Imperial College London

Professor Hashim Ahmed

Faculty of MedicineDepartment of Surgery & Cancer

Chair in Urology (Clinical)
 
 
 
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Contact

 

hashim.ahmed

 
 
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Location

 

5L28Lab BlockCharing Cross Campus

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Summary

 

Publications

Publication Type
Year
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302 results found

Antonelli M, Johnston EW, Dikaios N, Cheung KK, Sidhu HS, Appayya MB, Giganti F, Simmons LAM, Freeman A, Allen C, Ahmed HU, Atkinson D, Ourselin S, Punwani Set al., 2019, Machine learning classifiers can predict Gleason pattern 4 prostate cancer with greater accuracy than experienced radiologists, European Radiology, ISSN: 0938-7994

OBJECTIVE: The purpose of this study was: To test whether machine learning classifiers for transition zone (TZ) and peripheral zone (PZ) can correctly classify prostate tumors into those with/without a Gleason 4 component, and to compare the performance of the best performing classifiers against the opinion of three board-certified radiologists. METHODS: A retrospective analysis of prospectively acquired data was performed at a single center between 2012 and 2015. Inclusion criteria were (i) 3-T mp-MRI compliant with international guidelines, (ii) Likert ≥ 3/5 lesion, (iii) transperineal template ± targeted index lesion biopsy confirming cancer ≥ Gleason 3 + 3. Index lesions from 164 men were analyzed (119 PZ, 45 TZ). Quantitative MRI and clinical features were used and zone-specific machine learning classifiers were constructed. Models were validated using a fivefold cross-validation and a temporally separated patient cohort. Classifier performance was compared against the opinion of three board-certified radiologists. RESULTS: The best PZ classifier trained with prostate-specific antigen density, apparent diffusion coefficient (ADC), and maximum enhancement (ME) on DCE-MRI obtained a ROC area under the curve (AUC) of 0.83 following fivefold cross-validation. Diagnostic sensitivity at 50% threshold of specificity was higher for the best PZ model (0.93) when compared with the mean sensitivity of the three radiologists (0.72). The best TZ model used ADC and ME to obtain an AUC of 0.75 following fivefold cross-validation. This achieved higher diagnostic sensitivity at 50% threshold of specificity (0.88) than the mean sensitivity of the three radiologists (0.82). CONCLUSIONS: Machine learning classifiers predict Gleason pattern 4 in prostate tumors better than radiologists. KEY POINTS: • Predictive models developed from quantitative multiparametric magnetic resonance imaging regarding the characterization of prostate cancer grade

Journal article

Bass EJ, Orczyk C, Grey A, Freeman A, Jameson C, Punwani S, Ramachandran N, Allen C, Emberton M, Ahmed HUet al., 2019, Targeted biopsy of the prostate: Does this result in improvement in detection of high-grade cancer or the occurrence of the Will Rogers phenomenon?, BJU International, ISSN: 1464-4096

OBJECTIVE: To investigate whether patients with Gleason 3 + 4 cancer on transrectal biopsy are upgraded after undergoing transperineal magnetic resonance imaging (MRI)-targeted biopsy and whether this has implications for current clinical practice. PATIENTS AND METHODS: In this retrospective analysis we examined 107 consecutive patients presenting at a single tertiary referral centre (July 2012 to July 2016) with prostate cancer of Gleason score 3 + 4 on transrectal ultrasonography (TRUS)-guided systematic non-targeted biopsy who then underwent a multiparametric MRI followed by MRI-targeted transperineal prostate biopsy for accurate risk stratification and localization. RESULTS: The patients' mean (sd) age was 67.0 (8.0) years, and they had a median (interquartile range) PSA concentration of 6.2 (4.7-9.6) ng/mL. Of the 107 patients, 84 (78.5%) had Gleason 3 + 4 on both transrectal systematic biopsy and transperineal MRI-targeted biopsy. Nineteen patients (17.8%) were upgraded to Gleason 4 + 3, three patients (3.0%) to Gleason 4 + 4 and one patient (1.0%) to Gleason 4 + 5. These differences were significant (P = 0.0006). Likewise, 23/107 patients (22%) had higher-risk disease based on their targeted biopsies. CONCLUSION: The use of targeted biopsy in men with impalpable cancer, ultimately upgraded one in five patients from favourable-intermediate- to unfavourable-intermediate-risk disease or worse. This has significant clinical implications for men considering active surveillance or radical treatment. Our risk calculators must now be validated using these data from targeted biopsy as the technique becomes widely adopted.

Journal article

Simmons LAM, Kanthabalan A, Arya M, Briggs T, Charman SC, Freeman A, Gelister J, Jameson C, McCartan N, Moore CM, van der Muelen J, Emberton M, Ahmed HUet al., 2019, Prostate Imaging Compared to Transperineal Ultrasound-guided biopsy for significant prostate cancer Risk Evaluation (PICTURE): a prospective cohort validating study assessing Prostate HistoScanning, PROSTATE CANCER AND PROSTATIC DISEASES, Vol: 22, Pages: 261-267, ISSN: 1365-7852

Journal article

Eldred-Evans D, Ahmed HU, 2019, Re-thinking active surveillance for the multiparametric magnetic resonance imaging era (vol 123, pg 376, 2019), BJU INTERNATIONAL, Vol: 123, Pages: 909-909, ISSN: 1464-4096

Journal article

Johnston EW, Bonet-Carne E, Ferizi U, Yvernault B, Pye H, Patel D, Clemente J, Piga W, Heavey S, Sidhu HS, Giganti F, O'Callaghan J, Brizmohun Appayya M, Grey A, Saborowska A, Ourselin S, Hawkes D, Moore CM, Emberton M, Ahmed HU, Whitaker H, Rodriguez-Justo M, Freeman A, Atkinson D, Alexander D, Panagiotaki E, Punwani Set al., 2019, VERDICT MRI for Prostate Cancer: Intracellular Volume Fraction versus Apparent Diffusion Coefficient., Radiology, Pages: 181749-181749

