Stage Prostate Cancer Research Articles

Ki67 and the apparent diffusion coefficient in postoperative prostate cancer with endocrine therapy.

Prostate-specific antigen (PSA) is a critical part of prostate cancer (PCa) screening, diagnosis, staging, and prognosis. However, elevated PSA levels can also be caused by several external factors. To improve the specificity and sensitivity of PSA in clinical practice, we explored whether markers or parameters may be used as prognostic targets for PCa by long-term follow-up. A total of 121 PCa patients who underwent laparoscopic radical prostatectomy (LRP) were included in our study, all of whom underwent imaging and preoperative pathological diagnosis. Endocrine therapy has long been applied to treat postoperative patients. The prognosis of enrolled patients was followed, and statistics were collected. Spearman's correlation analysis was applied to examine the relationship and clinical parameters. Kaplan-Meier analysis was used to process the clinical variables of PCa patients. Cox proportional hazards regression analysis was applied to examine univariate and multivariate variables. The Gleason score (GS), PSA, clinical stage, nerve infiltration, organ confinement, Ki67 and apparent diffusion coefficient (ADC) were significantly associated with prognosis (all P < 0.05). The GS, PSA, clinical stage, organ confined, Ki67, nerve infiltration and ADC were included in the multivariate analysis (all P < 0.05). Ultimately, Ki67 and the ADC were found to provide meaningful predictive information (both P < 0.05). Ki67 and the ADC may be clinically and analytically valid prognostic biomarkers and imaging parameters in PCa. They may be useful for predicting the prognosis and risk of PCa patients undergoing postoperative routine endocrine therapy.

Abstract 1243: RON receptor signaling enhances prostate cancer metastasis in Hi-Myc mice

Abstract Prostate cancer (PCa) is the second leading cause of cancer mortality among men globally. Death from PCa is typically due to the lack of effective treatments for advanced forms of prostate cancers including castration-resistant prostate cancer (CRPC) and metastatic prostate cancers (mPCa). Distantly metastasized cancers drop the 5-year survival rate from 98% to 30%. Understanding the intrinsic and extrinsic mechanisms that lead to the development of these advanced prostate cancers could improve treatment options. The RON receptor tyrosine kinase is a cell surface receptor, which is activated by growth factor ligands (HGFL or Gas6), which binding promotes several cancer phenotypes in various cancers including prostate cancer. Our laboratory has shown that RON is overexpressed in 86% of primary and 100% of metastatic human prostate cancers compared to normal prostate tissue. Additionally, we have shown that RON overexpression in the prostates of mice can induce Prostatic intraepithelial neoplasia (PIN) lesions, adenocarcinoma, and increases several cancer phenotypes including proliferation, cell survival, metastasis, and increased recruitment of tumor-associated macrophages. However, we have yet to explore the effect of RON on prostate cancer metastasis. We hypothesize that RON expression enhances metastasis by promoting an increase in the amount of disseminating prostate cancer cells. To test this hypothesis, the Hi-Myc mouse model has been employed. The MYC gene is one of the most dysregulated genes in prostate cancers and Myc expression has been detected in the early stages of prostate cancer development, PIN lesion, and all later stages of prostate cancer. Additionally, the Hi-Myc model is clinically relevant as prostate tumor development in this model is similar to that in humans in regard to progression from PIN lesions to adenocarcinoma. From the Hi-Myc model, we have generated two additional genetic modifications within prostate epithelial cells: 1) Hi-Myc mice with prostate-specific RON overexpression (OE) and 2) Hi-Myc mice with prostate-specific RON loss (ΔEpi). In this study we report that a lack of prostate RON expression diminishes adenocarcinoma development and metastasis within the Hi-Myc mouse model. Moreover, RON overexpression promotes the development of metastatic adenocarcinoma that was not observed in the prostates from Hi-Myc control mice. These studies suggest that RON expression supports the advancement of primary tumors to metastatic prostate cancer within the Hi-Myc mouse models. Therefore, future directions include determining the signaling pathways driven by RON that promotes this metastatic phenotype in both castration-sensitive and resistant tumors. Citation Format: Angelle D. Jones, Carissa Lester, Susan E. Waltz. RON receptor signaling enhances prostate cancer metastasis in Hi-Myc mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1243.

Abstract 6023: Plasma methylome landscape across the spectrum of prostate cancer progression, and differentially methylated region (DMR) based biomarkers of hormonal therapy failure in metastatic hormone-sensitive prostate cancer

Abstract Background: DNA silencing of gene expression can affect tumorigenesis, treatment outcomes and prognosis. Epigenetic silencing of tumor suppressor genes in prostate cancer detected in plasma at different stages of progression and its effect on clinical outcomes has not been determined. In a cohort study across different stages of prostate cancer (PC) progression, we performed plasma cell-free DNA (cfDNA)-based epigenomic profiling for determining the landscape of methylation and Differentially Methylated Region (DMR) classifiers and the potential impact on clinical outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) state. Methods: Plasma was collected prospectively in a longitudinal cohort study of 108 PC patients (pts) of which 24 had non-metastatic Local PC; 28 had mHSPC; 56 had mCRPC. cfDNA was used for enzymatic methylation sequencing (EM-seq) of a targeted panel of genes (N=441) implicated in prostate cancer biology. Methylation status at CpG islands of these genes were examined using Twist targeted cfDNA methylation assay. The Bismark program was used for methylation calls. Temporal trends of differentially methylated regions (DMRs) were identified in different states of progression by comparing the methylation status of target genes in localized PC, mHSPC and mCRPC states using a False Discovery Rate (FDR-q-value) of 0.2 or less. DMRs uniquely associated with mHSPC state were identified and determination of genes with DMRs in pts experiencing early failure of androgen deprivation therapy (ADT)-based therapies was performed. Early failure was defined as progression on ADT within 12 months. Results: We identified 304/441 genes that were differentially methylated between localized PC and advanced PC (mHSPC and mCRPC) (FDR&amp;lt;0.2), of which 237 genes differed between mHSPC and mCRPC (p&amp;lt;0.05) states. mHSPC pts were serially profiles before and after 3 months of ADT-based therapies. All 28 pts experienced a PSA response at 3-months and 112/237 genes showed significant change in methylation status in these serial samples taken before/after 3 months of ADT-based therapies. The median follow up of the cohort was 18 months (range 10-24). 6/28 mHSPC pts experienced early ADT failure (&amp;lt;12 months; median 10 months). 8/112 genes were significantly associated with early failures and included DMRs in RB1, FOXA1, SOX11. GSC, ALDH1L1, SCGB3A1, FLT4, and PTPRN2. Conclusions. A targeted cfDNA plasma liquid-biopsy based epigenomic profiling of PC cancer related genes was able to capture significant differences in DMRs across different states of cancer progression. Candidate differentially expressed CpG methylome gene biomarkers detected in plasma also identified biomarkers associated with early ADT-based treatment failure in mHSPC. Citation Format: Manish Kohli, Jodie Wong, Yijun Tian, Amir Bitaraf, Claire Hanson, Matt Larsen, Jennifer Lloyd, Julia Batten, Neeraj Agarwal, Umang Swami, Benjamin Maughan, Sumati Gupta, Jonathan Tward. Plasma methylome landscape across the spectrum of prostate cancer progression, and differentially methylated region (DMR) based biomarkers of hormonal therapy failure in metastatic hormone-sensitive prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6023.

