PSA Changes Research Articles

Interval Changes in PSMA PET/CT During Radium-223 Therapy for Metastatic Bone Disease from Castration-Resistant Prostate Cancer.

Radium-223, an alpha-emitting therapeutic radiopharmaceutical, prolongs overall survival (OS) in patients with symptomatic bone-predominant metastatic castration-resistant prostate cancer (mCRPC). PSMA PET/CT is a molecular imaging tool for whole-body imaging of prostate cancer and may inform on the mechanisms of radium-223 activity and treatment resistance in mCRPC patients. In an open-label, single-arm, prospective trial, we enrolled patients with bone-predominant mCRPC to undergo baseline PSMA PET/CT, 6 cycles of radium-223, and post-therapy PSMA PET/CT. We assessed the relationship between multiple parameters of interval change on PSMA PET/CT on aPROMISE PSMA automated analysis and a human reader, and laboratory measurements. Fourteen patients were enrolled and 9 patients completed both protocol-defined PSMA PET/CT. Of the 9 evaluable patients, 1 (11%) had a complete response and 8 (89%) had PSMA PET progressive disease. All patients showed decreases in PSMA uptake in some disease sites evident on the baseline scan. The change in overall burden of disease on PSMA PET was more strongly correlated with changes in PSA (ρ = 0.95) than ALP (ρ = 0.62). Progression in bone was a common finding on post-treatment PSMA PET/CT. PSMA PET was able to assess response in individual lesions during radium-223 therapy in mCRPC patients. PSMA PET responses in previously established disease sites were universal, but most patients also showed overall PSMA PET progression during 6 cycles of radium-223. Given high correlation with changes in PSA, PSMA PET may be of limited value in follow-up during or after radium-223 in bone-predominant mCRPC.

Targeting B7-H3 in prostate cancer: Phase 2 trial in localized prostate cancer using the anti-B7-H3 antibody enoblituzumab, with biomarker correlatives.

5015 Background: B7-H3/CD276, a member of the B7 superfamily, is highly expressed in prostate cancer (PCa) and is associated with rapid biochemical recurrence and early metastases. B7-H3 is the only checkpoint candidate to have a presumptive androgen receptor binding site, suggesting interaction with the androgen axis. Enoblituzumab (MacroGenics) is an investigational humanized Fc-optimized B7-H3–targeting antibody that induces antibody dependent cellular cytotoxicity (ADCC). Methods: In this phase 2 single-arm biomarker-rich neoadjuvant trial, men with operable intermediate- and high-risk localized prostate cancer (Grade Groups 3-5) were enrolled to evaluate the safety, anti-tumor efficacy, and immunogenicity of enoblituzumab when given prior to prostatectomy. Patients received enoblituzumab (15 mg/kg IV weekly x 6) prior to surgery. Prostate glands were harvested 2 weeks after the last dose, and were examined for pathologic and immunologic endpoints. The co-primary outcomes were safety and PSA0 at 1 year post-op. Pre-planned secondary outcomes were PSA and Gleason grade group change from biopsy to prostatectomy. Results: 32 men were enrolled. Grade 3/4 adverse events occurred in 12% of patients. One patient developed a grade-3 infusion reaction, and one had immune myocarditis that improved with steroids. Pre-prostatectomy PSA declines of >10% were observed in 31% of patients (95% CI: 16-50%). PSA0 at 1 year post-op was seen in 66% of men (95% CI: 47-81%). Median time to PSA recurrence was not reached, with a median follow-up of 30 months. Gleason group upgrade, no change, and downgrade was observed in 13%, 37%, and 50% of patients. Gleason grade group changes were significantly associated with enoblituzumab treatment compared to 1:1 matched historical controls (p=0.023). Tumor microenvironment profiling by NanoString GeoMx spatial proteomics and PanCancer IO 360 mRNA expression analysis revealed post-treatment upregulation of CD8+ T cells, PD-1/PD-L1 expression, and immune activation (granzyme B, IFN signaling, myeloid inflammation). There was a significant association between CD8+ T-cell increases and Gleason grade group declines. First-in-human antigen spread profiling revealed no safety concerns. TCR sequencing showed focused peripheral expansion of tumor associated T-cell clones that correlated with PSA0 at 1 year. Whole exome and RNAseq data, and clinical correlations, will be presented. Conclusions: In this neoadjuvant trial, inhibition of B7-H3 with enoblituzumab demonstrated favorable safety and encouraging activity in localized PCa patients. Data suggest robust intratumoral induction (adaptive upregulation) of immune checkpoints, T-cell activation, and myeloid inflammation. Enoblituzumab-induced peripheral expansion of tumor associated T-cell clones may be associated with tumor control. Clinical trial information: NCT02923180.

MP43-14 EXTERNAL VALIDATION OF A MODEL PREDICTING INCREASE IN GLEASON GRADE FOR MEN ON ACTIVE SURVEILLANCE IN THE GAP3 CONSORTIUM DATABASE

