bone metastases and 3 also visceral involvement. All were considered high-volume disease by CHAARTED criteria. During castration-sensitive phase (mCSPC), all patients were treated with continuous androgen blockade (median 21.0 months, range 12.8-124.5), and 1 with orchidectomy. Two patients had experienced withdrawal syndrome with bicalutamide. Three patients were previously treated with docetaxel (2 mCSPC, 1 mCRPC). The duration of response to AA (median of 6.6 months, range 3.0-16.8), and the magnitude of PSA reduction (78.8%, range 8.4%-91.7%) were variable. AAWS was associated with symptom improvement in 1 patient. Two patients started subsequent treatment immediately (docetaxel, cabazitaxel) while two started only upon PSA rise (AA rechallenge and docetaxel); the remaining patient is still responding 22.3 weeks after AA discontinuation. Prednisolone was stopped in 2 patients and switched to dexamethasone in the other 3. Four patients have died, 6.8 to 15.8 months after AA withdrawal.

Conclusions: Prostate cancer patients in the Maroni area have advanced stage, high grade Gleason score, less use of curative (prostatectomy, radiotherapy) and palliative treatments (essentially radiotherapy). Patients have social precarity and cultural specificities which lead to management difficulties. Finally, they are suffering from the inadequacy of the health care supply. However, since 07/2019 this hospital can deliver medical treatments and plan a patient education program. But it is insufficient. In a first step implementation of radiotherapy should be discussed, health care access should be facilitated, particularly in cooperation with Surinam. In a second step education should allow earlier diagnosis and eventually permit early diagnosis.

Conclusions: AAWS is poorly understood, with variable presentation and evolution. We observed AAWS both in patients treated with AA in first line and patients previously exposed to docetaxel. It is unclear whether the response was due to AA discontinuation or to the steroid manipulation. Although AAWS may be associated with durable symptomatic and biochemical response, and allow for longer chemotherapy-free survival in some patients, its clinical role is still unclear.

FACTORS PREDICTING OUTCOME WITH MULTI-RESISTANT ADVANCED PROSTATE CANCER TREATED WITH PROSTATE SPECIFIC MEMBRANE ANTIGEN RADIOLIGAND THERAPY. A SYSTEMATIC REVIEW AND METAANALYSIS

TREATMENT SEQUENCING IN METASTATIC CASTRATION RESISTANT PROSTATE CANCER (MCRPC) AFTER PROGRESSION UNDER AN ANDROGEN RECEPTOR SIGNALING INHIBITOR (ARSI) AND TO DOCETAXEL: RESULTS IN LONG RESPONDERS TO PREVIOUS ARSIS

Finn Edler von Eyben, main office, DAV Institute of Engineering & Technology, India Glenn Bauman Rie von Eyben Çiğdem Soydal, Nuclear medicine, Ankara University, Turkey Giovanni Paganelli

Gil Falcao, urology, centro hospitalar universitario lisboa central, Portugal Rui Bernardino Thiago Guimaraes Mariana Medeiros Vanessa Andrade João Guerra Miguel Gil Cabrita Carneiro Luis Campos Pinheiro

Introduction & objectives: Some patients with metastatic multiresistant and castration-resistant prostate cancer (mCRPC) are given prostate-specific membrane antigen (PSMA) radioligand therapy (PRLT). The systematic review and meta-analysis of PRLT for mCRPC aimed to evaluate whether specific patient characteristics and specific schedules for PRLT are associated with a long overall survival (OS).

Introduction & objectives: Prostate cancer is a leading cause of mortality. Taxanes (Docetaxel, Cabazitaxel) and ARSIs (Enzalutamide, Abiraterone) have been crucial to prolong survival. A timely and wise sequencing of these drugs can improve outcomes. The CARD trial presented at ESMO 2019 clarified that clinical outcomes are better with Cabazitaxel vs an alternate ARSI after progression under Docetaxel and a previous ARSI. Patients included responded < 12 months to a previous ARSI. The clinical outcomes of sequencing with an alternate ARSI in patients with a longer response of >12 months to a previous ARSI were not considered in this trial. We propose to analyse and compare outcomes in this subset of patients.

Material and Methods: The review followed recommendations by Preferred Reporting Items for Systematic reviews and MetaAnalysis. Pubmed, Embase, and ClinicalTrials.gov were searched up to April 4, 2020. Twenty-two original research articles and two duplicates reported 1812 patients. Clinical characteristics and schedules for PRLT were evaluated using conventional statistical methods. Results: Most patients had bone metastases. Median overall survival (OS) was 13 mos. Asymptomatic patients and patients with only lymph node metastases had longer OS than those with impaired PS and more advanced metastases. Patients treated with an intensified schedule of PRLT had longer OS than those treated with a conventional schedule. Half of the patients (48%) obtained a maximal PSA decline ≥50% and these patients had a longer OS than those who had less PSA decline (p = 1.7 x 10-6, Fishers test). Ten percent of evaluated patients had anemia grade 3, 3% had leukopenia grade 3, and 3% had thrombocytopenia grade 3. Serious hematologic adverse effects did not differ significantly between conventional and intensified PRLT.

Materials & Methods: mCRPC men treated with a 3rdline after progression under Docetaxel and an ARSI between January 2014 and January 2020 in three different Centres were included. Progression was defined when a decision of treatment discontinuation was made, either because of biochemical, image or clinical progression. Analysis was performed in 3 subgroups: Cabazitaxel as 3rdline (3rdLCabazitaxel); 3rdline with an alternate ARSI with a <12 months response to a previous ARSI (<12mARSI) and the other group with a >12 months response to an ARSI (>12mARSI).Speed Statistics (SPSS v23) was used for statistical analysis. Results: The total population (n= 47) had a mean follow up time of 65,97 months (38,16 - 73,77CI 95%). Mean Overall Survival (OS) was 48,19 months (28,44- 57,94 CI 95%) and mean time to progression after 3rdline (TTP3rdL) was 7,30 months (3,51-8,09 CI 95%). There was a longer OS in 3rd LCabazitaxel group (n=21) of 48,08 months (p=0,172; 26,72-61,44 CI 95%) than in groups on 3rd line ARSI. The group >12mARSI (n11) had a longer OS than <12mARSI (n=15) with 41,71months (32,45-46,98 CI 95%) VS 25,32 months (20,20 - 30,45 CI 95%). TTP3rdL results were longer for >12mARSI (p=0,684) with 10,57 months (CI 95% 1,63 – 15,5) than <12mARSI or 3rdLCabazitaxel, respectively 4,62 months (CI 95% 2,33 – 6,90) and 4,43 months (CI 95% 2,60-6,26).

Conclusions: If patients with mCRPC are treated with PRLT, patient characteristics and treatment intensity contribute to a high effectiveness.

Conclusions: In this exploratory evaluation a tendency for a longer OS with Cabazitaxel as 3rdline vs an alternate ARSI was also observed. Patients with a 3rdline alternate ARSI after a >12months response to a previous ARSI had a tendency for a longer OS than patients with <12months response. These results, although without statistical significance, may point towards variable responses to a 3rdline ARSI with different time of response to a previous ARSI. ARSIs may be a better option in frail and unfit for chemotherapy patients, therefore finding predictors of better response may be important for clinical management. Large prospective trials are needed to better clarify this aspect and to identify response biomarkers in this subset of patients. 7

CASTRATION-RESISTANT PROSTATE CANCER–CABAZITAXEL AS A RESCUE

VALIDATING SGK1 AS A THERAPEUTIC TARGET IN PROSTATE CANCER

Luke Ginnelly, NICR, University of Newcastle-upon-Tyne, United Kingdom Background: The androgen receptor (AR) plays a pivotal role in prostate cancer (PC). Androgen deprivation therapy (ADT) is a mainstay of PC treatment, but patients inevitably relapse to a fatal form of the disease called castrate-resistant prostate cancer (CRPC). Serum/glucocorticoid-regulated kinase 1 (SGK1) is highly upregulated in CRPC and therefore a potential therapeutic target. Inhibition of SGK1 using the small molecule compound GSK650394 reduces cell proliferation, however this compound is not particularly selective for the kinase. A new more selective inhibitor EMD638683 has not yet been used to validate SGK1’s role in prostate cancer.

Introduction & objectives: Prostate cancer (CaP) is among the most common cancers in males. Although most cases of prostate cancer are diagnosed and treated while disease is localized, some men have evidence of metastatic prostate cancer. Contemporary research has led to the development of multiple active treatment modalities for men with advanced disease, in addition to androgen deprivation therapy (ADT). Management of men with metastatic castration-resistant prostate cancer (mCRPC) involves the sequential use of these approaches, with the goals of prolonging survival, minimizing complications, and maintaining quality of life. CaP is androgen dependent in the beginning, but as time progresses, it becomes refractory to androgen deprivation treatment. At this stage, docetaxel has been used as standard treatment for years. Cabazitaxel has become the first chemotherapeutic agent which has been shown to increase survival for patients (pts) with mCRPC that progresses after docetaxel. The correlation of the oncological outcomes of pts age in mCRPC pts have not been unclear.

