ABSTRACT Spatially resolved DNA sequencing holds promise due to its potential utility in understanding cancer intra-tumour heterogeneity and tumour evolution in relation to tissue architecture. However, it has so far been used to a limited extent due to technical challenges and high cost of existing methods. Hence we aimed to develop a high throughput spatial genomic assay to obtain copy number alteration (CNA) information at user-defined spatial resolution. We derived CNA profiles from ultra-low coverage whole genome sequencing at sub-millimetre resolution from archival samples using a novel method called Adaptive Resolution Multiscale Spatial DNA sequencing (ARMS DNAseq). We used it to profile CNAs from more than 766 regions (tiles) from 3 patients, covering a total area of over 300 mm 2 , with 1.2–2.6 million mapped reads per tile and tile sizes of 0.1-0.99mm 2 . Using ARMS DNAseq, we delineate tumour evolution in a spatial context, and identify more tumour subclones that were obscured or incompletely represented in bulk multi-region whole genome sequencing. Next, we show associations between tumour subclones and morphology, and prediction of subclone identity from deep learning-derived image representations. Finally, we demonstrate multi-omic integration by alignment with spatial transcriptomic data, showing subclone-specific immune cell co-occurrence as well as transcriptional programmes cutting across subclone boundaries. ARMS DNAseq converts low-throughput, region-by-region profiling into a scalable and adaptable workflow for direct spatial copy number profiling from archival tissue sections.

Abstract Introduction: A priority in prostate cancer (PCa) research is development of precise risk stratification tools to enable early identification of men with aggressive tumours while minimizing overtreatment of others with indolent disease. With imaging playing a central role in the diagnosis and management of PCa, radiogenomics has been explored as a personalised medicine approach to improve risk stratification. This study aims to review and describe radiogenomic applications reported in the literature. Methods: Medline, Embase and Cochrane libraries were systematically searched using variations of search terms for articles reporting radiogenomic applications in PCa after 2010. Articles were included if the following were reported (1) genomic platform used; (2) method of determining region of interest (ROI) for radiomic feature extraction; (3) correlation analyses between radiomics and genomics. Results: A total of 267 articles were screened and 13 met the inclusion criteria following independent review by two authors. Majority (n=10/13) reported MRI-based applications involving 715 patients. Remaining modalities included ultrasound (n=1) and PET scan (n=2). Most (7/10) studies evaluating an MRI imaging modality, correlated bulk RNA-sequencing with radiomic features. Textural radiomics (n=6) features were most commonly reported to correlate with gene expression followed by histogram (n=2) and volumetric features (n=1). MRI radiomics significantly correlated with hypoxia related genes in 4 studies. The textural feature (Gray Level Co-occurrence Matrix) was seen to correlate with ANGPTL4 expression in 3 studies. Median AUC for a radiogenomic model to predict presence of clinically significant PCa was 0.746. Only 4 studies (MRI-based n=3, ultrasound-based n=1) externally validated the developed model. Most (9/13) studies used a manual qualitative approach to register imaging loci with site of tissue acquisition for genomic analysis. Conclusion: There is significant heterogeneity in the reporting and design of prostate cancer radiogenomic studies. A signal suggesting and association of MRI textural radiomic features have been consistently observed in several studies but lack validation. Citation Format: Thineskrishna Anbarasan, Matilda Dichmont, Sandy Figiel, Bartlomiej Papiez, Alastair Lamb, Richard Bryant, Ian Mills. A systematic review of radiogenomic applications in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2621.

Background Prostate cancer (PCa) is the most common male malignancy in the western world. Many men (40%) are diagnosed with localised low or intermediate-risk PCa, which is suitable for active surveillance (AS). AS affords careful monitoring to identify changes in otherwise non-life-threatening cancers. While AS reduces overtreatment (and quality of life impact), long-term compliance can be poor, with many men undergoing radical treatment after starting AS.Methods and analysis Finasteride in Active Surveillance for men with low and intermediate-risk prostate cancer (FINESSE) is a prospective, open-label, two-arm, phase 3 trial, in which men with low or intermediate PCa are randomised (1:1) to receive AS with or without finasteride (5 mg once a day for 2 years). Randomisation is stratified by age and PCa risk. AS includes regular prostate-specific antigen testing, MRI scans and the offer of repeat biopsy (at 3 years, or if imaging suggests progression). Additional MRI scans and/or biopsies will be performed for biochemical or clinical indications. We aim to recruit 550 men (aged 50 to 75 years) from up to eight sites. Active outpatient follow-up will be for 3-5 years (depending on date recruited), followed by passive registry-based follow-up for up to 10 years. Primary outcome is adherence to AS. Secondary outcomes include rates and type of disease progression, treatments received (for PCa and benign prostatic enlargement), overall and PCa-specific mortality, an understanding of patients/professionals views of this approach and health-related quality of life. An external panel of experts blinded to allocation will review all AS cessation and progression events. Trial pathologist's and radiologist's, blinded to allocation, will review representative cases. Analysis is Intention to Treat.Ethics and dissemination The study received Health Research Authority and South-Central Oxford Research Ethics Committee (14/12/2021: 21/SC/0349) and CTA/MHRA (29/12/2021: 21304/0274/001-0001) approvals. Results will be made available to providers and researchers via publicly accessible scientific journals.Trial registration number ISRCTN16867955

New spatial molecular technologies are poised to transform our understanding and treatment of urological cancers. By mapping the spatial molecular architecture of tumours, these platforms uncover the complex heterogeneity within and around individual malignancies, offering novel insights into disease development, progression, diagnosis, and treatment. They enable tracking of clonal phylogenetics in situ and immune-cell interactions in the tumour microenvironment. A whole transcriptome/genome/proteome-level spatial analysis is hypothesis generating, particularly in the areas of risk stratification and precision medicine. Current challenges include reagent costs, harmonisation of protocols, and computational demands. Nonetheless, the evolving landscape of the technology and evolving machine learning applications have the potential to overcome these barriers, pushing towards a future of personalised cancer therapy, leveraging detailed spatial cellular and molecular data. Patient summary Tumours are complex and contain many different components. Although we have been able to observe some of these differences visually under the microscope, until recently, we have not been able to observe the genetic changes that underpin cancer development. Scientists are now able to explore molecular/genetic differences using approaches such as “spatial transcriptomics” and “spatial proteomics”, which allow them to see genetic and cellular variation across a region of normal and cancerous tissue without destroying the tissue architecture. Currently, these technologies are limited by high associated costs, and a need for powerful and complex computational analysis workflows. Future advancements and results through these new technologies may assist patients and their doctors as they make decisions about treating their cancer.