You have accessJournal of UrologyCME1 May 2022MP43-14 EXTERNAL VALIDATION OF A MODEL PREDICTING INCREASE IN GLEASON GRADE FOR MEN ON ACTIVE SURVEILLANCE IN THE GAP3 CONSORTIUM DATABASE Daan Nieboer, Ivo de Vos, Lui Shiong Lee, Phillip Stricker, Mark Frydenburg, Anders Bjartell, Jose Rubio-Briones, Axel Semjonow, Antti Rannikko, Mieke van Hemelrijck, Christian Pavlovich, Peter Carroll, and Monique Roobol Daan NieboerDaan Nieboer More articles by this author , Ivo de VosIvo de Vos More articles by this author , Lui Shiong LeeLui Shiong Lee More articles by this author , Phillip StrickerPhillip Stricker More articles by this author , Mark FrydenburgMark Frydenburg More articles by this author , Anders BjartellAnders Bjartell More articles by this author , Jose Rubio-BrionesJose Rubio-Briones More articles by this author , Axel SemjonowAxel Semjonow More articles by this author , Antti RannikkoAntti Rannikko More articles by this author , Mieke van HemelrijckMieke van Hemelrijck More articles by this author , Christian PavlovichChristian Pavlovich More articles by this author , Peter CarrollPeter Carroll More articles by this author , and Monique RoobolMonique Roobol More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002609.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We have previously developed a dynamic prediction model predicting increase in Gleason grade on biopsy for men with prostate cancer (PCa) treated with active surveillance (AS). The model was based on a joint model for longitudinal and survival data predicting the risk of increase in gleason grade at biopsy using PSA, change in PSA, prostate volume and whether or not a positive lesion was found on MRI. It allows for dynamic predictions, updating the risk of increase in Gleason grade as new PSA, MRI, and biopsy data becomes available. We now aimed to validate the previously developed prediction model. METHODS: External validation of our previously developed model was performed using the six largest cohorts in the GAP3 database v3.3 containing information on MRI (John Hopkins, UCSF, UCL, MUSIC, Valencia, Sydney). The time-dependent area under the ROC (AUC) was used to quantify the ability of the prediction model to predict Gleason grade upgrading using all available information at a certain timepoint. RESULTS: Data from 2,086 patients were used for external validation. The median age at diagnosis was 64 (59-68 25th-75th percentile) and median PSA at diagnosis was 5.4 (4.1-7.3). The overall median follow-up time was 3.7 years (range: 1.4-5.1 years). Most cohorts showed a time-dependent AUC ranging between 0.65-0.80 (Figure 1), similar to the time-dependent AUC of our at model development (range 0.70-0.75). Only the time-dependent AUC for UCL and Johns Hopkins were lower (range 0.60-0.65). CONCLUSIONS: The discriminative ability of our developed model was confirmed at external validation. Further research should investigate possible sources of heterogeneity in the observed discriminative ability in the different cohorts. Source of Funding: This work was supported by the Movember Foundation. The funder did not play any role in the study design, collection, analysis or interpretation of data, or in the drafting of this paper. This abstract was submitted on behalf of the Movember Foundation’s Global Action Plan Prostate Cancer Active Surveillance (GAP3) consortium © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e746 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daan Nieboer More articles by this author Ivo de Vos More articles by this author Lui Shiong Lee More articles by this author Phillip Stricker More articles by this author Mark Frydenburg More articles by this author Anders Bjartell More articles by this author Jose Rubio-Briones More articles by this author Axel Semjonow More articles by this author Antti Rannikko More articles by this author Mieke van Hemelrijck More articles by this author Christian Pavlovich More articles by this author Peter Carroll More articles by this author Monique Roobol More articles by this author Expand All Advertisement PDF DownloadLoading ...

MP29-07 FIVE-YEAR OUTCOMES AFTER AQUABLATION COMPARED TO TURP: THE FINAL WATER STUDY RESULTS

You have accessJournal of UrologyCME1 May 2022MP29-07 FIVE-YEAR OUTCOMES AFTER AQUABLATION COMPARED TO TURP: THE FINAL WATER STUDY RESULTS Peter Gilling Peter GillingPeter Gilling More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002572.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To compare five-year safety and efficacy outcomes after Aquablation or transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms (LUTS) related to benign prostate hyperplasia (BPH). METHODS: 181 patients with BPH were assigned at random (2:1 ratio) to either Aquablation or TURP. Patients and follow-up assessors at each site were blinded to treatment. Assessments included International Prostate Symptom Score (IPSS), Male Sexual Health Questionnaire (MSHQ), International Index of Erectile Function (IIEF) and uroflow (Qmax). RESULTS: The primary safety endpoint was successfully achieved at 3 months where the Aquablation group had a lower event rate compared to TURP (26% vs. 42%, p=.0149 for superiority). The rate of persistent grade 1 events (all of which were retrograde ejaculation) at month 3 was lower (7% vs. 25%, p=.0004) after Aquablation and the rate of grade 2 and above events was similar across groups (20% for Aquablation vs. 23% for TURP, p=.3038). The primary efficacy endpoint was successfully achieved at 6 months where the mean IPSS decreased from baseline by 16.9 points for Aquablation and 15.1 points for TURP; the mean difference in change score at 6 months was 1.8 points larger for Aquablation (p<.0001 for non-inferiority, p=.1346 for superiority).At five years, IPSS scores improved by 15.5 points in the Aquablation group and 13.5 points in TURP (p=.3768, 95% CI for difference -6.4 to 2.5 points). Improvements in maximum flow rate (Qmax) were large in both groups at 10.4 and 9.0 cc/sec for Aquablation and TURP, respectively (p=.9078, 95% CI for difference -4.3 to 7.0). PSA was reduced in both groups; the change in PSA at month 60 did not differ across groups (p=.9460). CONCLUSIONS: Aquablation data at five years has been shown to be durable and consistent across all years of follow-up and comparable to TURP. Retrograde ejaculation rates were less for Aquablation. *On behalf of WATER study investigators. Source of Funding: PROCEPT BioRobotics © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e471 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Peter Gilling More articles by this author Expand All Advertisement PDF DownloadLoading ...

MP35-14 PATIENT SATISFACTION AFTER SWITCHING TO ORAL TESTOSTERONE UNDECANOATE IN MEN CURRENTLY RECEIVING TESTOSTERONE THERAPY: AN OPEN-LABEL SINGLE-CENTER PHASE IV CLINICAL TRIAL

You have accessJournal of UrologyCME1 May 2022MP35-14 PATIENT SATISFACTION AFTER SWITCHING TO ORAL TESTOSTERONE UNDECANOATE IN MEN CURRENTLY RECEIVING TESTOSTERONE THERAPY: AN OPEN-LABEL SINGLE-CENTER PHASE IV CLINICAL TRIAL Rohit Reddy, Mehul Patel, and Ranjith Ramasamy Rohit ReddyRohit Reddy More articles by this author , Mehul PatelMehul Patel More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002589.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone deficiency (TD) is defined by an insufficient production of testosterone (T) combined with symptoms such as decreased libido. Multiple delivery systems such as gels and injections are currently available; however, oral formulations have been unavailable in the United States due to hepatoxicity and variable bioavailability. Oral formulations of T are convenient, easy to use, and avoid the problems of other forms of testosterone therapy (TT) such as painful injections and transference. Jatenzo® is a novel US FDA approved formulation of oral T undecanoate that provides a uniform response. In this study, we evaluated patient satisfaction of Jatenzo® as compared to other forms of T. We hypothesize Jatenzo® will have similar patient satisfaction compared to other forms. METHODS: Qualifying patients between ages 18 and 65 with TD symptoms and two T levels <300 ng/dL were recruited into this 26-week single-center open-label non-randomized phase IV clinical trial. Patients were required to previously have received TT, completed an adequate washout period, and then were started on Jatenzo®. The primary outcome was Treatment Satisfaction Questionnaire for Medication (TSQM-9), a validated questionnaire for medication satisfaction, as well as changes in TD symptoms as measured by the quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire at the 3 and 6 month intervals compared to baseline. Serum T, PSA, hematocrit, and estradiol were also evaluated at each time point. RESULTS: Of the patients recruited, 53% were previously on subdermal pellets, 27% on intramuscular injections, 13% on dermal gels, and 7% on nasal gels. T levels increased from a baseline mean of 201 ng/dL to 686 ng/dL at 1 month and 527 ng/dL at 3 months. Patient satisfaction as measured by TSQM-9 remained similar on oral T undecanoate at 38.3 compared to 39.3 on the prior TT. TD symptoms as measured by qADAM were also similar at 34 compared to 33.5 on prior TT. No significant difference was noted in side effects such as polycythemia or changes in estradiol and PSA. CONCLUSIONS: Oral T undecanoate appears to provide similar patient satisfaction and similar improvement in TD symptoms as other forms of TT. In addition, it increases serum total T to the normal range (300–1000 ng/dL) in >90% of men without a difference in side effect profile. Source of Funding: Investigator-initiated grant provided by Clarus Therapeutics to RR. Trial registration: NCT04983940. Registered 30 July 2021. https://clinicaltrials.gov/ct2/show/NCT04983940 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e592 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rohit Reddy More articles by this author Mehul Patel More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF DownloadLoading ...