Aims: Identify whether SGK1 is a genuine regulator of AR and PC cell growth and therefore a valid therapeutic target in CRPC. Methods: Cell count studies were used to measure the impact of SGK1 inhibitors EMD638683 and GSK650394 on PC cell proliferation. Western blot and quantitative reverse transcription PCR (RT-qPCR) were used to determine the impact of the SGK1 inhibitors on AR expression and activity in PC. Results: EMD638683 was unable to robustly arrest cell proliferation in PC cell models, though it was able to reduce expression of AR target genes (with moderate consistency). In contrast, GSK650394 reduced SGK1 activity and arrested cell proliferation in a range of PC cell lines, however our results suggest its effect on cell proliferation was due to off-target actions on other pathways.

Materials and Methods: In this study, we evaluated a total of 26 pts who progressed despite docetaxel treatments, had ECOG performance score between 0-2, and used cabazitaxel treatment 25 mg/m2 at every 3 weeks, and prednisolone 5 mg twice a day for mCRPC diagnosis in Centro Hospitalar Universitário Lisboa Central from June 2016 to January 2020, retrospectively. We assessed the prognostic significance of cabazitaxel, focusing on pts age and the correlation of efficacy between docetaxel and cabazitaxel. Demographic and clinical data were collected and the information was cross-checked with that of the pharmaceutical services. Significance (p) of less than 0.05 was considered statistically significant. Statistical analysis was performed in Stata.

Conclusions: SGK1 can at least partially regulate AR, but further work is needed to conclude whether it is important enough to be a valid therapeutic target in CRPC.

Results: The median overall survival (OS) periods after the introduction of cabazitaxel was 15,4 months. A 40% PSA response to cabazitaxel was achieved in 22 (85%) pts. A 40% PSA response to cabazitaxel was achieved in 13 (50.0%) pts with ≥75 years and 13 (50%) pts with less than 75 years. There was no significant correlation between the PSA response and pts’ age (p = 0.093). A 30% PSA response to cabazitaxel was achieved in 17 (65%) and 9 (35%) pts with and without that to docetaxel, respectively. There was no significant correlation of the PSA response between docetaxel and cabazitaxel (p = 0.087). Univariate and multivariate analysis revealed that there were no significant correlation of pts age, the response to prior docetaxel therapy or cycles of docetaxel therapy with shorter OS. Conclusions: These results suggest that cabazitaxel is a safe and effective treatment option for mCRPC pts who progress after docetaxel and indicate that the introduction of cabazitaxel for mCRPC pts could result in oncological outcomes without any association with pts’s age and the profiles of previous docetaxel therapy.

PROSTATE ULTRAHYPOFRACTIONATION IN THE COVID-19 ERA: POTENTIAL IMPACT ON A UK CENTRE William Griffiths, Oncology, Newcastle upon Tyne Hospitals NHS Froundation Trust, United Kingdom Rachel A Pearson Ian Pedley John Frew Xue Jiang Robert Chandler Introduction & Objectives: The HYPO-RT-PC trial [1] was the first to demonstrate non-inferiority of ultra-hypofractionated (UHF) radiotherapy compared to conventionally fractionated radiotherapy for prostate cancer treatment in intermediate to high risk prostate cancer. Additionally, a recent meta-analysis [2] has reported similar DFS in localized prostate cancer for UHF compared to conformal and hypofractionated radiotherapy. Most recently, the PACE-B trial [3] is running a non inferiority trial exploring UHF outcomes and is the first to compare SABR delivered as 36.25Gy/5 without accompanying hormone treatment [3]. Survival and late toxicity data are still awaited but early toxicity data shows that early toxicity is comparable between groups [3]. With these promising results, and anticipating a change to ultrahypofractionation SABR, we set out to establish what such a move would mean for our patients and service provision at our centre. Materials & Methods: To explore this we took 100 patients with prostate cancer that were treated with our standard hypofractionated 60Gy/20 radiotherapy between April and July 2019 and collected the following data: Basic demographics, clinical information (PSA, Gleason score, T score and Performance Status), treatment information (hormone treatment and duration of therapy), other clinical information (bilateral hip replacements, concurrent use of anticoagulation). From this we then established a PACE-B risk level for each patient as per the following criteria: PACE-B low/intermediate risk (suitable for SABR): Clinical stage T2c and below, PSA <20ng/ml, Gleason score 7 (3+4 only) and PS 0-2 [3]. Clinical notes including MDT and consultant clinics were reviewed for each patient and information at time of presentation was used to give the best reflection of the options future patients would have when first being referred to our service. Results: The median age of the cohort was 71 years (range 5180) and 100% had a Performance Status of 0-2. Risk stratification by PACE-B criteria for low/intermediate/high risk was 0%, 27% and 73% respectively. 3% of the cohort had bilateral hip replacements and 27% were on anticoagulant/antiplatelet therapy. In terms of hormone treatment, 85% of our PACE-B cohort (low/ intermediate risk) was prescribed 6 months of hormone therapy. 99% of high risk patients received hormone treatment and 70% of these received at least two years treatment. Conclusions: 27% of patients with prostate cancer treated with 60Gy/20 in a 4-month period in 2019 would be eligible for ultrahypofractionation SABR radiotherapy as per PACE-B criteria. Implementation of UHF without hormone treatment could therefore considerably increase capacity on the radiotherapy treatment machines and has obvious benefits to patients; reducing number of hospital visits and sparing hormone sideeffects is very relevant in the COVID-19 pandemic era.

Guillaume Grisay, Oncology, Université Catholique de Louvain, Belgium Julien Pierrard Confente Caterina, oncology, CH Jolimont, Belgium Sarah Lejeune Yannick Neybuch Nicolas Christian Emmanuel Serontl, Medical Oncology, Hôpital de Jolimont, Belgium Jean-François Rosier

Luísa Jerónimo Alves, Urology, Hospital Beatriz Ângelo, Portugal José Vicente Sánchez-González Tomás B. C. Moretti Nelson Peixoto Kris Maes

IMPACT OF MODERN IMAGING TOOLS ON MANAGEMENT OF PROSTATE CANCER, A SINGLE CENTER EVALUATION

OUTCOMES OF HIGH-RISK PROSTATE CANCER AFTER ROBOTIC-ASSISTED RADICAL PROSTATECTOMY: REAL-LIFE EXPERIENCE

Introduction & objectives: Prostate cancer (PCa) is the second most common male cancer in the world, and is currently the second cause of malignancy-related desease in the USA and Europe. The definition of high risk PCa varies among the published data hampering results comparison between studies. Radical prostatectomy (RP) is traditionally adopted as part of a multimodal therapy. In this context, retrospective studies demonstrated that upfront RP results in decreased mortality and reduction in the use of adjunctive treatments and their side effects. Furthermore, this approach provides a better risk stratification. The aim of our study is to analyse functional and oncological outcomes of high-risk PCa submitted to robotic-assisted radical prostatectomy (RARP) in our institution.

Introduction & objectives: The Prostate specific membrane antigen positron emission tomography (PSMA-PET) allows a more accurate stadification of prostate cancer compared to conventional imaging. However, whether the PSMA-PET significantly changes the management of patients (pts) with prostate cancer remains unclear. Methods: We retrospectively included in this analysis all prostate cancer pts who performed both PSMA-PET and conventional imaging (bone scan (BS), abdominal magnetic resonance imaging (MRI) and thoraco-abdominal computed tomography (CT)) between January 2017 and June 2020 in our center. We evaluated the discordance in evaluating number of lesions between these two imaging assays as well as the percentage of pts in which the therapeutic management initially decided with conventional imaging was modified based on PSMA-PET.

Material and Methods: We retrospectively evaluated all patients (pts) with high risk prostate cancer undergoing RARP, from 2015 to 2019, in Hospital da Luz, in Lisbon. Study entry criteria were one of the following: Gleason score >7 at surgical specimen, pT3/4, positive lymph nodes or PSA>20ng/dL. Statistical analysis was performed with the use of SPSS version 24.

Results: 60 pts were included in this analysis. All pts performed conventional imaging; PSMA-PET was performed in 25 pts (42%) for initial staging at prostate cancer diagnosis due to equivocal lesion or unfavorable intermediate-high risk group using D’Amico classification (Groupe A) and in 35 pts (58%) for a biochemical recurrence (Groupe B).

Results: A total of 94 pts were included, with a mean age of 64(+/-6) years-old. The median PSA at diagnosis was 8,2 [2,6;38] ng/dL. Thirty-five patients (37%) were gleason 8 or higher, 22 (23%) were pT3b and 18 (19%) showed nodal involvement. At 3 months post-surgery 71 (76%) pts were continent. At 12 months of follow-up, 90 (96%) pts were continent and 28 (30%) pts were potent. With a median follow-up of 23 [2;62] months, 26 pts have recurred. Of those, 18 (19%) underwent complementary RT and 7 (7%) received ADT. Biochemical recurrence free survival was 61.4% (SE=7.0) and median time to RT and to ADT was 16,5 [3;46] and 7 [0;46] months, respectively. Three pts (3%) developed metastasis with 5-ys metastasis free survival of 90.8% (SE=5.2). Mortality of the studied population was 3% with a mean survival time of 59.7 (SE=1.9) months.

