Y chromosome variation and prostate cancer ancestral disparities.

Prostate cancer (PCa) is marked by significant ancestral bias, with African men disproportionately impacted. However, genome profiling studies have yet to explore the mutational landscape and disparity contribution of the male-determining Y chromosome. Using a cohort of 106 African and 57 European PCa cases, biased toward aggressive presenting primary disease, we performed complete Y chromosome interrogation for inherited and somatic variance.

Methylation reprogramming associated with aggressive prostate cancer and ancestral disparities.

African men are disproportionately impacted by aggressive prostate cancer (PCa). Key to this disparity both genetic and environmental factors, alluding to epigenetic modifications. However, African-inclusive prostate tumour DNA methylation studies are lacking.

Rare pathogenic structural variants show potential to enhance prostate cancer germline testing for African men.

Prostate cancer (PCa) is highly heritable, with men of African ancestry at greatest risk and associated lethality. Lack of representation in genomic data means germline testing guidelines exclude for Africans. Established that structural variations (SVs) are major contributors to human disease and prostate tumourigenesis, their role is under-appreciated in familial and therapeutic testing.

The Germline and Somatic Origins of Prostate Cancer Heterogeneity.

This study uncovered 223 recurrently mutated driver regions using the largest cohort of prostate tumors to date. It reveals associations between germline SNPs, somatic drivers, and tumor aggression, offering significant insights into how prostate tumor evolution is shaped by germline factors and the timing of somatic mutations.

Irreversible electroporation of localised prostate cancer downregulates immune suppression and induces systemic anti-tumour T-cell activation - IRE-IMMUNO study.

Objectives: To prospectively compare systemic anti-tumour immune responses induced by irreversible electroporation (IRE) and robot-assisted radical prostatectomy (RARP) in patients with localised intermediate-risk prostate cancer (PCa).

Patients And Methods: Between February 2021 and June 2022, before and after treatment (at 5, 14 and 30 days) peripheral blood samples of 30 patients with localised PCa were prospectively collected. Patient inclusion criteria were: International Society of Urological Pathologists Grade 2-3, clinical cancer stage ≤T2c, prostate-specific antigen level <20 ng/mL).

The impact of telomere length on prostate cancer aggressiveness, genomic instability and health disparities.

The telomere repetitive TTAGGG motif at the ends of chromosomes, serves to preserve genomic integrity and chromosomal stability. In turn, genomic instability is a hallmark of cancer-implicating telomere disturbance. Prostate cancer (PCa) shows significant ancestral disparities, with men of African ancestry at the greatest risk for aggressive disease and associated genomic instability.

Ga-PSMA-PET/CT in addition to mpMRI in men undergoing biopsy during active surveillance for low- to intermediate-risk prostate cancer: study protocol for a prospective cross-sectional study.

Background: In active surveillance there is significant interest in whether imaging modalities such as multiparametric magnetic resonance imaging (mpMRI) or Gallium prostate-specific membrane antigen positron emission tomography/computerized tomography (Ga-PSMA-PET/CT) can improve the detection of progression to clinically significant prostate cancer (csPCa) and thus reduce the frequency of prostate biopsies and associated morbidity. Recent studies have demonstrated the value of mpMRI in active surveillance; however, mpMRI does miss a proportion of disease progression and thus alone cannot replace biopsy. To date, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown additive value to mpMRI in its ability to detect prostate cancer (PCa) in the primary diagnostic setting.

Prostate-specific membrane antigen positron emission tomography in addition to multiparametric magnetic resonance imaging and biopsies to select prostate cancer patients for focal therapy.

Objective: To evaluate the additional value of prostate-specific membrane antigen positron emission tomography (PSMA-PET) to conventional diagnostic tools to select patients for hemi-ablative focal therapy (FT).

Patients And Methods: We performed a retrospective analysis on a multicentre cohort (private and institutional) of 138 patients who underwent multiparametric magnetic resonance imaging (mpMRI), PSMA-PET, and systematic biopsies prior to radical prostatectomy between January 2011 and July 2021. Patients were eligible when they met the consensus criteria for FT: PSA <15 ng/mL, clinical/radiological T stage ≤T2b, and International Society of Urological Pathology (ISUP) grade 2-3.

Alterations in the Epigenetic Machinery Associated with Prostate Cancer Health Disparities.

Prostate cancer is driven by acquired genetic alterations, including those impacting the epigenetic machinery. With African ancestry as a significant risk factor for aggressive disease, we hypothesize that dysregulation among the roughly 656 epigenetic genes may contribute to prostate cancer health disparities. Investigating prostate tumor genomic data from 109 men of southern African and 56 men of European Australian ancestry, we found that African-derived tumors present with a longer tail of epigenetic driver gene candidates (72 versus 10).

Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement.

Context: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up.

Objective: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings.

Novel radiomic analysis on bi-parametric MRI for characterizing differences between MR non-visible and visible clinically significant prostate cancer.

Background: around one third of clinically significant prostate cancer (CsPCa) foci are reported to be MRI non-visible (MRI─).

Objective: To quantify the differences between MR visible (MRI+) and MRI CsPCa using intra- and peri-lesional radiomic features on bi-parametric MRI (bpMRI).

Methods: This retrospective and multi-institutional study comprised 164 patients with pre-biopsy 3T prostate multi-parametric MRI from 2014 to 2017.

The relationship between biochemical recurrence and number of lymph nodes removed during surgery for localized prostate cancer.