Importance:Cribriform prostate cancer is associated with poor outcomes; however, its optimal treatment strategy remains unclear in the absence of randomized data. Objective:To retrospectively analyze the results of the PROTECT randomized clinical trial to establish the association between cribriform-positive and cribriform-negative prostate cancer and 15-year risk of metastasis in patients who underwent active monitoring, surgery, or radiotherapy. Design, Setting, and Participants:Between 1999 and 2009, the PROTECT phase 3 randomized clinical trial enrolled 1643 men with clinically localized prostate cancer who were randomly assigned to receive active monitoring, surgery, or radiotherapy with neoadjuvant androgen deprivation therapy (ADT). In this secondary analysis of the PROTECT trial, a centralized histopathologic review was conducted on available diagnostic biopsy slides to classify patients as cribriform-positive if they had invasive cribriform carcinoma and/or intraductal carcinoma. Data were collected from January 25, 2024, to October 11, 2024, and were analyzed from October 14, 2024, to January 30, 2025. Exposures:Age, prostate-specific antigen (PSA), Gleason score, and cribriform status. Main Outcomes and Measures:The primary outcome was progression to metastatic disease (bony, visceral, or lymph node metastases on imaging or PSA >100 ng/mL). Multivariable Cox proportional hazards regression models, adjusted for randomization variables, were incorporated to assess 15-year metastasis risk. Cumulative incidence curves were compared using the Gray test. Both intention-to-treat and per-protocol analyses were performed. Results:Among 712 men (mean [SD] age, 62.0 [5.0] years) whose biopsies were retrospectively reviewed, 93 (13.1%) had cribriform-positive disease and 42 (5.9%) developed metastasis. In the intention-to-treat cohort, cribriform-positive disease significantly increased the risk of metastasis (hazard ratio [HR], 3.61 [95% CI, 1.60-8.11]; P = .003). Radiotherapy with neoadjuvant ADT significantly reduced metastasis risk (HR, 0.35 [95% CI, 0.16-0.78]; P = .04) (15-year cumulative incidence in patients with cribriform-positive disease, 8%), while surgery delayed metastasis but did not significantly improve long-term outcomes compared with active monitoring (HR, 0.52 [95% CI, 0.25-1.08]; P = .09) (15-year cumulative incidence in patients with cribriform-positive disease, 26% for surgery and 25% for active monitoring). Among patients with cribriform-negative disease, incidence of metastasis was low and did not differ by treatment. Similar per-protocol results were noted. Conclusions and Relevance:The findings of this secondary analysis of the PROTECT randomized clinical trial suggest that cribriform morphology was a strong, independent predictor of 15-year metastasis among patients with prostate cancer and that radiotherapy with neoadjuvant ADT was associated with a reduced long-term risk of metastasis. Conversely, outcomes were favorable for most patients with cribriform-negative disease, supporting their eligibility for active surveillance. Trial Registration:ClinicalTrials.gov Identifier: NCT02044172.

Risk stratification remains a key challenge in prostate cancer (PCa) management involves risk stratification, and identification of the subgroup of patients at highest risk of progressing from localised to metastatic disease is critical. Multiparametric MRI (mpMRI) is key in the PCa diagnostic pathway. By integrating clinical parameters, mpMRI radiomics and spatial transcriptomics (ST), this novel “Radio-Spatial Genomics” platform offers an exciting opportunity to identify mpMRI radiomic features associated with important biological aspects of PCa linked to an aggressive disease phenotype. Multi-regional spatial transcriptomics (Visium 10x Genomics) was performed on archived formalin-fixed paraffin-embedded prostatectomy sections from patients recruited to a local trial (ISRCTN10046036). Axial sections were sequenced using ST (8 per patient) from 2 patients with Gleason 4+4 PCa and preoperative mpMRI available was used for this study. Anatomical landmarks on mpMRI were segmented by a radiologist. Using a proportional size algorithm and a convolutional neural network (ProsRegNet), T2-axial MRI slices were aligned and registered to histopathology sections. An application, SpatialStitcher, was developed on Python 3.7.0 to digitally stitch separate ST sections for image registration. Using the prostatic capsule and urethra as landmarks, histopathology sections from 2 patients were co-registered to corresponding T2-axial MRI slices. In total, a median of 114670 whole transcriptome sequenced barcoded ST spots were co-registered to 30424 pixels on MRI per patient. A median DICE correlation score of 0.942, 0.738 and 0.756 was achieved for capsule, tumour and BPH nodules respectively. AMACR (marker for PCa) expression inversely correlated with T2 MRI intensity-based radiomic features (r = -0.763), consistent with the tumour being hypointense. Differential gene expression analysis between hyperintense peri-tumoural and hypointense tumour regions revealed enrichment for genes involved in mucosal immune response. In this study, we report preliminary results of mapping MRI with ST using machine learning to identify genotypic changes based on radiomics. This novel “Radio-Spatial Genomics” model may allow the detection of clinically relevant genotypic features from diagnostic prostate mpMRI imaging. Thineskrishna Anbarasan, Sandy Figiel, Sophia M. Abusamra, Wencheng Yin, Nithesh Ranasinha, James T. Grist, Dan J. Woodcock, Richard J. Bryant, Ruth McPherson, Freddie C. Hamdy, Bartlomiej Papiez, Ian G. Mills, Alastair D. Lamb. Integrating multiparametric MRI with spatial transcriptomics to identify “Radio-Spatial Genomic” features of prostate cancer using artificial intelligence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3684.

