Audit of cancer yields after prostate MRI using both the PI-RADS version 2 and Likert scoring systems.

AIM: To audit diagnostic yields of the updated magnetic resonance imaging (MRI)-directed prostate cancer diagnostic service according to Prostate Imaging - Reporting and Data System (PI-RADS) version 2 and Likert assessments, comparing outcomes of the two scoring systems. MATERIALS AND METHODS: Consecutive men with suspected cancer undergoing prostate MRI were included. Biopsy rates and histological diagnostic yields of all and International Society of Urological Pathology Grade Group (ISUP GG) ≥2 cancers according to PI-RADS and Likert assessment categories were documented and outcomes compared. RESULTS: Of 326 men (91% biopsy naive), 177 (54%) underwent transrectal (n=119) or transperineal (n=58) ultrasound-guided biopsies; 92% with negative MRI avoided immediate biopsies following multidisciplinary team (MDT) review. All cancer and ISUP GG ≥ 2 cancer-detection rates increased with increasing suspicion scores. Prospective paired PI-RADS and Likert scoring was undertaken in 323/326 studies, with 87% concordance rate. High concordance between PI-RADS and Likert scores was observed in negative MRI (99%) and score 5 (96%). High discordance was demonstrated in the PI-RADS 4 group (32% with PI-RADS 4 categories up-risked to Likert 5). All cancer and ISUP GG ≥ 2 cancer detection rates for MRI score ≥3 were 78% and 63%, and for MRI score ≥4 were 75% and 61%, respectively for both PI-RADS and Likert scoring systems. CONCLUSIONS: Most men with negative prostate MRI can avoid immediate biopsies following MDT review. Performance of PI-RADS and Likert scoring systems in clinically significant cancer detection after positive MRI is equivalent. Discordance between PI-RADS and Likert systems seems mostly confined to PI-RADS 4 categories.

Sacral Insufficiency Fracture Following Pelvic Radiotherapy in Gynaecological Malignancies: Development of a Predictive Model.

AIMS: To investigate the time-to-event and the evolution of sacral insufficiency fractures in gynaecological patients receiving pelvic external beam radiotherapy (EBRT) in relation to dosimetric and imaging parameters across a spectrum of radiotherapy delivery techniques, and to develop a predictive model with a clinical nomogram to identify those at risk of sacral insufficiency fracture. MATERIALS AND METHODS: Patients who received radical or adjuvant pelvic EBRT for gynaecological malignancy between 2014 and 2019 were identified. The data collected were: demographics and clinical details; radiotherapy planning data: dose, fractionation, technique (fixed-field intensity-modulated radiotherapy, adaptive arc, and non-adaptive arc), 60 Gy simultaneous integrated boost. Each plan was examined to determine the sacral dose in 5%/Gy3 increments. Follow-up magnetic resonance scans were reviewed for insufficiency fractures, defined as linear low T1-weighted signal intensity with a high short-T1 inversion recovery (STIR) signal. The site of insufficiency fracture was recreated on the planning computed tomography, the dose to insufficiency fracture contours was recorded and insufficiency fractures were determined as healed with resolution of high STIR signal. Univariable analysis was conducted of the clinical variables. The area under the receiver operator characteristic curve and odds ratio of the risk prediction model with 95% confidence interval are reported with a nomogram for use in clinical practice. RESULTS: 115 patients were identified; the median imaging follow-up was 12 months (2-47). 37.4% developed sacral insufficiency fractures; 93.0% were detected within 12 months of EBRT. At the final radiological follow-up, 83.7% of insufficiency fractures remained active. The radiotherapy delivery technique was not associated with insufficiency fracture after adjusting for patient age (P = 0.115). The location of the 60 Gy simultaneous integrated boost planning target volume did not impact upon the site of insufficiency fracture or the dose received by the insufficiency fracture sites. Age and V40Gy3 are predictors for insufficiency fracture and form the clinical risk model (receiver operator characteristic 0.72). CONCLUSIONS: Age and V40Gy3 predict sacral insufficiency fractures; future work should focus on optimising radiotherapy planning with adoption of a bone-sparing planning approach for those patients at high risk of insufficiency fracture.