In the Group A, 10 pts (40%) presented a discordance; new lesions were detected with PSMA-PET in 7 pts (lymph nodes (LN) in 4 pts and non-lymph node lesions in 3 pts). Conversely, PSMA-PET was negative in 3 pts initially positive at conventional imaging for LN in 2 pts and for non-LN lesion in 1 pt. Out of these 10 pts, the management was changed in only 3 pts; 2 were declined for a radical treatment due to distant metastases detected with PSMA-PET and 1 pt initially deemed ineligible benefited from radical treatment. In the Group B, 24 pts (69%) presented a discordance; compared to conventional imaging, PSMA-PET detected new lesions in 20 pts (LN in 10 pts and non-LN lesions in 10 pts). Conversely, PSMA-PET was negative in 4 pts initially positive at conventional imaging for LN in 2 pts and for non-lymph node lesion in 2 pts. Among these 24 pts, a modification of therapeutic management was proposed in 20 pts; 12 were treated with stereotactic ablative radiotherapy (SABR) instead of androgen deprivation therapy (ADT), 6 were treated with systemic treatment instead of SABR and 2 with expectative management instead of SABR or ADT.

Conclusion: Consensus about the best approach in high risk/locally advanced PCa has not been reached yet. Radical prostatectomy, as part of a multimodal approach, showed encouraging oncological outcomes when compared with RT plus ADT alone. Although the results presented are based on a short median follow-up time, functional and oncological outcomes are in line with the published data on this issue. In these preliminary results, we highlight the fact that 87 pts were free of ADT and its potential side effects.

Conclusion: The use of new imaging techniques is a useful improvement in the management of prostate cancer, especially in the biochemical recurrence where it can result in modification of management.

Athul John, School of Medicine, University of Adelaide, Australia Rick Catterwell Luke Selth Michael O Callaghan Hritik John, Medicine, University of Adelaide, Australia

Kgomotso Mathabe, Urology, University of Pretoria, South Africa Sean Mark Patrick, School of Health Systems and Public Health, University of Pretoria, South Africa Evelyn Moshokoa

GLEASON GRADE GROUP AT POSITIVE MARGIN PREDICTS BIOCHEMICAL RECURRENCE - A META-ANALYSIS

THE PATHOLOGICAL FEATURES OF PROSTATE CANCER IN SOUTH AFRICAN MEN: WHAT IS THE PREVALENCE OF LOCAL INVASION AT DIAGNOSIS?

Introduction: The relevance of positive surgical margins (PSM) after undergoing radical prostatectomy (RP) remains controversial, given the reported inconsistencies in the ability of PSM to predict biochemical recurrence (BCR) and oncological outcomes.

Introduction: Prostate cancer is the most common solid organ malignancy in men worldwide. Biochemistry and histology form the cornerstone of assessing patients with suspected prostate cancer. Refinement of PSA as a marker as well as the search for the ideal marker continue. Histology reports hold many secrets to prostate cancer. Some of these are reported and some of those used to inform stratification and prognostication tools. The commonly used risk stratification models (D’Amico), prognostication models (Kattan’s nomogram) and Epstein’s criteria for indolence do not take into account evidence of local infiltration on biopsy.

Objectives: To systematically review and perform a metaanalysis of studies investigating the role of primary Gleason grade, Gleason score or Gleason grade group of positive surgical margins (PSM) after radical prostatectomy (RP) in predicting biochemical recurrence (BCR) and oncological outcomes. Methods: A systematic search was conducted using MEDLINE, Scopus, Embase and Cochrane databases according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Studies published between 2004 and 2019 were included. The quality of the studies selected was assessed, and a protocol was registered in advance (PROSPERO: CRD42019131800). The primary outcome measure was BCR. Secondary outcome measures included disease-specific survival, disease progression-free period and overall mortality during the follow-up period.

Objectives: To describe the biochemistry and histology of prostate cancer in a tertiary hospital in Johannesburg, South Africa. Materials and methods: The histology reports of all prostate specimens which showed cancer, at a tertiary hospital in Johannesburg over 5 years, were reviewed on the following parameters: completeness of reporting based per ICCR guidelines, age, PSA level, Gleason grade and local infiltration.

Results: Our systematic search yielded 3113 unique results. Ten studies were selected for meta-analysis. Sample sizes of PSM cohorts varied from 200 - 956, while median follow up ranged from 1.5 to 13 years. Most studies used BCR as a surrogate marker for disease progression; only two studies reported other oncological outcomes. Meta-analysis was performed in selected groups (primary Gleason grade, Gleason score and Gleason grade group). Primary Gleason grade (PGG) 4 or 5 at PSM was found to be predictive of BCR (HR 1.66, [95% CI 1.37- 2.02 ], p <0.01 ). Gleason grade group (GGG) >1 at margin was also predictive of biochemical recurrence compared to GGG 1. (GGG 2 (HR 2.35, [95% CI 1.6 - 3.46 ], p < 0.001), GGG 3 (HR 3.95, [95% CI 1.82 - 8.57 ], p = 0.005), GGG 4 (HR 7.17, [95% CI 1.76 - 29.17 ], p = 0.006) and GGG 5 (HR 12.37, [95% CI 1.80 - 84.82], p = 0.01)

Results: There were 726 specimens available for review; 644 (88.7%) came from core needle biopsies, the rest were obtained from radical or open prostatectomies, TURP and radical cystoprostatectomies. The completeness of reports based on ICCR guidelines: regarding the criteria which are required histological tumour type and tumour grade were reported in 100% of specimens. The tumour extent based on number of positive cores was reported in 63.4% and as a percentage of the specimen in 83.95%. Local infiltration a recommended criteria was reported in 83.9%. Perineural, lymphovascular, extra-capsular or seminal vesicle invasion constitute local infiltration. Our local reporting practices surpass the ICCR standards.

Conclusion: Gleason score, PGG and GGG of PSM are associated with a significantly increased risk of BCR. Longer-term studies are needed to investigate the utility of PGG, Gleason score or GGG of PSM in its ability to detect not only BCR but other outcomes such as systemic progression, cancer-related mortality, and overall survival.

The mean age at presentation was 69.2 years (+/- SD = 10.6 years), 2.2% of patients were ≤ 50 years old, 27.9% were ≥ 75 years old. The median PSA was 57.6 ng/mL (range 0.7 – 20 000 ng/ml), 70% had PSA ≥ 20 ng/ml and 10% had PSA ≥ 1000 ng/ml. The majority of specimens came from core needle biopsies; the systematic protocol was used in 92% of cases, followed by sextant, limited and saturation protocols. Regarding the Gleason grade, 61% of specimens had high-grade disease, with a further 14% showing intermediate grade disease. The ISUP grade groups 4 and 5 made up 49.5% of the specimens. Local infiltration was reported in 609 (83.9%) specimens and found to be present in 404. Only three specimens had no local invasion.

Conclusion: In our cohort of histologically proven prostate cancer at a tertiary centre over 5 years, the majority of patients had advanced and possibly aggressive disease at presentation as shown by high PSA, high grade disease and local infiltration. More than half had perineural infiltration. The quality of our histology reports surpasses the standards set by the ICCR.

PATIO – EMPOWERING PROSTATE CANCER PATIENTS IN SCIENCE Marie Niederleithinger, Applied Translational Research, Ludwig Boltzmann Institute Applied Diagnostics, Vienna, Austria Mijailovic Sanja Ekkehard Büchler, Board, Selbsthilfe Prostatakrebs, Amelie Dorn Markus Mitterhauser Introduction & objectives: Patient involvement and engagement in medicine and healthcare has received increased attention in recent years, also in the scientific field. However, involving patients in research activities in order to tap into their pool of lived experience and knowledge, and enable closing research gaps, is still scarce. In this context, the project PATIO (Patient Involvement in Oncology), which we introduce in this presentation, aims to be a game-changer, exploring the testing ground of prostate cancer (PCa) research. Materials and Methods: Together with experienced patients and relatives, the interdisciplinary team aims to develop a (digital) engagement tool which will serve as a portal for the large community of people affected by PCa to engage and share their lived experiences and developed solutions after PCa treatment. In this way, the researchers want to bring the largely unexploited pool of lived experience back to science and find targeted approaches for improving the quality of life (QoL) after the diagnosis “PCa”. The underlying research questions highlight challenges and developed coping strategies by patients to close research gaps. PATIO will make use of Open Innovation in Science (OIS) approaches, such as co-creation and co-design methods, as well as an eco-system setting for cross-disciplinary actor engagement. This approach is novel and promising, particularly in the field of medicine and oncology. Through a guided process, experience from patients and other affected persons will be fed back to research. A digital platform, co-designed by the diverse actor groups, will be a unique tool for engagement and source of innovation potential. Results and Conclusions: PATIO brings together actors from society, medicine and the humanities in a balanced partnership of equals. The OIS approach gives the project a unique and largely unrivaled framework in the field of oncology in Austria. The team reports on first results, shares their experience on the process design and discusses potential impulses to the field of PCa research and healthcare.