BACKGROUND:Prostate cancer diagnosis requires biopsy, traditionally performed under local anaesthetic with ultrasound guidance via a transrectal approach (TRUS). Local anaesthetic ultrasound-guided transperineal biopsy (LATP) is gaining popularity in this setting; however, there is uncertainty regarding prostate sampling, infection rates, tolerability, side-effects, and cost-effectiveness. TRANSLATE was a randomised clinical trial that aimed to compare detection of Gleason Grade Group (GGG) 2 or higher prostate cancer, side-effects, tolerability, and patient-reported outcomes, after LATP versus TRUS biopsy. METHODS:In this randomised clinical trial which was done at ten hospitals in the UK, patients aged 18 years or older were eligible if investigated for suspected prostate cancer based on elevated age-specific prostate-specific antigen or abnormal digital rectal examination, and if biopsy-naive having received pre-biopsy MRI on a 1·5 or higher Tesla scanner. Individuals were excluded if they had any previous prostate biopsy, extensive local disease easily detectable by any biopsy (prostate-specific antigen >50 ng/mL or entire gland replaced by tumour on MRI), symptoms of concurrent or recent urinary tract infection, history of immunocompromise, need for enhanced antibiotic prophylaxis, absent rectum, or inability to position in lithotomy. Participants were randomly assigned in a 1:1 ratio to receive LATP or TRUS biopsy, using web-based software with a randomisation sequence using a minimisation algorithm to ensure balanced allocation across biopsy groups for minimisation factors (recruitment site, and location of the MRI lesion). The primary outcome was detection of GGG 2 or higher prostate cancer, analysed in the modified intention-to-treat population (all randomly assigned to treatment who had a biopsy result available). Key secondary endpoints assessing post-biopsy adverse events were infection, bleeding, urinary and sexual function, tolerability, and patient-reported outcomes. This trial is registered with ClinicalTrials.gov (NCT05179694) and at ISRCTN (ISRCTN98159689), and is complete. FINDINGS:Between Dec 3, 2021, and Sept 26, 2023, 2078 (76%) of 2727 assessed individuals were eligible, and 1126 (41%) of 2727 agreed to participate. 1044 (93%) of the 1126 participants were White British. Participants were allocated to TRUS (n=564) or LATP (n=562) biopsy, and were followed up at time of biopsy, and at 7 days, 35 days, and 4 months post-biopsy. We found GGG 2 or higher prostate cancer in 329 (60%) of 547 participants with biopsy results randomly assigned to LATP compared with 294 (54%) of 540 participants with biopsy results randomly assigned to TRUS biopsy (odds ratio [OR] 1·32 [95% CI 1·03-1·70]; p=0·031). Infection requiring admission to hospital within 35 days post-biopsy occurred in 2 (<1%) of 562 participants in the LATP group compared with 9 (2%) of 564 in the TRUS group. No statistically significant difference was observed in the reporting of overall biopsy-related complications (LATP 454 [81%] of 562 vs TRUS 436 [77%] of 564, OR 1·23 [95% CI 0·93 to 1·65]), urinary retention requiring catheterisation (LATP 35 [6%] of 562 vs TRUS 27 [5%] of 564), urinary symptoms (median International Prostate Symptom Score: LATP 8 [IQR 4-14] vs TRUS 8 [4-13], OR 0·36 [95% CI -0·38 to 1·10]), nor sexual function (median International Index of Erectile Function score: LATP 5 [2-25] vs TRUS 8 [3-24], OR -0·60 [-1·79 to 0·58]) at 4 months after biopsy. Trial participants more commonly reported LATP biopsy to be immediately painful and embarrassing compared with TRUS (LATP 216 [38%] of 562 vs TRUS 153 [27%] of 564; OR 1·84 [95% CI 1·40 to 2·43]). Serious adverse events occurred in 14 (2%) of 562 participants in the LATP group and 25 (4%) of 564 in the TRUS group. INTERPRETATION:Among biopsy-naive individuals being investigated for possible prostate cancer, biopsy with LATP led to greater detection of GGG 2 or higher disease compared with TRUS. These findings will help to inform patients, clinicians, clinical guidelines, and policy makers regarding the important trade-offs between LATP and TRUS prostate biopsy. FUNDING:National Institute for Health and Care Research (NIHR) Health Technology Assessment.

Objectives:This study aims to explore the opinions and attitudes of patients and clinicians regarding the use of artificial intelligence (AI) in the diagnosis of prostate biopsies, with a focus on acceptance and trust in the use of AI, and factors that may impact this. Subjects and methods:Surveys were sent to patient members of UK-based prostate cancer support groups and to a group of clinicians managing patients with prostate cancer (or suspected prostate cancer). Results:Of 130 patient respondents, 94% expressed acceptance of AI assistance in the diagnosis of prostate biopsies when a pathologist retains responsibility for the final diagnosis, but regard it as the responsibility of the pathologist to decide whether AI is used in this setting. Similar responses were noted among the nine clinician respondents. Regarding factors with potential impact on acceptance of AI, an understanding of how the AI was tested and its performance in comparison with a pathologist was considered to be more important than how the technology was developed, and half (51%) of patients suggested that access to additional information might impact their acceptance of AI. Conclusion:Understanding the perspectives of stakeholders is key to the successful clinical implementation of AI in the histological diagnosis of prostate biopsies. Our study shows a high level of acceptance of AI for the diagnosis of prostate biopsies among patients if a pathologist retains oversight of the diagnosis and the decision as to when AI is used. Furthermore, it suggests similar levels of acceptance among clinicians. Our study provides insight into areas for educational focus to enhance understanding of AI in this setting.

Prostate cancer (PCa) exhibits significant intratumoral heterogeneity, driving a spectrum of phenotypes ranging from indolent disease to aggressive metastasis, challenging risk stratification and treatment. A key feature of this heterogeneity is clonal diversity, encompassing both cancer cells and their interactions with the surrounding stromal microenvironment. Understanding clonal dynamics and stromal influences on tumor progression is crucial for identifying factors that contribute to metastasis and disease lethality, ultimately improving risk stratification and therapeutic strategies. We performed organ-wide spatial transcriptomic analyses (VisiumTM v2, 10x Genomics) on formalin-fixed paraffin-embedded tissues from ten patients with primary, nodal metastatic PCa and biopsy samples, recruited to a local trial (ISRCTN10046036). Two pathologists meticulously annotated each spot, including benign, Gleason grade, stroma, and immune cells. Fastq data were processed using SpaceRangerTM, and inferred clonal genomic identities were analyzed with SpatialInferCNV (https://github.com/aerickso/SpatialInferCNV). We reconstructed clonal evolution using phylogenetic trees and analyzed stromal gene expression around distinct tumor clones using differential expression analyses. In addition, we performed multiplex imaging on consecutive sections to assess protein expression and correlate it with gene expression data, enabling the identification of key tumor-stroma interactions associated with metastatic progression. We analyzed 122 spatial transcriptomics capture areas, collectively representing over 1, 000, 000 spots (55 µm diameter), or approximately 16, 000, 000 cells. We identified clonal subtypes across biopsy, primary and metastatic tissues, revealing distinct clonal relationships and polyclonal lymph node colonization at different evolutionary stages. Stromal cells around metastatic progenitor clones showed upregulation of antigen presentation and inflammatory pathway genes, contrasting with stromal profiles surrounding lethal clones (as defined by their ability to metastasize to lymph nodes). These findings suggest a dynamic interplay between tumor cells and their stroma, potentially influencing metastatic potential and immune evasion. This study provides a detailed cellular-level characterization of clonal heterogeneity in PCa and its relationship with stromal dynamics, offering insights into mechanisms driving metastatic progression. These insights could inform strategies for risk stratification and therapeutic intervention, including leveraging dual tumor-stromal profiles as biomarkers to distinguish lethal from indolent disease. Understanding the interplay between tumor clones and their stroma opens new avenues for targeted treatment approaches aimed at preventing metastasis and improving patient outcomes. Sandy Figiel, Mengxiao He, Wencheng Yin, Emmanouela Perisynaki, Renuka Teague, Thineskrishna Anbarasan, Eleanor O’Roberts, Nithesh Ranasinha, Sophia M. Abusamra, Trishna Desai, Dimitrios Doultsinos, Andrew Erickson, Srinivasa Rao, Clare Verrill, Richard Colling, Pelvender Gill, Tuomas Mirtti, Ibrahim Kulac, Karl Smith-Byrne, Ruth Travis, Charlotte Stadler, Richard J. Bryant, Freddie C. Hamdy, Dan J. Woodcock, Ian G. Mills, Joakim Lundeberg, Alastair D. Lamb. Mapping clonal heterogeneity and stromal dynamics in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2663.