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, and Restricted Diffusion for Cytometry in Tumors (VERDICT) model estimates three distinct signal components and associates them to (a) intracellular water, (b) water in the extracellular extravascular space, and (c) water in the microvasculature. Purpose To evaluate the repeatability, image quality, and diagnostic utility of intracellular volume fraction (FIC) maps obtained with VERDICT prostate MRI and to compare those maps with apparent diffusion coefficient (ADC) maps for Gleason grade differentiation. Materials and Methods Seventy men (median age, 62.2 years; range, 49.5-82.0 years) suspected of having prostate cancer or undergoing active surveillance were recruited to a prospective study between April 2016 and October 2017. All men underwent multiparametric prostate and VERDICT MRI. Forty-two of the 70 men (median age, 67.7 years; range, 50.0-82.0 years) underwent two VERDICT MRI acquisitions to assess repeatability of FIC measurements obtained with VERDICT MRI. Repeatability was measured with use of intraclass correlation coefficients (ICCs). The image quality of FIC and ADC maps was independently evaluated by two board-certified radiologists. Forty-two men (median age, 64.8 years; range, 49.5-79.6 years) underwent targeted biopsy, which enabled comparison of FIC and ADC metrics in the differentiation between Gleason grades. Results VERDICT MRI FIC demonstrated ICCs of 0.87-0.95. There was no significant difference between image quality of ADC and FIC maps (score, 3.1 vs 3.3, respectively; P = .90). FIC was higher in lesions with a Gleason grade of at least 3+4 compared with benign and/or Gleason grade 3+3 lesions (mean, 0.49 ± 0.17 vs 0.31 ± 0.12, respectively; P = .002). The difference in ADC between these groups did not reach statistical significanc

Journal article

Peters M, van Son MJ, Moerland MA, Kerkmeijer LGW, Eppinga WSC, Meijer RP, Lagendijk Ir JJW, Shah TT, Ahmed HU, van der Voort van Zijp JRNet al., 2019, MRI-guided ultrafocal HDR-brachytherapy for localised prostate cancer: median 4 year results of a feasibility study., International Journal of Radiation Oncology - Biology - Physics, ISSN: 0360-3016

INTRODUCTION: For the treatment of localised prostate cancer, focal therapy has the potential to cure with less side-effects than traditional whole-gland treatments. We report an update of toxicity, quality of life (QoL) and tumour control of our MRI-guided ultrafocal high-dose-rate (HDR) brachytherapy cohort. MATERIALS AND METHODS: Disease status was evaluated by systematic biopsies and 3T multiparametric MRI. The brachytherapy implant procedure under fused transrectal ultrasound/MRI guidance was followed by 1.5T MRI for contour adjustments and catheter position verification. In a single dose, 19Gy was delivered to the tumour with a margin of 5 mm. Genitourinary (GU) toxicity, gastro-intestinal (GI) toxicity and erectile dysfunction (ED) were graded with the CTCAE 4.0. QoL was measured with RAND-36, EORTC QLQ-C30 and EORTC QLQ-PR25. IPSS and IIEF scores were obtained. PSA was monitored, with biochemical recurrence defined as nadir+2ng/ml (Phoenix). RESULTS: Thirty patients with NCCN low(13%) to intermediate(87%) risk prostate cancer were treated between May 2013 and April 2016. Median follow-up was 4 years. Median age was 71 years (interquartile range 68-73), median iPSA 7.3 ng/ml (5.2-8.1). Maximum Gleason score was 4+3=7 (in 2 patients). All tumours were radiological (MRI) stage T2. No grade >2 GU or >1 GI toxicity occurred. IPSS only deteriorated temporarily. Pre-treatment IIEF mild ED deteriorated to moderate/severe ED in 50% of patients. Long-term clinically relevant QoL deterioration was seen in sexual activity and tiredness, while emotional and cognitive functioning improved. At 4 years, biochemical disease-free survival (BDFS) was 70% (95% CI 52-93%), metastases-free survival 93% (85-100%) and overall survival 100%. Of intraprostatic recurrences, 7/9 were out-of-field. CONCLUSION: Ultrafocal HDR-brachytherapy conveys minimal GU/GI toxicity and has a marginal effect on QoL. An early decline in erectile function was seen. Tumour control outcomes are poo

Journal article

Marconi L, Stonier T, Tourinho-Barbosa R, Moore C, Ahmed HU, Cathelineau X, Emberton M, Sanchez-Salas R, Cathcart Pet al., 2019, Robot-assisted radical prostatectomy after focal therapy: oncological, functional outcomes and predictors of recurrence, European Urology, ISSN: 0302-2838

There are few data on the outcomes and toxicity of radical prostatectomy (RP) among men experiencing local recurrence of prostate cancer (PC) following focal therapy (FT). To characterise perioperative, oncological, and functional outcomes after salvage robot-assisted RP (S-RALP) and determine the risk factors for S-RALP failure, we conducted a multicentre cohort study of 82 patients undergoing S-RALP after FT. All had histological confirmation of PC recurrence, with metastatic disease excluded using pelvic magnetic resonance imaging, a bone scan, and/or positron emission tomography/computed tomography. Progression-free survival was 74%, 48%, and 36% at 12, 24, and 36mo after surgery, respectively. The 12-mo continence rate was 83%. There were no intraoperative complications and no major postoperative complications. On multivariable analysis, only infield recurrence (hazard ratio [HR] 3.77, 95% confidence interval [CI] 1.11-12.85; p=0.03) and pT3b stage (HR 5.0, 95% CI 1.53-16.39; p=0.008) were independent predictors of recurrence. This study represents the largest series of salvage surgery after FT and shows that this approach is safe with no increase in toxicity when compared to primary RALP. Men identified as having infield recurrence after FT appear to have phenotypically aggressive disease and should be counselled regarding the potential need for a multimodal therapeutic approach. PATIENT SUMMARY: Robotic surgery after focal therapy for prostate cancer is safe and achieves postoperative continence results similar to those for robotic radical prostatectomy in treatment-naïve patients. However, if the cancer recurrence is within the previously treated field, the oncological prognosis seems to be worse.