MP01-18 GREENLIGHT PHOTOVAPORIZATION OF THE PROSTATE IN HIGH-MEDICAL-RISK PATIENTS: AN ANALYSIS OF THE GLOBAL GREENLIGHT GROUP (GGG) DATABASE

You have accessJournal of UrologyCME1 May 2022MP01-18 GREENLIGHT PHOTOVAPORIZATION OF THE PROSTATE IN HIGH-MEDICAL-RISK PATIENTS: AN ANALYSIS OF THE GLOBAL GREENLIGHT GROUP (GGG) DATABASE David-Dan Nguyen, Claudia Deyirmendjian, Kyle Law, Naeem Bhojani, Dean Elterman, Bilal Chughtai, Franck Bruyere, Luca Cindolo, Giovanni Ferrari, Carlos Vasquez-Lastra, Tiago Borelli-Bovo, Edgardo Becher, Hannes Cash, Maximillian Reimann, Enrique Rijo, Vincent Misrai, and Kevin Zorn David-Dan NguyenDavid-Dan Nguyen More articles by this author , Claudia DeyirmendjianClaudia Deyirmendjian More articles by this author , Kyle LawKyle Law More articles by this author , Naeem BhojaniNaeem Bhojani More articles by this author , Dean EltermanDean Elterman More articles by this author , Bilal ChughtaiBilal Chughtai More articles by this author , Franck BruyereFranck Bruyere More articles by this author , Luca CindoloLuca Cindolo More articles by this author , Giovanni FerrariGiovanni Ferrari More articles by this author , Carlos Vasquez-LastraCarlos Vasquez-Lastra More articles by this author , Tiago Borelli-BovoTiago Borelli-Bovo More articles by this author , Edgardo BecherEdgardo Becher More articles by this author , Hannes CashHannes Cash More articles by this author , Maximillian ReimannMaximillian Reimann More articles by this author , Enrique RijoEnrique Rijo More articles by this author , Vincent MisraiVincent Misrai More articles by this author , and Kevin ZornKevin Zorn More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002513.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous analyses of the safety and effectiveness of GreenLight photoselective vaporization of the prostate (PVP) in high-medical-risk (HMR) patients were limited by their small sample size and the ability to adjust for important confounders. We sought to characterize the adjusted outcomes of GreenLight PVP in HMR patients using data from the largest international database. METHODS: Data were obtained from the Global GreenLight Group (GGG) database which pools data of eight high-volume, experienced surgeons, from a total of seven international centers. All men with established benign prostatic hyperplasia who underwent GreenLight PVP using the XPS-180 W system between 2011 and 2019 were eligible for the study. HMR patients were defined as patients with ASA III or greater and were compared to non-HMR patients. Analyses were adjusted for patient age and prostate volume. RESULTS: In the HMR group, patients on average were older and had smaller prostates than the non-HMR control group. Pre-operatively, HMR patients had greater PVR and worse QoL. Compared to non-HMR patients, transfusions occurred more frequently (2.6% vs. 0.14%, p<0.01) and the odds of readmission were elevated [OR 2.0, (95% CI 1.4–2.8, p<0.01)] among HMR patients. Twelve months postoperatively, HMR patients experience greater improvement in QoL than the control group [+0.54 (95% CI 0.07–1.0, p=0.02)]. PVR also decreased 93.1ml more in HMR than in non-HMR patients after 12 months (95% CI 33.6–152.6, p<0.01). PSA and Qmax change did not differ significantly between both study arms. CONCLUSIONS: We found that GreenLight PVP is safe and effective in improving functional outcomes in higher-risk patients with severe systemic disease. Though absolute risks remain low, GreenLight PVP is associated with higher odds of transfusion and readmission in the high-risk cohort. The findings of our study reaffirm current guidelines that propose PVP as a viable treatment option for HMR patients. Source of Funding: No funding or other financial support was received © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e8 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information David-Dan Nguyen More articles by this author Claudia Deyirmendjian More articles by this author Kyle Law More articles by this author Naeem Bhojani More articles by this author Dean Elterman More articles by this author Bilal Chughtai More articles by this author Franck Bruyere More articles by this author Luca Cindolo More articles by this author Giovanni Ferrari More articles by this author Carlos Vasquez-Lastra More articles by this author Tiago Borelli-Bovo More articles by this author Edgardo Becher More articles by this author Hannes Cash More articles by this author Maximillian Reimann More articles by this author Enrique Rijo More articles by this author Vincent Misrai More articles by this author Kevin Zorn More articles by this author Expand All Advertisement PDF DownloadLoading ...

Total Tumor Volume on 18F-PSMA-1007 PET as Additional Imaging Biomarker in mCRPC Patients Undergoing PSMA-Targeted Alpha Therapy with 225Ac-PSMA-I&T.