NON-CODING MITOCHONDRIAL RNAS AS TARGET FOR DEVELOPMENT OF POTENT THERAPY AGAINST PROSTATE CANCER

TARGETED LITERATURE REVIEW (TLR) OF THE REAL-WORLD TREATMENT PATTERNS AND OUTCOMES AMONG MCRPC PATIENTS IN EU5, JAPAN AND AUSTRALIA

Jaime Villegas Olavarría, Centro de Medicina Veterinaria, Universidad Andres Bello - Fundación Ciencia & Vida, Chile Erick Sandoval Francisca Guevara Vincenzo Borgna Royer Melendez Sebastian Valenzuela Luis O Burzio

Louisa Oliver, PROVE, Adelphi Values Prove, Manchester UK, United Kingdom Sameer Ghate Irene Shui Alician Gayle On-yee Wong Jeri Kim Sarah Payne Neal Shore

Introduction: Prostate cancer (PCa) is one of the most common causes of male cancer-related death in western nations. In advances stages of disease, the treatments are mostly palliatives. Therefore, there is a pressing need for novel therapeutic strategies which will alter the natural history of prostate cancer. Human cells express a family of noncoding mitochondrial RNAs (ncmtRNAs). Normal proliferating cells express both sense and antisense transcripts (SncmtRNA and ASncmtRNAs). However, tumor cells in culture or human biopsies express only the SncmtRNA and down regulate the ASncmtRNAs. This expression pattern is independent of tumor origin and distinguish tumor cell from normal cell. The goal of this work was to evaluate the effect of antisense therapy in vitro and in vivo.

Introduction: Life prolonging therapies for metastatic castration resistant prostate cancer (mCRPC) patients have dramatically increased overall survival (OS) over the last decade; but, given the rapidity of these drug approvals, the optimal sequencing of therapies is unclear. The objective of this TLR was to summarize the literature on the real-world treatment patterns and outcomes among mCRPC patients in the European five (EU5), Japan (JPN) and Australia (AUS). Methods: A TLR was conducted across nine databases in OVID to capture English language studies published 01/2014–05/2019 on treatment patterns and outcomes for mCRPC patients. 4,732 papers were identified and screened for inclusion. Ten conference proceedings from 2014–2019 were searched.

Material & Methods: For in vitro assays we used four cell lines to study the effect of antisense therapy over cell proliferation and marker of apoptosis and cell proliferation. The four cell lines (PC3, LNCaP, 22Rv1 and VCaP) were transfected with 100 nM of an oligonucleotide complementary to ASncmtRNAs (ANDES1537), after 72h treatment cell death and proliferation rate was evaluated by tripan blue assay and western blot was used to evaluate the levels of cyclins B1 and D1, PCNA, survivin and BclXl. For in vivo assays 5exp6 cells (22Rv1 and PC3) were injected subcutaneously (sc) in the right flank of Balb-c mice (5 per group). When tumor reached 100 mm3 we injected 50 ug of ANDES1537 intraperitonially in several different regimes. We compared the effect of antisense treatment in vivo againts docetaxel and enzalutamide.

Results: 74 articles (EU5 n=57; JPN n=14; AUS n=3) reported on treatment patterns, progression-free survival (PFS) or OS of mCRPC approved therapies. Therapies most likely to be chosen in the 1L were docetaxel (DOC) (EU5 n=28; JPN n=4; AUS n=1), followed by new hormonal agents (NHA), abiraterone acetate (AA) (EU5 n=11; JPN n=11; AUS n=2) and enzalutamide (ENZ) (EU5 n=6; JPN n=12; AUS n=2). Cabazitaxel (CAB) was preferred in the 2L+ (EU5 n=14; JPN n=5, AUS n=1). No data were captured on radium-223 in JPN or AUS. Few studies reported outcomes for treatment sequences. In JPN, NHA-NHA was the most common treatment sequence reported (n=5). For AA-ENZ, median PFS1=6.3 mos (n=1), PFS2=3.4 mos (n=1) and OS=25.4 mos–not reached (n=2). For ENZ-AA, median PFS1=5–5.5 mos (n=2), PFS2=2.9–3.4 mos (n=2) and OS=9.1–24.2 mos (n=3). Most articles in EU5 focused on treatment sequences with DOC as a 1L therapy, followed by AA (n=15) or CAB (n=9) as a 2L therapy. For DOC-AA, median PFS2=5.3–7.4 mos (n=2) and OS=11.5–26 mos (n=8). For DOCCAB, median PFS2=6.3 mos (n=1) and OS=11–15.3 mos (n=7). Data heterogeneity and limitations were recognized.

Results: We found that antisense treatment in vitro induces a potent negative effect over cell proliferation rate in the four cell lines. Depending of the cell line analyzed, we observed a differential effect in levels of protein involved in control of cell proliferation, as cyclins B1,D1 or antiapoptotic markers as survivin and Bcl-xL proteins. Moreover, we found that antisense therapy affect severely the capacity of four cell lines to form spheres in vitro, suggesting that this treatment is a potent therapeutic tool because affect negatively the CSC. The next step was to evaluate the effect of the therapy in a pre-clinical model. Therefore, 25 mice were subcutaneously injected with 5 millions PC3 cells. When the tumor reach an average volume of 80-100 mm3, 10 doses of 50 ug ANDES1537 were injected via intra-peritoneal every other day with or without docetaxel. Compared with control group or docetaxe alone, we observed, that ANDES1537 treatment induce a strong delay in tumor growth in vivo.

Conclusions: mCRPC treatment selection and sequencing vary across global regions, likely reflective of differences in the reimbursement landscape, approval dates, treatment setting, physician preference and patient characteristics. Further analyses on these factors and the impact on clinical outcomes are needed.

Conclusion: Our results suggest that this antisense approach can be a novel a potent therapeutic tool for prostate cancer therapy. The effect of combined therapy will be discussed. Grant: FONDEF ID18i10239. ANID. Chile

Conclusions: In this primary endpoint analysis, ipat + abi as first-line treatment for mCRPC resulted in significantly improved rPFS and antitumor activity vs pbo + abi in patients with PTENloss mCRPC, but not in the ITT. The safety profile was in line with known and potential risks. ClinicalTrials.gov ID: NCT03072238

IPATENTIAL150: PHASE III STUDY OF IPATASERTIB (IPAT) PLUS ABIRATERONE (ABI) VS PLACEBO (PBO) PLUS ABI IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC)

Previously presented at ESMO Congress 2020, IPATential150: Phase III study of ipatasertib (ipat) plus abiraterone (abi) vs placebo (pbo) plus abi in metastatic castration-resistant prostate cancer (mCRPC), Johann de Bono et al. - Reused with permission

David Olmos, Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre - CNIO, Spain David Olmos Johann de Bono Sergio Bracarda Cora N. Sternberg Kim N Chi Shahneen Sandhu Christophe Massard Nobuaki Matsubara Boris Alekseev Rustem Gafanov Francis Parnis Gary L. Buchschacher Jr Luis Corrales, Medical Oncology, CIMCA Michael Borre Gustavo Alves Josep Garcia, PDO, Roche, United Kingdom Marie-Laurence Harle-Yge Geng Chen Matthew J. Wongchenko Christopher Sweeney Introduction & objectives: PI3K/AKT and androgen receptor (AR) signalling are dysregulated in mCRPC. PTEN loss (40%-50% of mCRPC) results in activation of AKT, the ipat target, and worse outcomes. Preclinically, dual pathway inhibition has greater antitumor activity than AR inhibition. IPATential150 is a Phase III, randomised, double-blind study evaluating the efficacy and safety of adding ipat to abi in asymptomatic or mildly symptomatic patients previously untreated for mCRPC. Materials & Methods: Patients with mCRPC were randomised 1:1 to receive ipat (400 mg/day) + abi (1000 mg/day) + prednisone (5 mg bid) or pbo + abi + prednisone. Coprimary endpoints were investigator-assessed radiographic (r) PFS by PCWG3 criteria in patients with PTEN-loss tumours by immunohistochemistry (IHC; PTEN-loss in â&#x2030;Ľ 50% of tumour cells) and in the overall ITT. Secondary endpoints included time to PSA progression, PSA response rate, confirmed ORR (per RECIST 1.1 + PCWG3) in ITT patients and patients with PTEN-loss tumours by IHC, and rPFS in patients with PTEN-loss tumours by next-generation sequencing (NGS). Results: 1101 patients were randomised: 547 to ipat + abi and 554 to pbo + abi. Median follow-up was 19 months. In PTEN loss by IHC patients, median rPFS was 18.5 months (95% CI: 16.3, 22.1) with ipat and 16.5 months (95% CI: 13.9, 17.0) with pbo (HR: 0.77; 95% CI: 0.61, 0.98; P = 0.0335); in ITT patients, rPFS was 19.2 months (95% CI: 16.5, 22.3) with ipat and 16.6 months (95% CI: 15.6, 19.1) with pbo (HR: 0.84; 95% CI: 0.71, 0.99; P = 0.0431). Secondary endpoints favoured the combination arm (Table). Serious adverse events (AEs) occurred in 40% and 23% of ipat and pbo patients, respectively; AEs leading to discontinuation of ipat/ pbo occurred in 21% and 5%.

increased NLR group (HR 0.63; p=0.058). Variation in PLR did not show a significant association with survival (33.8 months versus 25.9 months; HR 0.83; p=0.53).

NEUTROPHIL TO LYMPHOCYTE RATIO (NLR), PLATELET TO LYMPHOCYTE RATIO (PLR) AND ITS KINETICS AS PROGNOSTIC MARKERS FOR PATIENTS WITH METASTATIC CASTRATION RESISTANT PROSTATE CANCER TREATED WITH ENZALUTAMIDE

Conclusions: Both PLR and NLR were prognostic in this analysis. PLR ≥140 and NLR ≥2.8 at baseline were associated with worse OS. Early NLR increase is also associated with worse survival outcomes in this group of patients. NLR kinetics might be a useful biomarker for predicting the prognosis of mCRPC patients who are treated with ENZ. Further prospective studies are needed to validate pretreatment haematological profile and its variation as a prognostic tool.