Journal article

Stabile A, Orczyk C, Hosking-Jervis F, Giganti F, Arya M, Hindley RG, Dickinson L, Allen C, Punwani S, Jameson C, Freeman A, McCartan N, Montorsi F, Briganti A, Ahmed HU, Emberton M, Moore CMet al., 2019, Medium term oncological outcomes in a large cohort of men treated with either focal or hemi-ablation using HIFU for primary localized prostate cancer, BJU International, ISSN: 1464-4096

OBJECTIVE: To report medium-term oncological outcomes in patients receiving primary focal treatment with HIFU for PCa. PATIENTS AND METHODS: Consecutive men treated by means of primary focal HIFU for PCa at two centres by 6 treating clinicians were assessed. Patients were submitted to either a focal ablation or hemiablation using HIFU (Sonablate 500). The primary objective of the study was to assess medium-term oncological outcomes defined as overall survival, freedom from biopsy failure, freedom from any further treatment and freedom from radical treatment after focal HIFU. The secondary objective was to evaluate the changes in pathological features among patients treated by means of focal HIFU over time. We also assessed the relationship between year of surgery and 5-years retreatment probability. RESULTS: One thousand and thirty-two men treated between November 2005 and October 2017 were assessed. The median age was 65 yrs and median prostate-specific antigen was 7 ng/ml. The majority of patients had Gleason score of 3+4 or above (80.3%). Median follow-up was 36 months (IQR: 14-64). The overall survival at 24, 60 and 96 months was 99%, 97% and 97%, respectively. Freedom from biopsy failure, defined as absence of Gleason 3+ 4 disease, was 84%, 64% and 54% at 24, 60 and 96 months. Freedom from any further treatment was 85, 59 and 46% at 24, 60 and 96 months, respectively. Roughly 70% of patients retreated received a 2nd focal treatment. Freedom from radical treatment was 98%, 91% and 81% at 24, 60 and 96 months. During the study period we have seen an increase in the proportion of patients undergoing focal HIFU with Gleason 3+4 disease and with T2 mpMRI staged disease. Finally, we report a reduction over time in the proportion of men undergoing re-treatment within 5-years of first treatment. CONCLUSIONS: Focal HIFU for PCa is a feasible therapeutic strategy with acceptable survival and oncological results, with a reduction in the 5 year retreatment rates over the l

Journal article

Eldred-Evans D, Ahmed HU, 2019, Re-thinking active surveillance for the multiparametric magnetic resonance imaging era, BJU INTERNATIONAL, Vol: 123, Pages: 376-377, ISSN: 1464-4096

Journal article

Miah S, Tharakan T, Gallagher KA, Shah TT, Winkler M, Jayasena CN, Ahmed HU, Minhas Set al., 2019, The effects of testosterone replacement therapy on the prostate: a clinical perspective [version 1; referees: 2 approved], F1000Research, Vol: 8, ISSN: 2046-1402

Male hypogonadism is a clinical syndrome characterized by low testosterone and symptoms of androgen deficiency. Prostate cancer remains a significant health burden and cause of male mortality worldwide. The use of testosterone replacement therapy drugs is rising year-on-year for the treatment of androgen deficiency and has reached global proportions. As clinicians, we must be well versed and provide appropriate counseling for men prior to the commencement of testosterone replacement therapy. This review summarizes the current clinical and basic science evidence in relation to this commonly encountered clinical scenario. There is gathering evidence that suggests, from an oncological perspective, that it is safe to commence testosterone replacement therapy for men who have a combination of biochemically confirmed androgen deficiency and who have either had definitive treatment of their prostate cancer or no previous history of this disease. However, patients must be made aware and cautioned that there is a distinct lack of level 1 evidence. Calls for such studies have been made throughout the urological and andrological community to provide a definitive answer. For those with a diagnosis of prostate cancer that remains untreated, there is a sparsity of evidence and therefore clinicians are "pushing the limits" of safety when considering the commencement of testosterone replacement therapy.

Journal article

Miah S, Servian P, Patel A, Lovegrove C, Skelton L, Shah TT, Eldred-Evans D, Arya M, Tam H, Ahmed HU, Winkler Met al., 2019, A prospective analysis of robotic targeted MRI-US fusion prostate biopsy using the centroid targeting approach, Journal of Robotic Surgery, ISSN: 1863-2483

Robotic prostate biopsy is an emerging technology. Recent development of this tool has allowed the performance of a transperineal prostate biopsy allowing pre-programmed standardized biopsy schemes. Prospective data collection was undertaken in 86 consecutive men who underwent robotically assisted transperineal prostate biopsy. All underwent a multi-parametric MRI pre-biopsy with centroid targeting followed by systematic template prostate biopsy. For the purposes of this study, our definition of clinically significant prostate cancer (csPCa) is any Gleason score > 6. Mean (SD) age, median (IQR) PSA, and median (IQR) prostate volume were 64.24 (6.97) years, of 7.79 ng/ml (6.5) and 45.06 cc (28), respectively. Overall, 44 (51.2%) men were diagnosed with csPCa. csPCa was detected in the targeted biopsies alone in 35 (40.1%) men. The addition of the 12-zone template biopsy increased the yield of csPCa for another 9 (10.5%) men. Of these 9 men, the majority (7) harbored primary pattern 3 disease and only 1 was identified to have high-grade disease. Out of these 9 men, 7 of them had the identification of csPCa in the sector, where a target was contained within that zone. Robotic-assisted prostate biopsy in our study has demonstrated a high detection of csPCa when combined with limited near-field sampling. Our study suggests the use of more accurate biopsy schemes such as ring-targeting of lesions to mitigate against systematic and random mathematical errors. Adoption of this tool and biopsy strategy would potentially avoid the increased morbidity associated with whole gland systematic unguided biopsies.