Extension of prostate cancer beyond the primary site by local invasion or nodal metastasis is associated with poor prognosis. Despite significant research on tumour evolution in prostate cancer metastasis, the emergence and evolution of cancer clones at this early stage of expansion and spread are poorly understood. We aimed to delineate the routes of evolution and cancer spread within the prostate and to seminal vesicles and lymph nodes, linking these to histological features that are used in diagnostic risk stratification. We performed whole-genome sequencing on 42 prostate cancer samples from the prostate, seminal vesicles and lymph nodes of five treatment-naive patients with locally advanced disease. We spatially mapped the clonal composition of cancer across the prostate and the routes of spread of cancer cells within the prostate and to seminal vesicles and lymph nodes in each individual by analysing a total of > 19,000 copy number corrected single nucleotide variants. In each patient, we identified sample locations corresponding to the earliest part of the malignancy. In patient 10, we mapped the spread of cancer from the apex of the prostate to the seminal vesicles and identified specific genomic changes associated with the transformation of adenocarcinoma to amphicrine morphology during this spread. Furthermore, we show that the lymph node metastases in this patient arose from specific cancer clones found at the base of the prostate and the seminal vesicles. In patient 15, we observed increased mutational burden, altered mutational signatures and histological changes associated with whole genome duplication. In all patients in whom histological heterogeneity was observed (4/5), we found that the distinct morphologies were located on separate branches of their respective evolutionary trees. Our results link histological transformation with specific genomic alterations and phylogenetic branching. These findings have implications for diagnosis and risk stratification, in addition to providing a rationale for further studies to characterise the genetic changes causally linked to morphological transformation. Our study demonstrates the value of integrating multi-region sequencing with histopathological data to understand tumour evolution and identify mechanisms of prostate cancer spread.

Prostate-specific membrane antigen (PSMA) is increasingly used to image prostate cancer in clinical practice. We sought to develop and test a humanised PSMA minibody IAB2M conjugated to the fluorophore IRDye 800CW-NHS ester in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) to image prostate cancer cells during surgery. The minibody was evaluated pre-clinically using PSMA positive/negative xenograft models, following which 23 men undergoing RARP between 2018 and 2020 received between 2.5 mg and 20 mg of IR800-IAB2M intravenously, at intervals between 24 h and 17 days prior to surgery. At every step of the procedure, the prostate, pelvic lymph node chains and extra-prostatic surrounding tissue were imaged with a dual Near-infrared (NIR) and white light optical platform for fluorescence in vivo and ex vivo. Histopathological evaluation of intraoperative and postoperative microscopic fluorescence imaging was undertaken for verification. Twenty-three patients were evaluated to optimise both the dose of the reagent and the interval between injection and surgery and secure the best possible specificity of fluorescence images. Six cases are presented in detail as exemplars. Overall sensitivity and specificity in detecting non-lymph-node extra-prostatic cancer tissue were 100 https://www.isrctn.com/ISRCTN10046036 .

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD09)1 May 2024PD09-06 EXPLORING STROMAL DYNAMICS IN PROSTATE CANCER: INSIGHTS FROM SPATIAL TRANSCRIPTOMIC ANALYSES Sandy Figiel, Wencheng Yin, Mengxiao He, Renuka Teague, Thineskrishna Anbarasan, Nithesh Ranasinha, Sophia Abusamra, Reema Singh, Dimitrios Doultsinos, Ninu Poulose, Andrew Erickson, Clare Verrill, Richard Colling, Pelvender Gill, Richard J. Bryant, Olivier Cussenot, Massimo Loda, Freddie C. Hamdy, Dan J. Woodcock, Ian G. Mills, Joakim Lundeberg, Solna Sweden, and Alastair D. Lamb Sandy FigielSandy Figiel , Wencheng YinWencheng Yin , Mengxiao HeMengxiao He , Renuka TeagueRenuka Teague , Thineskrishna AnbarasanThineskrishna Anbarasan , Nithesh RanasinhaNithesh Ranasinha , Sophia AbusamraSophia Abusamra , Reema SinghReema Singh , Dimitrios DoultsinosDimitrios Doultsinos , Ninu PouloseNinu Poulose , Andrew EricksonAndrew Erickson , Clare VerrillClare Verrill , Richard CollingRichard Colling , Pelvender GillPelvender Gill , Richard J. BryantRichard J. Bryant , Olivier CussenotOlivier Cussenot , Massimo LodaMassimo Loda , Freddie C. HamdyFreddie C. Hamdy , Dan J. WoodcockDan J. Woodcock , Ian G. MillsIan G. Mills , Joakim LundebergJoakim Lundeberg , Solna SwedenSolna Sweden , and Alastair D. LambAlastair D. Lamb View All Author Informationhttps://doi.org/10.1097/01.JU.0001008572.33286.63.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer's prognosis varies widely, from indolent to aggressive forms causing metastasis and death. The lack of reliable diagnostic tools and effective treatments poses substantial challenges in its management and research. Understanding the mechanisms driving prostate cancer's diversity is crucial for improved treatment. Spatial genomics has allowed us to define clonal heterogeneity, revealing insights into the cancer's origin and emphasising the stroma's role in tumour development, fostering growth and immune evasion. This study explores the stroma in primary and metastatic prostate cancer tissue, aiming to identify transformation-promoting factors. METHODS: We conducted spatial transcriptomic analyses (Visium v2) on FFPE tissues from primary and nodal metastatic tissues. We analysed expression data using spatial inferred copy number variations and constructed a phylogenetic tree to describe clonal events in tumour regions (https://github.com/aerickso/SpatialInferCNV). We performed differential gene expression analyses of stromal cells around each tumour clone, employing combined cellular deconvolution. RESULTS: We found significant variations within stromal cells around distinct tumour clones. Interestingly, we found upregulation of genes associated with antigen presentation and inflammatory response pathways in the stroma surrounding ancestor tumour clones that had not yet acquired metastatic potential. For example, gene CD74 was