Prostagram magnetic resonance imaging in a screening population: Prostate Imaging-Reporting and Data System or Likert?

OBJECTIVE: To compare biopsy recommendation rates and accuracy of the Prostate Imaging-Reporting and Data System, version 2 (PI-RADSv2) with the Likert scale for detection of clinically significant and insignificant prostate cancer in men screened within the Imperial Prostate 1 Prostate Cancer Screening Trial Using Imaging (IP1-PROSTAGRAM). PATIENTS AND METHODS: Men aged 50-69 years were screened with Prostagram MRI. Scans were prospectively reported using both PI-RADSv2 (excluding dynamic contrast-enhanced sequence score) and 5-point Likert scores by expert uro-radiologists. Systematic and targeted transperineal biopsy was recommended if the scan was scored ≥ 3, based on either reporting system. The proportion of patients recommended for biopsy and detection rates for Grade Groups (GGs) 1 and ≥ 2 were compared. Receiver operating characteristic (ROC) analysis was performed to compare performance. RESULTS: A total of 406 men underwent Prostagram MRI. The median (interquartile range) age and prostate-specific antigen level were 57 (53-61) years and 0.91 (0.56-1.74) ng/mL, respectively. At MRI score ≥ 3, more patients were recommended for biopsy based on Likert criteria (94/406; 23%, 95% confidence interval [CI] 19.2%-27.6%) compared to PI-RADSv2 (72/406; 18%, 95% CI 14.2%-21.9%; P = 0.03). For MRI scores ≥ 4, PI-RADSv2 and Likert scales led to 43/406 (11%, 95% CI 7.9%-14.1%) and 35/406 (9%, 95% CI 6.2%-11.9%) men recommended for biopsy (P = 0.40). For GG ≥ 2 detection, PIRADSv2 and Likert detected 22% (95% CI 11.4%-30.8%, 14/72) and 16% (95% CI 9.5%-25.3%, 15/94), respectively (P = 0.56). For GG1 cancers detection these were 11% (95% CI 4.3%-19.6%, seven of 72) vs 11% (95% CI 4.7%-17.8%, nine of 94; P = 1.00). The accuracy of PI-RADSv2 and Likert scale was similar (area under the ROC curve 0.64 vs 0.65, P = 0.95). CONCLUSIONS: In reporting non-contrast-enhanced Prostagram MRI in a screening population, the PI-RADSv2 and Likert scoring systems were equally accurate; however, Likert scale use led to more men undergoing biopsy without a subsequent increase in significant cancer detection rates. To improve reporting of Prostagram MRI, either the PI-RADSv2 or a modified Likert scale or a standalone scoring system should be developed.

Evaluation of Outcomes Following Focal Ablative Therapy for Treatment of Localized Clinically Significant Prostate Cancer in Patients >70 Years: A Multi-institute, Multi-energy 15-Year Experience.

PURPOSE: In older patients who do not wish to undergo watchful waiting, focal therapy could be an alternative to the more morbid radical treatment. We evaluated the role of focal therapy in patients 70 years and older as an alternative management modality. MATERIALS AND METHODS: A total of 649 patients across 11 UK sites receiving focal high-intensity focused ultrasound or cryotherapy between June 2006 and July 2020 reported within the UK-based HEAT (HIFU Evaluation and Assessment of Treatment) and ICE (International Cryotherapy Evaluation) registries were evaluated. Primary outcome was failure-free survival, defined by need for more than 1 focal reablation, progression to radical treatment, development of metastases, need for systemic treatment, or prostate cancer-specific death. This was compared to the failure-free survival in patients undergoing radical treatment via a propensity score weighted analysis. RESULTS: Median age was 74 years (IQR: 72, 77) and median follow-up 24 months (IQR: 12, 41). Sixty percent had intermediate-risk disease and 35% high-risk disease. A total of 113 patients (17%) required further treatment. Sixteen had radical treatment and 44 required systemic treatment. Failure-free survival was 82% (95% CI: 76%-87%) at 5 years. Comparing patients who had radical therapy to those who had focal therapy, 5-year failure-free survival was 96% (95% CI: 93%-100%) and 82% (95% CI: 75%-91%) respectively (P < .001). Ninety-three percent of those in the radical treatment arm had received radiotherapy as their primary treatment with its associated use of androgen deprivation therapy, thereby leading to potential overestimation of treatment success in the radical treatment arm, especially given the similar metastases-free and overall survival rates seen. CONCLUSIONS: We propose focal therapy to be an effective management option for the older or comorbid patient who is unsuitable for or not willing to undergo radical treatment.

