HistoScanningTM to Detect and Characterize Prostate Cancer—a Review of Existing Literature

Purpose of Review: The widely acknowledged limitations of the standard prostate cancer (PCa) diagnostic paradigm have provided an impetus to explore novel imaging modalities to diagnose, localize, and risk stratify PCa. As the body of literature focused on HistoScanning™(HS) grows, there is need for a comprehensive review of the clinical efficacy of this technology. Recent Findings: Eighteen original, English language articles were found to adequately study the use of HistoScanning™ for prostate cancer diagnosis in the clinical setting. The articles were found by conducting a bibliographic search of PubMed in April 2017 in addition to utilizing references. The studies are divided into four groups based on study design. Study methods and quantitative data are summarized for each of the relevant articles. The results are synthesized to evaluate the utility of HistoScanning™ for the purpose of diagnosing PCa. Summary: Despite the promise of early pilot studies, there is a lack of consistent results across a number of further investigations of HistoScanning™. This becomes increasingly evident as study size increases. As various other modern diagnostic modalities continue to develop, the future of HistoScanning™, both alone and in conjunction with these technologies, remains unclear

The Agrobacterium-mediated transformation of common wheat (Triticum aestivum L.) and triticale (x Triticosecale Wittmack): role of the binary vector system and selection cassettes

The influence of two binary vector systems, pGreen and pCAMBIA, on the Agrobacterium-mediated transformation ability of wheat and triticale was studied. Both vectors carried selection cassettes with bar or nptII driven by different promoters. Two cultivars of wheat, Kontesa and Torka, and one cultivar of triticale, Wanad, were tested. The transformation rates for the wheat cultivars ranged from 0.00 to 3.58% and from 0.00 to 6.79% for triticale. The best values for wheat were 3.58% for Kontesa and 3.14% for Torka, and these were obtained after transformation with the pGreen vector carrying the nptII selection gene under the control of 35S promoter. In the case of the bar selection system, the best transformation rates were, respectively, 1.46 and 1.79%. Such rates were obtained when the 35S::bar cassette was carried by the pCAMBIA vector; they were significantly lower with the pGreen vector. The triticale cultivar Wanad had its highest transformation rate after transformation with nptII driven by 35S in pCAMBIA. The bar selection system for the same triticale cultivar was better when the gene was driven by nos and the selection cassette was carried by pGreen. The integration of the transgenes was confirmed with at least three pairs of specific starters amplifying the fragments of nptII, bar, or gus. The expression of selection genes, measured by reverse transcriptase polymerase chain reaction (RT-PCR) in relation to the actin gene, was low, ranging from 0.00 to 0.63 for nptII and from 0.00 to 0.33 for bar. The highest relative transcript accumulation was observed for nptII driven by 35S and expressed in Kontesa that had been transformed with pGreen

Prostate cancer measurements on serial MRI during active surveillance: it’s time to be PRECISE

OBJECTIVE: The PRECISE criteria for reporting multiparametric MRI in patients on active surveillance (AS) for prostate cancer (PCa) score the likelihood of clinically significant change over time using a 1-5 scale, where 4 or 5 indicates radiological progression. According to the PRECISE recommendations, the index lesion size can be reported using different definitions of volume (planimetry or ellipsoid formula) or by measuring one or two diameters. We compared different measurements using planimetry as the reference standard and stratified changes according to the PRECISE scores. METHODS: We retrospectively analysed 196 patients on AS with PCa confirmed by targeted biopsy who had two MR scans (baseline and follow-up). Lesions were measured on T2 weighted imaging (T2WI) according to all definitions. A PRECISE score was assessed for each patient. RESULTS: The ellipsoid formula exhibited the highest correlation with planimetry at baseline (ρ = 0.97) and follow-up (ρ = 0.98) imaging, compared to the biaxial measurement and single maximum diameter. There was a significant difference (p < 0.001) in the yearly percentage volume change between radiological regression/stability (PRECISE 2-3) and progression (PRECISE 4-5) for planimetry (39.64%) and for the ellipsoid formula (46.78%). CONCLUSION: The ellipsoid formula could be used to monitor tumour growth during AS. Evidence of a significant yearly percentage volume change between radiological regression/stability (PRECISE 2-3) and progression (PRECISE 4-5) has been also observed. ADVANCES IN KNOWLEDGE: The ellipsoid formula is a reasonable surrogate for planimetry in capturing tumour volume changes on T2WI in patients on imaging-led AS. This is also associated with radiological changes using the PRECISE recommendations

