To investigate the diagnostic performance and interreader agreement of intraprostatic prostate cancer (PCa) detection, local extension and staging using [18F]PSMA-1007 PET in primary PCa, with whole-mount radical prostatectomy specimens as the reference standard. This prospective study included 66 patients with biopsy-proven PCa who underwent [18F]PSMA-1007 PET/MRI prior to radical prostatectomy. Four nuclear medicine physicians independently evaluated intraprostatic lesions, T stage, extracapsular extension (ECE), seminal vesicle invasion (SVI) and bilaterality, based on PROMISE V2 criteria and a standardized scoring template. Diagnostic accuracy was calculated using whole-mount histopathology as reference. Interreader agreement was assessed using Fleiss’ and weighted kappa statistics. Accurate lesion-level detection of dominant intraprostatic malignant lesions was achieved across readers with mean sensitivity of 96

In patients treated with salvage lymph node dissection (sLND) for nodal recurrence of prostate cancer, whether radioguided surgery (RGS) might improve oncologic outcomes as compared with template sLND remains unknown. This study included 259 patients who experienced a prostate-specific antigen (PSA) rise and nodal-only recurrence after radical prostatectomy and underwent pelvic sLND at 11 tertiary referral centers between 2012 and 2022. Lymph node recurrence was documented by prostate-specific membrane antigen positron emission tomography scans. The outcomes included biochemical recurrence (BCR) and clinical recurrence (CR) after sLND. The probability of freedom from each outcome was calculated using Kaplan-Meier analyses. A Cox regression analysis was used to test the hypothesis that surgical technique for sLND (template vs RGS) might be associated with oncologic outcomes. Overall, 80 (31%) and 179 (69%) patients received template and radioguided sLND, respectively. PSA level at sLND was higher in the template than in the radioguided group (median: 1.3 vs 0.6 ng/ml; p < 0.0001), whereas the number of positive nodes on final pathology did not differ between the groups (p = 0.13). The first postoperative PSA level was higher in the template than in the radioguided group (median: 0.5 vs 0.1 ng/ml; p < 0.0001). Overall, there were 181 cases of BCR and 76 cases of CR after sLND. The median follow-up for survivors was 21 mo (interquartile range: 7, 36). The 2-yr BCR-free survival rate for patients in the template versus RGS sLND group was 18% (95% confidence interval [CI]: 9%, 29%) versus 30% (95% CI: 22%, 37%). The 2-yr CR-free survival rate for the template versus RGS sLND group was 51% (95% CI: 35%, 65%) versus 73% (95% CI: 65%, 80%). On multivariable analyses, we did not find evidence of a statistically significant difference between the groups with respect to BCR after sLND (p = 0.7), whereas men treated with RGS had a lower risk of CR after sLND than those receiving template sLND (hazard ratio: 0.51; 95% CI: 0.29, 0.92; p < 0.026). Results of the sensitivity analyses were generally consistent with our main findings. Our data suggest that, in men with node-recurrent prostate cancer treated with sLND, RGS may offer important surgical guidance for surgeons, and this may eventually translate into improved oncologic outcomes. Awaiting further evidence on long-term outcomes of RGS, our study represents the most solid comparative data on different techniques for sLND and provides relevant data for counseling patients with node-only recurrent prostate cancer.