Journal article

van Luijtelaar A, Greenwood BM, Ahmed HU, Barqawi AB, Barret E, Bomers JGR, Brausi MA, Choyke PL, Cooperberg MR, Eggener S, Feller JF, Frauscher F, George AK, Hindley RG, Jenniskens SFM, Klotz L, Kovacs G, Lindner U, Loeb S, Margolis DJ, Marks LS, May S, Mcclure TD, Montironi R, Nour SG, Oto A, Polascik TJ, Rastinehad AR, De Reyke TM, Reijnen JS, de la Rosette JJMCH, Sedelaar JPM, Sperling DS, Walser EM, Ward JF, Villers A, Ghai S, Fütterer JJet al., 2019, Focal laser ablation as clinical treatment of prostate cancer: Report from a Delphi consensus project, World Journal of Urology, ISSN: 0724-4983

PURPOSE: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. METHODS: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings. RESULTS: Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation. CONCLUSION: Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.

Journal article

Shah T, Ahmed H, 2019, Early-medium medium-term outcomes of primary focal cryotherapy to treat nonmetastatic clinically significant prostate cancer from a prospective multicentre registry, European Urology, ISSN: 0302-2838

BackgroundFocal cryotherapy can be used to treat patients with clinically significant nonmetastatic prostate cancer to reduce side effects.ObjectiveEarly-medium-term cancer control and functional outcomes.Design, setting, and participantsA prospective registry-based case series of 122 consecutive patients undergoing focal cryotherapy between October 1, 2013, and November 30, 2016, in five UK centres. Median follow-up was 27.8 mo [interquartile range (IQR) 19.5–36.7]. A total of 35 patients (28.7%) had National Comprehensive Cancer Network (NCCN) high risk and 87 (71.3%) had intermediate risk disease. Risk and zonal stratification included multiparametric magnetic resonance imaging (mpMRI) with targeted and systematic biopsies, or transperineal mapping biopsies.InterventionFocal cryoablation of MR-visible tumours.Outcome measurements and statistical analysisFollow-up involved prostate-specific antigen (PSA) monitoring, mpMRI, and for-cause biopsies. Primary outcome was failure-free survival (FFS), defined as transition to radical, whole-gland, or systemic therapy, or metastases/death. Secondary outcomes included adverse events and functional outcomes.Results and limitationsA total of 80 (65.6%) had anterior ablation, 23 (19.7%) combined posterior and anterior ablation, and two (1.6%) posterior ablation alone (SeedNet or Visual-ICE, BTG plc). Median age was 68.7 yr (IQR 64.9–73.8) and preoperative PSA 10.8 ng/ml (IQR 7.8–15.6). Overall FFS at 3 yr was 90.5% [95% confidence interval (CI) 84.2–97.3]. When stratified for the NCCN risk group, 3-yr outcomes were 84.7% (95% CI 71.4–100) in high risk and 93.3% (95% CI 86.8–100) in intermediate risk. At last follow-up, incontinence defined as any pad use was 0/69 (0%) and erectile dysfunction (defined as erections insufficient for penetration) was 5/31 (16.1%). Limitations include lack of long-term outcomes.ConclusionsFocal cryotherapy primarily for anterior intermediate and high-risk prost

Journal article

Miah S, Dunford C, Edison M, Eldred-Evans D, Gan C, Shah TT, Lunn P, Winkler M, Ahmed HU, Gibbons N, Hrouda Det al., 2019, A prospective clinical, cost and environmental analysis of a clinician-led virtual urology clinic, Annals of The Royal College of Surgeons of England, Vol: 101, Pages: 30-34, ISSN: 0035-8843

INTRODUCTION: Minimally invasive parathyroidectomy (MIP) for primary hyperparathyroidism is dependent upon accurate prediction of single-gland disease on the basis of preoperative imaging and biochemistry. The aims of this study were to validate currently available predictive models of single-gland disease in two UK cohorts and to determine if these models can facilitate MIP. MATERIAL AND METHODS: We collected data prospectively from our weekly follow-up virtual clinic over a continuous four-month period between July and September 2017. RESULTS: In total, we reviewed 409 patients. Following virtual clinic consultation, 68.5% of our patients were discharged from further follow-up. The majority of our patients (male 57.7%, female 55.5%) were of working age. The satisfaction scores were high, at 90.1%, and there were no reported adverse events as a result of using the virtual clinic. Our calculated cost savings were £18,744, with a predicted 12-month cost saving of £56,232. The creation of additional face-to-face clinic capacity has created an estimated 12-month increase in tariff generation for our unit of £72,072. In total, 4623 travel miles were avoided by patients using the virtual clinic, with an estimated avoided carbon footprint of 0.35-1.45 metric tonnes of CO2e, depending on mode of transport. Our predicted 12-month avoided carbon footprint is 1.04-4.04 metric tonnes of CO2e. CONCLUSIONS: Our virtual clinic model has demonstrated a trifecta of positive outcomes, namely, clinical, financial and environmental benefits. The environmental importance and benefits of a virtual clinic should be promoted as a social enterprise value when engaging stakeholders in setting up such a urological service. We propose the adoption of our virtual clinic model in those urological units considering this method of telemedicine.

Journal article

Johnston EW, Latifoltojar A, Sidhu HS, Ramachandran N, Sokolska M, Bainbridge A, Moore C, Ahmed HU, Punwani Set al., 2018, Multiparametric whole-body 3.0-T MRI in newly diagnosed intermediate- and high-risk prostate cancer: diagnostic accuracy and interobserver agreement for nodal and metastatic staging, European Radiology, ISSN: 0938-7994