Abstract 1343: Mesenchymal cell populations associated with different stages of prostate cancer progression in mice and human

Abstract Mesenchymal cells in the prostate cancer (PCa) tumor microenvironment (TME) contribute to the biological and clinical history of PCa. Indeed, mesenchymal cells heavily interact with cancer cells, immune cells, and the other cellular and non-cellular components of the TME to favor or hinder carcinogenesis and tumor progression. Using a comprehensive array of genetically engineered mouse models (GEMMs) of prostate cancer, 8 mesenchymal populations with different transcriptional programs are preferentially enriched in specific GEMMs at different stages of PCa. Here, we determine the transferability of this mesenchymal cluster designation from mice PCa models to human PCa cases. To this end, we compared: a) Tmprss2-ERG (T-ERG) mouse and ERG+ human cases; b) Pb4-Cre+/-;Ptenf/f;LSL-MYCN+/+;Rb1f/f (PRN) mouse and PCa bone metastasis. We generated scRNA-seq data for &amp;gt; 8000 mesenchymal cells from ERG+ (n=6) and ERG- (n=3) PCa patients, and we retrieved data for bone metastasis mesenchymal cells (osteoblasts, osteoclasts, endothelial cells, pericytes; 1,872 total cells) from GSE143791. To transfer the stromal mouse clusters’ labels to human data, human gene symbols were converted to their mouse counterparts, then both datasets were restricted to overlapping genes. For the human PCa cases, label transfer was performed through ‘ingest’ using the scRNA-seq data from the mouse T-ERG model as reference for the human ERG+ cases and data from the remaining GEMMs as reference for the human ERG- cases. For bone metastases cases, mouse stromal data from all GEMMs were used to project the 8 stromal clusters to the mesenchymal cells in the bone metastases microenvironment. Not surprisingly, ERG+ human samples were enriched (&amp;gt; 60% of total stromal cells) in mouse stroma clusters predominantly present in T-ERG mouse model, characterized by the expression of Wnt regulators and AR. Common populations to all murine models, representing myofibroblasts and immunomodulatory fibroblasts (expressing Gpx3, C3, C7, Cfh), were also commonly present in patients, irrespectively to the ERG status. In the PCa bone metastases, mesenchymal clusters enriched in the PRN model were strongly represented in human bone metastases, comprising &amp;gt; 60% of total stromal cells. These cells were characterized by high expression of POSTN and MKI67, as well as bone-specific genes like BGN. Altogether, these findings suggest that our mesenchymal cluster designation developed using GEMMs can be meaningfully applied to human PCa, and that the different transcriptional programs we identified in distinct mesenchymal population are conserved across species. This lays the foundation for the utilization of defined genetically-engineered models in defining the interactions and cross-talks between different mesenchymal populations in relation to cancer and immune cells and other components of the TME in human prostate cancer. Citation Format: Mohamed Omar, Hubert Pakula, Filippo Pederzoli, Giuseppe N. Fanelli, Tania Panellinni, Ryan Carelli, Silvia Rodrigues, Caroline Fidalgo-Ribeiro, Pier V. Nuzzo, Lucie V. Emmenis, Mohammad Mohammad, Madhavi Jere, Caitlin Unkenholz, David Rickman, Christopher Barbieri, Brian Robinson, Luigi Marchionni, Massimo Loda. Mesenchymal cell populations associated with different stages of prostate cancer progression in mice and human [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1343.

Abstract 4203: A prospective study of birth weight and prostate cancer risk: extended analysis in the Health Professionals Follow-up Study

Abstract Introduction: Birth weight, a potential marker of the in utero hormonal and growth factor milieu, has been associated with an increased risk of prostate cancer (PCa) in some, but not all, previous studies. It was also associated with a non-significantly greater risk of advanced stage PCa (relative risk [RR] = 1.37, 95% confidence interval [CI]: 0.61-3.05 for ≥10 lbs compared to 7.0-8.4 lbs, p-trend = 0.087) in our previous analysis in the Health Professionals Follow-up Study (HPFS). However, these suggestive findings were based on a relatively small number of advanced stage cases and short follow-up. We have now updated our previous analysis of birthweight and PCa risk in the HPFS with an additional 14 years of follow-up. Method: Birth weight was assessed by self-report on the 1994 follow-up questionnaire using pre-specified categories. PCa diagnoses were ascertained on each biennial follow-up questionnaire and confirmed by medical record review. Cox proportional hazards regression was used to evaluate the association between birth weight and PCa risk through 2016. Result: Of the 17,949 eligible men who reported their birth weight in 1994, 3,167 were subsequently diagnosed with PCa. With the exception of a suggestive positive trend between increasing birth weight and high-grade PCa (RRadj per pound: 1.06; 95% CI: 0.98-1.16; p-trend=0.15), no associations were observed between birth weight and risk of total, organ-confined, low-grade, advanced stage, lethal, or fatal PCa. Conclusion: Overall, no association was observed between birth weight and PCa risk and mortality in this large prospective cohort study of US male health professionals. Table 1. Associations between self-reported birth weight and prostate cancer in the Health Professionals Follow-up Study, 1994-2016 Birth weight (lbs) &amp;lt;5.5(&amp;lt;2,495 g) 5.5-6.9(2,495-3,174 g) 7.0-8.4(3,175-3,855 g) 8.5-9.9(3,856-4,535 g) ≥10.0(≥4,536 g) Per 1 lb (454g) increase Total prostate cancer Cases/person-years 125/17,019 518/80,053 1,931/297,495 396/60,445 197/22,993 HRa (95% CI) 0.98 (0.81-1.18) 0.86 (0.78-0.95) 1.00 0.85 (0.76-0.95) 0.98 (0.84-1.13) 1.01 (0.96-1.05) High-grade prostate cancer (Score 4+3 and higher) Cases/person-years 23/17,117 119/80,434 453/299,015 105/60,741 52/23,148 HRa (95% CI) 0.76 (0.50-1.16) 0.83 (0.68-1.03) 1.00 0.93 (0.75-1.16) 1.03 (0.76-1.39) 1.06 (0.98-1.16) Advanced stage prostate cancer (T3b+) at diagnosis Cases/person-years 4/17,135 29/80,516 109/299,370 25/60,811 12/23,195 HRa (95% CI) 0.53 (0.19-1.46) 0.91 (0.60-1.40) 1.00 0.98 (0.62-1.54) 1.02 (0.54-1.92) 1.08 (0.91-1.29) Lethal prostate cancer Cases/person-years 11/17,127 70/80,491 225/299,247 51/60,791 27/23,178 HRa (95% CI) 0.81 (0.43-1.50) 1.15 (0.86-1.52) 1.00 1.07 (0.78-1.47) 1.01 (0.66-1.54) 1.00 (0.89-1.13) Fatal prostate cancer Cases/person-years 10/17,551 59/82,316 197/307,363 43/62,246 23/23,996 HRa (95% CI) 0.88 (0.45-1.67) 1.17 (0.86-1.60) 1.00 1.11 (0.78-1.56) 1.03 (0.65-1.63) 1.00 (0.87-1.14) RR=relative risk; CI = confidence interval a Adjusted for age, calendar time, race, smoking status, family history of prostate cancer (yes or no), PSA testing in &amp;gt;50% of previous cycles (yes or no), physical activity, diabetes, diet (tomato sauce intake, coffee, and energy intake), alcohol intake, multivitamin use, vitamin E supplement use, and aspirin use. Citation Format: Qinran Liu, Yiwen Zhang, Jane B. Vaselkiv, Lorelei A. Mucci, Edward L. Giovannucci, Elizabeth A. Platz, Siobhan Sutcliffe. A prospective study of birth weight and prostate cancer risk: extended analysis in the Health Professionals Follow-up Study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4203.