Rita Sofia Vitorino da Silva Paiva, Medical Oncology, Centro Hospitalar Universitário Lisboa Norte, Portugal Filipa Ferreira, Medical Oncology, HSFX-CHLO, Portugal Inês Teles Grilo João Moreira-Pinto Rita Gameiro-Santos Anuraj Paramanande Cecília Melo Alvim, Medical Oncology, Centro Hospitalar Universitário Lisboa Norte, Portugal Sara Damaso Miguel Maria Escoval Lopes Esperança Martins, Medical Oncology, Centro Hospitalar Lisboa Norte, Portugal Isabel Gomes Fernandes Helena Luna Pais Raquel Lopes Brás, Oncology, Centro Hospitalar Universitário Lisboa Norte, Portugal Pedro Miguel Duarte Simões, Medical Oncology Department, Hospital Beatriz Ângelo, Portugal João Godinho Isabel Fernandes Luis Costa Introduction: Pretreatment inflammatory factors, including neutrophil, lymphocyte and platelet counts as well as the ratios between them such as neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) have been associated as potential prognostic markers for patients with metastatic castration resistant prostate cancer (mCRPC) treated with Enzalutamide (ENZ). However, there is still lack of data on how to use this tool in clinical practice. Our goal was to evaluate the correlation between NLR and PLR, as well as its kinetics, and overall survival (OS) and progression free survival (PFS) Methods: Retrospective analysis of all patients with mCRPC treated with ENZ for at least 12 weeks, followed at six national different centres since January 2015. Clinical and pathological data was collected from clinical files. PLR and NLR were calculated from the ratio of absolute counts of platelets, lymphocytes and neutrophils on the peripheral blood at baseline. PLR and NLR were stratified into two groups, <140 and ≥140, <2.8 and ≥2.8, respectively. Cutoff values were obtained with ROC curves. Primary endpoint was to evaluate PLR and NLR relation and its variation at 12 weeks (any increase or decrease) to overall survival (OS) and progression free survival (PFS). Survival analysis was performed using Kaplan-Meier method and Cox regression. Results: 162 patients were included with a median age at beginning of treatment of 71.8 years old. ECOG was mainly 0-1. Median follow up was 11.6 months. Median OS was 25.3 months and median PFS was 13.6 months. OS was not reached (NR) for PLR <140 and 19.5 months for PLR ≥140 (HR 0.43; p=0.002) and PFS was 16.3 and 9 months, respectively (HR 0.67; p=0.061). For NLR, OS was 33.8 months for NLR <2.8 and 22.4 for NLR ≥2.8 (HR 0.52; p=0.055) and PFS was 14.9 months and 9.7 months (HR 0.79; p=0.314), respectively. 72.9% (n=102) of patients showed a decrease in NLR at 12 weeks. Decrease in NLR was associated with better OS (25.9 months versus 17.4; HR 0.51; p=0.015). PFS was 14.9 months for decreased NLR group and 10.8 months for the

Materials & methods: An interview analysis to identify techniques used in the delivery of care to prostate cancer patients in 20 centres across five European countries is ongoing, with 16 centres assessed to date. To ensure that a comprehensive view of care is obtained, a wide range of healthcare professionals directly involved in the care of prostate cancer patients are being interviewed, including oncologists, urologists, nurses, radiographers, psychologists and physiotherapists. Examples of best practices in care delivery that are identified in interviews are categorised by the centre and country in which they are observed. Best practice examples will be reviewed by representatives from each centre and prioritised by consensus, based on the ability of each example to address the most significant challenges and unmet needs common to the five countries.

MAPPING THE QUALITY OF PROSTATE CANCER CARE IN EUROPE Heather Payne, Oncology, University College London Hospitals, United Kingdom Antonio Alcaraz Georg Bartsch, Urology, Markuskrankenhaus, Germany Alberto Briganti Antonio GĂłmez CaamaĂąo Miguel Ă ngel Climent Gaetano Facchini Stefano Fanti Hilary Glen Stefan Hinz Robert Jones Ahmed Khalil Jean-Pierre Lotz Javier Puente Phil Reynolds, Radiotherapy, Clatterbridge cancer centre, United Kingdom Bernardo Rocco Herbert Sperling Robert Stevenson

Results: Best practice examples identified to date have undergone preliminary thematic analysis, with emerging results outlined below. Further analysis and advocacy of these themes will be undertaken by representatives from each centre once all centre assessments are complete. Conclusions: The data will evolve as more centre visits are performed. Numerous distinct approaches are seen in European prostate cancer centres to address common challenges in the delivery of care to patients. Next steps will be to assess how these best practice examples can be implemented in different healthcare systems to optimise the care of patients with prostate cancer, and how their impact can be measured. The final results will be disseminated to the wider prostate cancer care community via various activities.

Introduction & objectives: Despite substantial advances in the diagnosis and treatment of prostate cancer in recent years, the quality of care experienced by patients across Europe remains variable. Barriers to improving service provision include the multifaceted nature of specialist care, specific challenges related to the patient cohort, structural inefficiencies, and a lack of reliable evidence to support interventions. Inconsistencies in the delivery of care have been reported in literature at all stages of the patient journey, with a corresponding impact on patient experience.

No. of examples (some seen in multiple centres)

Theme

Example

Patient education, engagement and empowerment

Digital patient diaries

Connecting with others

Primary care decision making algorithm

Truly multidisciplinary care

Combined clinics

Technology, research and innovation

Remote follow up of selected patients

Standards, protocols and ways of working

Postoperative risk stratification tool

Dedicated side effect services

Physical activity programme

Psychological support

Screening for mental health problems

HCP education

Radiology and physics training for oncologists

RATE OF ADVERSE MORPHOLOGICAL FEATURES AFTER RADICAL PROSTATECTOMY

OPTIMIZATION OF PET PROTOCOL AND INTERRATER RELIABILITY OF 18F-PSMA-11 IMAGING OF PROSTATE CANCER

Andrei Petrashevskii, Urology, N. N. Alexandrov National Cancer Centre, Belarus Alexander Rolevich

Sarah Piron, Lab of Radiopharmacy, Ghent University, Belgium Kathia De Man, Nuclear Medicine, Universiteit Gent, Belgium Vanessa Schelfhout Nick Van Laeken Ken Kersemans Eric Achten Filip De Vos Piet Ost

Introduction & objectives: Radical prostatectomy (RP) is a treatment for patients with prostate cancer (PCa), but the presence of adverse morphological features (AMF), including a positive resection margin, extracapsular extension (ECE) of the tumor, invasion of seminal vesicles (ISV), and metastatic lesion of lymph nodes, affects the further prognosis and may serve as an indication for adjuvant treatment. In our study, we estimated the incidence of AMF in a sequential series of RP performed in the period from July 1, 2019 to December 30, 2019.

Introduction & objectives: In recent years, prostate specific membrane antigen (PSMA) has been the most widely studied target for imaging of recurrent and metastatic prostate cancer. 18F-PSMA-11 was evaluated for safety, biodistribution and dosimetry in a previously published study. A Phase 2 study should be conducted to determine the scan protocol which can be applied in following studies and clinical practice. Several scan parameters such as dosage, acquisition time and scan duration were evaluated, as well as the effect of furosemide administration on lesion visualisation.

Materials & methods: The study included all patients who underwent RP for PCa in the period from July 1 to December 30, 2019.The frequency of AMF was analyzed according to the clinical and morphological parameters of tumor aggressiveness (PSA before treatment, Gleason sum in biopsy,% of positive bars, clinical stage and cancer risk according to EAU). AMFs were divided into 1) prevalence rates (ECE, ISV, metastatic lymph node involvement) and 2) positive resection margins.

Materials & methods: 44 patients were randomly assigned to a dosage group (2.0 ± 0.2 or 4.0 ± 0.4 MBq/kg 18F-PSMA-11). Patients received a full-body PET/CT 1h and 3h after radiotracer injection with a scan duration of 3 min/bed position. Images were reconstructed for 1.5 and 3 min/bed position. Patients were intravenously administered 0.5 mg/kg furosemide with a max dose of 40 mg. To evaluate the furosemide effect, 22 additional patients received one PET/CT 1h after administration of 2 MBq/kg 18F-PSMA-11 with a scan duration of 3 min/bed position. To this group, no furosemide was administered. Images were scored on image quality using a 7 point scale and each suspicious lesion was described. To assess interrater reliability, two nuclear physicians scored all scans independently and described all observed suspicious lesions.

During the specified period, 143 RPs were performed at our institution. The median age of the patients was 61 (46-75) years. The median PSA level before treatment was 9.0 (3.3-96) ng / ml. Low oncological risk was found in 15 patients (10%), intermediate - in 33 (23%), high - in 85 patients (59%). In 10 cases (8%) there was not enough data to determine the risk group. Results: According to morphological examination, a positive resection margin after RP was found in 67 cases (47%). The incidence of ECE or ISV was 87 (61%), metastases in regional lymph nodes - 19 (13%) cases. At least one AMF was detected in 103 (72%) patients. The incidence of AMF was statistically significant and correlated with the Gleason score (p = 0.011), the percentage of positive bars in the biopsy (p = 0.005), and the PSA level (p = 0.04), but not with cancer risk (p = 0.1). When analyzing the pathomorphological indicators of the prevalence of the tumor process, the latter were statistically significant and associated with all preoperative indicators of tumor aggressiveness (except for the clinical stage), including oncological risk, while the frequency of the positive surgical margin correlated only with the PSA level before surgery (p = 0.01).

