Background Although the use of multiparametric magnetic resonance imaging (mpMRI) in active surveillance (AS) for prostate cancer is of increasing interest, existing data are derived from small cohorts. Objective We describe clinical, histological, and radiological outcomes from an established AS programme, where protocol-based biopsies were omitted in favour of MRI-led monitoring. Design, setting, and participants Data on 672 men enrolled in AS between August 2004 and November 2017 (inclusion criteria: Gleason 3 + 3 or 3 + 4 localised prostate cancer, presenting prostate-specific antigen <20 ng/ml, and baseline mpMRI) were collected from the University College London Hospital (UCLH) database. Outcome measurements and statistical analysis Primary outcomes were event-free survival (EFS; event defined as prostate cancer treatment, transition to watchful waiting, or death) and treatment-free survival (TFS). Secondary outcomes included rates of all-cause or prostate cancer–related mortality, metastasis, and upgrading to Gleason ≥4 + 3. Data on radiological and histological progression were also collected. Results and limitations More than 3800 person-years (py) of follow-up were accrued (median: 58 mo; interquartile range 37–82 mo). Approximately 84.7% (95% confidence interval [CI]: 82.0–87.6) and 71.8% (95% CI: 68.2–75.6) of patients remained on AS at 3 and 5 yr, respectively. EFS and TFS were lower in those with MRI-visible (Likert 4–5) disease or secondary Gleason pattern 4 at baseline (log-rank test; p <  0.001). In total, 216 men were treated. There were 24 deaths, none of which was prostate cancer related (6.3/1000 py; 95% CI: 4.1–9.5). Metastases developed in eight men (2.1 events/1000 py; 95% CI: 1.0–4.3), whereas 27 men upgraded to Gleason ≥4 + 3 on follow-up biopsy (7.7 events/1000 py; 95% CI: 5.2–11.3). Conclusions The rates of discontinuation, mortality, and metastasis in MRI-led surveillance are comparable with those of standard AS. MRI-visible disease and/or secondary Gleason grade 4 at baseline are associated with a greater likelihood of moving to active treatment at 5 yr. Further research will concentrate on optimising imaging intervals according to baseline risk. Patient summary In this report, we looked at the outcomes of magnetic resonance imaging (MRI)-based surveillance for prostate cancer in a UK cohort. We found that this strategy could allow routine biopsies to be avoided. Secondary Gleason pattern 4 and MRI visibility are associated with increased rates of treatment. We conclude that MRI-based surveillance should be considered for the monitoring of small prostate tumours.

No abstract

Context Multiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and invisibility on mpMRI remains uncertain. Objective To systematically review the literature on differential gene expression between mpMRI-visible and mpMRI-invisible prostate cancer, and to use bioinformatic analysis to identify enriched processes or cellular components in genes validated in more than one study. Evidence acquisition We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to January 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The primary endpoint was differential genetic features between mpMRI-visible and mpMRI-invisible tumours. Secondary endpoints were explanatory links between gene function and mpMRI conspicuity, and the prognostic value of differential gene enrichment. Evidence synthesis We retrieved 445 articles, of which 32 met the criteria for inclusion. Thematic synthesis from the included studies showed that mpMRI-visible cancer tended towards enrichment of molecular features associated with increased disease aggressivity, including phosphatase and tensin homologue ( PTEN ) loss and higher genomic classifier scores, such as Oncotype and Decipher. Three of the included studies had accompanying publicly available data suitable for further bioinformatic analysis. An over-representation analysis of these datasets revealed increased expression of genes associated with extracellular matrix components in mpMRI-visible tumours. Conclusions Prostate cancer that is visible on mpMRI is generally enriched with molecular features of tumour development and aggressivity, including activation of proliferative signalling, DNA damage, and inflammatory processes. Additionally, there appears to be concordant cellular components and biological processes associated with mpMRI conspicuity, as highlighted by bioinformatic analysis of large genetic datasets. Patient summary Prostate cancer that is detected by magnetic resonance imaging (MRI) tends to have genetic features that are associated with more aggressive disease. This suggests that MRI can be used to assess the likelihood of aggressive prostate cancer, based on tumour visibility.

|Senescent cells accumulate with age in all tissues. Although senescent cells undergo cell-cycle arrest, these cells remain metabolically active and their secretomeknown as senescence-associated secretory phenotype (SASP) -is responsible for a systemic pro-inflammatory state, which contributes to an inflammatory microenvironment. Senescent cells can be found in the ageing prostate and the SASP and can be linked to benign prostatic hyperplasia and prostate cancer. Indeed, a number of signalling pathways provide biological plausibility for the role of senescence in both BPH and prostate cancer, although proving causality is difficult. The theory of senescence as a mechanism for prostate disease has a number of clinical implications, and could offer opportunities for targetting in the future.

Objectives To report on the methods, peri‐operative outcomes and histopathological concordance between frozen and final section from the NeuroSAFE PROOF feasibility study (NCT03317990). Patients and Methods Between May 2018 and March 2019, 49 patients at two UK centres underwent robot‐assisted radical prostatectomy (RARP). Twenty‐five patient were randomized to NeuroSAFE RARP (intervention arm) and 24 to standard RARP (control arm). Frozen section was compared to final paraffin section margin assessment in the 25 patients in the NeuroSAFE arm. Operation timings and complications were collected prospectively in both arms. Results Fifty neurovascular bundles (NVBs) from 25 patients in the NeuroSAFE arm were analysed. When analysed by each pathological section (n = 250, average five per side), we noted a sensitivity of 100%, a specificity of 99.2%, and an area under the curve (AUC) of 0.994 (95% confidence interval [CI] 0.985 to 1; P ≤0.001). On an NVB basis (n = 50), sensitivity was 100%, specificity was 92.7%, and the AUC was 0.963 (95% CI 0.914 to 1; P ≤0.001). NeuroSAFE RARP lasted a mean of 3 h 16 min (knife to skin to off table, 95% CI 3 h 2 min–3 h 30 min) compared to 2 h 4 min (95% CI 2 h 2 min–2 h 25 min; P ≤0.001) for standard RARP. There was no morbidity associated with the additional length of operating time on in the NeuroSAFE arm. Conclusion This feasibility study demonstrates the safety, reproducibility and excellent histopathological concordance of the NeuroSAFE technique in the NeuroSAFE PROOF trial. Although the technique increases the duration of RARP, this does not cause short‐term harm. Confirmation of feasibility has led to the opening of the fully powered NeuroSAFE PROOF randomized controlled trial, which is currently under way at four sites in the UK.