To investigate the relationship between [18F]PSMA-1007 PET parameters and biochemical recurrence-free survival (BCR-FS) in high-risk primary prostate cancer patients receiving neoadjuvant hormonal treatment. This prospective randomized, double-blind, placebo-controlled phase II trial included 89 high-risk primary prostate cancer patients who received a pelvic [18F]PSMA-1007 PET/MRI prior to and following neoadjuvant hormonal treatment. Patients were randomly assigned to neoadjuvant hormonal treatment with degarelix + apalutamide (n = 45) or degarelix + matching placebo (n = 44) for 3 months followed by radical prostatectomy and extended pelvic lymph node dissection. The following [18F]PSMA-1007 PET parameters were determined on the pre- and posttreatment [18F]PSMA-1007 PET: (i) semi-quantitative [18F]PSMA-1007 PET parameters such as SUVmax, SUVmean, PSMA-expressing volume and total lesion activity, and their absolute and relative differences; (ii) number of pelvic lymph node, distant and extraprostatic (i.e. pelvic lymph node and distant) metastases determined on [18F]PSMA-1007 PET; (iii) [18F]PSMA-1007 PET-based response criteria (aPERCIST and RECIP 1.0); (iv) molecular imaging TNM-stage as determined by PROMISE V2. 35

Background PSMA PET is the standard imaging modality for biochemically recurrent prostate cancer (BCR PCa). How-ever, the role of whole-body MRI (wb-MRI) remains unclear. This study presents an intra-individual comparison of PSMA PET and wb-MRI in patients with BCR PCa.Materials and methods This post-hoc analysis of a prospective, single-center trial included patients with BCR PCa, who underwent hybrid [68Ga]Ga-PSMA-11 or [18F]PSMA-1007 PET/MRI. Inclusion required at least two years of follow-up data after the PET/MRI, including histopathological results, imaging, and post-treatment serum PSA response. PSMA PET and wb-MRI scans were independently assessed for suspicious malignant lesions at patient and region level. Lesion verifica-tion was based on follow-up data to classify true positive (TP) and false positive findings. We compared the TP detection rate, positive predictive value (PPV), and number of TP malignant lesions between PSMA PET and wb-MRI.Results A total of 82 patients were included. At patient level, PSMA PET had significantly higher TP detection rate than wb-MRI (100% vs. 66%, p = 0.0005) and detected more TP lesions (mean 2.2 vs. 1.3, p = 0.0021). At overall region level, PSMA PET outperformed wb-MRI in TP detection rate (90% vs. 60%, p = 0.0042) and number of TP lesions (mean 2.0 vs. 1.0, p = < 0.0001). Organ-specific analysis revealed significantly higher number of TP lesions on PSMA PET for pelvic lymph nodes (mean 2.0 vs. 1.2, p = 0.016) and all lymph nodes (mean 2.9 vs. 1.2, p = 0.028). For all distant regions, PSMA PET showed higher TP detection rate (95% vs. 60%, p = 0.039). No significant differences were observed in PPV between PSMA PET and wb-MRI at patient level and all region levels.Conclusion In patients with BCR PCa, wb-MRI (i) demonstrates a significantly lower TP detection rate than PSMA PET, (ii) shows equivalent PPV and (iii) detects significantly fewer TP lesions.Trial registration ClinicalTrials.gov identifier NCT03327675

BACKGROUND AND OBJECTIVE:High-risk prostate cancer (PCa) carries a substantial risk of recurrence and progression after radical prostatectomy (RP). The ARNEO trial previously showed that apalutamide (APA) plus degarelix (DEG) improved the rates of minimal residual disease (MRD) and organ-confined pathology (ypT2) compared with matching placebo (PBO). This study aims to assess the oncological and quality-of-life outcomes of neoadjuvant DEG + APA compared with DEG + PBO. METHODS:ARNEO was a double-blind, randomised, PBO-controlled phase 2 trial investigating neoadjuvant DEG + APA in high-risk PCa patients eligible for RP. Patients received 3 mo of neoadjuvant DEG + APA or DEG + PBO. No adjuvant or salvage therapy was given unless biochemical recurrence (BCR) occurred. Quality-of-life data were collected