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. We describe clinical, histological, and radiological outcomes from an established AS programme, where protocol-based biopsies were omitted in favour of MRI-led monitoring. 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. 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. 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). 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. 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.

The intracellular volume fraction derived from Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumors (VERDICT) MRI enables better differentiation of a Gleason 4 lesion from beni... Background Biologic specificity of diffusion MRI in relation to prostate cancer aggressiveness may improve by examining separate components of the diffusion MRI signal. The Vascular, Extracellular,...

Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression.

Whilst multi-parametric magnetic resonance imaging (mp-MRI) has been a significant advance in the diagnosis of prostate cancer, scanning all patients with elevated prostate specific antigen (PSA) levels is considered too costly for widespread National Health Service (NHS) use, as the predictive value of PSA levels for significant disease is poor. Despite the fact that novel blood and urine tests are available which may predict aggressive disease better than PSA, they are not routinely employed due to a lack of clinical validity studies. Furthermore approximately 40 % of mp-MRI studies are reported as indeterminate, which can lead to repeat examinations or unnecessary biopsy with associated patient anxiety, discomfort, risk and additional costs. We aim to clinically validate a panel of minimally invasive promising blood and urine biomarkers, to better select patients that will benefit from a multiparametric prostate MRI. We will then test whether the performance of the mp-MRI can be improved by the addition of an advanced diffusion-weighted MRI technique, which uses a biophysical model to characterise tissue microstructure called VERDICT; Vascular and Extracellular Restricted Diffusion for Cytometry in Tumours. INNOVATE is a prospective single centre cohort study in 365 patients. mp-MRI will act as the reference standard for the biomarker panel. A clinical outcome based reference standard based on biopsy, mp-MRI and follow-up will be used for VERDICT MRI. We expect the combined effect of biomarkers and VERDICT MRI will improve care by better detecting aggressive prostate cancer early and make mp-MRI before biopsy economically viable for universal NHS adoption. INNOVATE is registered on ClinicalTrials.gov, with reference NCT02689271 .

Fractional intracellular volume–derived Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumor analysis of multiparametric MRI findings resulted in better classification of clinic... Background In men suspected of having prostate cancer (PCa), up to 50% of men with positive multiparametric MRI (mpMRI) findings (Prostate Imaging Reporting and Data System [PI-RADS] or Likert scor...

Saliva represents an ideal matrix for diagnostic biomarker development as it is readily available and requires no invasive collection procedures. However, salivary RNA is labile and rapidly degrades. Previous attempts to isolate RNA from saliva have yielded poor quality and low concentrations. Here we compare collection and processing methods and propose an approach for future studies. The effects of RNA stabilisers, storage temperatures, length of storage and fasting windows were investigated on pooled saliva samples from healthy volunteers. Isolated RNA was assessed for concentration and quality. Bacterial growth was investigated through RT-PCR using bacterial and human primers. Optimal conditions were implemented and quality controlled in a clinical setting. The addition of RNAlater increased mean RNA yield from 4912 ng/μl to 15,473 ng and RNA Integrity Number (RIN) from 4.5 to 7.0. No significant changes to RNA yield were observed for storage at room temperature beyond 1 day or at -80 °C. Bacterial growth did not occur in samples stored at ambient temperature for up to a week. There was a trend towards higher RNA concentration when saliva was collected after overnight fasting but no effect on RIN. In the clinic, RNA yields of 6307 ng and RINs of 3.9 were achieved, improving on previous reports. The method we describe here is a robust, clinically feasible saliva collection method using preservative that gives high concentrations and improved RINs compared to saliva collected without preservative.