External validation of a risk model predicting failure of salvage focal ablation for prostate cancer.

OBJECTIVES: To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset. PATIENTS AND METHODS: Patients with biopsy-confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014-2018; six centres), and from the high-intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK-based registries (2006-2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post-salvage with discrimination (concordance index [C-index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically-reasonable risk threshold ranges of 0.14-0.52 and 0.26-0.36 were considered, corresponding to previously published pooled 2-year recurrence-free survival rates for salvage local treatments. RESULTS: A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow-ups, and 72/168 (43%) within 2 years. The C-index was 0.65 (95% confidence interval 0.58-0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14-0.52 risk threshold range, and all of the 0.26-0.36 range. CONCLUSION: In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow-up is recommended.

Multiparametric ultrasound versus multiparametric MRI to diagnose prostate cancer (CADMUS): a prospective, multicentre, paired-cohort, confirmatory study.

BACKGROUND: Multiparametric MRI of the prostate followed by targeted biopsy is recommended for patients at risk of prostate cancer. However, multiparametric ultrasound is more readily available than multiparametric MRI. Data from paired-cohort validation studies and randomised, controlled trials support the use of multiparametric MRI, whereas the evidence for individual ultrasound methods and multiparametric ultrasound is only derived from case series. We aimed to establish the overall agreement between multiparametric ultrasound and multiparametric MRI to diagnose clinically significant prostate cancer. METHODS: We conducted a prospective, multicentre, paired-cohort, confirmatory study in seven hospitals in the UK. Patients at risk of prostate cancer, aged 18 years or older, with an elevated prostate-specific antigen concentration or abnormal findings on digital rectal examination underwent both multiparametric ultrasound and multiparametric MRI. Multiparametric ultrasound consisted of B-mode, colour Doppler, real-time elastography, and contrast-enhanced ultrasound. Multiparametric MRI included high-resolution T2-weighted images, diffusion-weighted imaging (dedicated high B 1400 s/mm2 or 2000 s/mm2 and apparent diffusion coefficient map), and dynamic contrast-enhanced axial T1-weighted images. Patients with positive findings on multiparametric ultrasound or multiparametric MRI underwent targeted biopsies but were masked to their test results. If both tests yielded positive findings, the order of targeting at biopsy was randomly assigned (1:1) using stratified (according to centre only) block randomisation with randomly varying block sizes. The co-primary endpoints were the proportion of positive lesions on, and agreement between, multiparametric MRI and multiparametric ultrasound in identifying suspicious lesions (Likert score of ≥3), and detection of clinically significant cancer (defined as a Gleason score of ≥4 + 3 in any area or a maximum cancer core length of ≥6 mm of any grade [PROMIS definition 1]) in those patients who underwent a biopsy. Adverse events were defined according to Good Clinical Practice and trial regulatory guidelines. The trial is registered on ISRCTN, 38541912, and ClinicalTrials.gov, NCT02712684, with recruitment and follow-up completed. FINDINGS: Between March 15, 2016, and Nov 7, 2019, 370 eligible patients were enrolled; 306 patients completed both multiparametric ultrasound and multiparametric MRI and 257 underwent a prostate biopsy. Multiparametric ultrasound was positive in 272 (89% [95% CI 85-92]) of 306 patients and multiparametric MRI was positive in 238 patients (78% [73-82]; difference 11·1% [95% CI 5·1-17·1]). Positive test agreement was 73·2% (95% CI 67·9-78·1; κ=0·06 [95% CI -0·56 to 0·17]). Any cancer was detected in 133 (52% [95% CI 45·5-58]) of 257 patients, with 83 (32% [26-38]) of 257 being clinically significant by PROMIS definition 1. Each test alone would result in multiparametric ultrasound detecting PROMIS definition 1 cancer in 66 (26% [95% CI 21-32]) of 257 patients who had biopsies and multiparametric MRI detecting it in 77 (30% [24-36]; difference -4·3% [95% CI -8·3% to -0·3]). Combining both tests detected 83 (32% [95% CI 27-38]) of 257 clinically significant cancers as per PROMIS definition 1; of these 83 cancers, six (7% [95% CI 3-15]) were detected exclusively with multiparametric ultrasound, and 17 (20% [12-31]) were exclusively detected by multiparametric MRI (agreement 91·1% [95% CI 86·9-94·2]; κ=0·78 [95% CI 0·69-0·86]). No serious adverse events were related to trial activity. INTERPRETATION: Multiparametric ultrasound detected 4·3% fewer clinically significant prostate cancers than multiparametric MRI, but it would lead to 11·1% more patients being referred for a biopsy. Multiparametric ultrasound could be an alternative to multiparametric MRI as a first test for patients at risk of prostate cancer, particularly if multiparametric MRI cannot be carried out. Both imaging tests missed clinically significant cancers detected by the other, so the use of both would increase the detection of clinically significant prostate cancers compared with using each test alone. FUNDING: The Jon Moulton Charity Trust, Prostate Cancer UK, and UCLH Charity and Barts Charity.