Background: PSMA-based alpha therapy using 225Ac-PSMA-I&T provides treatment for metastatic castration-resistant prostate cancer (mCRPC), even after the failure of 177Lu-PSMA radioligand therapy (RLT). In clinical routine, the total tumor volume (TTV) on PSMA PET impacts therapy outcomes and plays an increasing role in mCRPC patients. Hence, we aimed to assess TTV and its changes during 225Ac-PSMA-I&T RLT. Methods: mCRPC patients undergoing RLT with 225Ac-PSMA-I&T with available 18F-PSMA-1007 PET/CT prior to therapy initiation were included. TTV was assessed in all patients using established cut-off values. Image derived, clinical and biochemistry parameters (PSA, LDH, AP, pain score) were analyzed prior to and after two cycles of 225Ac-PSMA. Changes in TTV and further parameters were directly compared and then correlated with established response criteria, such as RECIST 1.1 or mPERCIST. Results: 13 mCRPC patients were included. The median overall survival (OS) was 10 months. Prior to 225Ac-PSMA RLT, there was no significant correlation between TTV with other clinical parameters (p > 0.05 each). Between short-term survivors (STS, <10 months OS) and long-term survivors (LTS, ≥10 months OS), TTV and PSA were comparable (p = 0.592 & p = 0.286, respectively), whereas AP was significantly lower in the LTS (p = 0.029). A total of 7/13 patients completed two cycles and underwent a follow-up 18F-PSMA-1007 PET/CT. Among these patients, there was a significant decrease in TTV (median 835 vs. 201 mL, p = 0.028) and PSA (median 687 ng/dL vs. 178 ng/dL, p = 0.018) after two cycles of 225Ac-PSMA RLT. Here, percentage changes of TTV after two cycles showed no direct correlation to all other clinical parameters (p > 0.05 each). In two patients, new PET-avid lesions were detected on 18F-PSMA-1007 PET/CT. However, TTV and PSA were decreasing or stable. Conclusion: PET-derived assessment of TTV is an easily applicable imaging biomarker independent of other established parameters prior to 225Ac-PSMA RLT in these preliminary follow-up data. Even after the failure of 177Lu-PSMA, patients with extensive TTV seem to profit from RLT. All but one patient who was eligible for ≥2 cycles of 225Ac-PSMA-RLT demonstrated drastic TTV decreases without direct correlation to other biomarkers, such as serum PSA changes. Changes in TTV might hence improve the response assessment compared to standard classifiers by reflecting the current tumor load independent of the occurrence of new lesions.

A single arm phase II study of bone-targeted Sn-117\xa0m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases

BackgroundSeveral bone-seeking radionuclides have been developed for palliation of metastatic bone pain since 1956, however, so far radium-223 dichloride is the first and only Food and Drug Administration (FDA) approved targeted alpha therapy for metastatic castration-resistant prostate cancer (mCRPC) based on ALSYMPCA phase 3 study. While radium-223 does improve pain and overall survival outcomes, the improvement can come at the expense of side effects such as bone marrow toxicity. The development of new and better treatment with long-standing pain relief is clearly an unmet medical need.MethodsThe study is a non-randomized phase II study. The study population consists of 25 patients with CRPC who had progressed on any lines of prior therapies and whose serum testosterone level is less than 50 ng/dl and have metastatic lesions to at least two bone sites, with at least one site that has clinically meaningful pain at baseline (≥ 4 on an 11-point intensity scale). Eligible patients will be given two cycles of Sn-117 m-DTPA every 8 weeks or 56 days. Treatment will be administered by slow IV injection over 5–10 min. Retreatment after two cycles is allowed if patients meet the following retreatment criteria. The primary objective is to evaluate the efficacy of Sn-117 m-DTPA on sustained pain response in patients with CRPC metastatic to at least two bone sites and at least one with clinically meaningful pain at baseline (≥ 4 on an 11-point pain intensity scale). Sustained pain response is defined as: 1) achieving pain index ≤ 3 within a 12-week period and 2) maintaining pain index ≤ 3 over a 16-week period. The secondary objectives are: safety and tolerability, measurement of Sn-117 m-DTPA activity by gamma-camera dosimetry scans, therapeutic efficacy, time to the first symptomatic skeletal event, duration of pain response, changes in PSA and ALP levels, patient-reported outcomes and progression free survival and overall survival.DiscussionSn-117 m-DTPA is a unique bone-targeting theranostic radiopharmaceutical agent that selectively binds most heavily to bone metastases sites. This study will be the first prospective phase II trial to assess the pain efficacy and anti-tumor activity of Sn-117 m-DTPA in mCRPC with at least one clinically meaningful pain at baseline.Trial registration.ClincialTrials.gov Identifier: NCT04616547.

Immunotherapy to prevent progression on active surveillance study (IPASS): A phase II, randomized, double-blind, controlled trial of PROSTVAC in prostate cancer patients who are candidates for active surveillance.

249 Background: Immunotherapy could potentially prevent disease progression for early-stage prostate cancer. In this randomized Phase 2 clinical trial, we evaluated the clinical effects of PROSTVAC, a vaccinia/fowlpox viral vector-based immunotherapy that contains PSA and three T-cell costimulatory molecules, in patients with localized prostate cancer. Methods:154 patients with clinically localized, low- or favorable intermediate-risk prostate cancer active surveillance were randomized (2:1) to receive 7 doses of subcutaneous PROSTVAC or placebo (empty fowlpox vector) over 140 days. Post-intervention prostate biopsy was performed 7-14 days after the last dose. Participants were followed for 6 months post-treatment. The primary outcome was change from baseline to post-vaccination in CD4 and CD8 T cell infiltration in biopsy tumor tissue. Secondary outcomes included changes in prostate biopsy Gleason grade (Grade Group) and serum PSA. Results: There were no differences in CD4 and CD8 densities (count of cells/mm2) in post-treatment biopsy tumor tissue between groups ( p = 0.63 and p = 0.75, respectively). Compared to placebo, patients who received PROSTVAC were less likely to demonstrate upgrading at follow-up biopsy, but this difference did not attain significance (22% vs. 40%, p= 0.08). There was no difference in the change of PSA from baseline to 6 months post-treatment between arms ( p= 0.30). Conclusions: In this first-of-kind trial of immunotherapy for localized prostate cancer, PROSTVAC was well tolerated but did not elicit significant prostate tissue T-cell responses compared to placebo. The favorable post-treatment biopsy grade findings in PROSTVAC patients merit further evaluation and longer-term clinical follow-up. Clinical trial information: NCT02326805.

Real-world experience with relugolix.