Abstract 3509: 1,25-dihydroxyvitamin D3-mediated suppression of genes associated with cell cycle regulation and actin organization in a non-malignant African American prostate cell line

Abstract Vitamin D is a steroid hormone that confers anti-proliferative and anti-inflammatory properties in prostate cells. Vitamin D deficiency is associated with advanced prostate cancer (PCa) stage, grade, and increased mortality. Since AA men are more likely to be vitamin D deficient compared to EA men, elucidating the pleiotropic effects of vitamin D may provide additional drug targets to mitigate disparate outcomes for AA men with PCa. Total RNA sequencing (RNAseq) was performed on an AA prostate cell line, RC-77N/E, derived from non-malignant epithelial tissue obtained from a PCa patient. We compared untreated RC-77N/E cells with RC-77N/E cells treated with 10 nM of vitamin D3 metabolite, 1α,25(OH)2D3 at 24h. Bioinformatic analysis, public cohort data mining, and RT-qPCR was performed to filter and validate selected statistically significant differentially expressed genes from RNAseq analysis. Our comparison of 1α,25(OH)2D3 treated versus untreated control RC-77N/E cell replicates revealed, 1601 significantly differentially expressed genes (DEGs) (FDR p &amp;lt; 0.05). Ingenuity Pathway Analysis software was used to conduct pathway enrichment analysis, which predicted repression of signaling pathways involved in actin cytoskeleton organization, epithelial-mesenchymal transitioning, adherens junction pathway, and RhoA pathway signaling with high enrichment z-score and statistically significant p-value. We additionally report predicted repression of PCa cell viability, invasion, cell proliferation and organismal death, for disease and function. We prioritized differentially expressed genes by identifying genes with 1) vitamin D response elements (VDREs) and 2) predicted poor prognosis, by performing overall survival analyses using The Cancer Genome Atlas (TCGA) Prostate Adenocarcinoma (PRAD) Cohort. We identified ANLN (Anillin) and ECT2 (Epithelial Cell Transforming 2), which were further validated using an AA tumor/benign contralateral matched clinical cohort, and a public cohort study using a non-malignant European prostate cell line, RWPE1. Our data suggest 1α,25(OH)2D3 significantly downregulates ANLN and ECT2 (FDR p &amp;lt; 0.05) in the RC-77N/E cell line, where survival analyses in the TCGA PRAD cohort show low expression of both ANLN and ECT2 are associated with significantly better overall survival outcome (p &amp;lt; 0.05). In our clinical cohort validations, both ANLN and ECT2 also show significantly decreased expression in non-malignant compared to tumor (p &amp;lt; 0.05). In conclusion, our study provides more insight of vitamin D3 regulation of PCa biomarkers and their potential roles in AA prostate cancer prevention, adjuvant treatment, as well as improving cancer survivor outcome Citation Format: Jabril R. Johnson, Rachel N. Martini, Yate Yuan-Ching, Leanne Woods-Burnham, Mya Walker, Greisha L. Ortiz-Hernandez, Dorothy Galloway, Melissa B. Davis, Sean K. Kimbro, Adam B. Murphy, Rick A. Kittles. 1,25-dihydroxyvitamin D3-mediated suppression of genes associated with cell cycle regulation and actin organization in a non-malignant African American prostate cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3509.

Abstract 3634: Overexpression of PLK1 activates IL4/JAK/STAT6 signaling in prostatic tumor-microenvironment

Abstract The correlation between PLK1 expressions with prostate cancer (PCa) stages was identified by analyzing the transcriptome profile of PLK1 in patients from the Cancer Genome Atlas (TCGA) database, and scoring the protein expression in a clinical tissue microarray (TMA) cohort. Integrating our prostate-specific PLK1 knock-in mouse model, we established an oncogenic role for PLK1 in PCa progression. To elucidate the underlying mechanism, we investigated the impact of PLK1 overexpression on prostatic tumor microenvironment (TME) in vivo. In addition, in vitro co-culture systems with both epithelial cells and macrophages were designed to uncover the regulatory function of PLK1 in macrophage polarization. We found that PLK1 induces phosphorylation of JAK3, activates the JAK/STAT6 pathway in cancer cells, and increases the secretion of IL4, which enables macrophage polarization towards the M2 phenotype in TME—ultimately accelerating PCa development. Finally, pharmaceutical inhibition of STAT6 signaling significantly reverses the PLK1-mediated M2 polarization and, subsequently, inhibits the progression of PCa. Our findings provide clinical and pre-clinical evidence to characterize the role of PLK1 in promoting PCa and novel insights into the regulatory mechanism of PLK1 in the TME. We also provide strong support for the clinical potential of targeting STAT6 for advanced PCa therapy. Citation Format: Ruixin Wang, Xiaoqi Liu. Overexpression of PLK1 activates IL4/JAK/STAT6 signaling in prostatic tumor-microenvironment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3634.