highly expressed in the stroma around ancestor clone (clone B) compared to descendant clone (clone C) in the apex of the prostate. We also observed this discrepancy in the base, where we identified a lethal clone that had spread to the lymph nodes. Indeed, the stroma around the ancestor clone (clone C1) is enriched in IGHA1, compared to the stroma around the lethal clone (clone X1). CONCLUSIONS: Our study reveals altered stromal gene expression surrounding different tumour clones, highlighting the dynamic interplay between cancer cells and their microenvironment. This distinctive stromal profile offers mechanistic insights underpinning phenotypic variability. It raises the possibility of using the stroma as a window to differentiate tumour lethality from indolent disease, as well as offering targets for personalised treatment strategies. Download PPT Source of Funding: The present work was supported by Cancer Research UK (CRUK), Hanson Trust Research, the John Black Charitable Foundation, Prostate Cancer Foundation, NIHR Oxford Biomedical Research Centre, European Research Council, Swedish Society for Cancer Research © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e181 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Sandy Figiel More articles by this author Wencheng Yin More articles by this author Mengxiao He More articles by this author Renuka Teague More articles by this author Thineskrishna Anbarasan More articles by this author Nithesh Ranasinha More articles by this author Sophia Abusamra More articles by this author Reema Singh More articles by this author Dimitrios Doultsinos More articles by this author Ninu Poulose More articles by this author Andrew Erickson More articles by this author Clare Verrill More articles by this author Richard Colling More articles by this author Pelvender Gill More articles by this author Richard J. Bryant More articles by this author Olivier Cussenot More articles by this author Massimo Loda More articles by this author Freddie C. Hamdy More articles by this author Dan J. Woodcock More articles by this author Ian G. Mills More articles by this author Joakim Lundeberg More articles by this author Solna Sweden More articles by this author Alastair D. Lamb More articles by this author Expand All Advertisement PDF downloadLoading ...

Atypical small acinar proliferation (ASAP), found in 5% of prostate biopsies, represents a focus of atypical cells that fall short of a cancer diagnosis.1 ASAP may be associated with a diagnosis of prostate cancer (PCa) upon repeat biopsy in 25%–50% of patients within 5 years.1 The proportion of these cases that may be classified as being intermediate- or high-grade PCa varies in the literature, ranging from 6.0% to 22.5%.2, 3 Until recently, diagnosis of ASAP was an indication for early repeat biopsy in international guidelines. However, recent studies referenced by the European Association of Urology (EAU) guidelines suggest low rates of subsequent Gleason grade group (GG) ≥ 2 PCa, similar to following a previous negative biopsy, leading to a softening of the recommendation for ASAP as an indication for performing early repeat biopsy.4 We therefore aimed to test the hypothesis that prostate cancer diagnosed on early re-biopsy after detection ASAP is always low grade by interrogating a large prospective pathology database. We also aimed to determine the time interval between detection of ASAP and diagnosis of csPCa, if present. We scrutinised pathology records according to a prospectively derived protocol (ID: CU96T) for all consecutive patients with ASAP on needle biopsy, transurethral resection of the prostate (TURP) chippings, or holmium laser enucleation of the prostate (HoLEP) specimens between January 2010 and November 2021 at a single tertiary institution. We classified pathological upgrading to csPCa as any Gleason pattern 4 disease identified within 2 years of the initial biopsy/TURP/HoLEP specimen detecting ASAP. Where available, we reviewed pre-biopsy multiparametric MRI (mpMRI) reports for PI-RADS scores at the time of ASAP diagnosis and obtained the prostate volume in order to derive the PSA density (PSAD). A multi-variable logistic regression model (including age, PSAD and PI-RADS) was constructed to determine factors associated with the development of csPCa. Approximately 13 240 prostate samplings were performed (11 240 needle biopsy and 2000 HoLEP/TURP specimens) over the 10-year period. ASAP was identified in 617 (4.7%) biopsy samplings, involving 523 patients. Of these, 51 (9.7%) patients had a pre-existing history of PCa and were excluded from further analysis, leaving a sample size of 472 individuals with de novo ASAP (Table 1). The baseline characteristics of the cohort are summarised in Table 1. Two hundred and thirty-seven (50.2%) patients had a repeat biopsy (Table S1) within a median of 92 days (IQR: 56–283). The median PSA within 3–6 months of ASAP detection was higher amongst patients who underwent repeat biopsy (6.7 vs. 5.08 ng/ml, p = 0.001) consistent with clinical judgement advocating repeat biopsy. In the 248 of 472 (52.5%) patients with pre-biopsy MRI, logistic regression revealed age <65 years (OR: 3.11; 95% CI: 1.74–5.69), PSAD > 0.15 ng/ml2 (OR: 2.06; 95% CI: 1.13–3.80), and PI-RADS ≥ 3 (OR: 1.88; 95% CI: 1.05–3.42) were independently associated with patients undergoing repeat biopsy following detection of ASAP. In the 237 patients who underwent repeat biopsies, intermediate- or high-grade PCa (GG ≥ 2) was found in 57 (24.1%) patients (18 high-grade [GG 4/5] versus 39 intermediate-grade [GG 2/3]) within 2 years at a median interval of 128 days (IQR: 61–260). Low-grade PCa (GG1) was detected in 77 (32.5%) patients. GG ≥ 2 PCa was detected on the ipsilateral side of ASAP diagnosis in 46 of 57 (80.8%) patients, which we therefore hypothesise to be related to the original diagnosis of ASAP. Amongst patients who underwent repeat biopsy following detection of ASAP, mpMRI was performed with PI-RADS data available for 74 patients (31.2%; from December 2014). Of these, 48 (64.8%) patients had PI-RADS ≥ 3. A PSAD > 0.15 ng/ml2 at time of ASAP diagnosis was independently associated (OR: 3.21; 95% CI: 1.12–9.74) with the detection of GG ≥ 2 PCa (Table 1). A subgroup of 16 patients with pre-biopsy PI-RADS 4–5 lesions were not found to have csPCa on repeat biopsy within 2 years. Repeat mpMRI (median interval of 526 days from detection of ASAP) was performed in 14 of 16 of these patients, of which five lesions were downgraded to