A systematic review and meta-analysis of the diagnostic accuracy of biparametric prostate MRI for prostate cancer in men at risk.

INTRODUCTION: Multiparametric magnetic resonance imaging (mpMRI), the use of three multiple imaging sequences, typically T2-weighted, diffusion weighted (DWI) and dynamic contrast enhanced (DCE) images, has a high sensitivity and specificity for detecting significant cancer. Current guidance now recommends its use prior to biopsy. However, the impact of DCE is currently under debate regarding test accuracy. Biparametric MRI (bpMRI), using only T2 and DWI has been proposed as a viable alternative. We conducted a contemporary systematic review and meta-analysis to further examine the diagnostic performance of bpMRI in the diagnosis of any and clinically significant prostate cancer. METHODS: A systematic review of the literature from 01/01/2017 to 06/07/2019 was performed by two independent reviewers using predefined search criteria. The index test was biparametric MRI and the reference standard whole-mount prostatectomy or prostate biopsy. Quality of included studies was assessed by the QUADAS-2 tool. Statistical analysis included pooled diagnostic performance (sensitivity; specificity; AUC), meta-regression of possible covariates and head-to-head comparisons of bpMRI and mpMRI where both were performed in the same study. RESULTS: Forty-four articles were included in the analysis. The pooled sensitivity for any cancer detection was 0.84 (95% CI, 0.80-0.88), specificity 0.75 (95% CI, 0.68-0.81) for bpMRI. The summary ROC curve yielded a high AUC value (AUC = 0.86). The pooled sensitivity for clinically significant prostate cancer was 0.87 (95% CI, 0.78-0.93), specificity 0.72 (95% CI, 0.56-0.84) and the AUC value was 0.87. Meta-regression analysis revealed no difference in the pooled diagnostic estimates between bpMRI and mpMRI. CONCLUSIONS: This meta-analysis on contemporary studies shows that bpMRI offers comparable test accuracies to mpMRI in detecting prostate cancer. These data are broadly supportive of the bpMRI approach but heterogeneity does not allow definitive recommendations to be made. There is a need for prospective multicentre studies of bpMRI in biopsy naïve men.

Diagnostic yields in patients with suspected prostate cancer undergoing MRI as the first-line investigation in routine practice.

AIM: To document cancer yields of magnetic resonance imaging (MRI)-directed biopsies in men with suspected prostate cancer referred to secondary care. MATERIALS AND METHODS: Men with suspected cancer undergoing multiparametric prostate MRI as the first-line investigation were included in the present study. Systematic transrectal prostate biopsies with/without cognitive targeted biopsies were performed. Diagnostic yields of International Society of Urological Pathology (ISUP) ≥2 cancers by the Prostate Imaging Reporting and Data System (PI-RADS) category were recorded. Impacts of prostate-specific antigen (PSA) density on biopsy results and yields of non-targeted biopsies in MRI non-suspicious prostate sextants assessed. RESULTS: Of 262 men (90.5% biopsy naive), 86 (33%) MRI examinations were negative (PI-RADS 1-2) and 176 (67%) positive (PI-RADS 3: 8%; PI-RADS 4: 21%; PI-RADS 5: 38%). Two hundred and thirteen of 262 patients underwent a biopsy. ISUP ≥2 cancer detection rates were 8% (5/61) for PI-RADS 1-2, 18% (3/17) for PI-RADS 3, 49% (22/45) for PI-RADS 4, and 80% (72/90) for PI-RADS 5. Proportions of ISUP ≥2 increased with higher PSA densities in positive patients (%ISUP ≥2 for PSA density groups <0.12, 0.12 to <0.15 and ≥ 0.15 was 0%, 0%, 25% for PI-RADS 3, 21%, 33%, 68% for PI-RADS 4 and 40%, 83%, 89% for PI-RADS 5 respectively). ISUP ≥2 cancers were twice as likely in tumour adjacent sextants (52% versus 24%), without upgrading of gland level histology from insignificant to clinically significant prostate cancer by the sampling of normal-appearing tumour non-adjacent sextants. CONCLUSIONS: One third of men can avoid biopsy after negative MRI. Cancer detection rates increase with PSA density values within positive MRI suspicion categories. Sampling normal-appearing tumour non-adjacent sextants may be unnecessary for whole-gland therapy.

Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015.

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged.

Assessing response to treatment of bone metastases from breast cancer: what should be the standard of care?

Bone is the most common site for breast cancer metastases, occurring in up to 70% of those with metastatic disease. In order to effectively manage these patients, it is essential to have consistent, reproducible and validated methods of assessing response to therapy. We present current clinical practice of imaging response assessment of bone metastases. We also review the biology of bone metastases and measures of response assessment including clinical assessment, tumour markers and imaging techniques; bone scans (BSs), computed tomography (CT), positron emission tomography, magnetic resonance imaging (MRI) and whole-body diffusion-weighted MRI (WB DW-MRI). The current standard of care of BSs and CT has significant limitations and are not routinely recommended for the purpose of response assessment in the bones. WB DW-MRI has the potential to address this unmet need and should be evaluated in clinical trials.

Prostate MRI: who, when, and how? Report from a UK consensus meeting.

The current pathway for men suspected of having prostate cancer [transrectal biopsy, followed in some cases by magnetic resonance imaging (MRI) for staging] results in over-diagnosis of insignificant tumours, and systematically misses disease in the anterior prostate. Multiparametric MRI has the potential to change this pathway, and if performed before biopsy, might enable the exclusion of significant disease in some men without biopsy, targeted biopsy in others, and improvements in the performance of active surveillance. For the potential benefits to be realized, the setting of standards is vital. This article summarizes the outcome of a meeting of UK radiologists, at which a consensus was achieved on (1) the indications for MRI, (2) the conduct of the scan, (3) a method and template for reporting, and (4) minimum standards for radiologists.

The diagnostic accuracy and cost-effectiveness of magnetic resonance spectroscopy and enhanced magnetic resonance imaging techniques in aiding the localisation of prostate abnormalities for biopsy: a systematic review and economic evaluation.