Abstract 2877: Profiling of myeloid-derived suppressor cells in Pten-deficient in prostate cancer progression

Abstract Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of immature immune cells that expand during cancer and can induce potent immune suppression. These cells play critical roles in supporting tumor growth and progression and their induction has been associated with the inactivation of PTEN. To date, few therapies targeting these cells are available which is partly due to their increasingly complex nature and context-dependent functions. Moreover, there is no clear definition to identify these cells. Enhancing our understanding of this cell population will aid in developing more effective cancer therapies. Here, we used gene expression profiling, flow cytometry, and quantitative immunohistochemistry to characterize tumor-infiltrating and circulating MDSCs in prostate carcinogenesis and progression in transgenic mouse models of prostate cancer driven by the conditional inactivation of Pten and Trp53. Transcriptomic profiling revealed enrichment of various myeloid-derived cell signatures in the early stages of prostate cancer including MDSCs, macrophages, and neutrophils. Flow cytometric analysis confirmed the increased infiltration of CD11b+/Ly6G+ (polymorphonuclear MDSCs (pMDSCs)) and CD11b+/Ly6C+ (monocytic MDSCs (mMDSCs)) cells in prostate tumors. The temporal dynamics of tumor-infiltrating myeloid cells were further profiled and showed that pMDSC and mMDSC abundances were 1.6 and 5.7-fold higher, respectively, in older mice with late-stage locally invasive adenocarcinomas (AdCa) compared to younger mice with early-stage prostatic intraepithelial neoplasia (PIN). In both instances, pMDSCs comprised most of the leukocyte infiltrate, however, mMDSCs tended to be positively correlated with tumor burden in AdCa but not PIN. In peripheral blood, CD44+/CD62L+ immature neutrophils were associated with high tumor burden in aged mice. Treatments targeting the androgen receptor (AR) signaling further exacerbated pMDSC infiltration in tumors and was associated with resistance to second androgen receptor-targeted agent (ARTA) therapy in a model of castration resistant prostate cancer. Our findings indicate that MDSCs are a prominent population in Pten-null prostate cancer and are implicated with resistance to prostate cancer treatment. MDSCs constitute a potentially targetable population and these models serve as viable platforms to further investigate their biological activity and further evaluate novel MDSC-directed therapies. Citation Format: Marco A. De Velasco, Yurie Kura, Noriko Sako, Naomi Ando, Kazuko Sakai, Eri Banno, Shogo Adomi, Mitsuhisa Nishimoto, Takafumi Minami, Yasunori Mori, Kazutoshi Fujita, Masahiro Nozawa Nozawa, Kazuhiro Yoshimura, Kazuto Nishio, Hirotsugu Uemura. Profiling of myeloid-derived suppressor cells in Pten-deficient in prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2877.

Abstract 5792: The novel therapeutic diiminoquinone exhibits anticancer effects on human prostate cancer cells in 2D and 3D in vitro models

Abstract Aim: To investigate the anticancer potential of the novel quinone DIQ on prostate cancer (PCa) cells in two-dimensional (2D) and three-dimensional (3D) in vitro. Methods: The anti-proliferative effect of DIQ on PC3 and DU145 PCa cell lines was determined in vitro by using 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and trypan blue exclusion assays. In addition, the potency of DIQ was tested on the formation and size of PCa cell-derived prostatospheres and organoids grown in a specialized 3D-culture system. Also, 3D organoids were established from fresh tissue samples representing different stages of PCa obtained from consented patients who underwent radical prostatectomy at the American University of Beirut Medical Center (AUBMC) according to appropriate Institutional Review Board (IRB) approval guidelines. This model was used to assess DIQ individualized tumor response on organoids growth and the effect was evaluated by quantifying the number of organoids formed (OFC) and calculating the average size (diameters). Results: Our results showed that DIQ significantly attenuated cell proliferation and viability in PC3 and DU145 PCa cell lines. DIQ also reduced the formation ability and size of PC3 and DU145 prostatospheres and organoids at sub-toxic doses of 1 µM. Potently, DIQ displayed a significant decrease in both the count and the size of the different patient-derived organoids as compared to their respective control. Conclusion: This study provides promising clues for the use of the novel anticancer therapeutic DIQ in targeting CSCs, findings that may have promising therapeutic implications for PCa patients. Citation Format: Amani Yehya, Alissar Monzer, Kevork Wakimian, Fatima Ghamlouche, Nour Saheb, Ayman Tawil, Hala Gali-Muhtasib, Deborah Mukherji, Albert El-Hajj, Wassim G. Abou-Kheir. The novel therapeutic diiminoquinone exhibits anticancer effects on human prostate cancer cells in 2D and 3D in vitro models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5792.

Abstract 5261: Prostate specific sustained anti androgen delivery to delay early stage prostate cancer progression

Abstract Prostate cancer is the most common cancer in men. Commensurate with risk, current approaches to localized prostate cancer include prostatectomy, prostate radiation with or without radiation therapy or active surveillance. Recent data suggest that systemic anti-androgen therapy with enzalutamide reduced the risk of prostate cancer progression in men on active surveillance but was associated with considerable side effects. We developed a novel polymer-based drug delivery method to provide sustained localized drug administration of anti-androgens selectively to the prostate. In vitro and in vivo mouse and canine studies show that this drug eluting implant delivers sustained high prostate to plasma therapeutic anti-androgen levels for an anticipated range of 2 years while preventing accumulation of anti-androgens in the liver, lungs, heart and brain. We performed a proof of concept study in a canine prostate model implanting an 15mm x 1mm bicalutamide eluting implant into each lobe of the prostate. Bicalutamide levels in the prostate measured near the implant at 6 months were 3250 ± 1622 ng/g, n = 3 compared to 3809 ± 638 ng/g, n = 3 to those achieved at steady-state oral administration. Plasma and other off target levels were over 1000-fold lower in the implant cohort compared to oral administration: Plasma: 5.9 ± 0.2 ng/ml, liver: 11.3 ±4.3 ng/g, and brain: 5.4 ±0.8 ng/g versus plasma: 18170 ± 3820 ng/ml, liver: 35407 ±8510 ng/g, and brain: 8870 ±1797 ng/g. The implants were well tolerated without local toxicity and imaged easily with ultrasound. The design characteristics of the implant facilitates minimally invasive surgical implantation under standard image guidance and withstands the concomitant use of prostate radiation. This novel technology warrants future clinical exploration of prostate specific anti-androgen therapy for (neo)adjuvant therapy or in active surveillance. Tissue Bicalutamide oral (2m)(ng/g) Bicalutamide implant (6m)(ng/g) Plasma 18,170 (3820) 5.9 (0.2) Prostate 3,809 (638) 3,250 (1622) Liver 35,407 (8510) 11.3 (4.3) Cerebrum 8,870 (1797) 5.4 (0.8) Cerebellum 8,737 (1550) 6.2 (1.3) Spleen 7,727 (1288) 4.2 (0.9) Lung 27,013 (2896) 11.3 (4.3) Heart 11,737 (3491) 10.0 (1.9) Kidneys 17,413 (6581) 8.5 (2.0) Citation Format: Pujan Desai, Maithili Rairkar, Nela Pawlowska, Scott Thomas, Pamela N. Munster. Prostate specific sustained anti androgen delivery to delay early stage prostate cancer progression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5261.