The Role of Percentage of Prostate-specific Antigen Reduction After Focal Therapy Using High-intensity Focused Ultrasound for Primary Localised Prostate Cancer. Results from a Large Multi-institutional Series

Focal therapy (FT) for prostate cancer (PCa) is emerging as a novel therapeutic approach for patients with low- to intermediate-risk disease, in order to provide acceptable oncological control, whilst avoiding the side effects of radical treatment. Evidence regarding the ideal follow-up strategy and the significance of prostate-specific antigen (PSA) kinetics after treatment is needed. In this study, we aimed to assess the value of the percentage of PSA reduction (%PSA reduction) after FT in predicting the likelihood of any additional treatment or any radical treatment. We retrospectively analysed a multicentre cohort of 703 men receiving FT for low- and intermediate-risk PCa. Overall, the rates of any additional treatment and any radical treatment were 30% and 13%, respectively. The median follow-up period was 41 mo. The median %PSA reduction after FT was 73%. At Cox multivariable analysis, %PSA reduction was an independent predictor of any additional treatment (hazard ratio [HR]: 0.96; p 90%, the probability of any additional treatment within 5 yr was 20%. Conversely, for %PSA reduction of <10%, the probability of receiving any additional treatment within 5 yr was roughly 70%. This study is the first to assess the role of %PSA reduction in the largest multicentre cohort of men receiving FT for PCa. Given the lack of standardised follow-up strategies in the FT field, the use of the %PSA reduction should be considered

Natural history of prostate cancer on active surveillance: stratification by MRI using the PRECISE recommendations in a UK cohort

Objectives: The PRECISE recommendations for magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer (PCa) include repeated measurement of each lesion, and attribution of a PRECISE radiological progression score for the likelihood of clinically significant change over time. We aimed to compare the PRECISE score with clinical progression in patients who are managed using an MRI-led AS protocol. Methods: A total of 553 patients on AS for low- and intermediate-risk PCa (up to Gleason score 3 + 4) who had two or more MRI scans performed between December 2005 and January 2020 were included. Overall, 2161 scans were retrospectively re-reported by a dedicated radiologist to give a PI-RADS v2 score for each scan and assess the PRECISE score for each follow-up scan. Clinical progression was defined by histological progression to ≥ Gleason score 4 + 3 (Gleason Grade Group 3) and/or initiation of active treatment. Progression-free survival was assessed using Kaplan-Meier curves and log-rank test was used to assess differences between curves. Results: Overall, 165/553 (30%) patients experienced the primary outcome of clinical progression (median follow-up, 74.5&nbsp;months; interquartile ranges, 53–98). Of all patients, 313/553 (57%) did not show radiological progression&nbsp;on MRI (PRECISE 1–3), of which 296/313 (95%) had also no clinical progression. Of the remaining 240/553 patients (43%) with radiological progression&nbsp;on MRI (PRECISE 4–5), 146/240 (61%) experienced clinical progression (p &lt; 0.0001). Patients with radiological progression&nbsp;on&nbsp;MRI (PRECISE 4-5) showed a trend to an increase in PSA density. Conclusions: Patients without radiological progression on MRI (PRECISE 1-3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. Key Points: • Patients&nbsp;without radiological progression on MRI (PRECISE 1–3) during&nbsp;AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. • Clinical progression was almost always detectable in patients with radiological progression on MRI (PRECISE 4–5)&nbsp;during AS. • Patients with radiological progression&nbsp;on MRI (PRECISE 4–5)&nbsp;during AS showed a trend to an increase in PSA density