at predefined time points. The prespecified secondary endpoints included a between-arm comparison of testosterone recovery (testosterone ≥150 ng/ml), BCR within 3 yr (prostate-specific antigen ≥0.2 ng/ml), BCR-free survival (BCR-FS), and quality of life according to treatment allocation. Quality of life was assessed using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form, International Index of Erectile Function-5 items, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 questionnaires. Exploratory analyses included metastasis-free survival (MFS) and the relation of outcomes according to pathological outcomes. KEY FINDINGS AND LIMITATIONS:With a median follow-up of 54 mo, the 3-yr BCR rate was not significantly different between groups (24% with DEG + APA vs 39% with DEG + PBO; relative risk 0.63 [95% confidence interval {CI} 0.34-1.19], p = 0.18). BCR-FS was not associated with treatment allocation (hazard ratio 0.72 [95% CI 0.37-1.41]; p = 0.34) or MRD achieved (p = 0.93). However, BCR-FS was significantly longer in patients with ypT2 or specimen-confined disease (p ≤ 0.0001). Similar outcomes regarding 3-yr BCR rates and MFS were found. The median testosterone (>150 ng/dl) recovery time was 5 mo in both the groups (p = 0.36). Quality-of-life outcomes were not different at each time point (p > 0.47). Importantly, the ARNEO trial was powered for a difference in MRD rates (primary endpoint) and not for the reported secondary endpoints. CONCLUSIONS AND CLINICAL IMPLICATIONS:At 3-yr follow-up, no differences were seen in the 3-yr BCR rate or BCR-FS between patients treated with neoadjuvant DEG + APA and those treated with DEG + PBO. Achieving MRD was not predictive of better outcomes, whereas ypT2 and specimen-confined disease were strongly associated with improved BCR-FS and MFS. Quality of life remained similar between groups at all time points.

Background and objective:Lymph node-positive (pN1) prostate cancer (PCa) is a heterogeneous disease, and a clear definition of prognostic groups is urgently needed. We aimed to assess cancer-related mortality (CRM) in different prognostic groups of pN1 patients, created based on the pathological PCa characteristics and number of positive lymph nodes (LN+). Methods:We conducted a retrospective, multicentre cohort study including 894 patients with pN1 disease treated at 15 European high-volume centres. Independent predictors for CRM were identified and pooled. A prognostic model was constructed for the prediction of CRM, accounting for death from other causes as a competing risk. The 10-yr cumulative risk of mortality was assessed. Key findings and limitations:Our model was based on pT stage (pT2-3a vs pT3b-4), surgical margin (SM) status (positive vs negative), and number of LN+ (1-4 vs >4), and included three prognostic groups. The favourable-prognosis group includes patients with pT2-3a and one to four LN+, or pT3b-4 with negative SM status. The intermediate-prognosis group included patients with pT2-3a disease and more than four LN+, or pT3b-4 disease, one to four LN+, and positive SM status. Patients in the poor-prognosis group had all three high-risk factors present. The C-index of this model was 0.73. The 10-yr cumulative CRM rates were 12% (95% confidence interval: 7.3-16%), 32% (24-40%), and 58% (40-76%), respectively, with significant differences between groups (hazard ratio 2.2-6.4, p < 0.005). Conclusions and clinical implications:The pN1 patient population is extremely heterogeneous, with an increased risk of death from PCa rather than death from other causes. In this group of patients, primary cancer characteristics (pT stage, number of LN+, and SM status) still represent the driving factors of CRM. Patient summary:Men with positive lymph nodes on pathology have an increased risk of dying from prostate cancer, rather than from other causes. Our proposed model stratifies patients into groups with different cancer-related prognosis and may aid in personalised clinical decision-making in a postoperative setting.