Abstract 3083: Targeting androgen receptor coregulators to enhance enzalutamide sensitivity in prostate cancer

Abstract Steroid hormone signaling axes drive proliferation and survival in prostate cancer (PCa), breast and other cancers. In late stage PCa, the androgen receptor (AR) is therapeutically antagonized with success, for example with Enzalutamide (Enza). Although initially successful, resistance emerges associated with tissue plasticity and patient mortality. Enza-resistance mechanisms include altered AR coregulator interactions. Identifying which coregulators change Enza sensitivity is attractive as they may represent new drug targets but challenging given the multitude of coregulators expressed in PCa and the diverse roles they play in transcription and translation.To meet this challenge, we designed a bioinformatic workflow to identify under-investigated yet clinically-impactful coregulators. We tested coactivators (CoA, n~750), corepressors (CoR, n ~600), and mixed function coregulators (Mixed, n~600) associations with patient outcome in TCGA PCa cohorts; applied partial correlation analyses to reveal coregulators that impacted AR target genes; utilized DepMap essentiality scores to rank importance; and examined interactions in publicly available AR RIME data. The impact of the top ranked coregulators (n=18) on Enza sensitivity was examined using shRNA or siRNA approaches, and with inhibitor drugs in Enza-resistant PCa cell lines (LNCaP C42B, 22Rv1). Finally, coregulator expression was examined in single cell RNA-Seq from PCa 3D organoids derived from the PBCre4:Ptenf/f:Rb1f/f (DKO) and the PBCre4:Ptenf/f:Rb1f/f:Trp53f/f (TKO) PCa mouse model, which recapitulate the loss of Enza sensitivity and lineage plasticity. ShRNA targeting coregulators was undertaken in organoids. The bioinformatics workflow identified 18 coregulators, including CoA (e.g., WDR5, KAT7, BLM, SMARCC1), CoR (e.g., SETDB1, PSPC1), and Mixed (e.g., KDM5A, BPTF, TCEGR1) to screen for impact on Enza. KAT7 shRNA modulated Enza sensitivity, regulated expression of AR target genes, and synergized with a KAT7 inhibitor (WM3835) to enhance Enza sensitivity. Similarly, a BLM inhibitor (ML216) synergized with Enza. Interestingly, although WDR5 siRNA alone did not alter Enza responses, the combination of KAT7 shRNA and WDR5 siRNA significantly potentiated Enza responses. Similarly, SMARCC1 shRNA cooperated with siRNA to several targets (TBX3, BPTF, or SETDB1) to enhance Enza responses. Smarcc1 and Tbx3 were upregulated in Enza-resistant neuroendocrine PCa, and the recently identified Pou2f3 Enza-resistant phenotypes, and Bptf was upregulated in the Tff3 Enza-resistant phenotype. We have shRNA targeted Blm, Smarcc1, Tbx3, and Bptf in the DKO and TKO organoids and are measuring the impact of Enza responses. Overall, we have identified potentially novel AR coregulators that associate with the development of therapy resistance and shown that targeting these coregulators may augment Enza sensitivity in PCa. Citation Format: Rayzel C. Fernandes, Debasis Nayak, Damien A. Leach, Meenalakshmi Chinnam, Wilbert Zwart, David W. Goodrich, Moray J. Campbell, Charlotte L. Bevan. Targeting androgen receptor coregulators to enhance enzalutamide sensitivity in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3083.

Abstract 5594: Association of circulating cell-free DNA and prostate cancer risk groups in patients undergoing proton therapy

Abstract Even after radiation treatment, prostate cancer (PCa) patients receiving radiotherapy (RT) are still at risk for disease progression and recurrence. Predicting outcomes associated with cancer treatment is critical to PCa survivorship given that the 5-year survival rates for local and regional stage PCa is nearly 100%. Radiogenomics is a promising field of research focused on identifying genomic markers that can provide clinically useful prognostic predictions regarding radiation response and can potentially serve as the basis for personalized RT where cancer management is tailored to fit each individual patient. Circulating cell-free (ccfDNA) DNA has been found to 1) be associated with radiation sensitivity or toxicity, 2) relapse or recurrence, and 3) risk for the development of metastases before, during or following photon RT. Proton therapy, alternative to photon therapy, is a promising treatment that can reduce excess radiation dose and, in turn, the risk for adverse events. However, few studies have been done to determine if ccfDNA can predict response in proton radiation, which purports superior dose distribution, avoiding healthy tissues, minimizing the exit dose, and potentially reducing overall toxicity. The overall aim of this study is to determine if the quantity of ccfDNA is associated with PCa risk groups. We hypothesized that PCa patients within the highest risk group have quantitatively increased levels of ccfDNA compared to those in low and intermediate risk groups. This study leveraged the University of Florida Health Proton Therapy Institute Outcomes Tracking Protocol biobank of PCa patients with plasma and serum collected before, during and after proton RT. Isolation of ccfDNA at baseline, during treatment, and following treatment was undertaken and ccfDNA quantities were compared among patients in the low, intermediate and high risk groups using ANOVA. Our results indicate that the quantity difference between baseline and day 14 of treatment (p=0.055), 2 weeks post-treatment (p=0.54), and 4 weeks post-treatment (p=0.002) was associated with risk group. There was trend towards increasing ccfDNA quantity, as risk group increased; however, there was no correlation between risk group and treatment times using the Pearson correlation. Our results were consistent in that high ccfDNA quantity was associated with PCa risk. This is the first study determining the application of ccfDNA quantity on prostate cancer outcomes in patients undergoing proton RT. Identifying the determinants of radiation-related adverse outcomes will help inform impending predictive genomic technologies and improve cancer-related outcomes and survivorship. Citation Format: Andrew Bass, Johnny Velasquez, Moein Rajaei, Curtis Bryant, Nancy Mendenhall, Luisel J. Ricks-Santi. Association of circulating cell-free DNA and prostate cancer risk groups in patients undergoing proton therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5594.