OBJECTIVES: To determine the diagnostic accuracy and interobserver concordance of whole-body (WB)-MRI, vs. 99mTc bone scintigraphy (BS) and 18fluoro-ethyl-choline (18F-choline) PET/CT for the primary staging of intermediate/high-risk prostate cancer. METHODS: An institutional review board approved prospective cohort study carried out between July 2012 and November 2015, whereby 56 men prospectively underwent 3.0-T multiparametric (mp)-WB-MRI in addition to BS (all patients) ± 18F-choline PET/CT (33 patients). MRI comprised pre- and post-contrast modified Dixon (mDixon), T2-weighted (T2W) imaging, and diffusion-weighted imaging (DWI). Patients underwent follow-up mp-WB-MRI at 1 year to derive the reference standard. WB-MRIs were reviewed by two radiologists applying a 6-point scale and a locked sequential read (LSR) paradigm for the suspicion of nodal (N) and metastatic disease (M1a and M1b). RESULTS: The mean sensitivity/specificity of WB-MRI for N1 disease was 1.00/0.96 respectively, compared with 1.00/0.82 for 18F-choline PET/CT. The mean sensitivity and specificity of WB-MRI, 18F-choline PET/CT, and BS were 0.90/0.88, 0.80/0.92, and 0.60/1.00 for M1b disease. ROC-AUC did not show statistically significant improvement for each component of the LSR; mean ROC-AUC 0.92, 0.94, and 0.93 (p < 0.05) for mDixon + DWI, + T2WI, and + contrast respectively. WB-MRI had an interobserver concordance (κ) of 0.79, 0.68, and 0.58 for N1, M1a, and M1b diseases respectively. CONCLUSIONS: WB-MRI provides high levels of diagnostic accuracy for both nodal and metastatic bone disease, with higher levels of sensitivity than BS for metastatic disease, and similar performance to 18F-choline PET/CT. T2 and post-contrast mDixon had no significant additive value above a protocol comprising mDixon and DWI alone. KEY POINTS: • A whole-body MRI protocol comprising unenhanced mDixon and diffusion-weighted imaging provides high levels of diagnostic accuracy

Journal article

Marra G, Ploussard G, Ost P, De Visschere PJL, Briganti A, Gandaglia G, Tilki D, Surcel CI, Tsaur I, Van Den Bergh RCN, Kretschmer A, Borgmann H, Gontero P, Ahmed HU, Valerio M, EAU-YAU Prostate Cancer Working Partyet al., 2018, Focal therapy in localised prostate cancer: real-world urological perspective explored in a cross-sectional European survey, Urologic Oncology: Seminars and Original Investigations, Vol: 36, Pages: 529.e11-529.e22, ISSN: 1078-1439

INTRODUCTION: The urological community's opinion over focal therapy (FT) for prostate cancer (PCa) has never been assessed. Our aim was to investigate the current opinion on FT in the European urological community. METHODS: A 25-item questionnaire was devised according to the Cherries checklist and distributed through SurveyMonkey using a web link from November 2016 to October 2017. After a pilot validation (n = 40 urologists), the survey was sent through EAU and 9 other national European urological societies mailing list. Twitter was also used. RESULTS: We received 484 replies from 51 countries. Almost half (44.8%, n = 217) stated FT would represent a step forward, and 52.0% (n = 252) would suggest FT to a patient. Almost three-quarters (70.8%, n = 343) agreed FT will become a standard option after improvements in patient selection (n = 66) or when its effectiveness will be proven (n = 78), or both (n = 199). Most frequently used definition of FT was treatment of all significant (life-threatening) cancer foci whilst leaving untreated the rest of the gland (39.3%, n = 190). FT use was considered as an alternative to whole-gland treatments by 29.7% (n = 144), and to AS by 25.0% (n = 121). On multivariate analysis, FT availability and publications were associated with a positive opinion on FT. Conversely, attending International congresses, treating high PCa volumes and high percentages of high-risk PCa was associated with a negative opinion. CONCLUSIONS: FT is considered as an attractive option for PCa treatment by the European urological community sampled by our survey. FT availability positively influences these thoughts. The present survey suggests whilst some early adopters already embraced FT, the relative majority of the urological community is prone to embrace FT in the near future, once current areas of debate are solved.

Journal article

Simmons LAM, Kanthabalan A, Arya M, Briggs T, Barratt D, Charman SC, Freeman A, Hawkes D, Hu Y, Jameson C, McCartan N, Moore CM, Punwani S, van der Muelen J, Emberton M, Ahmed HUet al., 2018, Accuracy of Transperineal Targeted Prostate Biopsies, Visual Estimation and Image Fusion in Men Needing Repeat Biopsy in the PICTURE Trial, JOURNAL OF UROLOGY, Vol: 200, Pages: 1227-1233, ISSN: 0022-5347

Journal article

Dikaios N, Giganti F, Sidhu HS, Johnston EW, Appayya MB, Simmons L, Freeman A, Ahmed HU, Atkinson D, Punwani Set al., Multi-parametric MRI zone-specific diagnostic model performance compared with experienced radiologists for detection of prostate cancer, European Radiology, ISSN: 0938-7994

OBJECTIVES: Compare the performance of zone-specific multi-parametric-MRI (mp-MRI) diagnostic models in prostate cancer detection with experienced radiologists. METHODS: A single-centre, IRB approved, prospective STARD compliant 3 T MRI test dataset of 203 patients was generated to test validity and generalisability of previously reported 1.5 T mp-MRI diagnostic models. All patients included within the test dataset underwent 3 T mp-MRI, comprising T2, diffusion-weighted and dynamic contrast-enhanced imaging followed by transperineal template ± targeted index lesion biopsy. Separate diagnostic models (transition zone (TZ) and peripheral zone (PZ)) were applied to respective zones. Sensitivity/specificity and the area under the receiver operating characteristic curve (ROC-AUC) were calculated for the two zone-specific models. Two radiologists (A and B) independently Likert scored test 3 T mp-MRI dataset, allowing ROC analysis for each radiologist for each prostate zone. RESULTS: Diagnostic models applied to the test dataset demonstrated a ROC-AUC = 0.74 (95% CI 0.67-0.81) in the PZ and 0.68 (95% CI 0.61-0.75) in the TZ. Radiologist A/B had a ROC-AUC = 0.78/0.74 in the PZ and 0.69/0.69 in the TZ. Radiologists A and B each scored 51 patients in the PZ and 41 and 45 patients respectively in the TZ as Likert 3. The PZ model demonstrated a ROC-AUC = 0.65/0.67 for the patients Likert scored as indeterminate by radiologist A/B respectively, whereas the TZ model demonstrated a ROC-AUC = 0.74/0.69. CONCLUSION: Zone-specific mp-MRI diagnostic models demonstrate generalisability between 1.5 and 3 T mp-MRI protocols and show similar classification performance to experienced radiologists for prostate cancer detection. Results also indicate the ability of diagnostic models to classify cases with an indeterminate radiologist score. KEY POINTS: • MRI diagnostic models had similar performance