Nomogram predicting the probability of spontaneous stone passage in patients presenting with acute ureteric colic.

OBJECTIVES: To develop a nomogram that could predict spontaneous stone passage (SSP) in patients presenting with acute ureteric colic who are suitable for conservative management. SUBJECT/PATIENTS: A 2517 patient dataset was utilised from an international multi-centre cohort study (MIMIC, A Multi-centre Cohort Study Evaluating the role of Inflammatory Markers In Patients Presenting with Acute Ureteric Colic) of patients presenting with acute ureteric colic across 71 secondary care hospitals in the United Kingdom, Ireland, Australia, and New Zealand. Inclusion criteria mandated a non-contrast CT-KUB. METHODS: SSP was defined as the 'absence of the need for intervention'. The model was developed using logistic regression and backwards selection (to achieve lowest AIC) in a subset from 2009-2015 (n=1728) and temporally validated on a subset from 2016-2017 (n=789). RESULTS: Of the 2517 patients, 1874 had SSP (74.5%). Mean age (±[SD]) was 47 (±14.7) years and 1892 were male (75.2%). At the end of the modelling process, gender: male (OR 0.8, 95%CI 0.64-1.01, p=0.07), neutrophil count (OR 1.03, 95%CI 1.00-1.06, p = 0.08), hydronephrosis (OR 0.79, 95%CI 0.59-1.05, p=0.1), hydroureter (OR 1.3, 95%CI 0.97-1.75, p =0.08), stone size >5-7mm (OR 0.2, 95%CI 0.16-0.25, p<0.0001), stone size >7mm (OR 0.11, 95%CI 0.08-0.15, p<0.001), middle ureter stone position (OR 0.59, 95%CI 0.43-0.81, p=0.001), upper ureter stone position (OR 0.31, 95%CI 0.25-0.39, p<0.001) ), medical expulsive therapy use (OR 1.36, 95%CI 1.1 - 1.67, p = 0.001), oral NSAID use (OR 1.3, 95%CI 0.99 - 1.71, p=0.06), and rectal NSAID use (OR1.17, 95%CI 0.9 - 1.53, p=0.24) remained. Concordance-statistic (C-statistic) was 0.77 (95%CI 0.75 - 0.80) and a nomogram was developed based on these. CONCLUSION: The presented nomogram is available to use as an online calculator via www.BURSTurology.com and could allow clinicians and patients to make a more informed decision on pursuing conservative management versus early intervention.

A BURST-BAUS consensus document for best practice in the conduct of scrotal exploration for suspected testicular torsion: the Finding consensus for orchIdopeXy In Torsion (FIX-IT) study.