MP77-10 STAGE AND GRADE MIGRATION OF PROSTATE CANCER DURING THE COVID-19 PANDEMIC

You have accessJournal of UrologyCME1 Apr 2023MP77-10 STAGE AND GRADE MIGRATION OF PROSTATE CANCER DURING THE COVID-19 PANDEMIC Edoardo Beatrici, Muhieddine Labban, Benjamin V. Stone, Dejan K. Filipas, Nicola Frego, Sandeep S. Voleti, Nicolò Maria Buffi, Giovanni Lughezzani, Firas Abdollah, Adam S. Kibel, Alexander P. Cole, and Quoc-Dien Trinh Edoardo BeatriciEdoardo Beatrici More articles by this author , Muhieddine LabbanMuhieddine Labban More articles by this author , Benjamin V. StoneBenjamin V. Stone More articles by this author , Dejan K. FilipasDejan K. Filipas More articles by this author , Nicola FregoNicola Frego More articles by this author , Sandeep S. VoletiSandeep S. Voleti More articles by this author , Nicolò Maria BuffiNicolò Maria Buffi More articles by this author , Giovanni LughezzaniGiovanni Lughezzani More articles by this author , Firas AbdollahFiras Abdollah More articles by this author , Adam S. KibelAdam S. Kibel More articles by this author , Alexander P. ColeAlexander P. Cole More articles by this author , and Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The COVID-19 pandemic likely affected the healthcare system’s ability to deliver prostate cancer care services. Herein, we sought to evaluate prostate cancer's stage and grade migration resulting from the COVID-19 pandemic. METHODS: We retrospectively analyzed the National Cancer Database (NCDB) for men with prostate cancer between 2018-2020. We divided our cohort into the “Pre-Pandemic” (2018/2019) and “Pandemic” (2020) periods. Stage and grade of prostate cancer were stratified according to the severity of disease: PSA value (≤20 vs. >20), clinical T stage (cT1-T2 vs. cT3-T4), clinical M stage (cM0 vs. cM1), International Society of Uropathology (ISUP) grade group (ISUP 1-2-3 vs. ISUP 4-5), and D’Amico risk classification (low risk vs. intermediate & high risk). Pearson’s chi-square test was used to assess differences in the distribution of stage and grade across the two periods. We performed multivariable logistic regressions to estimate the effect of the “Pandemic” period on stage and grade distribution adjusting for clinical and socioeconomic covariates. RESULTS: A total of 398,719 men were diagnosed with prostate cancer during the “Pre-pandemic” (70.6%) and “Pandemic” (29.4%) periods (Table 1). On univariable comparisons, an increase in stage/grade across the two periods was demonstrated (all p<0.001). After adjusting for covariates, compared to the “Pre-pandemic”, the “Pandemic” period was associated with increased odds of PSA >20 levels (aOR 1.06; 95% CI 1.03 – 1.08; p-value <0.001), cT3-4 stages (aOR 1.12; 95% CI 1.08 – 1.16; p<0.001), cM1 stage (aOR 1.15; 95% CI 1.12 – 1.18; p<0.001), ISUP grade group 4 or 5 (aOR 1.03; 95% CI 1.01 – 1.05; p=0.003) and D’Amico Intermediate & High risk groups (aOR 1.15; 95% CI 1.13 – 1.18; p<0.001). CONCLUSIONS: The COVID-19 pandemic was associated with significant changes in the distribution of both stage and grade of prostate cancer. Possible explanations for this migration include a better selection of patients for prostate biopsy during the pandemic or changes in prostate cancer screening patterns. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1105 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Edoardo Beatrici More articles by this author Muhieddine Labban More articles by this author Benjamin V. Stone More articles by this author Dejan K. Filipas More articles by this author Nicola Frego More articles by this author Sandeep S. Voleti More articles by this author Nicolò Maria Buffi More articles by this author Giovanni Lughezzani More articles by this author Firas Abdollah More articles by this author Adam S. Kibel More articles by this author Alexander P. Cole More articles by this author Quoc-Dien Trinh More articles by this author Expand All Advertisement PDF downloadLoading ...

PD22-05 IS PRE OPERATIVE PSMA (PROSTATE SPECIFIC MEMBRANE ANTIGEN) PET/CT A RELIABLE PREDICTOR OF PELVIC LYMPH NODE METASTASIS IN INTERMEDIATE AND HIGH RISK LOCALISED PROSTATE CANCER:A MULTI CENTRE RETROSPECTIVE ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023PD22-05 IS PRE OPERATIVE PSMA (PROSTATE SPECIFIC MEMBRANE ANTIGEN) PET/CT A RELIABLE PREDICTOR OF PELVIC LYMPH NODE METASTASIS IN INTERMEDIATE AND HIGH RISK LOCALISED PROSTATE CANCER:A MULTI CENTRE RETROSPECTIVE ANALYSIS Kishore Ta, Dinesh Cherian, Deepak Kaddu, Bikramjit Sodhi, Ravi Chandran, and Ginil Kumar Pooleri Kishore TaKishore Ta More articles by this author , Dinesh CherianDinesh Cherian More articles by this author , Deepak KadduDeepak Kaddu More articles by this author , Bikramjit SodhiBikramjit Sodhi More articles by this author , Ravi ChandranRavi Chandran More articles by this author , and Ginil Kumar PooleriGinil Kumar Pooleri More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003295.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Functional imaging techniques have been incorporated into conventional anatomical imaging to help improve identification of metastasis in normal sized nodes The primary objective of this study was to retrospectively analyse the percentage of patients “negative for metastasis” on 68Ga PSMA PETCT that translated to absent pelvic node metastasis on histopathology (Negative predictive value-NPV). The secondary objective was to analyse if pathological T stage and biopsy ISUP grades influenced the NPV of the PSMA PET CT. METHODS: A total of 217 biopsy-proven, treatment-naive, intermediate and high-risk (D’Amico classification) localised prostate cancer patients from two institutions were included in the study. All the patients had undergone a pre operative PSMA PET/ CT assessment of their pelvic lymph nodes and the patients “negative for metastasis” underwent Robotic assisted radical prostatectomy with extended pelvic lymph node dissection-ePLND. RESULTS: 49/217 patients had positive nodes despite PSMA PET/CT showing no evidence of lymph node metastasis,of which 27(55.10%) of them were obese. Thus the negative predictive value(NPV) was 77.42%. The NPV of PSMA PET CT in patients with intermediate risk prostate cancer was 86.9% compared to 71.43% in patients with high risk prostate cancer. As the ISUP biopsy grade increased the NPV decreased from 94.12% in ISUP 1 to 44.83%(p<0.0001) in ISUP 5.On retrospective analysis, all intermediate risk patients with a <pT3 stage had a 100% NPV on the PSMA PET/CT while high risk patients with a <pT3 had a NPV of 91.6%.The secondary objective was to analyse if T stage influenced the NPV .In comparison to organ confined disease(pT2) the NPV of those with disease extending beyond the prostate(pT3) was significantly lower, (80.36% vs100%) in intermediate risk and (66.97% vs 91.6%)in high risk patients. CONCLUSIONS: PSMA PET CT cannot replace e PLND with respect to accurate preoperative lymph nodal staging in intermediate and high risk prostate cancer since the NPV is below 95% (86.9%,71.43% respectively. PSMA PET CT is also not accurate with the T staging because pre operative T2 was upstaged to pT3 in 66.6 % of intermediate risk and 81.9% of high risk patients.Thus preoperative PSMA PET CT is not reliable for accurate T and N staging and e PLND should be the standard of care for precise staging in intermediate and high risk localized prostate cancer. Source of Funding: Self funded study © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e666 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kishore Ta More articles by this author Dinesh Cherian More articles by this author Deepak Kaddu More articles by this author Bikramjit Sodhi More articles by this author Ravi Chandran More articles by this author Ginil Kumar Pooleri More articles by this author Expand All Advertisement PDF downloadLoading ...