57 Background: Gonadotropin-releasing hormone (GnRH) antagonists were developed in part to avoid testosterone flare to achieve faster and more consistent testosterone suppression. Relugolix (Rel) was given FDA approval for use in prostate cancer (PCa) based on the phase 3 HERO trial but some real-world concerns include compliance, affordability, and performance in patients transitioning from another GnRH agent or in combination with other therapeutic agents. The aim of our study was to evaluate the real-world implications of prescribing and/or switching to Rel. Methods: A single institution retrospective study was conducted on patients prescribed Rel. Treatment data including concomitant therapeutic agents were collected. Compliance data was measured via chart review and pharmacy dispensary records. Patients were classified as either newly castrated or transitioning from another agent. PSA and testosterone levels were tabulated. Reported adverse effects (AE), and reasons for discontinuation if applicable including financial toxicity were noted. Results: 50 patients were reviewed; 15 (30%) treated for adjuvant, 18 (36%) for biochemical recurrence, and 17 (34%) for metastatic PCa. 12% were on concomitant therapy with abiraterone, 4% with enzalutamide, and 2% with apalutamide. 80% reported compliance to Rel. 5 (10%) never filled the prescription. 30 (60%) were newly castrated (castration restart or naïve) while 16 (36%) were transitioned from another GnRH. No changes in PSA or testosterone were noted in patients switched form injected GnRH to Rel. The most common documented AE effects included hot flashes 24%, fatigue, 29%, and weight gain 9%. No unexpected toxicity was reported in combination with abiraterone. Of 11 patients who discontinued therapy, 45% did so due to cost, 36% due to AE, and 27% due to therapy completion. 4 of 16 (25%) of those who transitioned from injection GnRH felt symptoms were worse on Rel. Conclusions: In our early experience with Rel, patients did comply to therapy based on self-reporting, pharmacy fill dates, and laboratory evidence of castration. However, financial toxicity was and remains a significant barrier both accessing Rel and remaining on Rel therapy. While a differential toxicity was reported by those who switched from injection GnRH, sometimes leading to discontinuation, there were no new safety signals reported, especially in combination with abiraterone.

Randomized controlled trial of GnRH antagonist monotherapy versus GnRH agonist plus bicalutamide (CAB) for patients with metastatic hormone-sensitive prostate cancer (mHSPC) (KYUCOG-1401).

99 Background: To investigate a clinical response of GnRH antagonist monotherapy against CAB therapy for mHSPC. Methods: Histopathological confirmed mHSPC patients were randomly assigned to GnRH antagonist monotherapy group (Group A) and CAB group (Group B). A deferred CAB therapy by adding bicalutamide to GnRH antagonist was performed in Group A after PSA progression. The primary endpoint was PSA progression free survival (PSA-PFS). The secondary endpoints were time to CAB treatment failure (CAB-TTF), radiographic progression free survival (rPFS), overall survival (OS), change of PSA, effect on hormone dynamics, change of bone metabolic markers, effect on lipid metabolism, adverse events (AE). This trial was registered with UMIN-CTR (UMIN000014243). Results: A total of 200 patients (101 patients in Group A and 99 in Group B) were registered from June 2014 to June 2017. The PSA-PFS was significantly better in Group B (HR (95% CI) =1.40 (1.01-1.95), p=0.041) as shown in the table. Time to CAB treatment failure (TTF) tended to be better in Group A, but there was no statistically significant difference in CAB-TTF between two groups (Table). rPFS and OS were also not statistically significant difference (Table). Time to PSA nadir was significantly shorter in Group B (HR (95% CI) = 0.72 (0.54 - 0.97), p = 0.028). The proportion of patients whose serum testosterone did not reach or maintain the castration level was more frequent in Group A (significant difference at 60 weeks, p = 0.046). There was no significant difference in the effect of bone metabolic markers and lipid metabolism between two groups. In terms of AE, injection-site-reaction was more frequent in Group A. Conclusions: LH-RH agonist CAB therapy (Group B) prolonged PSA-PFS compared to LH-RH antagonist monotherapy (Group A), probably due to the higher frequency of insufficient achievement of castration level in Group A. However, a deferred CAB therapy by adding bicalutamide to GnRH antagonist resulted in no difference in CAB-TTF, rPFS and OS. Clinical trial information: UMIN000014243.[Table: see text]

CALCIUM CARBONATES EFFECT ON PARTICLE SIZE DISTRIBUTION AND TEXTURE CLASSES IN CALCAREOUS SOILS IN SULAIMANI GOVERNORATE.

This experiment was carried out to study the effect of removal of CaCO3 on particle size distribution (PSD) and texture classes in some soils in Sulaimani Governorate, Kurdistan region, Iraq. Thirty four soil samples were collected from different calcareous soil horizons. These soils were analyzed for CaCO3 and the carbonates were ranged from 51.9 and 42.63 g kg-1. The three weighted soil textures (sand, silt and clay) were determined before any removal of the CaCO3 and after the removal of CaCO3. The sand fraction ranged from 87.6 to 316.0 g gk-1 while the clay fraction ranged from 237.7 to 614.7 g kg-1 and the silt fraction was slightly higher than clay fraction. The results showed that removal of CaCO3 led to a change in PSD in all the samples and 85% of those changed textural class. The carbonates did not show a uniform distribution in soil particle size and generally carbonates were most accumulated in sand and silt size. The soil had the most prevalent PSA change in the silt and sand fractions following CaCO3 removal. The maximum significant correlation between particle size distribution before and after carbonates removal was related to clay particles (P< 0.01) but the correlation was not significant between the silt components. Therefore, we recommend that all calcareous soil samples from the semiarid be pretreated for CaCO3 removal prior to particle-size analysis and subsequent textural classification.

High-Intensity Focused Ultrasound (HIFU) Focal Therapy for Localized Prostate Cancer with MRI-US Fusion Platform.