OBJECTIVES: To produce a best practice consensus guideline for the conduct of scrotal exploration for suspected testicular torsion using formal consensus methodology. MATERIALS AND METHODS: A panel of 16 expert urologists, representing adult, paediatric, general, and andrological urology used the RAND/UCLA Appropriateness Consensus Methodology to score a 184 statement pre-meeting questionnaire on the conduct of scrotal exploration for suspected testicular torsion. The collated responses were presented at a face-to-face online meeting and each item was rescored anonymously after a group discussion, facilitated by an independent chair with expertise in consensus methodology. Items were scored for agreement and consensus and the items scored with consensus were used to derive a set of best practice guidelines. RESULTS: Statements scored as with consensus increased from Round 1 (122/184, 66.3%) to Round 2 (149/200, 74.5%). Recommendations were generated in ten categories: consent, assessment under anaesthetic, initial incision, intraoperative decision making, fixation, medical photography, closure, operation note, logistics and follow-up after scrotal exploration. Our statements assume that the decision to operate has already been made. Key recommendations in the consent process included the discussion of the possibility of orchidectomy and the possibility of subsequent infection of the affected testis or wound requiring antibiotic therapy. If after the examination under anaesthesia, the index of suspicion of testicular torsion is lower than previously thought, then the surgeon should still proceed to scrotal exploration as planned. A flow chart guiding decision making dependent on intraoperative findings has been designed. If no torsion is present on exploration and the bell clapper deformity is absent, the testis should not be fixed. When fixing a testis using sutures, 3 or 4-point is acceptable and non-absorbable sutures are preferred. CONCLUSIONS: We have produced consensus recommendations to inform best practice in the conduct of scrotal exploration for suspected testicular torsion.

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study.

OBJECTIVE: To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. PATIENTS AND METHODS: This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. RESULTS: Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3-34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1-30.2), UTUC (n = 128) 1.14% (95% CI 0.77-1.52), renal cancer (n = 107) 1.05% (95% CI 0.80-1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32-2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03-1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90-4.15; P < 0.001), male sex 1.30 (95% CI 1.14-1.50; P < 0.001), and smoking 2.70 (95% CI 2.30-3.18; P < 0.001). CONCLUSIONS: A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer.

Evaluation of functional outcomes after a second focal high-intensity focused ultrasonography (HIFU) procedure in men with primary localized, non-metastatic prostate cancer: results from the HIFU Evaluation and Assessment of Treatment (HEAT) registry.

OBJECTIVES: To assess change in functional outcomes after a second focal high-intensity focused ultrasonography (HIFU) treatment compared with outcomes after one focal HIFU treatment. PATIENTS AND METHODS: In this multicentre study (2005-2016), 821 men underwent focal HIFU for localized non-metastatic prostate cancer. The patient-reported outcome measures of International Prostate Symptom Score (IPSS), pad usage and erectile function (EF) score were prospectively collected for up to 3 years. To be included in the study, completion of at least one follow-up questionnaire was required. The primary outcome was comparison of change in functional outcomes between baseline and follow-up after one focal HIFU procedure vs after a second focal HIFU procedure, using IPSS, Expanded Prostate Cancer Index Composite (EPIC) and International Index of Erectile Function (IIEF) questionnaires. RESULTS: Of 821 men, 654 underwent one focal HIFU procedure and 167 underwent a second focal HIFU procedure. A total of 355 (54.3%) men undergoing one focal HIFU procedure and 65 (38.9%) with a second focal HIFU procedure returned follow-up questionnaires, respectively. The mean age and prostate-specific antigen level were 66.4 and 65.6 years, and 7.9 and 8.4 ng/mL, respectively. After one focal HIFU treatment, the mean change in IPSS was -0.03 (P = 0.02) and in IIEF (EF score) it was -0.4 (P = 0.02) at 1-2 years, with no subsequent decline. Absolute rates of erectile dysfunction increased from 9.9% to 20.8% (P = 0.08), leak-free continence decreased from 77.9% to 72.8% (P = 0.06) and pad-free continence from 98.6% to 94.8% (P = 0.07) at 1-2 years, respectively. IPSS prior to second focal HIFU treatment compared to baseline IPSS prior to first focal HIFU treatment was lower by -1.3 (P = 0.02), but mean IPSS change was +1.4 at 1-2 years (P = 0.03) and +1.2 at 2-3 years (P = 0.003) after the second focal HIFU treatment. The mean change in EF score after the second focal HIFU treatment was -0.2 at 1-2 years (P = 0.60) and -0.5 at 2-3 years (P = 0.10), with 17.8% and 6.2% of men with new erectile dysfunction. The rate of new pad use was 1.8% at 1-2 years and 2.6% at 2-3 years. CONCLUSION: A second focal HIFU procedure causes minor detrimental effects on urinary function and EF. These data can be used to counsel patients with non-metastatic prostate cancer prior to considering HIFU therapy.