394 Background: High-risk prostate cancer (PCa) patients have a high risk of biochemical recurrence (BCR) and metastatic progression following local therapy. The ARNEO trial is a double-blind, placebo-controlled trial, evaluating the role of neoadjuvant degarelix with or without apalutamide before radical prostatectomy (RP) in men with high-risk PCa. Previously, we demonstrated that patients receiving neoadjuvant degarelix + apalutamide (n=45) had significantly better pathological response in terms of pT2 disease (51% vs. 27%; p=0.022) and minimal residual disease (MRD) (37.8% vs. 9.1%, p=0.002) compared to patients receiving degarelix alone (n=44). However, it was yet unclear if these improved pathological outcomes were also associated with improved oncological outcomes. Methods: High-risk PCa patients were randomly assigned 1:1 to degarelix + apalutamide versus degarelix + placebo for 12 weeks followed by radical prostatectomy. Follow-up of patients included PSA and testosterone testing every 6 months. No adjuvant radiotherapy was given. However, at time of PSA relapse (PSA >0.2 ng/ml) patients received a PSMA PET/CT. In case of negative imaging at time of BCR, patients received salvage radiotherapy to the prostate bed (+/- pelvic region). Results: All patients had a minimum follow-up of 36 months. Median follow-up was 46.5 months (IQR 42-53.5) in the degarelix + placebo arm and 46 months (IQR 42-53) in the degarelix + apalutamide arm. Median time to testosterone recovery (>50 ng/dl) was 6 and 7 months, respectively ( p = 0.15 ). In total, 14 (31%) patients in the degarelix + apalutamide arm developed BCR compared to 18 (41%) patients in the placebo arm (p=0.3). No statistically significant difference in BCR was observed between patients who achieved MRD and patients without MRD at final pathology (35% vs 38%; p = 1 ). However, ypT2 disease at final pathology was highly associated with improved BCR-free survival (11% vs 52%; p < 0.0001 ). Finally, we also looked at the prognostic value of achieving specimen-confined disease (SCD; defined as ypT2-3a AND negative surgical margins AND pN0). Patients with SCD at final pathology also had a significantly better BCR-free survival, compared to those patients without SCD (18% vs 65%; p < 0.0001 ). Conclusions: At 3 years follow-up, no statistically significant difference in terms of BCR was observed between patients treated with neoadjuvant degarelix + apalutamide or degarelix alone. MRD was not associated with improved BCR-free survival. However, ypT2 and SCD disease following neoadjuvant hormonal therapy was highly associated with improved BCR-free survival, suggesting that ypT2 and SCD disease might be used as a surrogate endpoints for improved BCR-free survival. Clinical trial information: NCT03080116 .

International Society of Urological Pathology grade group 1 (GG 1) prostate cancer (PCa) is generally considered insignificant, with recent suggestions that it should even be considered as "noncancerous". We evaluated outcomes for patients with GG 1 PCa on biopsy (bGG 1) and high -risk features (prostate -specific antigen [PSA] >20 ng/ml and/or cT3-4 stage) to challenge the hypothesis that every case of bGG 1 PCa has a benign disease course. We used the multi -institutional EMPaCT database, which includes data for 9508 patients with high -risk PCa undergoing surgery. We included patients with bGG 1 PCa ( n = 848) in our analysis and divided them into three groups according to PSA >20 ng/ml, cT3-4 stage, or both. The estimated 10-yr cancer -specific survival (CSS) rate was 96% in the overall population, 88% in the group with both PSA >20 ng/ml and cT3-4 stage, 97% in the group with PSA >20 ng/ml alone, and 98% in the group with cT3-4 stage alone. Similar CSS outcomes were found in subgroups with GG 1 PCa on pathology ( n = 502) and with GG 1 on biopsy diagnosed after 2005 ( n = 253). Study limitations include the lack of magnetic resonance imaging (MRI) staging and MRI-targeted biopsies. In conclusion, patients with GG 1 and either PSA >20 ng/ml or cT3-4 stage have a low risk of dying from their cancer after surgery. However, patients with GG 1 PCa and both PSA >20 ng/ml and cT3-4 stage are at higher risk of cancerspecific mortality and active treatment should be discussed for this subgroup. Patient summary: We assessed outcomes for patients diagnosed with low-grade prostate cancer on biopsy who also had one or two factors associated with high risk disease. Men with both of those risk factors had a higher risk of dying from their prostate cancer. Active treatment should be discussed for this subgroup of patients. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).