Prostate Radiofrequency Focal Ablation (ProRAFT) Trial: A Prospective Development Study Evaluating a Bipolar Radiofrequency Device to Treat Prostate Cancer

PURPOSE: To determine early efficacy of bipolar radiofrequency ablation with a coil design (bRFA) for focal ablation of clinically significant localised prostate cancer (sPCa)visible at mpMRI. MATERIAL AND METHODS: A prospective IDEAL phase 2 development study (NCT02294903) recruited treatment naive patients with a single focus of localised sPCa (Gleason 7 or 4 mm or more of Gleason 6) concordant with a lesion visible on multi-parametric MRI. Intervention was a focal ablation with a bRFA system (Encage®, Trod Medical) encompassing the lesion and a predefined margin using nonrigid MRI-ultrasound fusion. Primary outcome was the proportion of men with absence of sPCa on biopsy at 6 months. Trial follow up comprised serum PSA, mpMRI at 1 week, 6 and 12 months post ablation. Validated patient reported outcome measures (PROMs) for urinary, erectile and bowel functions and adverse events monitoring system were used. Analyses were done on a per-protocol basis. RESULTS: 20 of 21 patients recruited received the intervention. Baseline characteristics were a median age of 66 years (IQR 63-69), pre-operative median PSA of 7.9 ng/ml (5.3-9.6), 18 (90%) had Gleason 7 with median maximum cancer of 7 mm (IQR 5-10) for a median 2.8 cc mpMRI lesions (IQR 1.4-4.8). Targeted biopsy of the treated area (median number of cores=6, IQR 5-8) showed absence of sPCa in 16/20 men (80%), concordant with mpMRI. There was a low profile of side effects at PROMs analysis and no serious adverse events. CONCLUSIONS: Focal therapy of sPCa associated with an MRI lesion using bRFA showed early efficacy to ablate cancer with low rates of genitourinary and rectal side-effects

Outcomes of the RAFT Trial: Robotic surgery After Focal Therapy

OBJECTIVES: To report toxicity of treatment observed in men participating in the Robotic surgery After Focal Therapy (RAFT) clinical trial. SUBJECTS/PATIENTS AND METHODS: Men were eligible for this prospective single group interventional study if they had histologically confirmed recurrent/residual prostate adenocarcinoma following primary FT. The short-form Expanded Prostate Cancer Index Composite (EPIC-26) measured prior to salvage robotic prostatectomy (S-RARP) and 3-monthly post-operatively together with Clavien-Dindo complications (I-IV). Secondary outcomes included biochemical recurrence-free survival (BCFS) following surgery and need for salvage treatment after surgery. This study is registered with ClinicalTrials.gov NCT03011606. RESULTS: 24 men were recruited between February 2016 and September 2018. 1 patient withdrew from the trial after consenting and before S-RARP. 23 men completed 12-month post S-RARP follow-up. Median EPIC-26 urinary continence scores initially deteriorated after 3 months (82.4 versus 100) but there was no statistically significant difference from baseline at 12 months (100 versus 100, p=0.31). Median lower urinary tract symptom scores improved after 12 months compared to baseline (93.8 versus 87.5, p=0.01). At 12 months, 19/23 (83%) were pad-free and 22/23 (96%) required 0/1 pads. Median sexual function subscale scores deteriorated and remained low at 12 months (22.2 versus 58.3, p<0.001). Utilising a minimally important difference of 9 points, at 12 months after surgery 17/23 (74%) reported urinary continence to be "better" or "not different" to pre-operative baseline. The corresponding figure for sexual function (utilising a minimally important difference of 12 points) was 7/23 (30%). There was no statistically significant difference on median bowel/hormonal subscale scores. Only a single patient had a post-operative complication (Clavien-Dindo Grade I). BCFS at 12 months after surgery was 82.6% (95% confidence interval [CI]: 60.1% - 93.1%] while 4/23 (17%) received salvage radiation. CONCLUSIONS: The RAFT clinical trial suggests toxicity of surgery after FT is low, with good urinary function outcomes, albeit sexual function deteriorated overall. Oncological outcomes at 12 months appear acceptable