BACKGROUND: In the UK, prostate cancer (PC) is the most common cancer in men. A diagnosis can be confirmed only following a prostate biopsy. Many men find themselves with an elevated prostate-specific antigen (PSA) level and a negative biopsy. The best way to manage these men remains uncertain. OBJECTIVES: To assess the diagnostic accuracy of magnetic resonance spectroscopy (MRS) and enhanced magnetic resonance imaging (MRI) techniques [dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted MRI (DW-MRI)] and the clinical effectiveness and cost-effectiveness of strategies involving their use in aiding the localisation of prostate abnormalities for biopsy in patients with prior negative biopsy who remain clinically suspicious for harbouring malignancy. DATA SOURCES: Databases searched--MEDLINE (1946 to March 2012), MEDLINE In-Process & Other Non-Indexed Citations (March 2012), EMBASE (1980 to March 2012), Bioscience Information Service (BIOSIS; 1995 to March 2012), Science Citation Index (SCI; 1995 to March 2012), The Cochrane Library (Issue 3 2012), Database of Abstracts of Reviews of Effects (DARE; March 2012), Medion (March 2012) and Health Technology Assessment database (March 2012). REVIEW METHODS: Types of studies: direct studies/randomised controlled trials reporting diagnostic outcomes. INDEX TESTS: MRS, DCE-MRI and DW-MRI. Comparators: T2-weighted magnetic resonance imaging (T2-MRI), transrectal ultrasound-guided biopsy (TRUS/Bx). Reference standard: histopathological assessment of biopsied tissue. A Markov model was developed to assess the cost-effectiveness of alternative MRS/MRI sequences to direct TRUS-guided biopsies compared with systematic extended-cores TRUS-guided biopsies. A health service provider perspective was adopted and the recommended 3.5% discount rate was applied to costs and outcomes. RESULTS: A total of 51 studies were included. In pooled estimates, sensitivity [95% confidence interval (CI)] was highest for MRS (92%; 95% CI 86% to 95%). Specificity was highest for TRUS (imaging test) (81%; 95% CI 77% to 85%). Lifetime costs ranged from £3895 using systematic TRUS-guided biopsies to £4056 using findings on T2-MRI or DCE-MRI to direct biopsies (60-year-old cohort, cancer prevalence 24%). The base-case incremental cost-effectiveness ratio for T2-MRI was <£30,000 per QALY (all cohorts). Probabilistic sensitivity analysis showed high uncertainty surrounding the incremental cost-effectiveness of T2-MRI in moderate prevalence cohorts. The cost-effectiveness of MRS compared with T2-MRI and TRUS was sensitive to several key parameters. LIMITATIONS: Non-English-language studies were excluded. Few studies reported DCE-MRI/DW-MRI. The modelling was hampered by limited data on the relative diagnostic accuracy of alternative strategies, the natural history of cancer detected at repeat biopsy, and the impact of diagnosis and treatment on disease progression and health-related quality of life. CONCLUSIONS: MRS had higher sensitivity and specificity than T2-MRI. Relative cost-effectiveness of alternative strategies was sensitive to key parameters/assumptions. Under certain circumstances T2-MRI may be cost-effective compared with systematic TRUS. If MRS and DW-MRI can be shown to have high sensitivity for detecting moderate/high-risk cancer, while negating patients with no cancer/low-risk disease to undergo biopsy, their use could represent a cost-effective approach to diagnosis. However, owing to the relative paucity of reliable data, further studies are required. In particular, prospective studies are required in men with suspected PC and elevated PSA levels but previously negative biopsy comparing the utility of the individual and combined components of a multiparametric magnetic resonance (MR) approach (MRS, DCE-MRI and DW-MRI) with both a MR-guided/-directed biopsy session and an extended 14-core TRUS-guided biopsy scheme against a reference standard of histopathological assessment of biopsied tissue obtained via saturation biopsy, template biopsy or prostatectomy specimens. STUDY REGISTRATION: PROSPERO number CRD42011001376. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Phase Ib trial of radiotherapy in combination with combretastatin-A4-phosphate in patients with non-small-cell lung cancer, prostate adenocarcinoma, and squamous cell carcinoma of the head and neck.

BACKGROUND: The vascular disrupting agent combretastatin-A4-phosphate (CA4P) demonstrated antitumour activity in preclinical studies when combined with radiation. METHODS: Patients with non-small-cell lung cancer (NSCLC), prostate adenocarcinoma, and squamous cell carcinoma of the head and neck (SCCHN) received 27 Gy in 6 fractions treating twice weekly over 3 weeks, 55 Gy in 20 fractions over 4 weeks, and 66 Gy in 33 fractions over 6 weeks respectively. CA4P was escalated from 50 mg/m2 to 63 mg/m2. CA4P exposure was further increased from one to three to six doses. Patients with SCCHN received cetuximab in addition. RESULTS: Thirty-nine patients received 121 doses of CA4P. Dose-limiting toxic effects (DLTs) of reversible ataxia and oculomotor nerve palsy occurred in two patients with prostate cancer receiving weekly CA4P at 63 mg/m2. DLT of cardiac ischaemia occurred in two patients with SCCHN at a weekly dose of 50 mg/m2 in combination with cetuximab. Three patients developed grade 3 hypertension. Responses were seen in 7 of 18 patients with NSCLC. At 3 years, 3 of 18 patients with prostate cancer had prostate-specific antigen relapse. CONCLUSIONS: Radiotherapy with CA4P appears well tolerated in most patients. The combination of CA4P, cetuximab, and radiotherapy needs further scrutiny before it can be recommended for clinical studies.