Purpose: To assess whether completeness of pelvic lymph node dissection (PLND) as measured by lymph node yield reduces biochemical recurrence (BCR) in men undergoing radical prostatectomy (RP) for prostate cancer (PCa), stratified according to Briganti nomogram-derived risk (≥5% vs. < 5%) of lymph node invasion (LNI).

Methods: Retrospective study of 3724 men who underwent RP between January 1995 and January 2015 from our prospectively collected institutional database.

Median 4-year outcomes of salvage irreversible electroporation for localized radio-recurrent prostate cancer.

Objectives: To evaluate the safety, and short to mid-term oncological and quality-of-life (QoL) outcomes of focal irreversible electroporation (IRE) for radio-recurrent prostate cancer (PCa) at a median follow-up of 4 years.

Patients And Methods: This was a single-centre series of men with biopsy-proven radio-recurrent PCa treated with IRE between December 2013 and February 2022, with a minimum follow-up of 6 months. Follow-up included magnetic resonance imaging at 6 months, and standard transperineal saturation template biopsies at 12 months.

Synchronous vs independent reading of prostate-specific membrane antigen positron emission tomography (PSMA-PET) and magnetic resonance imaging (MRI) to improve diagnosis of prostate cancer.

Objectives: To identify whether synchronous reading of multiparametric magnetic resonance imaging (mpMRI) and Ga-PSMA-11 positron emission tomography (PET)/computed tomography (prostate-specific membrane antigen [PSMA-PET]) images can improve diagnostic performance and certainty compared with mpMRI/PSMA-PET reported independently and synthesized, while also assessing concordance between imaging modalities and agreement with histopathology.

Methods: This was a retrospective analysis of 100 patients randomly selected from the PRIMARY trial, a prospective Phase II multicentre imaging trial. Three dual-trained radiologist/nuclear medicine physicians re-reported the mpMRI and PSMA-PET both independently and synchronously for the same patients in random order, blinded to previous results.

Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers.

Background: African ancestry is a significant risk factor for advanced prostate cancer (PCa). Mortality rates in sub-Saharan Africa are 2.5-fold greater than global averages.

African-specific molecular taxonomy of prostate cancer.

Prostate cancer is characterized by considerable geo-ethnic disparity. African ancestry is a significant risk factor, with mortality rates across sub-Saharan Africa of 2.7-fold higher than global averages.

Predictive Value of Cribriform and Intraductal Carcinoma for the Nomogram-based Selection of Prostate Cancer Patients for Pelvic Lymph Node Dissection.

Objective: To assess the predictive value of biopsy-identified cribriform carcinoma and/or intraductal carcinoma (CR/IDC) within the Briganti and MSKCC nomograms predicting lymph node metastasis (LNM) in patients with primary prostate cancer (PCa).

Methods: We retrospectively included 393 PCa patients who underwent radical prostatectomy with extended pelvic lymph node dissection at 3 tertiary referral centers. We externally validated 2 prediction tools: the Briganti 2012 nomogram and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram.

Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging to Detect Residual Prostate Cancer Following Irreversible Electroporation-A Multicenter Validation Study.

Background: Accurate monitoring following focal treatment of prostate cancer (PCa) is paramount for timely salvage treatment or retreatment.

Objective: To evaluate the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) to detect residual PCa in the short-term follow-up of focal treatment with irreversible electroporation (IRE) using transperineal or transrectal template ± targeted biopsies.

Design, Setting, And Participants: A retrospective international multicenter study of men with biopsy-proven PCa, treated with focal IRE, and followed by mpMRI (index-test) and template biopsies (reference-test) between February 2013 and January 2021, was conducted.

Outcomes of salvage radical prostatectomy after initial irreversible electroporation treatment for recurrent prostate cancer.

Objective: To evaluate: (i) safety, (ii) feasibility, and medium-term (iii) oncological and (iv) functional outcomes of salvage radical prostatectomy (sRP) for recurrent localised prostate cancer (PCa) following initial focal therapy using irreversible electroporation (IRE).

Patients And Methods: An international, multicentre and retrospective analysis of prospectively collected data of patients that underwent sRP for recurrent localised PCa after initial primary IRE treatment. Data were reported on (i) surgical complications, (ii) feasibility of sRP reported by surgeons, (iii) time interval between IRE and sRP and pathology results, and (iv) urinary continence, erectile function, and quality of life.

Robot-Assisted Prostate-Specific Membrane Antigen-Radioguided Surgery in Primary Diagnosed Prostate Cancer.

The objective of this study was to evaluate the safety and feasibility of Tc-based prostate-specific membrane antigen (PSMA) robot-assisted-radioguided surgery to aid or improve the intraoperative detection of lymph node metastases during primary robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa). Men with primary high-risk PCa (≥ cT3a, International Society of Urological Pathology (ISUP) grade group ≥ 3 or prostate-specific antigen of ≥ 15 ng/mL) with potential lymph node metastasis (Briganti nomogram risk > 10% or on preoperative imaging) were enrolled in the study. Patients underwent staging Ga-PSMA PET/CT scanning.

Salvage robot-assisted radical prostatectomy following focal ablation with irreversible electroporation: feasibility, oncological and functional outcomes.

Background: To report the feasibility, oncological and functional outcomes of salvage robot-assisted radical prostatectomy (sRARP) for recurrent prostate cancer (PCa) after irreversible electroporation (IRE).

Methods: This was a retrospective analysis of patients who underwent sRARP by a single high-volume surgeon after IRE treatment in our institution. Surgical complications, oncological and functional outcomes were assessed.