MP75-01 ASSOCIATION BETWEEN SOCIODEMOGRAPHIC FACTORS AND DIAGNOSIS OF ADVANCED PROSTATE CANCER IN EARLY LIFE

You have accessJournal of UrologyCME1 Apr 2023MP75-01 ASSOCIATION BETWEEN SOCIODEMOGRAPHIC FACTORS AND DIAGNOSIS OF ADVANCED PROSTATE CANCER IN EARLY LIFE Shayan Smani, Madison Novosel, Victoria Marks, Farah Jeong, Preston Sprenkle, and Michael Leapman Shayan SmaniShayan Smani More articles by this author , Madison NovoselMadison Novosel More articles by this author , Victoria MarksVictoria Marks More articles by this author , Farah JeongFarah Jeong More articles by this author , Preston SprenklePreston Sprenkle More articles by this author , and Michael LeapmanMichael Leapman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003349.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A subset of patients are diagnosed with lethal prostate cancer early in life, before PSA screening is typically initiated. To identify opportunities for improved detection we evaluated patient clinical and sociodemographic factors associated with advanced versus localized prostate cancer diagnosis across the age spectrum. METHODS: We conducted a retrospective cohort study using the National Cancer Database, identifying patients diagnosed with prostate cancer in 2004-2016. We compared characteristics of patients diagnosed at advanced (cN1 or M1) versus localized (cT1-4N0M0) stage. Using multivariable logistic regression, we evaluated the associations among patient clinical and sociodemographic factors and advanced diagnosis, stratifying patients by age as <55 (before screening is usually initiated), 55-65, 65-75, and >75 years. RESULTS: We identified 668,486 patients who met inclusion criteria (mean age at diagnosis 64.6 years), including 33,455 (5.0%) with advanced disease at diagnosis. Uninsured (odds ratio, OR=3.78, 95% confidence interval, CI 3.56-4.02) and Medicaid-insured (OR 2.84, 95% CI 2.70-3.00) versus commercially insured patients were more likely to be diagnosed with advanced disease, however this effect was more pronounced for younger patients. Among patients <55 years, uninsured (OR 4.63, 95% CI 4.08-5.25) and Medicaid (OR 3.59, 95% CI 3.22-3.99) versus commercially insurance were associated with greater odds of advanced cancer at diagnosis. Similarly, residence in the lowest versus highest income quintile (OR 1.21, 95% CI 1.04-1.40) was associated with increased odds of advanced prostate cancer in patients <55 years. Black versus White race was associated with increased odds of advanced prostate cancer at diagnosis later in life (OR 1.15, 95% CI 1.11-1.19), however race was not significantly associated with stage of prostate cancer in those <55 years (p=0.29). CONCLUSIONS: Sociodemographic disparities in advanced stages of prostate cancer diagnosis were more pronounced in younger patients, particularly with respect to insurance status. These findings may support greater attention to differential use of early prostate cancer screening by health insurance. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1079 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shayan Smani More articles by this author Madison Novosel More articles by this author Victoria Marks More articles by this author Farah Jeong More articles by this author Preston Sprenkle More articles by this author Michael Leapman More articles by this author Expand All Advertisement PDF downloadLoading ...

Using of 18 fluorine labeled prostatic specific membrane antigen positron emission tomography-computed tomography in staging of prostatic cancer in correlation with prostate specific antigen level

Using of 18 fluorine labeled prostatic specific membrane antigen positron emission tomography-computed tomography in staging of prostatic cancer in correlation with prostate specific antigen level

MP67-01 THE IMPACT OF LYMPHOVASCULAR INVASION ON LONG-TERM CANCER OUTCOMES FOLLOWING RADICAL PROSTATECTOMY

You have accessJournal of UrologyCME1 Apr 2023MP67-01 THE IMPACT OF LYMPHOVASCULAR INVASION ON LONG-TERM CANCER OUTCOMES FOLLOWING RADICAL PROSTATECTOMY Niranjan Sathianathen, Marc Furrer, Clancy Mulholland, Nathan Lawrentschuk, and Niall Corcora Niranjan SathianathenNiranjan Sathianathen More articles by this author , Marc FurrerMarc Furrer More articles by this author , Clancy MulhollandClancy Mulholland More articles by this author , Nathan LawrentschukNathan Lawrentschuk More articles by this author , and Niall CorcoraNiall Corcora More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003330.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lymphovascular invasion (LVI) has been shown to be associated with higher grade and stage of prostate cancer. However, the literature is scarce on its ability to predict long-term oncological outcomes. Therefore, we aim to evaluate the impact of LVI on long-term prostate cancer outcomes following radical prostatectomy. METHODS: A consecutive sample of patients with localised prostate cancer undergoing radical prostatectomy in a multicentre database was included in the analysis. Postoperative PSA measurements and clinical examinations were taken at 3, 6 and 12 months and afterwards yearly. Further diagnostic imaging was obtained with a rising PSA or clinical suspicion. Recurrence-free survival (RFS) and metastases-free survival (MFS) were analysed as a time-to-event outcome using Kaplan-Meier analyses with log-rank tests. To assess the effect of LVI, we created multivariable Cox proportional hazards models adjusting for relevant clinical and demographic characteristics. Ethics committee approval was obtained. RESULTS: A total of 3,732 men were included for analysis with a median follow-up of 44 months. LVI was detected in 18% (n=682). LVI was more common with increasing ISUP grade [RR 4.2, 95%CI 3.8-4.6] and pathological stage [RR 6.5, 95%CI 5.9-7.2]. The incidence of metastasis at 5-years was 12%. Men that were LVI+were more likely to develop metastatic disease than those that were LVI- (39% vs 6%, p<0.01). LVI was an independent predictor of metastasis [HR 2.2, 95%CI 1.7-3.0] and biochemical recurrence [HR 2.1, 95%CI 1.8-2.5]. This finding was consistently noted on subgroup analysis of men with both intermediate- and high-risk prostate cancer. CONCLUSIONS: Lymphovascular invasion is a prognostic indicator of adverse recurrence- and metastasis-free survival following surgery for prostate cancer. This can assist with risk-stratification following radical treatment and possibly aid decision-making regarding adjuvant treatment. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e943 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Niranjan Sathianathen More articles by this author Marc Furrer More articles by this author Clancy Mulholland More articles by this author Nathan Lawrentschuk More articles by this author Niall Corcora More articles by this author Expand All Advertisement PDF downloadLoading ...