Likert vs PI-RADS v2: a comparison of two radiological scoring systems for detection of clinically significant prostate cancer.

OBJECTIVE: To compare the clinical validity and utility of Likert assessment and the Prostate Imaging Reporting and Data System (PI-RADS) v2 in the detection of clinically significant and insignificant prostate cancer. PATIENTS AND METHODS: A total of 489 pre-biopsy multiparametric magnetic resonance imaging (mpMRI) scans in consecutive patients were subject to prospective paired reporting using both Likert and PI-RADS v2 by expert uro-radiologists. Patients were offered biopsy for any Likert or PI-RADS score ≥4 or a score of 3 with PSA density ≥0.12 ng/mL/mL. Utility was evaluated in terms of proportion biopsied, and proportion of clinically significant and insignificant cancer detected (both overall and on a 'per score' basis). In those patients biopsied, the overall accuracy of each system was assessed by calculating total and partial area under the receiver-operating characteristic (ROC) curves. The primary threshold of significance was Gleason ≥3 + 4. Secondary thresholds of Gleason ≥4 + 3, Ahmed/UCL1 (Gleason ≥4 + 3 or maximum cancer core length [CCL] ≥6 or total CCL≥6) and Ahmed/UCL2 (Gleason ≥3 + 4 or maximum CCL ≥4 or total CCL ≥6) were also used. RESULTS: The median (interquartile range [IQR]) age was 66 (60-72) years and the median (IQR) prostate-specific antigen level was 7 (5-10) ng/mL. A similar proportion of men met the biopsy threshold and underwent biopsy in both groups (83.8% [Likert] vs 84.8% [PI-RADS v2]; P = 0.704). The Likert system predicted more clinically significant cancers than PI-RADS across all disease thresholds. Rates of insignificant cancers were comparable in each group. ROC analysis of biopsied patients showed that, although both scoring systems performed well as predictors of significant cancer, Likert scoring was superior to PI-RADS v2, exhibiting higher total and partial areas under the ROC curve. CONCLUSIONS: Both scoring systems demonstrated good diagnostic performance, with similar rates of decision to biopsy. Overall, Likert was superior by all definitions of clinically significant prostate cancer. It has the advantages of being flexible, intuitive and allowing inclusion of clinical data. However, its use should only be considered once radiologists have developed sufficient experience in reporting prostate mpMRI.

Added value of diffusion-weighted images and dynamic contrast enhancement in multiparametric magnetic resonance imaging for the detection of clinically significant prostate cancer in the PICTURE trial.

OBJECTIVE: To determine the additional diagnostic value of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced imaging (DCE) in men requiring a repeat biopsy within the PICTURE study. PATIENTS AND METHODS: PICTURE was a paired-cohort confirmatory study in which 249 men who required further risk stratification after a previous non-magnetic resonance imaging (MRI)-guided transrectal ultrasonography-guided biopsy underwent a 3-Tesla (3T) multiparametic (mp)MRI consisting of T2-weighted imaging (T2W), DWI and DCE, followed by transperineal template prostate mapping biopsy. Each mpMRI was reported using a LIKERT score in a sequential blinded manner to generate scores for T2W, T2W+DWI and T2W+DWI+DCE. Area under the receiver-operating characteristic curve (AUROC) analysis was performed to compare the diagnostic accuracy of each combination. The threshold for a positive mpMRI was set at a LIKERT score ≥3. Clinically significant prostate cancer was analysed across a range of definitions including UCL/Ahmed definition 1 (primary definition), UCL/Ahmed definition 2, any Gleason ≥3 + 4 and any Gleason ≥4 + 3. RESULTS: Of 249 men, sequential MRI reporting was available for 246. There was a higher rate of equivocal lesions (44.6%) using T2W alone compared to the addition of DWI (23.9%) and DCE (19.8%). Using the primary definition of clinically significant disease, there was no significant difference in the overall accuracy between T2W, with an AUROC of 0.74 (95% confidence interval [CI] 0.68-0.80), T2W+DWI at 0.76 (95% CI 0.71-0.82), and T2W+DWI+DCE, with an AUROC of 0.77 (95% CI 0.71-0.82; P = 0.55). The AUROC values remained comparable using other definitions of clinically significant disease including UCL/Ahmed definition 2 (P = 0.79), Gleason ≥3 + 4 (P = 0.53) and Gleason ≥4 + 3 (P = 0.53). CONCLUSIONS: Using 3T MRI, a high level of diagnostic accuracy can be achieved using T2W as a single parameter in men with a prior biopsy; however, such a strategy can lead to a higher rate of equivocal lesions.

Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic: results from the Multi-centre cohort study evaluating the role of Inflammatory Markers In patients presenting with acute ureteric Colic (MIMIC) study.

OBJECTIVES: To assess the relationship of white blood cell count (WBC) and other routinely collected inflammatory and clinical markers including stone size, stone position, and medical expulsive therapy use (MET), with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic, as there are conflicting data on the role of WBC and other inflammatory markers in SSP in patients with acute ureteric colic. PATIENTS AND METHODS: Multicentre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across four countries (UK, Republic of Ireland, Australia, and New Zealand). In all, 4170 patients presented with acute ureteric colic and a computed tomography confirmed single ureteric stone. Our primary outcome measure was SSP, as defined by the absence of need for intervention to assist stone passage (SP). Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. RESULTS: In all, 2518 patients were discharged with conservative management and had further follow-up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, neutrophils count, nor C-reactive protein (CRP) predicted SSP, with an adjusted odds ratio (OR) of 0.97 (95% confidence interval [CI] 0.91-1.04, P = 0.38), 1.06 (95% CI 0.99-1.13, P = 0.1) and 1.00 (95% CI 0.99-1.00, P = 0.17), respectively. MET also did not predict SSP (adjusted OR 1.11, 95% CI 0.76-1.61). However, stone size and stone position were significant predictors. SSP for stones <5 mm was 89% (95% CI 87-90) compared to 49% (95% CI 44-53) for stones ≥5-7 mm, and 29% (95% CI 23-36) for stones >7 mm. For stones in the upper ureter the SSP rate was 52% (95% CI 48-56), middle ureter was 70% (95% CI 64-76), and lower ureter was 83% (95% CI 81-85). CONCLUSION: In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management neither WBC, neutrophil count, nor CRP, helps determine the likelihood of SSP. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our present findings represent the most comprehensive SP rates for each millimetre increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention.

Localising occult prostate cancer metastasis with advanced imaging techniques (LOCATE trial): a prospective cohort, observational diagnostic accuracy trial investigating whole-body magnetic resonance imaging in radio-recurrent prostate cancer.

BACKGROUND: Accurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer. METHODS/DESIGN: The LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort. DISCUSSION: The LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway. TRIAL REGISTRATION: LOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816.

Patient Reported Outcome Measures for Transperineal Template Prostate Mapping Biopsies in the PICTURE Study.