Results: The 4 MBq/kg group received for all reconstructed images (60 min p.i., 1.5 and 3 min/bed position and 180 min p.i., 1.5 and 3 min/bed position) the highest median image quality score compared to the 2 MBq/kg group (p-values 0.001132, 0.007741, 0.0007 and 0.001987, respectively). When comparing all reconstructed images, the highest image quality score was given to images at 60 min p.i., 3 min/bed position for both dosage groups (score 5 and 6 for 2 and 4 MBq/kg, respectively). The addition of furosemide administration decreased the interference score with one point (p = 0.01106) and facilitated the evaluation of lesions in proximity to the ureters. The interrater reliability for the comparison of each lesion separately after 40+ PSMA scan readings showed an increasing κ value from 0.78 (95% CI, 0.65 – 0.92) to 0.94 (95% CI, 0.87 – 1).

Conclusions: The analyzed cohort of patients after RP for PCa showed a high incidence of AMF was revealed. According to the weak connection between indicators of tumor aggressiveness and the frequency of positive resection margins, the clinical significance of the latter is questionable.

Conclusions: Although the results suggest imaging with an administered activity of 4.0 ± 0.4 MBq/kg, preference will be given to 2.0 ± 0.2 MBq/kg due to the small difference in absolute score (max 1 point) and the ALARA principle. For evaluation of lesions in proximity to the ureters, the co-administration of a diuretic can be useful. The increase of the κ value from 0.78 to 0.94 suggests a learning curve in the interpretation of 18F-PSMA-11 images.

DETECTION RATE OF CLINICALLY SIGNIFICANT CANCER USING MAGNETIC RESONANCE IMAGING/ ULTRASOUND COGNITIVE-FUSION PROSTATE BIOPSY Sarah Silverman, Molecular Biology, Colgate University, United States Lev Elterman Purpose: To explore possible parameters that would minimize the necessity of patients undergoing prostate biopsies (Bx) and evaluate detection rates of prostate cancer using magnetic resonance imaging (MRI)/ultrasound (US) cognitive-fusion Bx. Materials and Methods: This is a retrospective chart review study of patients who underwent magnetic resonance MRI/ US cognitive-fusion or standard 12-core transrectal ultrasound (sTRUS) prostate Bx. 334 men who underwent Bx between 2015 to 2020 were included in this study; 112 of whom first underwent a high-field strength 3.0 Tesla MRI. Images were processed and interpreted through invivo DynaCAD multiparametric analysis software. Clinically significant prostate cancer (csPCa) was defined as Gleason score ≥3+4=7. Results: Of the 112 men (mean age 67 ± 7.9, mean PSA level 10 ± 9.5 ng/mL) who received prostate Bx after MRI, 68 men (43%) had suspicious lesions (≥PI-RADS 3). There was no csPCa found amongst patients with negative MRIs and PSA densities <0.1 (MRI negative vs sTRUS p=0.000017). Of the patients with negative MRIs and low risk cancer (Gleason 3+3=6), 70% of patients had one positive core (1:70%, 2:10%, 3:20%). None of these patients required active treatment. All patients with negative MRI and PSA densities <0.1 required no treatment (MRI negative vs sTRUS p=0.000015). Overall detection rate of cancer using MRI/US cognitive-fusion of suspicious lesions of PI-RADS 3 was 29% (n=12), of PI-RADS 4 was 89% (n=16), and of PI-RADS 5 was 100% (n=9). Conclusion: Patients with negative MRI and PSA densities <0.1 required no active treatment indicating potential role MRI and PSA density might play in identifying patients who would not benefit from prostate Bx. Data strongly suggests that further research is needed to identify parameters that would minimize the necessity of patients undergoing prostate Bx as well as to compare cancer detection rates of MRI/US cognitive-fusion to MRI/US fusion Bx to minimize resources needed to perform Bx.

FINAL OVERALL SURVIVAL (OS) ANALYSIS OF PROFOUND: OLAPARIB VS PHYSICIAN’S CHOICE OF ENZALUTAMIDE OR ABIRATERONE IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) AND HOMOLOGOUS RECOMBINATION REPAIR (HRR) GENE ALTERATIONS

CHEMOPREVENTION OF CARCINOGEN-INDUCED PROSTATE CANCER BY POLYPRENOLS FROM CONIFEROUS TREES: EXPERIMENTAL STUDY Murazov Yaroslav, Scientific Laboratory of Cancer Chemoprevention and Oncopharmacology, FSBI «N.N. Petrov National Medical Research Centre of Oncology» of the Ministry of Healthcare of the Russian Federation, Russia Kuzhanov Andrey Denis Prokhorov, oncourology, Russian Research Center for Radiology and Surgical Technologies, Russia

Antoine Theiry-Vuillemin, Medical Oncology, Centre Hospitalier de Besançon, France Maha Hussain Joaquin Mateo Karim Fizazi Fred Saad Neal Shore Shahneen Sandhu Kim N Chi Oliver Sartor Neeraj Agarwal David Olmos Przemyslaw Twardowski Guilhem Roubaud Mustafa Özgüroglu, MEDICAL ONCOLOGY, ISTANBUL UNIVERSITY-CERRAHPAŞA, Turkey Jinyu Kang Joseph Burgents Christopher Gresty Claire Corcoran Carrie A Adelman Johann de Bono

Introduction & Objectives: A promising strategy in the system of prevention of prostate cancer (PCa) and its precursors is chemoprevention using low-toxic agents of natural (plant) origin. The goal of present study was evaluation of the anticarcinogenic effects of a highly purified polyprenols complex (PC) from the needles of Picea Abies (L.) and Pinus sylvestris L. in a rat model of carcinogen-induced prostate carcinogenesis. Materials & methods: The study included 82 outbred mature male Wistar rats. Induction of prostate carcinogenesis was carried out using our own modification of the combined model with the administration of the carcinogen N-methyl-Nnitrosourea and mixture of testosterone propionate/testosterone phenylpropionate/testosterone isocaproate/testosterone caproate following surgical castration of animals. Rats were divided into three groups: an experimental group (n = 32) animals received PC diluted in vegetable oil; negative control (n = 38) - animals received vegetable oil; intact control (n = 12) animals without intervention. Duration of the experiment was 56 weeks. At the end of the study, as well as in animals euthanized in the terminal condition, the prostate and seminal vesicles were processed by standart histological technique. Serial sections of all lobes of the prostate and seminal vesicles were analysed by two independent pathologists.

Introduction and objectives: The Phase III randomized, openlabel PROfound trial (NCT02987543) met its primary endpoint of significantly prolonged radiographic progression-free survival with olaparib vs physician’s choice of enzalutamide or abiraterone (control arm) in patients with mCRPC with progression on prior therapy and alterations in BRCA1, BRCA2 or ATM (Cohort A), and in the overall population (Cohorts A+B) with alterations in any of 15 prespecified genes with a direct or indirect role in HRR. It was the first positive Phase III trial in a biomarker selected population of patients with mCRPC and highlighted the importance of genomic testing. Here we report the final OS data from the trial.

Results: Compared with the negative control group, the PC significantly reduced the overall incidence of prostatic intraepithelial neoplasia (PIN) from 76,5% to 44,7% (RR=0,59; 95% CI 0,38-0,91; p = 0,0186), the incidence of PIN in the dorsolateral prostate-from 70,6% to 41,4%, the incidence of PIN in the ventral lobes from 47,1% to 20,7%. Compared with the negative control group, the complex significantly reduced the overall incidence of PCa from 64,7% to 34,5% (RR=0,53; 95% CI 0,30-0,93; p = 0,0275), the incidence of PCa in the dorsolateral prostate from 58,8% to 24,1%. After long term administration of PC there was a trend towards a decrease in the frequency of metastatic PCa from 32,4% to 20,7%.

Materials and Methods: Men with mCRPC and disease progression on a prior next-generation hormonal agent (eg enzalutamide or abiraterone) were randomized 2:1 to olaparib or control treatment. Patients could cross over to olaparib upon radiographic disease progression. Following a hierarchical multiple testing procedure, a prespecified key secondary endpoint of OS in Cohort A was analysed by stratified log-rank test, with the two-sided 5% alpha split at the interim analysis (0.01) and final analysis (0.047). Prespecified sensitivity analysis of OS adjusting for the impact of crossover of patients was conducted using rank-preserving structural failure time models.

Conclusion: In our experimental study PC demonstrated anticancerogenic effects againsts PIN and PCa. Further clinical intervention studies may be promising for the primary chemoprevention of PCa in men with an increased risk of developing this disease.

Expected results: Final OS will be reported for Cohort A and for the overall population, as well as OS adjusted for patients in the control arm who switched to olaparib after progression. Additionally, updated safety results from the trial will be described. Expected conclusions: The PROfound study will demonstrate whether olaparib monotherapy leads to a clinically meaningful benefit in OS compared with enzalutamide or abiraterone, for patients with mCRPC and HRR gene alterations whose disease had progressed on prior treatment with a next-generation hormonal agent. 19

CASE REPORTS Conclusions: Peritoneal carcinomatosis of PCa is uncommon. To our knowledge, we report the second case of symptomatic malignant ascites leading to a diagnosis of metastatic prostate adenocarcinoma with isolated peritoneal carcinomatosis (first report by Megalli et al. in 1973).