Journal article

Ball D, Kim NH, McFarlane A, Shah T, Peters M, Gomez E, Miah S, Guillaumier S, Afzai N, Dudderidge T, Hosking-Jervis F, Eldred-Evans D, Hindley R, Lewl H, McCartan N, Moors C, Arya M, Nigam R, Ogden C, Persad R, Shah K, Virdi J, Emberton M, Ahmed H, Winkler Met al., 2018, Propensity Score-Matched Comparison of Focal High Intensity Focused Ultrasound (HIFU) to Laparoscopic Radical Prostatectomy (LRP) for Clinically Significant Localised Prostate Cancer, National-Cancer-Research-Institute (NCRI) Cancer Conference, Publisher: NATURE PUBLISHING GROUP, Pages: 45-45, ISSN: 0007-0920

Conference paper

Miah S, Hoskings-Jervis F, Eldred-Evans D, Shah T, Laniado M, Hindley R, Doherty A, Sinclair A, Burke D, Bhardwa J, Karim O, Montgomery B, Bott S, Barber N, Nigam R, Arya M, Winkler M, Allen C, Ahmed Het al., 2018, Image fusion targeted prostate biopsy in 771 men at risk: a multi-centre evaluation showing low diagnostic yield of significant cancer in non-targeted biopsies, National-Cancer-Research-Institute (NCRI) Cancer Conference, Publisher: NATURE PUBLISHING GROUP, Pages: 31-31, ISSN: 0007-0920

Conference paper

Miah S, Winkler M, Ahmed HU, 2018, Re: Predictors of infectious complications after targeted prophylaxis for prostate needle biopsy, European Urology, Vol: 74, Pages: 523-524, ISSN: 0302-2838

Papagiannopoulos D, Abern M, Wilson N, et alJ Urol 2018;199:155–60Experts’ summary:Papagiannopoulos et al [1] are to be congratulated on their reporting of over 5000 men undergoing transrectal ultrasound-guided (TRUS) prostate biopsy with targeted antimicrobial prophylaxis with preprocedure rectal swab cultures. This method led to an overall infectious complication rate of 1.1%, whilst it was 3.9% for those harbouring a fluoroquinolone-resistant organism (odds ratio 9.98). Their article concluded that one should consider using alternative biopsy approaches to minimise infectious complications in this higher-risk cohort who harbour fluoroquinolone resistance.

Journal article

Bass EJ, Freeman A, Jameson C, Punwani S, Moore CM, Arya M, Emberton M, Ahmed HUet al., 2018, Prostate cancer diagnostic pathway: Is a one-stop cognitive MRI targeted biopsy service a realistic goal in everyday practice? A pilot cohort in a tertiary referral centre in the UK, BMJ Open, Vol: 8, ISSN: 2044-6055

Objectives To evaluate the feasibility of a novel multiparametric MRI (mpMRI) and cognitive fusion transperineal targeted biopsy (MRTB) led prostate cancer (PCa) diagnostic service with regard to cancer detection and reducing time to diagnosis and treatment.Design Consecutive men being investigated for possible PCa under the UK 2-week wait guidelines.Setting Tertiary referral centre for PCa in the UK.Participants Men referred with a raised prostate-specific antigen (PSA) or abnormal digital rectal examination between February 2015 and March 2016 under the UK 2-week rule guideline.Interventions An mpMRI was performed prior to patients attending clinic, on the same day. If required, MRTB was offered. Results were available within 48 hours and discussed at a specialist multidisciplinary team meeting. Patients returned for counselling within 7 daysPrimary and secondary outcome measures Outcome measures in this regard included the time to diagnosis and treatment of patients referred with a suspicion of PCa. Quality control outcome measures included clinically significant and total cancer detection rates.Results 112 men were referred to the service. 111 (99.1%) underwent mpMRI. Median PSA was 9.4 ng/mL (IQR 5.6–21.0). 87 patients had a target on mpMRI with 25 scoring Likert 3/5 for likelihood of disease, 26 4/5 and 36 5/5.57 (51%) patients received a local anaesthetic, Magnetic resonance imaging targeted biopsy (MRTB). Cancer was detected in 45 (79%). 43 (96%) had University College London definition 2 disease or greater. The times to diagnosis and treatment were a median of 8 and 20 days, respectively.Conclusions This approach greatly reduces the time to diagnosis and treatment. Detection rates of significant cancer are high. Similar services may be valuable to patients with a potential diagnosis of PCa.

Journal article

Hamdy FC, Elliott D, le Conte S, Davies LC, Burns RM, Thomson C, Gray R, Wolstenholme J, Donovan JL, Fitzpatrick R, Verrill C, Gleeson F, Singh S, Rosario D, Catto JWF, Brewster S, Dudderidge T, Hindley R, Emara A, Sooriakumaran P, Ahmed HU, Leslie TAet al., 2018, Partial ablation versus radical prostatectomy in intermediate-risk prostate cancer: the PART feasibility RCT, Health Technology Assessment, Vol: 22, ISSN: 1366-5278

BackgroundProstate cancer (PCa) is the most common cancer in men in the UK. Patients with intermediate-risk, clinically localised disease are offered radical treatments such as surgery or radiotherapy, which can result in severe side effects. A number of alternative partial ablation (PA) technologies that may reduce treatment burden are available; however the comparative effectiveness of these techniques has never been evaluated in a randomised controlled trial (RCT).ObjectivesTo assess the feasibility of a RCT of PA using high-intensity focused ultrasound (HIFU) versus radical prostatectomy (RP) for intermediate-risk PCa and to test and optimise methods of data capture.DesignWe carried out a prospective, multicentre, open-label feasibility study to inform the design and conduct of a future RCT, involving a QuinteT Recruitment Intervention (QRI) to understand barriers to participation.SettingFive NHS hospitals in England.ParticipantsMen with unilateral, intermediate-risk, clinically localised PCa.InterventionsRadical prostatectomy compared with HIFU.Primary outcome measureThe randomisation of 80 men.Secondary outcome measuresFindings of the QRI and assessment of data capture methods.ResultsEighty-seven patients consented to participate by 31 March 2017 and 82 men were randomised by 4 May 2017 (41 men to the RP arm and 41 to the HIFU arm). The QRI was conducted in two iterative phases: phase I identified a number of barriers to recruitment, including organisational challenges, lack of recruiter equipoise and difficulties communicating with patients about the study, and phase II comprised the development and delivery of tailored strategies to optimise recruitment, including group training, individual feedback and ‘tips’ documents. At the time of data extraction, on 10 October 2017, treatment data were available for 71 patients. Patient characteristics were similar at baseline and the rate of return of all clinical case report forms (CRFs) was 95%; the retu