OBJECTIVE To investigate the effect of a dietary supplement containing fermented soy on PSA, IPSS, changes in prostate volume and prostate cancer (PCa) development after a 6-month challenge in men at increased risk of PCa and negative previous biopsies. MATERIALS AND METHODS Patients with an elevated risk of PCa, defined by either 1 of the following criteria: PSA > 3 ng/ mL, suspect lesion at digital rectal examination (DRE), suspect lesion at transrectal ultrasound (TRUS)/magnetic resonance imaging (MRI) and previous negative prostate biopsies (at least 8 cores) within 12 months before inclusion. Statistical analysis was carried out using a non- parametric 1-sided paired Wilcoxon rank sum test, chi-square test, and Fisher's exact test. RESULTS In this trial, 94 patients were eligible for analysis. A PSA response was detected in 81% of the cases. In 25.8% (24/93) of patients, a decrease of at least 3 points on the IPSS was observed. The median prostate volume did not statistically change after 6 months ( P = .908). Patients with PSA modulation required fewer investigations and had fewer positive biopsies (P < .001) and significantly fewer ISUP >= 3 lesions (P = .02). CONCLUSION We observed a significantly lower PSA level after a 6-month challenge with a fermented soy- containing supplement, and an effect on IPSS in a subset of patients. Prescribing a fermented soy supplement in patients with an increased PCa risk could lead to a better selection of patients at real increased risk of having occult PCa. (c) 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy IV (PD61)1 May 2024PD61-05 ONCOLOGICAL OUTCOMES OF NEOADJUVANT DEGARELIX WITH APALUTAMIDE (ARNEO TRIAL) VERSUS STANDARD OF CARE PRIOR TO RADICAL PROSTATECTOMY FOR HIGH-RISK PROSTATE CANCER: A PROPENSITY SCORE MATCHED ANALYSIS Alexander Giesen, Gaëtan Devos, Lorenzo Tosco, Marcella Baldewijns, Thomas Gevaert, Karolien Goffin, Petit Valentin, Mai Cindy, Raskin Yannic, Van Haute Carl, Lieven Goeman, De Meerleer Gert, Berghen Charlien, Devlies Wout, Claessens Frank, Van Poppel Hendrik, Everaerts Wouter, and Joniau Steven Alexander GiesenAlexander Giesen , Gaëtan DevosGaëtan Devos , Lorenzo ToscoLorenzo Tosco , Marcella BaldewijnsMarcella Baldewijns , Thomas GevaertThomas Gevaert , Karolien GoffinKarolien Goffin , Petit ValentinPetit Valentin , Mai CindyMai Cindy , Raskin YannicRaskin Yannic , Van Haute CarlVan Haute Carl , Lieven GoemanLieven Goeman , De Meerleer GertDe Meerleer Gert , Berghen CharlienBerghen Charlien , Devlies WoutDevlies Wout , Claessens FrankClaessens Frank , Van Poppel HendrikVan Poppel Hendrik , Everaerts WouterEveraerts Wouter , and Joniau StevenJoniau Steven View All Author Informationhttps://doi.org/10.1097/01.JU.0001009352.31737.3d.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with high-risk prostate cancer (PCa) are at high risk of biochemical recurrence (BCR) and metastatic progression after local treatment. There is an unmet need for better treatments in this patient group. The double-blind, placebo-controlled ARNEO trial investigates the role of neoadjuvant degarelix with or without apalutamide (APA) before radical prostatectomy (RP) in men with high-risk PCa. Previously, we showed that patients receiving neoadjuvant degarelix+APA had significantly better pathological response (pT2 disease and minimal residual disease). However, the study did not include a control arm that received the current standard of care (SOC) in the form of surgery without neoadjuvant therapy. METHODS: In the ARNEO trial, high-risk PCa patients were randomly assigned 1:1 to degarelix with (n=45) or without (n=44) APA for 12 weeks, followed by RP. A propensity score-matched cohort that received the current SOC in the same period was extracted using age, ISUP score of the biopsy, iPSA, cN status and MRI T-stage as