SYMPTOMATIC PERITONEAL CARCINOMATOSIS AS THE INITIAL PRESENTATION OF METASTATIC PROSTATE CANCER

Initial treatment was performed with ADT alone due to patient choice, but we believe that combination therapy with docetaxel or second generation hormonotherapy would have been a better option.

João Paulo Baptista Godinho, Oncology, Hospital Beatriz Ângelo, Portugal Luísa Leal-Costa, Oncology, Hospital Beatriz Ângelo, Portugal Pedro Miguel Duarte Simões, Medical Oncology Department, Hospital Beatriz Ângelo, Portugal Carlota Sofia Vieira Baptista, Oncologia Médica, Hospital Beatriz Ângelo, Portugal Mafalda Casa-Nova José Luís Passos Coelho

The patient is on abiraterone/prednisolone therapy for 13 months with good tolerance and ongoing clinical, biochemical and radiological response.

Introduction: Prostate cancer (PCa) is the most frequent cancer in men. The most common sites of metastases are bone and lymph node, followed by lung and liver. Peritoneal metastases of PCa are rarely reported in the literature, particularly without involvement of other sites. We report a case of isolated peritoneal carcinomatosis as the initial clinical presentation of metastatic PCa. Patient Information and Clinical Findings: We report a 77 year-old male with ECOG performance status of 0 and past medical history of essential arterial hypertension and benign prostatic hyperplasia. The patient presented with abdominal enlargement in July 2018. An ultrasound documented ascites and abnormal omental thickening. A diagnostic paracentesis did not identify malignant cells. Further investigation with CT scan of thorax-abdomen-pelvis confirmed ascites and the abnormal thickening of the greater omentum, suggestive of peritoneal carcinomatosis, and an heterogeneous prostate. Upper gastro-intestinal (GI) endoscopy and colonoscopy were done to rule out GI cancer. The digital rectal exam described a “hard as a rock” prostate. A double sextant biopsy was performed and revealed a Gleason 5+4 adenocarcinoma. Serum PSA was 584 ng/mL and ascitic PSA was 2212 ng/mL with bone scan negative for metastases. Biopsy of omental thickening documented an adenocarcinoma with expression of PSA. Diagnosis and Treatment: Treatment options of PCa with isolated peritoneal metastases were extensively discussed with the patient that only accepted androgen deprivation therapy. There was a very good response, with resolution of ascites and a PSA decrease (nadir of 0.3 ng/mL in December 2018). Subsequently there was a slow and steady PSA rise, without ascites recurrence, that did not respond to hormonal manipulation with bicalutamide. In July 2019, there was an abrupt PSA rise up to 110 ng/mL associated with complaints of postprandial fullness. Serum testosterone was in accordance with castration levels; bone and CT scans only documented ascites and peritoneal carcinomatosis with no extra-peritoneal metastases. The patient refused chemotherapy. Treatment with abiraterone 1000mg/prednisolone 10mg daily was started with resolution of symptoms and a PSA decrease to a minimum of 1,08 ng/mL in January 2020, remaining in plateau ever since.

TREATMENT OF CASTRATIONRESISTANT PROSTATE CANCER

ISOLATED PERITONEAL CARCINOMATOSIS IN PROSTATE CANCER, MAYBE NOT SO RARE. ABOUT A CASE HIGHLIGHTING THE IMPORTANCE OF MODERN IMAGING AND EFFICACY OF ABIRATERONE ACETATE.

Luísa Leal-Costa, Oncology, Hospital Beatriz Ângelo, Portugal João Paulo Baptista Godinho, Oncology, Hospital Beatriz Ângelo, Portugal Pedro Miguel Duarte Simões, Medical Oncology Department, Hospital Beatriz Ângelo, Portugal Carlota Sofia Vieira Baptista, Oncologia Médica, Hospital Beatriz Ângelo, Portugal Ana Faria José Alberto Teixeira José Luís Passos Coelho

Emili Delchambre, urology, Université Catholique de Louvain, Belgium Emmanuel Seront, Medical Oncology, Hôpital de Jolimont, Belgium Stephane Rysselinck

Introduction: Prostate cancer (PC) is the most common malignancy in men. In hormone-naïve disease, treatment is based on androgen deprivation therapy (ADT) alone or in combination with either docetaxel or novel hormonal agents. Metastatic castration-resistant prostate cancer (mCRPC) has an unfavorable prognosis. Several treatment options have been approved in recent years. The optimal treatment sequence is unknown.

Metastatic prostate cancer remains a challenge for clinicians. Metastases involve mainly the bone compartment but visceral metastases could be found in up to 20% of metastatic patients and are associated with poor outcome. Peritoneal carcinomatosis is a very rare condition, particularly when not associated with other distant metastatic lesions. Peritoneal localization could easily be misdiagnosed in early stage when using conventional imaging. Even if the cause of this tropism is unknown, some authors suggested a causal link with previous laparoscopic surgery. We present the management of a patient with prostate cancer and isolated peritoneal carcinomatosis. In 2010, a 64 years-old man was diagnosed with a localized prostate cancer based on PSA increase (8ng/L). Pelvic magnetic resonance imaging (MRI) confirmed a T3 tumor based on TNM classification, without any evidence of lymph node. Biopsy showed a Gleason 7 (3+4) score. Bone scan and thoraco-abdominal computed tomography (CT) did not show any secondary lesion. External radiotherapy with concomitant androgen deprivation therapy (ADT; leuproreline for 18 months) was then performed with normalization of PSA (< 0,2ng/L) six months later. In 2014, PSA level raised progressively to 2.2 ng/ml with any suspect lesions on conventional imaging (bone scan and thoraco-abdominal CT). The very short PSA-DT led us to start ADT (degarelix) that resulted in a rapid normalization of PSA after 3 months. PSA was controlled as normal during 2 years but in 2016, it showed a rapid increase to 12ng/L, reflecting development of castration resistance. Bone scan and thoraco-abdominal CT were considered as normal but PSMA-PET showed diffuse peritoneal infra-centimetric lesions without any other suspect lesions in bone or in lymph node. Retrospective analysis of CT confirmed the presence of peritoneal lesions. Laparoscopy showed multiple suspicious lesion in the peritoneal cavity and biopsies confirmed poorly differentiated prostate adenocarcinoma. There was no sign of neuroendocrine, mucinous or small cell differentiation. Abiraterone Acetate was started and PSA level rapidly decreased to 0.4ng/L in three months. Peritoneal lesions disappeared at abdominal CT. Three years later the patient remains in radiological complete remission and with undetectable PSA.

Patient Information and Clinical Findings: We report a 51 year-old man with a diagnosis of early stage PC Gleason score 7 (3+4) in 1999. He underwent radical prostatectomy (pT2bN0, stage IIA). Diagnosis and Treatment: In 2003 there was a biochemical recurrence. Salvage radiotherapy (RT) was performed and the patient was started on ADT until 2013. In january 2013, after a new increase in PSA, an asymptomatic single bone metastasis in D2 was detected. The patient underwent RT to bone and zoledronic acid, with good biochemical response. In september 2013 the patient presented with back pain. PSA rose and new pleural, pulmonary, hepatic and lymph node metastases were detected. He completed 12 cycles of docetaxel until may 2014. There was symptomatic, radiological and biochemical response, with PSA <1ng/mL and an “almost complete” imaging response on CT scan. Zoledronic acid and ADT were maintained from may 2014 to march 2017, without progression. In april 2017, there was a new PSA rise and the patient complained of back pain and anorexia. CT revealed progression of pleural metastases. Docetaxel rechallenge for 12 cycles resulted in symptom resolution, PSA <1ng/mL and almost complete radiological response. Thereafter, PSA levels started to slowly rise until april 2018. Abiraterone was started, with no response: after 4 months, PSA continued to rise and pleural lesions reappeared. There was a PSA response after abiraterone withdrawal and steroid switch to dexamethasone. Cabazitaxel was started in september 2018. In april 2019 there was biochemical, symptomatic and radiological progression. Enzalutamide was started, with no response. Possible alternatives were discussed. Zoledronic acid was maintained. Peptide receptor radionuclide therapy prostatespecific membrane antigen (PRRT-PSMA) was requested. Unfortunately, the patient had a clinical decline in august 2019 and died in october 2019.

This case highlights the role of modern imaging such as PSMAPET in detection of early stage of metastatic disease, allowing early systemic treatment. Isolated carcinomatosis is probably underestimated but its incidence could progressively increase with the use of modern imaging. Furthermore, peritoneal carcinomatosis occurred in our patient in absence of previous laparoscopic surgery, suggesting hematological or lymphatic dissemination Finally, secondary hormonal agents such as abiraterone acetate resulted in long-lasting response.

Conclusions: This case illustrates the sequential use of several therapeutic agents in mCRPC. Palliative RT to bone in the oligometastatic setting, although not consensual, resulted in a biochemical response and has possibly delayed the need for systemic treatment. Of all the alternatives, docetaxel held the greatest clinical benefit, with an almost 34 month recurrence free period. Docetaxel rechallenge also proved to be of great clinical benefit, 5 years after documentation of mCRPC. While there was a 10-year response to ADT, abiraterone and enzalutamide failed to generate clinical responses.