Objective The study aimed at investigating the outcome of prostate HIFU focal therapy using the MRI-US fusion platform for treatment localization and delivery. Methods It is a prospectively designed case series of HIFU focal therapy for localized prostate cancer. The inclusion criteria include clinical tumor stage ≤T2, visible index lesion on multiparametric MRI less than 20 mm in diameter, absence of Gleason 5 pattern on prostate biopsy, and PSA ≤ 20 ng/ml. HIFU focal therapy was performed in the conventional manner in the beginning 50% of the series, whereas the subsequent cases were performed with MRI-US fusion platform. The primary outcome was treatment failure rate which is defined by the need of salvage therapy. Secondary outcomes included tumor recurrence in follow-up biopsy, PSA change, perioperative complications, and postoperative functional outcomes. Results Twenty patients underwent HIFU focal ablation. HIFU on an MRI-US fusion platform had a trend of a longer total operative time than the conventional counterpart (124.2 min vs. 107.1 min, p=0.066). There was no difference in the mean ablation volume to lesion volume ratio between the two. The mean PSA percentage change from baseline to 6-month is more significant in the conventional group (63.3% vs. 44.6%, p=0.035). No suspicious lesion was seen at 6-month mpMRI in all 20 patients. Two patients, one from each group, eventually underwent radical treatment because of the presence of clinically significant prostate cancer in the form of out-of-field recurrences during follow-up biopsy. No significant difference was observed before and after HIFU concerning uroflowmetry, SF-12 score, and EPIC-26 score. It was observed that energy used per volume was positively correlated with PSA density of the patient (r = 0.6364, p=0.014). Conclusion In conclusion, HIFU with conventional or MRI-US fusion platform provided similar oncological and functional outcomes.

Working Towards a New Definition of Biochemical Failure in the Era of Stereotactic Body Radiation Therapy for Prostate Cancer

Since the seminal Phoenix definition (nadir PSA+2) of biochemical failure (BCF) was published in 2006, increasingly more patients with low- and intermediate-risk prostate cancer (PCa) are being treated with stereotactic body radiation therapy (SBRT). Since SBRT leads to lower nadir PSA (nPSA) compared to conventionally fractionated RT, we investigated if an earlier nPSA+threshold can be used as an alternative definition of BCF.PSA kinetics from 9 institutions were retrospectively analyzed for patients with localized PCa treated definitively with SBRT alone from 2003 to 2018. Patients received 35 to 40 Gy in 5 fractions, 38 Gy in 4 fractions or 26 Gy in 2 fractions (EQD23 Gy = 70-95 Gy) per institutional standards. Cox multivariable regression model was used to determine the adjusted association of relative change in PSA kinetics with biochemical relapse-free survival (BRFS) and association of BCF with time to nadir+2.A total of 2061 patients were included. Median follow-up was 71.9 months (interquartile range [IQR], 41.2-96.0). BCF occurred in 140 (6.8%) of patients. Median nPSA was 0.16 ng/mL, median time to nPSA was 48 months. Sensitivity of Phoenix definition for BCF was 93%, compared to 96%, 100%, and 100% for nPSA+1.5, nPSA+1.0 and nPSA+0.5, respectively. False positive rate of Phoenix definition was 30%, compared to 41%, 58%, and 71% for nPSA+1.5, nPSA+1.0 and nPSA+0.5, respectively. In patients who developed BCF, lead time gained from an earlier nPSA+threshold definition compared to Phoenix definition was 6 (IQR 0-15.3), 0 (IQR 0-11.3), 0 (IQR 0-0) months for nPSA+0.5, nPSA+1.0 and nPSA+1.5, respectively. Relative change in PSA between 6 months and 18 months after treatment was significantly associated with BRFS (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.28-2.34, P < 0.0004). Among the 30% patients who had a false call of BCF due to PSA bounce, 48 (84.2%) reached nPSA+2 in ≤18 months, and 9 (15.8%) in > 18 months. In patients who had BCF, 27 (19.3%) reached nPSA+2 in ≤18 months, and 113 (80.7%) in > 18 months. Median time to nPSA+2 was significantly longer in patients with BCF (41 vs. 12 months, P < 0.002). BCF is associated with longer time to nPSA+2 (HR 0.13, 95% CI 0.09-0.20, P < 0.002).A lower nadir-based threshold provides minimal increase in sensitivity at the cost of a higher false positive rate and does not provide a clinically relevant lead time benefit for a pending BCF in patients with low- to intermediate-risk PCa undergoing SBRT. A rate-of-change based metric in the first 18 months post-SBRT is significantly associated with BRFS. Patients who have an early PSA bounce after SBRT rarely develop a true BCF and true BCF tends to happen later (> 18 months). Phoenix definition remains a valuable tool in the SBRT era. BCF should not be prematurely called which runs the risk of high rates of false positivity.

MP46-08 A MULTI-INSTITUTIONAL STUDY OF MRI/ULTRASOUND FUSION IMAGING AND BIOPSY IN COMBINATION WITH NANOPARTICLE DIRECTED FOCAL THERAPY FOR ABLATION OF PROSTATE TISSUE

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy (MP46)1 Sep 2021MP46-08 A MULTI-INSTITUTIONAL STUDY OF MRI/ULTRASOUND FUSION IMAGING AND BIOPSY IN COMBINATION WITH NANOPARTICLE DIRECTED FOCAL THERAPY FOR ABLATION OF PROSTATE TISSUE Arvin George, Steven Canfield, Joshua Jue, Sara Lewis, Matthew Davenport, Varaha Tammisetti, Mahir Maruf, Leonardo Borregalaes, Jon Schwartz, Naomi Halas, and Ardeshir Rastinehad Arvin GeorgeArvin George More articles by this author , Steven CanfieldSteven Canfield More articles by this author , Joshua JueJoshua Jue More articles by this author , Sara LewisSara Lewis More articles by this author , Matthew DavenportMatthew Davenport More articles by this author , Varaha TammisettiVaraha Tammisetti More articles by this author , Mahir MarufMahir Maruf More articles by this author , Leonardo BorregalaesLeonardo Borregalaes More articles by this author , Jon SchwartzJon Schwartz More articles by this author , Naomi HalasNaomi Halas More articles by this author , and Ardeshir RastinehadArdeshir Rastinehad More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002067.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Focal therapy is currently being evaluated as an alternative to whole gland therapy in men with low to intermediate risk prostate cancer. There are several different modalities that are utilized to focally treat prostate tissue/tumors, however most modalities have some degree of non-target ablation. We report the final results of the first in human, nanoparticle directed focal ablation of prostate tissue using MRI/Ultrasound fusion guidance. METHODS: This is an open-label, multi-center study of men with low to intermediate risk localized prostate cancer treated with a single-dose of AuroLase therapy and the focal excitation of neoplastic prostate tissue via nanoparticle directed excitation. Up to two focal areas of prostate cancer confirmed by MRI/Ultrasound guided biopsy with no disease appreciated outside of the region of each lesion were included. Efficacy of focal prostate tissue ablation was assessed by MRI/Ultrasound guided biopsy and serum PSA at 3 and 12 months. RESULTS: 45 men were enrolled in the study. 44 men completed infusion and ablation, with a total of 45 lesions included in the study. The mean PSA at baseline was 9.6, which decreased to 3.6 at 3 months and 4.9 at 12 months, p<0.01. 33 lesions (73.3%) were negative and 12 lesions (26.7%) were positive on 3 month and 12 month postablation biopsy, p=0.54. 1 patient underwent salvage cryotherapy at 12 months. Serum PSA, PSA velocity, change in PSA, and proportional change in PSA at baseline, 3 months, and 12 months were not significant predictors of lesion biopsy result. CONCLUSIONS: Ultra-focal ablation of neoplastic prostate tissue via nanoparticle directed excitation results in a 73.3% lesion ablation success rate confirmed by an end of study MRI/Ultrasound fusion guided biopsy of the treated lesion and standard template. Source of Funding: Sponsored by Nanospectra Biosciences, Inc. and Philips Healthcare © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e816-e816 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Arvin George More articles by this author Steven Canfield More articles by this author Joshua Jue More articles by this author Sara Lewis More articles by this author Matthew Davenport More articles by this author Varaha Tammisetti More articles by this author Mahir Maruf More articles by this author Leonardo Borregalaes More articles by this author Jon Schwartz More articles by this author Naomi Halas More articles by this author Ardeshir Rastinehad More articles by this author Expand All Advertisement Loading ...