matching factors for ARNEO patients treated with degarelix with APA. We decided to compare the oncological results between these two cohorts. RESULTS: We matched 38 patients from the degarelix+APA arm of the ARNEO study with 38 patients who were treated with SOC in our hospital during the same period. Median follow-up was 3 years. A total of 15 (39%) patients in the degarelix+APA arm developed a PSA increase after full testosterone recovery compared to 23 (61%) patients in the SOC arm (p=0.07). In the degarelix+APA arm, 7 (18%) patients received salvage treatment, compared to 15 (39%) patients in the matched cohort (p=0.04). In addition, no patients (0%) in the degarelix+APA arm developed metastatic disease, compared to 4 patients (11%) in the SOC arm (p=0.04). CONCLUSIONS: After 3 years of follow-up, no statistically significant difference in terms of rising PSA was observed between patients treated with neoadjuvant degarelix+APA or SOC. However, patients treated with intensified neoadjuvant treatment experienced improved metastatic disease-free survival and reduced need for adjuvant treatment. We await results after full follow-up of the ARNEO study to fully compare these cohorts. Download PPT Source of Funding: The ARNEO trial was sponsored by Janssen Pharmaceutical and Ferring Pharmaceuticals (product and budget funding). This had however no impact on this project and data was never in possession of these companies © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1281 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Alexander Giesen More articles by this author Gaëtan Devos More articles by this author Lorenzo Tosco More articles by this author Marcella Baldewijns More articles by this author Thomas Gevaert More articles by this author Karolien Goffin More articles by this author Petit Valentin More articles by this author Mai Cindy More articles by this author Raskin Yannic More articles by this author Van Haute Carl More articles by this author Lieven Goeman More articles by this author De Meerleer Gert More articles by this author Berghen Charlien More articles by this author Devlies Wout More articles by this author Claessens Frank More articles by this author Van Poppel Hendrik More articles by this author Everaerts Wouter More articles by this author Joniau Steven More articles by this author Expand All Advertisement PDF downloadLoading ...

Quantification of PSMA expression via PSMA PET is well-established, however quantification of PSMA via immunohistochemistry (IHC) is not standardized. Our aim was to determine the most optimal PSMA IHC scoring system to quantify PSMA expression with PSMA PET as reference standard. Primary intermediate- and high-risk prostate cancer patients received an [18F]PSMA-1007 PET/MRI followed by radical prostatectomy. SUVmax, SUVmean and Ki of the prostate tumor was determined. Prostate tumors were stained with anti-PSMA antibodies and scored by 2 readers via 10 IHC scoring systems: histochemical score (H-score), immunoreactivity scorepredominant intensity (IRSpredominant intensity), IRS classificationpredominant intensity, IRSmean intensity, IRS classificationmean intensity, Allred score, predominant expression pattern, Shannon diversity index (SDI), percentage negatively stained cells and total percentage positively stained cells. Spearman’s rank correlation coefficients (ρ) were calculated between PET parameters and IHC scoring systems. Interreader agreement for the IHC scoring systems was measured by the intraclass correlation coefficient (ICC). Fifty tumors in 46 patients were analysed. H-score had the best correlation with SUVmax (ρ 0.615 p < 0.0001) and SUVmean (ρ 0.570, p < 0.0001) and the second best correlation with Ki (ρ 0.411, p = 0.0030). SDI had the best correlation with Ki (ρ -0.440, p = 0.0014) and the second best correlation with SUVmax (ρ -0.516, p = 0.0001) and SUVmean (ρ -0.490, p = 0.0003). A moderate interreader agreement was observed for H-score (ICC 0.663, 95