TREATMENTS SEQUENCING IN METASTATIC PROSTATE CANCER NEW DIAGNOSED: MORE OPPORTUNITIES IN PROGRESSION FREE SURVIVAL. A CASE REPORT

OVERALL SURVIVAL, DISEASE PROGRESSION, AND QUALITY OF LIFE OF METASTATIC CRPC PATIENT ON ENZALUTAMIDE TREATMENT Donny Eka Putra, Urology, dr Dradjat Prawiranegara Hospital, Serang Banten, Indonesia Theddyon Bhenlie Apry Kusbin, Inpatient Department, Universitas Pelita Harapan, Indonesia

Marta Jiménez Navarro, Urology, University Hospital Nuestra Señora de la Candelaria, Spain Adrián Amador Robayna Almudena Carrion Valencia, Urology, University Hospital Nuestra Señora de la Candelaria, Spain

Background: Androgen deprivation therapy (ADT) is the preferred treatment modality for all stages of prostate cancer. It has also been accepted as the mainstay of treatment as it shows high efficacy. Enzalutamide, has been accepted as a second generation anti androgen in castration-resistant prostate cancer (CRPC) geriatric patients. However, multiple adverse effects of hormonal therapy are of particular concern given the prolong duration of the treatment and the high potential for adverse effects on patients’ functional status and quality of life. We hereby report the overall survival, disease progression, and managing fatigue as the side effect of long-term enzatulamide use in metastatic adenocarcinoma prostatic cancer that further progressed into CRPC.

Introduction: In the last years, the development of new drugs for metastatic castration-resistent prostate cancer (mCRPC) has improved survival. Abiraterone acetate (AA) is a novel hormonal agent that suppresses androgen synthesis, and is given in combination with prednisone (P) 5mg twice daily, to prevent the side effects associated with mineralocorticoid excess. RomeroLaorden and colleagues, on the phase II SWITCH trial, report that mCRPC patients treated with AA+P who were progressing responded when prednisone was changed to dexamethasone (“steroid switch”). Published data shows that after steroid switch, median progression free survival (PFS) is between 10 and 12 months. One of favorable prognostic factor identified for PFS is a long time of hormone sensitivity (>5 years).

Clinical findings: A 77 year old Chinese-Indonesian male was referred to our hospital with metastatic castration-resistant prostate cancer (mCRPC). Prostate biopsy result showed a Gleason score of 5+5=10. The patient also had a history of hypertension as well as type 2 diabetes mellitus. He had previously undergone hormonal therapy with LHRH agonist and bicalutamide for 5 years, but was shifted to enzatulamide therapy one year prior to referral. Strict periodic observation was carried out during the initial 6 months of enzatulamide therapy to monitor therapeutic outcome and side effects. The patient complained of severe lack of energy as measured by the functional assessment of the cancer therapy-prostate (FACT-P) questionnaire. The Activity of Daily Living (ADL) Barthel index assessment showed a mild dependence. To minimize the adverse effect, enzutalamide dose was reduced from the initial dose of 160 mg to 120 mg and resulted in improved fatigue symptoms. In March 2020, the patient presented with urinary retention demanding treatment with TURP and DJ stent re-insertion. During this time, the patient was also treated with increased drug dose to 160mg. At the given dose, the patient complained of persistent fatigue as well as a decreased appetite and difficulty swallowing requiring parenteral nutrition. Hence, the dose was further reduced to 80 mg, in which the patient reported improved fatigue symptoms. Upon re-evaluation, the patient reported an increase in energy level and Barthel's ADL index. The results of the patients’ PSA level evaluations are summarized in Figure 1. Moreover, a subsequent MRI evaluation revealed no additional metastases when compared to the result of prostatespecific membrane antigen (PSMA) done a year prior to the start of therapy.

Patient information: A 41 year old male patient presented with cauda equine syndrome and PSA level on 2700 ng/dl. He had no comorbidities and ride bike daily. Diagnosis and treatment: Prostate biopsy showed prostate adenocarcinoma (Gleason 3+4). Further test revealed bone metastases involving lumbar spinal and sacrum, and no visceral disease. Complete androgen deprivation therapy was started in February 2006. Twelve years later, in February 2018, became castration resistant: PSA arise to 347 ng/dl (previous in 152 ng/ dl; nadir <0,03 ng/dl), with castrate testosterone level. Bone scan shows progression of sacrum bone metastases, and continued with no visceral disease on CT scan. A new prostate biopsy was performed in order to exclude a neuroendocrine differentiation and no malignancy findings were obtained. At this time he started treatment with AA+P. 12 months later, PSA level rise to 532 ng/dl (previous stable around 394 ng/dl) with stable sacral metastasis and no new metastases in 18-F Choline PET/CT scan. Steroid switch was performed in February 2019. PSA level was progressively decreasing, and 16 months after switch (June 2020) is practically undetectable: 0,09 ng/dl. Bone scan shows partial regression of sacral metastasis. Until now, PFS is 16 months and still responding. Conclusions: In this case, it should be noted the long hormone sensitivity duration (12 years), identified as favorable prognostic factor for long PFS after steroid switch.

Conclusion: The management of adverse effects associated with long-term use enzatulamide is significant in order to maintain the quality of life and further improve the prognostic outcomes of CRPC patients, especially in geriatrics.

To date, in published data, this case suppose the lowest PSA level reached after the steroid switch, although probably it has no clinical relevance. In selected cases, this steroid switch is a cheap and safe option to obtain long term responses in patients with AA treatment.

Michał Wilk, Department of Oncology, Centre of Posgraduate Medical Education, Poland Anna Walaszkowska-Czyż Arkadiusz Rak Michał Piłka Sebastian Szmit

Anne-Emmanuella YEO, Radiation Oncology, Université Catholique de Louvain, Belgium Aurore Hendrix Nicolas Christian Confente Caterina Mansvelt Baudouin Emmanuel Seront

ACUTE CORONARY SYNDROME WITHOUT ST-ELEVATION IN A PATIENT WITH PROSTATE AND BLADDER CANCER: A CASE REPORT

ABOUT A CASE HIGHLIGHTING THE PLACE OF METASTASIS-DIRECTED THERAPY IN ISOLATED LIVER METASTASES IN PROSTATE CANCER

We present the case of a 70-year-old male patient with metastatic castration-resistant prostate cancer and bladder cancer, who suffered a non-ST-elevation myocardial infarction during abiraterone acetate treatment. The cause of ischemia was critical left main stem stenosis, and right coronary artery stenosis. Initially, the patient was qualified for conservative treatment, but due to the intensifying symptoms of myocardial ischemia, a invasive strategy was introduced. Two drug-eluting stents were implanted, leading to clinical improvement. Following the cardiac intervention, the patient was considered as a candidate for further anti-cancer therapy. Unfortunately, due to the bladder cancer progression, haemorrhage and anemia, his clinical condition exacerbated, and the patient died after 1 month from the myocardial infarct. Apart from the case description, a brief summary on the treatment of acute coronary syndromes without ST-segment elevation in cancer patients is presented as well.

Background: Metastatic prostate cancer remains a clinician challenge. Metastases involve mainly the bone compartment and can sometimes manifest as oligometastatic disease. In this setting, the role of metastasis-directed therapies (MDT) including surgery and stereotactic body ablative radiotherapy (SABR) are currently evaluated. Visceral metastases are less common and have very poor prognosis in prostate cancer. Whether treating isolated visceral metastases such as liver metastases with MDT could increase the prognosis of patients remains unknown. Case report: We report the management of a prostate cancer patient initially treated with radical prostatectomy and salvage radiotherapy and who progressed on androgen deprivation therapy (ADT) with PSA increase (10ng/ml) and detection on PSMA-PET and abdominal magnetic resonance imaging (MRI) of two centimetric liver metastases located in the segment IV. The biopsy confirmed prostate carcinoma without neuroendocrine differentiation. Abiraterone acetate (AA) was started inducing PSA decrease (0.15ng/ml) and radiological partial response after 6 months. We then performed SBRT and thermo-ablation concomitantly with AA; 6 months later, the radiological complete response on MRI and the absence of PSA increase led us to stop AA. Nine months after AA arrest, PSA increased (0.6 ng/ ml) with local liver progression on PSMA-PET and MRI. AA was then reintroduced; after 6 months, the absence of PSA decrease (1.1 ng/ml) and the local progression on imaging without any distant lesion led us to consider surgery; liver segmentectomy was performed with complete resection. AA was definitively discontinued and ADT was continued. Twelve months later, multiple liver metastases appeared. Our patient was unresponsive to docetaxel and responded only 6 months to cabazitaxel. He is currently on platinum-based chemotherapy with an excellent response. Sixty months after diagnosis of liver metastases, our patient is still alive. Among the patients with metastatic prostate cancer treated in our center between January 2016 and January 2020 (n=93), this patient was the only one presenting an oligometastatic visceral disease (less than 3 metastases) without bone metastasis. Conclusions: Isolated non-lymph node visceral metastasis is rarely described in prostate cancer and MDT is usually not considered. This case highlights the importance to consider MDT in isolated visceral metastases in order to delay local disease progression, allow interruption of systemic treatment and delay cytotoxic agents that could be potentially inefficient.

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