MP09-11 GREENLIGHT LASER PROSTATECTOMY: ARE OUTCOMES SUSTAINABLE AFTER A DECADE OF SURGERY? A SINGLE CENTER EXPERIENCE WITH UP TO 15 YEARS' FOLLOW-UP

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Surgical Therapy & New Technology II (MP09)1 Sep 2021MP09-11 GREENLIGHT LASER PROSTATECTOMY: ARE OUTCOMES SUSTAINABLE AFTER A DECADE OF SURGERY? A SINGLE CENTER EXPERIENCE WITH UP TO 15 YEARS' FOLLOW-UP Ahmed Ibrahim, Nawar Touma, Ahmad M. AlShammari, Serge Carrier, and Mélanie Aubé-Peterkin Ahmed IbrahimAhmed Ibrahim More articles by this author , Nawar ToumaNawar Touma More articles by this author , Ahmad M. AlShammariAhmad M. AlShammari More articles by this author , Serge CarrierSerge Carrier More articles by this author , and Mélanie Aubé-PeterkinMélanie Aubé-Peterkin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001982.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Since its introduction in 2005, GreenLight laser has been widely adopted as a convenient source of energy for surgical treatment of benign prostatic hyperplasia (BPH). However, there is paucity in the literature quantifying long-term outcomes (>10 years) of GreenLight laser prostatectomy. Herein, we report our single-center experience with long-term outcomes over a period of 15 years. METHODS: Between 2005 and 2020, a prospectively maintained database for patients undergoing GreenLight photovaporization of the prostate (PVP) for symptomatic BPH was reviewed. Three Generations of Green Light Laser were used over this time period. Patients with ≥10-years follow-up were included. Demographic and perioperative data were collected together with the International Prostate Symptoms Score (IPSS), Quality of Life (QoL), peak flow rate (Qmax), post-void residual urine (PVR), and PSA changes. In addition, perioperative and late adverse events were recorded. RESULTS: After a mean follow-up of 12.1 years (10-15 years), 124 patients were included with a mean age of 73.9 (range: 54- 85) years and a mean preoperative prostate size of 72.4±15.3mL. Demographic and perioperative data are presented in Table 1. Blood transfusion rate was 2.4%. Development of bladder neck contracture and urethral stricture were encountered in 7 (5.6%) and 9 (4.3%) of patients. 6 (4.8%) patients required repeat surgery for adenoma regrowth. Additionally, there were significant reductions in mean IPSS, QoL and PVR (60.4% and 65%, and 72.6%, respectively) (p <0.001). Likewise, there was a significant increase in Qmax (8.2 to 17.7 ml/s, p <0.001) with PSA reduction by 64.2 % compared to its baseline value. CONCLUSIONS: Our long-term functional outcomes support the durability of the GreenLight laser prostatectomy with acceptable long-term adverse events after a decade of surgery. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e163-e164 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ahmed Ibrahim More articles by this author Nawar Touma More articles by this author Ahmad M. AlShammari More articles by this author Serge Carrier More articles by this author Mélanie Aubé-Peterkin More articles by this author Expand All Advertisement Loading ...

MP01-14 XPEEDA TM HOLMIUM LASER VAPORESECTION VS GREENLIGHT XPS TM VAPORIZATION OF THE PROSTATE: RESULTS FROM A RANDOMIZED CONTROLLED TRIAL

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Surgical Therapy & New Technology I (MP01)1 Sep 2021MP01-14 XPEEDATM HOLMIUM LASER VAPORESECTION VS GREENLIGHT XPSTM VAPORIZATION OF THE PROSTATE: RESULTS FROM A RANDOMIZED CONTROLLED TRIAL Hazem Elmansy, Waleed Shabana, Abdulrahman Ahmad, Fabiola Oquendo, Amr Hodhod, Loay Abbas, Ryan Kelly, Shalyn Littlefield, Ahmed Kotb, and Walid Shahrour Hazem ElmansyHazem Elmansy More articles by this author , Waleed ShabanaWaleed Shabana More articles by this author , Abdulrahman AhmadAbdulrahman Ahmad More articles by this author , Fabiola OquendoFabiola Oquendo More articles by this author , Amr HodhodAmr Hodhod More articles by this author , Loay AbbasLoay Abbas More articles by this author , Ryan KellyRyan Kelly More articles by this author , Shalyn LittlefieldShalyn Littlefield More articles by this author , Ahmed KotbAhmed Kotb More articles by this author , and Walid ShahrourWalid Shahrour More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001962.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To compare the safety and efficacy of Holmium Laser XpeedaTM Vaporesection and GreenLight XPSTM Vaporization of the Prostate in patients with prostate glands ≤80 g METHODS: Eighty-six men with benign prostatic hyperplasia (BPH) and prostate glands ≤80 g scheduled for laser prostatectomy were included in this prospective randomized trial. Outcome measures including IPSS, QoL, flow rate, PVR, IIEF-15, ICIQ-SF, PSA, catheterization time, and TRUS prostate volume changes were collected and compared. Perioperative complications were also recorded. Patients were offered a trial of void (TOV) 3 hours after their procedures. All patients were discharged home on the same day and were followed up at 1, 3, and 6 months. RESULTS: There were no significant differences in preoperative baseline data between the two surgical groups. Successful same day TOV was noted in 72.2% and 72% of the XpeedaTM and GreenLight XPSTM patients, respectively p=0.98. The laser energy used was significantly lower in XpeedaTM group p=0.002. There were no significant differences in functional and sexual outcomes between both groups at 6 months. Operative parameters and postoperative outcomes are shown in Table 1. CONCLUSIONS: Holmium Laser Xpeeda™ Vaporesection and GreenLight XPSTM Vaporization are safe and effective in the treatment of BPH. Same-day discharge with early trial of void is a feasible option. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e6-e6 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hazem Elmansy More articles by this author Waleed Shabana More articles by this author Abdulrahman Ahmad More articles by this author Fabiola Oquendo More articles by this author Amr Hodhod More articles by this author Loay Abbas More articles by this author Ryan Kelly More articles by this author Shalyn Littlefield More articles by this author Ahmed Kotb More articles by this author Walid Shahrour More articles by this author Expand All Advertisement Loading ...