You have accessJournal of UrologyProstate Cancer: Markers II (PD42)1 May 2024PD42-08 CAN WE USE IMMUNOHISTOCHEMISTRY AS PREDICTING FACTOR OF SUCCESSFUL TREATMENT WITH INTENSIFIED NEOADJUVANT TREATMENT IN HIGH-RISK PROSTATE CANCER: A SUBANALYSIS OF THE ARNEO TRIAL? Alexander Giesen, Gaëtan Devos, Lorenzo Tosco, Marcella Baldewijns, Thomas Gevaert, Karolien Goffin, Petit Valentin, Mai Cindy, Raskin Yannic, Van Haute Carl, Lieven Goeman, De Meerleer Gert, Berghen Charlien, Devlies Wout, Claessens Frank, Van Poppel Hendrik, Everaerts Wouter, and Joniau Steven Alexander GiesenAlexander Giesen , Gaëtan DevosGaëtan Devos , Lorenzo ToscoLorenzo Tosco , Marcella BaldewijnsMarcella Baldewijns , Thomas GevaertThomas Gevaert , Karolien GoffinKarolien Goffin , Petit ValentinPetit Valentin , Mai CindyMai Cindy , Raskin YannicRaskin Yannic , Van Haute CarlVan Haute Carl , Lieven GoemanLieven Goeman , De Meerleer GertDe Meerleer Gert , Berghen CharlienBerghen Charlien , Devlies WoutDevlies Wout , Claessens FrankClaessens Frank , Van Poppel HendrikVan Poppel Hendrik , Everaerts WouterEveraerts Wouter , and Joniau StevenJoniau Steven View All Author Informationhttps://doi.org/10.1097/01.JU.0001008560.54103.65.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with high-risk prostate cancer (PCa) have a high risk of biochemical recurrence and metastatic progression after local treatment. New treatment modalities are emerging. The ARNEO study is a double-blind, placebo-controlled trial on the role of neoadjuvant degarelix with or without apalutamide before radical prostatectomy (RP) in men with high-risk PCa. Diagnostic biopsies from 76 patients were available for immunohistochemical (IHC) staining of ERG, PSMA, Ki67, GR, PTEN and p53. The primary endpoint of the study was minimal residual disease (MRD) on final pathology and the key secondary endpoint was biochemical recurrence (BCR). The correlation between IHC and BCR were studied. METHODS: Prostate biopsies were IHC stained for PTEN, ERG, PSMA, Ki67, P53 and GR. All IHC were interpreted by a dedicated uropathologist and coded as negative/positive (ERG, GR), low/high (PSMA, Ki67) or loss of function mutation/wild type (PTEN, p53). RESULTS: With a median follow-up of 32 months, 26 patients (29%) developed BCR. When comparing patients with negative and positive staining, 9 (28%) versus 12 (27%) patients and 10 (28%) versus 11 (28%) patients experienced BCR for ERG (p=0.94) and GR (p=0.98), respectively. Of patients with high PSMA expression, 13 patients (30%) developed BCR. Of patients with low PSMA expression, 8 (24%) developed BCR (p=0.56). Of patients with low Ki67, 5 (11%) patients developed BCR, while 16 (52%) patients with high Ki67 experienced BCR (p<0.001) (Figure 1). Finally, when comparing patients with a loss of function mutation and wild-type in PTEN and p53, 14 (30%) versus 7 (23%) and 6 (29%) versus 15 (27%) developed BCR, respectively. CONCLUSIONS: Our results suggest that a low Ki67 IHC score on diagnostic biopsy before neoadjuvant hormonal therapy could be used to predict PSA relapse after RP. IHC stains for ERG, PSMA, GR, PTEN and p53 did not predict BCR. Download PPT Source of Funding: The ARNEO trial was sponsored by Janssen Pharmaceutical and Ferring Pharmaceuticals (product and budget funding). This had however no impact on this project and data was never in possession of these companies © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e895 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Alexander Giesen More articles by this author Gaëtan Devos More articles by this author Lorenzo Tosco More articles by this author Marcella Baldewijns More articles