PURPOSE: Transperineal template prostate mapping biopsy is an increasingly used method of procuring tissue from men with suspected prostate cancer. We report patient related outcome measures and adverse events in men in the PICTURE trial (ClinicalTrials.gov NCT01492270) who underwent this diagnostic test. MATERIALS AND METHODS: A total of 249 men underwent multiparametric magnetic resonance imaging followed by transperineal template prostate mapping biopsy as a validation study. Functional outcomes before and after transperineal template prostate mapping were prospectively collected and recorded with questionnaires, including the I-PSS (International Prostate Symptom Score), the I-PSS-QoL (Quality of Life), the IIEF-15 (International Index of Erectile Function-15) and the EPIC (Expanded Prostate Cancer Index Composite) urinary function. RESULTS: Mean age was 62 years, median prostate specific antigen was 6.8 ng/ml and median gland size was 37 ml. At transperineal template prostate mapping biopsy a median of 49 cores (IQR 40-55) were taken. Mean time to complete the post-procedure patient related outcome measure questionnaires was 46 days. Adverse events included post-procedure acute urinary retention in 24% of patients, rectal pain in 26% and perineal pain in 41%. Transperineal template prostate mapping biopsy resulted in a statistically significant increase in scores on the I-PSS from 10.9 to 11.8 (p = 0.024) and the I-PSS-QoL from 1.57 to 1.76 (p = 0.03). The IIEF-15 erectile function score decreased by 23.2% from 47.7 to 38.7 (p <0.001). Significant deterioration was noted in all 5 of IIEF-15 functional domains, including erectile and orgasmic function, sexual desire, and intercourse and overall satisfaction (p <0.001). EPIC urinary scores showed no overall change from baseline. CONCLUSIONS: Transperineal template prostate mapping biopsy causes a high urinary retention rate and a detrimental impact on genitourinary functional outcomes, including deterioration in urinary flow and sexual function. Our findings can be used to ensure adequate counseling about transperineal template prostate mapping biopsies. The results point to a need for strategies such as multiparametric magnetic resonance imaging and targeted biopsies to minimize the harms of transperineal template prostate mapping biopsy.

Harnessing the immunomodulatory effect of thermal and non-thermal ablative therapies for cancer treatment.

Minimally invasive interventional therapies are evolving rapidly and their use for the treatment of solid tumours is becoming more extensive. The in situ destruction of solid tumours by such therapies is thought to release antigens that can prime an antitumour immune response. In this review, we offer an overview of the current evidence for immune response activation associated with the utilisation of the main thermal and non-thermal ablation therapies currently in use today. This is followed by an assessment of the hypothesised mechanisms behind this immune response priming and by a discussion of potential methods of harnessing this specific response, which may subsequently be applicable in the treatment of cancer patients. References were identified through searches of PubMed/MEDLINE and Cochrane databases to identify peer-reviewed original articles, meta-analyses and reviews. Papers were searched from 1850 until October 2014. Articles were also identified through searches of the authors' files. Only papers published in English were reviewed. Thermal and non-thermal therapies have the potential to stimulate antitumour immunity although the current body of evidence is based mostly on murine trials or small-scale phase 1 human trials. The evidence for this immune-modulatory response is currently the strongest in relation to cryotherapy and radiotherapy, although data is accumulating for related ablative treatments such as high-intensity focused ultrasound, radiofrequency ablation and irreversible electroporation. This effect may be greatly enhanced by combining these therapies with other immunostimulatory interventions. Evidence is emerging into the immunomodulatory effect associated with thermal and non-thermal ablative therapies used in cancer treatment in addition to the mechanism behind this effect and how it may be harnessed for therapeutic use. A potential exists for treatment approaches that combine ablation of the primary tumour with control and possible eradication of persistent, locally recurrent and metastatic disease. However, more work is needed into each of these modalities, initially in further animal studies and then subsequently in large-scale prospective human studies.

Histological outcomes after focal high-intensity focused ultrasound and cryotherapy.

INTRODUCTION: Focal therapy has increasingly become an accepted treatment option for patients with localised prostate cancer. Most follow-up protocols use a mixture of protocol biopsies or "for cause" biopsies triggered by a rising PSA. In this paper, we discuss the histological outcomes from these biopsies and their use in guiding subsequent management and trial development. METHODS: We conducted a literature search and reviewed the post-treatment biopsy results from studies on focal HIFU and focal cryotherapy. We subsequently reviewed the results of three recently published consensus statements released discussing many of the issues concerning focal therapy. RESULTS: Research suggests that 1 in 5 of all post-treatment biopsies after focal therapy are positive. However, the majority of these seemed to be from the untreated portion of the gland or met criteria for clinically insignificant disease. The histological outcomes from focal therapy are promising and confirm its effectiveness in the short to medium term. Furthermore re-treatment is possible whilst maintaining a low-side-effect profile. CONCLUSION: Debate is ongoing about the clinical significance of various levels of residual disease after focal therapy and the exact threshold at which to call failure within a patient who has had focal therapy.