Journal article

Lovegrove CE, Matanhelia M, Randeva J, Eldred-Evans D, Tam H, Miah S, Winkler M, Ahmed HU, Shah TTet al., 2018, Prostate imaging features that indicate benign or malignant pathology on biopsy, Translational andrology and urology, Vol: 7, Pages: S420-S435, ISSN: 2223-4691

Accurate diagnosis of clinically significant prostate cancer is essential in identifying patients who should be offered treatment with curative intent. Modifications to the Gleason grading system in recent years show that accurate grading and reporting at needle biopsy can improve identification of clinically significant prostate cancers. Extracapsular extension of prostate cancer has been demonstrated to be an adverse prognostic factor with greater risk of metastatic spread than organ-confined disease. Tumor volume may be an independent prognostic factor and should be considered in conjunction with other factors. Multi-parametric magnetic resonance imaging (MP-MRI) has become an increasingly important tool in the diagnosis and characterization of prostate cancer. MP-MRI allows T2-weighted (T2W) anatomical imaging to be combined with functional and physiological assessment. Diffusion-weighted imaging (DWI) has shown greater sensitivity, specificity and negative predictive value compared to prostate specific antigen (PSA) testing and T2W imaging alone and has a more positive correlation with Gleason score and tumour volume. Dynamic gadolinium contrast-enhanced (DCE) imaging can exhibit difficulties in distinguishing prostatitis from malignancy in the peripheral zone, and between benign prostatic hyperplasia (BPH) and malignancies in the transition zone (TZ). Computer aided diagnosis utilizes software to aid radiologists in detecting and diagnosing abnormalities from diagnostic imaging. New techniques of quantitative MRI, such as VERDICT MRI use tissue-specific factors to delineate different cellular and microstructural phenotypes, characterizing tissue properties with greater detail. Proton MR spectroscopic imaging (MRSI) is a more technically challenging imaging modality than DCE and DWI MRI. Over the last decade, choline and prostate-specific membrane antigen (PSMA) positron emission tomography (PET) have developed as better tools for staging than conventional imag

Journal article

Hamid S, Donaldson IA, Hu Y, Rodell R, Villarini B, Bonmati E, Tranter P, Punwani S, Sidhu HS, Willis S, van der Meulen J, Hawkes D, McCartan N, Potyka I, Williams NR, Brew-Graves C, Freeman A, Moore CM, Barratt D, Emberton M, Ahmed HUet al., 2018, The SmartTarget biopsy trial: a prospective, within-person randomised, blinded trial comparing the accuracy of visual-registration and magnetic resonance imaging/ultrasound image-fusion targeted biopsies for prostate cancer risk stratification, European Urology, ISSN: 0302-2838

Background: Multiparametric magnetic resonance imaging (mpMRI)-targeted prostate biopsies can improve detection of clinically significant prostate cancer and decrease the overdetection of insignificant cancers. Whether visual-registration targeting is sufficient or if augmentation with image-fusion software is needed is unknown. Objective: To assess concordance between the two methods.Design, Setting, and Participants: We conducted a blinded, within-person randomised, paired validating clinical trial. From 2014 to 2016, 141 men who had undergone a prior (positive or negative) transrectal ultrasound biopsy and had a discrete lesion on mpMRI (score 3 to 5) requiring targeted transperineal biopsy were enrolled at a UK academic hospital; 129 underwent both biopsy strategies and completed the study. Intervention: The order of performing biopsies using visual-registration and a computer-assisted MRI/ultrasound image-fusion system (SmartTarget) on each patient was randomised. The equipment was reset between biopsy strategies to mitigate incorporation bias. Outcome Measurements and Statistical Analysis: The proportion of clinically significant prostate cancer (primary outcome: Gleason pattern ≥3+4=7, maximum cancer core length ≥4 mm; secondary outcome: Gleason pattern ≥4+3=7, maximum cancer core length ≥6 mm) detected by each method was compared using McNemar's test of paired proportions.Results and Limitations: The two strategies combined detected 93 clinically significant prostate cancers (72% of the cohort). Each strategy detected 80/93 (86%) of these cancers; each strategy identified 13 cases missed by the other. Three patients experienced adverse events related to biopsy (urinary retention, urinary tract infection, nausea and vomiting). No difference in urinary symptoms, erectile function, or quality of life between baseline and follow-up (median 10.5 weeks) was observed. The key limitation was lack of parallel-group randomisation and limit on number

Journal article

Olivier J, Stavrinides V, Kay J, Freeman A, Pye H, Ahmed Z, Carmona Echeverria L, Heavey S, Simmons LAM, Kanthabalan A, Arya M, Briggs T, Barratt D, Charman SC, Gelister J, Hawkes D, Hu Y, Jameson C, McCartan N, Punwani S, van der Muelen J, Moore C, Emberton M, Ahmed HU, Whitaker HCet al., 2018, Immunohistochemical biomarker validation in highly selective needle biopsy microarrays derived from mpMRI-characterized prostates, The Prostate, ISSN: 0270-4137