by this author Thomas Gevaert More articles by this author Karolien Goffin More articles by this author Petit Valentin More articles by this author Mai Cindy More articles by this author Raskin Yannic More articles by this author Van Haute Carl More articles by this author Lieven Goeman More articles by this author De Meerleer Gert More articles by this author Berghen Charlien More articles by this author Devlies Wout More articles by this author Claessens Frank More articles by this author Van Poppel Hendrik More articles by this author Everaerts Wouter More articles by this author Joniau Steven More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract Intensified hormone therapy in combination with radiotherapy improves outcome for very high-risk locally advanced prostate cancer. The impact of hormone therapy with surgery, however, is uncertain. In order to understand this better, we ran an ancillary translational study on ARNEO (NCT03080116), a Phase 2 clinical trial, which randomized 89 locally-advanced prostate cancer patients to 12 weeks LHRHa +/- apalutamide (APA) followed by prostatectomy. We performed clinical-grade transcriptome-wide expression array analysis (Veracyte, Inc. San Diego, CA) of FFPE diagnostic core biopsies (N=89) and tumors removed at prostatectomy (N=32 LHRHa, N=23 LHRHa + APA). We also performed RNASeq on fresh frozen biopsies of prostatectomy tumors (N=42 LHRHa, N=45 LHRHa + apalutamide) and LHRHa-naive control cases (N=61) matched for clinical and pathological risk factors. Pre-surgery serum PSA decreased by a median of 98% (IQR:90.2-99.3) after hormone treatment. This decrease was better associated with tumor AR signaling (r2=0.11) versus pre-treatment serum PSA (r2=0.0005), or between pre-treatment serum PSA with diagnostic biopsies (r2=0.008). We confirmed APA more potently suppressed AR signaling than LHRHa alone, with no detectable difference in direction of effect for differentially regulated genes/pathways. LHRHa + APA had less residual tumor (median Residual Cancer Burden, RCB=0.48cm3) than in LHRHa (median RCB=1.7cm3) but in cases with sufficient tumor, we observed residual active AR signaling pathways at prostatectomy in both treatment arms. To orthogonally confirm this, we selected 28 ERG positive cases (by IHC pre-treatment) and found retained ERG expression in 12/13 on LHRHa and 10/15 on LHRHa + APA. Using pathway analysis in the RNAseq data, we identified LHRHa +/- APA induced down-regulation of AR, metabolic pathways, as well as DNA repair, and up-regulation of hallmark NOTCH, Hedgehog, TGF-beta, WNT and immune signaling (adjusted p-value cutoff=0.001). Comparing differentially expressed genes on RNASeq between treatment-naïve versus LHRHa +/- APA treated tumors, we observed STING1 as significantly higher in LHRHa +/- APA vs control (Wilcoxon rank sum test p-value <0.001). We found that expression of STING1 was positively correlated with hallmark interferon alpha response (r=0.7, rs=0.6) that was correlated with apoptosis (r=0.5, rs=0.5). Whilst we show that adding APA to LHRHa increases suppression of AR activity and ERG expression, we find that 12 weeks is insufficient to abrogate AR signaling in most tumors, despite ~98% decrease in serum PSA. We identify novel processes modulated in humans by potent suppression of androgen activity, including upregulation of STING1-type 1 interferon response as a potential key modulator of treatment effect. Citation Format: Mazlina Ismail, Wout Devlies, Marina Parry, Gaetan Devos, Stefanie Friedrich, Charles Parker, Larissa Mendes, Elai Davicioni, Mark Linch, Frank Claessens, Steven Joniau, Gerhardt Attard. Molecular effects of neo-adjuvant hormone therapy for locally advanced prostate cancer: An ancillary study of the ARNEO phase 2 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7568.