PD-0913 Local treatment to the primary tumor and PSA changes as prognostic factors in mCRPC

PD-0913 Local treatment to the primary tumor and PSA changes as prognostic factors in mCRPC

Role of multiparametric MRI in long-term surveillance following focal laser ablation of prostate cancer.

Determine the multiparametric magnetic resonance imaging (mpMRI) appearance of the prostate following focal laser ablation (FLA) for PCa and to identify imaging characteristics associated with recurrent disease. Retrospective analysis of patients who underwent FLA for low-intermediate risk PCa between 2010 and 2014 was performed. Early (median 4 months) and late mpMRI (median 49 months) follow-up were qualitatively assessed for T2-weighted, dynamic contrast enhanced (DCE) and diffusion weighted imaging (DWI) appearances and also compared to corresponding PSA values and biopsy results. 55 cancers were treated in 54 men (mean age 61.0 years). Early mpMRI was performed in 30 (54.5%) patients while late follow-up mpMRI in 42 (84%). Ill-defined scarring with and without atrophy at the treatment site were the most common appearances. In patients with paired MRI and biopsy, one of four patients with clinically significant PCa on biopsy (≥GG2 or≥6 mm GG1) showed hyperenhancement or restricted diffusion at early follow-up. At late follow-up, positive biopsies were seen in 5/8 (63%) cases with hyperenhancement and 5/6 (83%) cases with restricted diffusion at the treatment site. PSA change was not associated with biopsy results at either time point. mpMRI is able to document the morphological and temporal changes following focal therapy. It has limited ability to detect recurrent disease in early months following treatment. Late-term mpMRI is sensitive at identifying patients with recurrent disease. Small sample size is, however, a limitation of the study. Implementing MRI in follow-up after FT may be useful in predicting residual or recurrent PCa and therefore provide reliable outcome data.

Abstract 357: Cancer associated macrophage like cells predict aggressive disease in local and metastatic prostate cancers

Abstract Background: Prostate cancers (PC) are intrinsically complex, with few prognostic biomarkers that differentiate aggressive and indolent disease. Cancer associated macrophage like cells (CAMLs) have shown to be significant independent prognostic indicators for poor survival in tumors if engorged to ≥50μm. However, no group has examined CAMLs' in PC. In this prospective pilot study, we analyzed PSA &amp; ≥50μm CAML presence in (n=51) Stage I-III &amp; (n=41) metastatic PC (mPC) prior to the start of new treatments to examine CAMLs' on outcomes. We found that ≥50μm CAML presence significantly predicted worse patient survival in mPC. These preliminary results suggest that CAMLs may serve as a cheap, non-invasive prognostic biomarker that predicts for worse outcomes in both local &amp; mPC prior to new therapies. Methods: We prospectively recruited (n=92) PC patients in this pilot study to examine CAML's prognostic significance in non-metastatic (stages I-III) and mPC. Of (n=92) total patients, 15% (n=14/92) were stage I, 32% (n=29/92) stage II, 9% (n=8/92) stage III, and 45% (n=41/92) Stage IV. Prior to the induction of new therapy or first line therapy for newly diagnosed patients, 7.5mL peripheral baseline (BL) blood was collected. Blood was filtered via CellSieveTM microfiltration, which excludes cells by size ≥7μm. In parallel, changes in PSA was monitored to compare prognostic significance against ≥50μm CAMLs. Wilcoxon univariate analysis was used to analyze ≥50μm CAMLs and PSA in progression free survival (PFS) and overall survival (OS). Results: CAML's were identified in 78.9% (n=71/90) of available BL samples, with two samples failing from clotting. Stage I-III patients had an average of ~3 CAMLs/7.5mL blood, whereas mPCs contained ~6 CAMLs/7.5mL. Average CAML size increased linearly with advancing stage of disease with stage I patients averaging 23μm, stage II 33μm, stage III 65μm, and stage IV 78μm. Of available BL samples, 41% (n=38/90) patients with ≥50μm CAMLs significantly predicted for worse PFS (HR=10.0, p&amp;lt;0.001, 95%CI=0.07-0.31) and OS (HR=34.2, p&amp;lt;0.001, 95%CI=0.03-0.21). Further, ≥50μm CAMLs significantly predicted for poorer survival in mPC with PFS (HR=9.4, p=0.028, 95%CI=0.18-0.84) and OS (HR=5.1, p=0.003, 95%CI=0.07-0.53), but only non-significantly trended in non-metastatic disease. Initial analysis of PSA found that high PSA at BL was a significant predictor for worse outcomes in patients, while changes in PSA was not a predictor. Conclusions: CAMLs have shown potential as a predictive non-invasive blood based biomarker across multiple solid malignancies, and here we compared this biomarker in PC. While preliminary, these data suggests that engorged CAML presence prior to the start of new treatment may be a statistically significant predictor of survival in both the local and metastatic setting, and a larger validation cohort should be established. Citation Format: Daniel J. Gironda, Raymond Bergan, R K. Alpaugh, Daniel C. Danila, Tuan L. Chuang, Brenda Y. Hurtado, Thai Ho, Cha-Mei Tang, Daniel L. Adams. Cancer associated macrophage like cells predict aggressive disease in local and metastatic prostate cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 357.