INTRODUCTION: Diagnosing prostate cancer routinely involves tissue biopsy and increasingly image guided biopsy using multiparametric MRI (mpMRI). Excess tissue after diagnosis can be used for research to improve the diagnostic pathway and the vertical assembly of prostate needle biopsy cores into tissue microarrays (TMAs) allows the parallel immunohistochemical (IHC) validation of cancer biomarkers in routine diagnostic specimens. However, tissue within a biopsy core is often heterogeneous and cancer is not uniformly present, resulting in needle biopsy TMAs that suffer from highly variable cancer detection rates that complicate parallel biomarker validation. MATERIALS AND METHODS: The prostate cores with the highest tumor burden (in terms of Gleason score and/or maximum cancer core length) were obtained from 249 patients in the PICTURE trial who underwent transperineal template prostate mapping (TPM) biopsy at 5 mm intervals preceded by mpMRI. From each core, 2 mm segments containing tumor or benign tissue (as assessed on H&E pathology) were selected, excised and embedded vertically into a new TMA block. TMA sections were then IHC-stained for the routinely used prostate cancer biomarkers PSA, PSMA, AMACR, p63, and MSMB and assessed using the h-score method. H-scores in patient matched malignant and benign tissue were correlated with the Gleason grade of the original core and the MRI Likert score for the sampled prostate area. RESULTS: A total of 2240 TMA cores were stained and IHC h-scores were assigned to 1790. There was a statistically significant difference in h-scores between patient matched malignant and adjacent benign tissue that is independent of Likert score. There was no association between the h-scores and Gleason grade or Likert score within each of the benign or malignant groups. CONCLUSION: The construction of highly selective TMAs from prostate needle biopsy cores is possible. IHC data obtained through this method are highly reliable

Journal article

Brown LC, Ahmed HU, Faria R, Bosaily AE-S, Gabe R, Kaplan RS, Parmar M, Collaco-Moraes Y, Ward K, Hindley RG, Freeman A, Kirkham A, Oldroyd R, Parker C, Bott S, Burns-Cox N, Dudderidge T, Ghei M, Henderson A, Persad R, Rosario DJ, Shergill I, Winkler M, Soares M, Spackman E, Sculpher M, Emberton Met al., 2018, Multiparametric MRI to improve detection of prostate cancer compared with transrectal ultrasound-guided prostate biopsy alone: the PROMIS study, Health Technology Assessment, Vol: 22, ISSN: 1366-5278

BackgroundMen with suspected prostate cancer usually undergo transrectal ultrasound (TRUS)-guided prostate biopsy. TRUS-guided biopsy can cause side effects and has relatively poor diagnostic accuracy. Multiparametric magnetic resonance imaging (mpMRI) used as a triage test might allow men to avoid unnecessary TRUS-guided biopsy and improve diagnostic accuracy.ObjectivesTo (1) assess the ability of mpMRI to identify men who can safely avoid unnecessary biopsy, (2) assess the ability of the mpMRI-based pathway to improve the rate of detection of clinically significant (CS) cancer compared with TRUS-guided biopsy and (3) estimate the cost-effectiveness of a mpMRI-based diagnostic pathway.DesignA validating paired-cohort study and an economic evaluation using a decision-analytic model.SettingEleven NHS hospitals in England.ParticipantsMen at risk of prostate cancer undergoing a first prostate biopsy.InterventionsParticipants underwent three tests: (1) mpMRI (the index test), (2) TRUS-guided biopsy (the current standard) and (3) template prostate mapping (TPM) biopsy (the reference test).Main outcome measuresDiagnostic accuracy of mpMRI, TRUS-guided biopsy and TPM-biopsy measured by sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using primary and secondary definitions of CS cancer. The percentage of negative magnetic resonance imaging (MRI) scans was used to identify men who might be able to avoid biopsy.ResultsDiagnostic study – a total of 740 men were registered and 576 underwent all three tests. According to TPM-biopsy, the prevalence of any cancer was 71% [95% confidence interval (CI) 67% to 75%]. The prevalence of CS cancer according to the primary definition (a Gleason score of ≥ 4 + 3 and/or cancer core length of ≥ 6 mm) was 40% (95% CI 36% to 44%). For CS cancer, TRUS-guided biopsy showed a sensitivity of 48% (95% CI 42% to 55%), specificity of 96% (95% CI 94% to 98%)

Journal article

Brizmohun Appayya M, Adshead J, Ahmed HU, Allen C, Bainbridge A, Barrett T, Giganti F, Graham J, Haslam P, Johnston EW, Kastner C, Kirkham APS, Lipton A, McNeill A, Moniz L, Moore CM, Nabi G, Padhani AR, Parker C, Patel A, Pursey J, Richenberg J, Staffurth J, van der Meulen J, Walls D, Punwani Set al., 2018, National implementation of multi-parametric MRI for prostate cancer detection - recommendations from a UK consensus meeting, BJU International, Vol: 122, Pages: 13-25, ISSN: 1464-4096

OBJECTIVES: To identify areas of agreement and disagreement in the implementation of multi-parametric MRI (mpMRI) of the prostate in the diagnostic pathway. MATERIALS AND METHODS: Fifteen UK experts in prostate mpMRI and/or prostate cancer management across the UK (involving 9 NHS centres to provide for geographical spread) participated in a consensus meeting following the UCLA-RAND Appropriateness Method, and were moderated by an independent chair. The experts considered 354 items pertaining to who can request an mpMRI, prostate mpMRI protocol, reporting guidelines, training, quality assurance (QA) and patient management based on mpMRI levels of suspicion for cancer. Each item was rated for agreement on a 9-point scale. A panel median score of >/= 7 constituted 'agreement' for an item; for an item to reach 'consensus', a panel majority scoring was required. RESULTS: Consensus was reached on 59% of items (208/354); these were used to provide recommendations for the implementation of prostate mpMRI in the UK. Key findings include prostate mpMRI requests should be made in consultation with the urological team; mpMRI scanners should undergo quality assurance checks to guarantee consistently high diagnostic quality scans; scans should only be reported by trained and experienced radiologists to ensure that men with non-suspicious prostate mpMRI might consider avoiding an immediate biopsy. CONCLUSIONS: Our consensus statements demonstrate a set of criteria that are required for the practical dissemination of consistently high quality prostate mpMRI as a diagnostic test prior to biopsy in men at risk. This article is protected by copyright. All rights reserved.

Journal article

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