PI-RADS 3 and a further five to PI-RADS 1/2. Expressed as a proportion of all men with ASAP, PI-RADS score 4/5 was associated with the development of GG ≥ 2 PCa (OR: 5.86; 95% CI: 2.01–19.6), as expected for MRI visible lesions. There were 103 patients without pre-biopsy PI-RADS score (predating regular pre-biopsy MRI), hence excluded from the above regression analysis, ROC curve analysis showed that the AUC for PSAD > 0.15 ng/ml2 was 0.734 (95% CI: 0.642–0.827) for the detection of GG ≥ 2 PCa within 2 years (Figure S1). The positive predictive value (PPV) and negative predictive value (NPV) for PSAD threshold of 0.15 ng/ml2 were 68.8% and 83.3%. At a higher PSAD threshold of 0.20 ng/ml2, the PPV and NPV were 74.0% and 80.0%, respectively (Table S2) . The rate of detection of ASAP in our cohort is 4.7%, which is consistent with the rate of approximately 5% previously reported in the literature. Younger patients, those with a raised PSAD, and those with positive mpMRI findings (PI-RADS ≥ 3) were more likely to undergo re-biopsy. It is also likely that the decision to re-biopsy was influenced by guideline recommendations, which have varied during this time period. The rate of clinically important PCa, adopting a definition of any Gleason pattern 4 disease within 2 years, was 24.1%. This is at odds with studies suggesting GG≥ 2 PCa is not diagnosed after ASAP4 and is consistent with Kim et al. who reported GG ≥ 2 PCa in 19.6% of patients with ASAP, this being similar to reports in other contemporary studies.2, 5, 6 In a meta-analysis including 16 studies and 1796 patients, those who underwent repeat biopsy within 6 months of ASAP diagnosis, had lower clinically important PCa detection (9%) compared to those who had repeat biopsy after (22.1%).7 On analysis of repeat MRIs, 71.4% of patients with PI-RADS 4–5 lesions who did not have GG ≥ 2 PCa on repeat biopsy had the PI-RADS score downgraded to ≤3 upon repeat mpMRI. Although we only focused on ASAP, this is consistent with the report by Meng et al. who observed a PI-RADS score downgrade of 73% from PI-RADS 4–5 to ≤3 amongst patients with any benign biopsy sub-type.8 This may suggest that microenvironmental changes associated with ASAP could predispose to false positive mpMRI changes. PSAD > 0.15 ng/ml2 at time of ASAP diagnosis was independently associated with the subsequent detection of GG ≥ 2 PCa at repeat biopsy. A reduced rate of false positives was observed with increasing PSAD thresholds. In a report by Warlick et al., PSAD was an independent predictor of detection of GG ≥ 2 PCa at repeat biopsy within 1 year of a diagnosis of ASAP.9 We observed an association between the laterality of ASAP diagnosis and subsequent GG ≥ 2 PCa detection, highlighting importance for adequate ipsilateral sampling given tissue heterogeneity.10, 11 This study has several limitations. Firstly, the number of men who underwent repeat biopsy will have been influenced by clinical decision-making. Secondly, we only adjusted for a limited number of baseline clinicopathological variables as per our protocol. Next, the lack of a control group with completely negative biopsies precludes comparison to determine whether ASAP is an independent predictor for development of GG ≥ 2 PCa. Finally, this is single-centre data reflecting one pathology department's criteria for reporting ASAP. Overall, we must reject our initial hypothesis that prostate cancer diagnosed after ASAP is always low grade. Contrary to this supposition, we have observed an important rate of detection of GG ≥ 2 PCa following a previous diagnosis of ASAP at needle biopsy or following histological analysis of TURP/HoLEP specimens. These findings support that patients diagnosed with ASAP should be followed up for consideration of repeat mpMRI and/or sampling. Further studies may guide development of risk-stratification tools based on clinicopathologic factors such as PSAD and pre-biopsy mpMRI PI-RADS score at the time of initial ASAP diagnosis. This would enable clinicians to better counsel patients and identify those requiring more stringent follow-up, potentially with re-biopsy or repeat mpMRI follow-up. Conceptualisation: Mutie Raslan, Claudia Mercader, Francisco Lopez and Alastair D. Lamb. Data curation: Kanchan Ghosh, Philip Macklin, Richard Colling, Lisa Browning, Ian Roberts. Formal analysis: Thineskrishna Anbarasan, Mutie Raslan and Alastair D. Lamb. Methodology: Thineskrishna Anbarasan, Mutie Raslan, Richard J. Bryant, Richard Colling, Clare Verrill and Alastaiir D. Lamb. Supervision: Richard J. Bryant, Clare Verrill, Freddie C. Hamdy and Alastair D. Lamb. Writing (original draft): Thineskrishna Anbarasan, Mutie Raslan and Alastair D. Lamb. Writing (review and editing): Thineskrishna Anbarasan, Mutie Raslan, Kanchan Ghosh, Philip Macklin, Claudia Mercader, Tom Leslie, Freddie C. Hamdy, Richard Colling, Lisa Browning, Ian Roberts, Clare Verrill, Richard J. Bryant, Francisco Lopez and Alastair D. Lamb. We acknowledge the contribution of patients included and the Oxford Centre for Histopathology Research. Lisa Browning receives funding for a study (ArticulatePro) evaluating Paige Prostate, which is funded by the NHSX Artificial Intelligence in Health and Care Award: Driving system-wide improvements with real-world economics evidence and subspecialist-led adoption guidelines for full workflow implementation of AI with Paige Prostate cancer detection (Paige AI 2020, New York), grading and quantification tool in histopathology departments (AI_AWARD02269). Richard Colling is part funded by UKRI (WCT WVI MAP project and PathLAKE project in-kind partnership with Philips), mdxhealth (research funding), NHSX (ARTICULATE PRO: evaluating Paige AI), and the Clarendon Fund (University of Oxford). Richard Bryant receives grant funding for TRANSLATE Trial (NIHR-HTA: NIHR131233), PART Trial Funding (NIHR-HTA: 17/150/01), Cancer Research Clinician Scientist Fellowship (A22748). Participates in STAMINA Trial Programme Steering Committee. Ian Roberts receives consulting fees from Novartis and Travere Therapeutics and support for attending meetings from American Society of Nephrology, International Academy of Pathology and Asia Pacific Society of Nephrology. Alastair Lamb receives grant funding for TRANSLATE Trial (NIHR-HTA: NIHR131233). ADL was supported by a Cancer Research UK Clinician Scientist Fellowship award (C57899/A25812). Figure S1. Schematic summary of the sub-group of patients with complete clinicopathologic data available for regression analysis. Table S1. Demographics and clinical characteristics of patients with ASAP with respect to whether repeat biopsy was performed. Table S2. Positive (PPV) and negative (NPV) predictive values at various PSA density (PSAD) thresholds for development of GG ≥ 2 PCa within 2 years of ASAP diagnosis in the sub-group of patients without pre-biopsy mpMRI data (n = 103). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Background: Detection of metastatic disease is important to inform prostate cancer management. Objectives: Evaluate local and distant staging by initial 18F-PSMA-1007 PET in primary and secondary prostate cancer. Design, Setting, and Participants: We retrospectively identified a consecutive series of 18F-PSMA-1007 PET scans from the date of introduction of 18F-PSMA-1007 PET in September 2019 until April 2022 at a single UK tertiary referral center. Our protocol was registered in advance (OSF registration ID: KTE3R). Results: We identified 1335 PSMA-PET scans, from 1220 men. Across 623 initial scans for primary staging, we observed PSMA-PET avidity in 97.6% cases positive for local disease, 29.5% for nodal disease, and 26.5% for metastatic disease. PSMA-PET identified a 13.2% absolute increase in nodal lesions compared with MRI and a 24.0% absolute increase in metastatic lesions compared with MRI marrow. The sensitivity for detection of local disease among 79 patients who had radical prostatectomy was 96.2% for PSMA-PET vs 89.4% for multiparametric MRI. Across 612 scans for secondary staging, we observed PSMA-PET positive avidity in 51.2% of cases for local recurrence, 46.6% for nodal disease, and 43.0% for metastatic disease. When evaluated by the PSA range for patients receiving secondary staging, using the PSA values of 0.2 to 0.49, 0.5 to 0.99, 1 to 1.99, and ≥ 2 ng/mL, PSMA-PET scans were positive in 57.8%, 75.0%, 83.8%, and 95.5% of cases, respectively. PSMA-PET identified a 26.2% absolute increase in metastatic lesions compared with MRI marrow or other skeletal MRI (n = 61) and a 14.7% absolute increase in metastatic lesions compared with the bone scan (n = 42). Conclusion: 18F-PSMA-1007 PET identifies a higher number of nodal and metastatic lesions compared with conventional cross-sectional imaging. However, the high number of indeterminate lesions and stage migration necessitates discussion of 18F-PSMA-1007 PET imaging within a multidisciplinary team and places a higher burden on these teams.

Abstract Background The TRANSLATE (TRANSrectal biopsy versus Local Anaesthetic Transperineal biopsy Evaluation) trial assesses the clinical and cost-effectiveness of two biopsy procedures in terms of detection of clinically significant prostate cancer (PCa). This article describes the statistical analysis plan (SAP) for the TRANSLATE randomised controlled trial (RCT). Methods/design TRANSLATE is a parallel, superiority, multicentre RCT. Biopsy-naïve men aged ≥ 18 years requiring a prostate biopsy for suspicion of possible PCa are randomised (computer-generated 1:1 allocation ratio) to one of two biopsy procedures: transrectal (TRUS) or local anaesthetic transperineal (LATP) biopsy. The primary outcome is the difference in detection rates of clinically significant PCa (defined as Gleason Grade Group ≥ 2, i.e. any Gleason pattern ≥ 4 disease) between the two biopsy procedures. Secondary outcome measures are th eProBE questionnaire (Perception Part and General Symptoms) and International Index of Erectile Function (IIEF, Domain A) scores, International Prostate Symptom Score (IPSS) values, EQ-5D-5L scores, resource use, infection rates, complications, and serious adverse events. We describe in detail the sample size calculation, statistical models used for the analysis, handling of missing data, and planned sensitivity and subgroup analyses. This SAP was pre-specified, written and submitted without prior knowledge of the trial results. Discussion Publication of the TRANSLATE trial SAP aims to increase the transparency of the data analysis and reduce the risk of outcome reporting bias. Any deviations from the current SAP will be described and justified in the final study report and results publication. Trial registration International Standard Randomised Controlled Trial Number ISRCTN98159689, registered on 28 January 2021 and registered on the ClinicalTrials.gov (NCT05179694) trials registry.

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD09)1 May 2024PD09-08 SPATIAL TRANSCRIPTOMIC CLONAL DECONVOLUTION IDENTIFIES THE 'LETHAL CLONE' IN PROSTATE CANCER AS DEFINED BY ABILITY TO METASTASIZE TO LYMPH NODES Wencheng Yin, Sandy Figiel, Mengxiao He, Renuka Teague, Thineskrishna Anbarasan, Nithesh Ranasinha, Reema Singh, Ninu Poulose, Dimitrios Doultsinos, Sophia Abusamra, Andrew Erickson, Massimo Loda, Clare Verrill, Richard Colling, Pelvender Gill, Richard Bryant, Olivier Cussenot, Freddie Hamdy, Dan Woodcock, Ian Mills, Joakim Lundeberg, and Alastair Lamb Wencheng YinWencheng Yin , Sandy FigielSandy Figiel , Mengxiao HeMengxiao He , Renuka TeagueRenuka Teague , Thineskrishna AnbarasanThineskrishna Anbarasan , Nithesh RanasinhaNithesh Ranasinha , Reema SinghReema Singh , Ninu PouloseNinu Poulose , Dimitrios DoultsinosDimitrios Doultsinos , Sophia AbusamraSophia Abusamra , Andrew EricksonAndrew Erickson , Massimo LodaMassimo Loda , Clare VerrillClare Verrill , Richard CollingRichard Colling , Pelvender GillPelvender Gill , Richard BryantRichard Bryant , Olivier CussenotOlivier Cussenot , Freddie HamdyFreddie Hamdy , Dan WoodcockDan Woodcock , Ian MillsIan Mills , Joakim LundebergJoakim Lundeberg , and Alastair LambAlastair Lamb View All Author Informationhttps://doi.org/10.1097/01.JU.0001008572.33286.63.