MP17-16 COMPARING INTRADUCTAL CARCINOMA OF THE PROSTATE TO GRADE AND STAGE: A COPY NUMBER ALTERATION CHARACTERIZATION STUDY

You have accessJournal of UrologyCME1 Apr 2023MP17-16 COMPARING INTRADUCTAL CARCINOMA OF THE PROSTATE TO GRADE AND STAGE: A COPY NUMBER ALTERATION CHARACTERIZATION STUDY Helen Pantazopoulos, Afnan Al-Saleh, Mame Kany Diop, David Boucher Roy, Roy Nitulescu, Roula Albadine, and Dominique Trudel Helen PantazopoulosHelen Pantazopoulos More articles by this author , Afnan Al-SalehAfnan Al-Saleh More articles by this author , Mame Kany DiopMame Kany Diop More articles by this author , David Boucher RoyDavid Boucher Roy More articles by this author , Roy NitulescuRoy Nitulescu More articles by this author , Roula AlbadineRoula Albadine More articles by this author , and Dominique TrudelDominique Trudel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003237.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) is the most diagnosed cancer in North American men varying greatly at clinical presentation from indolent to aggressive tumors. An aggressive subtype of PCa is intraductal carcinoma of the prostate (IDC-P), identified in ∼20% of men with PCa. While accurate stratification of these high-risk patients is a clinical necessity, the question arose whether IDC-P could be related to the grade or not. We hypothesized that through the genomic characterization of IDC-P, we could explore the link between IDC-P, grade, and or stage. The objective of this study was to characterize the copy number alterations (CNAs) of IDC-P to aid in the characterization of these high-risk men, while exploring whether IDC-P should be integrated into the grade or stage of PCa. METHODS: We selected 462 radical prostatectomy specimens obtained through The Cancer Genome Atlas (TCGA). Specifically, 38 patients were excluded from the original TCGA cohort (n=500) due to stage T4 and incomplete genomic data. We further characterized the TCGA cohort by identifying the IDC-P status (present or not identified) for each patient through the online available tissue. For each patient, IDC-P status was evaluated alongside the CNAs of 488 genes involved in androgen receptor signaling and or carcinogenesis. RESULTS: Out of 462 patients, 41% (191/462) were IDC-P present, and these patients were mostly of high grade (53.9%) and advanced pT3b stage (38.7%). Overall, 38 genes were significantly associated to IDC-P growth, of which, 37 genes were novel and not unique to IDC-P or documented in PCa. Specifically, 10 genes were associated to chromosome 10q deletions, including the well-recognized PTEN, while 28 genes were associated to chromosome 8q amplifications. Of the IDC-P present men identified, 36% (69/191) of these men had multiple deletions and 16% (31/191) of these men had multiple amplifications. CONCLUSIONS: We found significant deletions in 10 genes and amplifications in 28 genes in IDC-P. Importantly, high-risk men with IDC-P have numerous deletions and amplifications in the identified 38 genes. We have identified novel genes, except for PTEN. Indeed, more than 2/3 of these genes are amplified on 8q and their expression could be targeted as biomarkers of IDC-P. We are exploring the presence of these anomalies in PCa and their relation to Grade group (especially cribriform pattern) and or stage. Together, these findings will genomically characterize IDC-P and allow for improved precision in the stratification of these high-risk patients. Source of Funding: Institut du Cancer de Montréal © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e219 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Helen Pantazopoulos More articles by this author Afnan Al-Saleh More articles by this author Mame Kany Diop More articles by this author David Boucher Roy More articles by this author Roy Nitulescu More articles by this author Roula Albadine More articles by this author Dominique Trudel More articles by this author Expand All Advertisement PDF downloadLoading ...

Quantification of Multi-Parametric Magnetic Resonance Imaging Based on Radiomics Analysis for Differentiation of Benign and Malignant Lesions of Prostate.

The most common cancer (non-cutaneous) malignancy among men is prostate cancer. Management of prostate cancer, including staging and treatment, playing an important role in decreasing mortality rates. Among all current diagnostic tools, multiparametric MRI (mp-MRI) has shown high potential in localizing and staging prostate cancer. Quantification of mp-MRI helps to decrease the dependency of diagnosis on readers' opinions. The aim of this research is to set a method based on quantification of mp-MRI images for discrimination between benign and malignant prostatic lesions with fusion-guided MR imaging/transrectal ultrasonography biopsy as a pathology validation reference. It is an analytical research that 27 patients underwent the mp-MRI examination, including T1- and T2- weighted and diffusion weighted imaging (DWI). Quantification was done by calculating radiomic features from mp-MRI images. Receiver-operating-characteristic curve was done for each feature to evaluate the discriminatory capacity and linear discriminant analysis (LDA) and leave-one-out cross-validation for feature filtering to estimate the sensitivity, specificity and accuracy of the benign and malignant lesion differentiation process is used. An accuracy, sensitivity and specificity of 92.6%, 95.2% and 83.3%, respectively, were achieved from a subset of radiomics features obtained from T2-weighted images and apparent diffusion coefficient (ADC) maps for distinguishing benign and malignant prostate lesions. Quantification of mp-MRI (T2-weighted images and ADC-maps) based on radiomics feature has potential to distinguish benign with appropriate accuracy from malignant prostate lesions. This technique is helpful in preventing needless biopsies in patients and provides an assisted diagnosis for classifications of prostate lesions.

MP55-03 CORRELATION BETWEEN PSMA PET/CT DATA AND PATHOLOGICAL TUMOUR STAGING AND GRADING OF PROSTATE CANCER

MP55-03 CORRELATION BETWEEN PSMA PET/CT DATA AND PATHOLOGICAL TUMOUR STAGING AND GRADING OF PROSTATE CANCER