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) epitomises intratumoural heterogeneity, a phenomenon that has hindered accurate risk stratification & treatment. A distinctive feature of this heterogeneity is the frequent occurrence of copy number alterations acquired by dividing cells, which can be used to define clonal heritage. The precise contribution of local cancer clones to lethal metastatic PCa is unclear. This study leveraged spatial transcriptomics technology to infer clonal genomic identity in PCa to identify regions of primary tumour that can metastasize to lymph nodes. METHODS: We collated FFPE samples from primary & nodal metastatic tissue of 4 patients recruited in trial (ISRCTN10046036). We performed spatial transcriptomics (Visium v2), processed fastq files using SpaceRanger & analysed with our published protocol (github.com/aerickso/SpatialInferCNV). Each section contains around 5,000 (6.5 mm2) or 14,000 (11 mm2) spots of 55 µm diameter with meticulous histological annotation by pathologist. We show the clonal relationships, location & distribution throughout prostate & nodal environment. RESULTS: We identified 11 clonal subtypes on epithelial tissue. We show the distinct features of specific clones which exist in both primary & lymph nodes metastases ("X clones") alongside their clonal ancestry as a phylogenetic tree. Interestingly, we observed subclonal events within the lymph nodes & evidence for polyclonal colonisation of lymph nodes at distinct time points in the evolution of primary disease. Specifically, we observed Chr10q loss, the location of PTEN, was an early event in the clonal ancestry of lethal disease. PTEN is a well-known tumour suppressor gene, the loss of which causes chromosomal instability. Chr8 gain/loss was an important later event in the transition to migratory behaviour possibly due to phenotypic versatility resulting from amplification of genes such as c-Myc. CONCLUSIONS: For the first time, we detail the clonal heterogeneity in PCa, with direct linkage to nodal metastases. Spatial transcriptomics with careful case selection & highly granular pathology, is a powerful tool to decipher clonal hierarchies & trace the evolution of lethal disease. This has important implications for risk stratification & treatment selection in PCa. Download PPT Source of Funding: The present work was supported by Cancer Research UK (CRUK), Hanson Trust Research, the John Black Charitable Foundation, Prostate Cancer Foundation, NIHR Oxford Biomedical Research Centre, European Research Council, Swedish Society for Cancer Research © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e182 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Wencheng Yin More articles by this author Sandy Figiel More articles by this author Mengxiao He More articles by this author Renuka Teague More articles by this author Thineskrishna Anbarasan More articles by this author Nithesh Ranasinha More articles by this author Reema Singh More articles by this author Ninu Poulose More articles by this author Dimitrios Doultsinos More articles by this author Sophia Abusamra More articles by this author Andrew Erickson More articles by this author Massimo Loda More articles by this author Clare Verrill More articles by this author Richard Colling More articles by this author Pelvender Gill More articles by this author Richard Bryant More articles by this author Olivier Cussenot More articles by this author Freddie Hamdy More articles by this author Dan Woodcock More articles by this author Ian Mills More articles by this author Joakim Lundeberg More articles by this author Alastair Lamb More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy II (MP52)1 May 2024MP52-09 EARLY RETURN TO CONTINENCE, ONCOLOGICAL SAFETY AND SIGNIFICANCE OF MEMBRANOUS URETHRAL LENGTH IN ANTERIOR RETZIUS SPARING ROBOT ASSISTED RADICAL PROSTATECTOMY (RARP) Nithesh M. Ranasinha, Anthony S. Bates, Thineskrishna Anbarasan, Abhishek Sharma, Richard J. Bryant, Tom Leslie, Aaron Leiblich, Francisco Lopez, and Alastair D. Lamb Nithesh M. RanasinhaNithesh M. Ranasinha , Anthony S. BatesAnthony S. Bates , Thineskrishna AnbarasanThineskrishna Anbarasan , Abhishek SharmaAbhishek Sharma , Richard J. BryantRichard J. Bryant , Tom LeslieTom Leslie , Aaron LeiblichAaron Leiblich , Francisco LopezFrancisco Lopez , and Alastair D. LambAlastair D. Lamb View All Author Informationhttps://doi.org/10.1097/01.JU.0001008864.84854.b7.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The anterior Retzius sparing (ARS) approach to robot-assisted radical prostatectomy (RARP) preserves key structures aligned with urinary continence. Moreover, unlike posterior approach Retzius sparing surgery, ARS maintains the familiar transperitoneal anterior approach and can be modified more easily to accommodate for oncological requirements. We investigated differences in early return to continence and oncological safety between ARS and standard anterior RARP, alongside pre-operative variables. METHODS: We conducted a retrospective review of a continuously-collected, prospectively-maintained RARP database at Oxford University Hospitals NHS Trust, Oxford, UK. Patients undergoing full or modified ARS were compared to patients undergoing non-ARS standard approach RARP surgery. Multiple regression analysis assessed pre-operative variables including membranous urethral length (MUL), age, BMI, MRI PIRADs score, prostate volume, and biopsy Gleason grade group on early return to continence (defined as 0-1 pad usage per day) and oncological safety (defined as positive surgical margin (PSM) rate). ROC curve analysis was used to identify MUL cut-offs to predict 6-week continence. RESULTS: Of 508 RARPs from 14/02/2017 to 21/08/2023, 429 ARS cases were compared to 79 non-ARS standard anterior approach cases.There was no difference in baseline pre-operative variables of MUL, age, BMI, MRI PIRADS, GGG and prostate volume between ARS and non-ARS cohorts.There was an increase in 6-week continence for ARS compared to non-ARS cohorts (292/420 (70%)vs 36/74 (49%), p=0.002). There was no difference in PSM rate in ARS vs non-ARS cohorts (104/429 (25%) vs 20/79 (25%) p=0.75) (Table 1).In the ARS cohort, lower age (OR 0.92; 95%CI 0.85 – 0.99) and longer MUL (OR 1.22; 95%CI 1.09 – 1.38) were independently associated with continence at 6-weeks.ROC curve analysis for MUL identified an 80% sensitivity for 6-week continence for MUL >11.4mm in ARS cohort vs >15mm in the non-ARS cohort. CONCLUSIONS: This study highlights improved early return to continence in the ARS vs non-ARS approaches without impacting oncological safety. We identify lower age and longer MUL as independent predictive factors for early return to continence in ARS patients. Source of Funding: Nil © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e855 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Nithesh M. Ranasinha More articles by this author Anthony S. Bates More articles by this author Thineskrishna Anbarasan More articles by this author Abhishek Sharma More articles by this author Richard J. Bryant More articles by this author Tom Leslie More articles by this author Aaron Leiblich More articles by this author Francisco Lopez More articles by this author Alastair D. Lamb More articles by this author Expand All Advertisement PDF downloadLoading ...