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Khoo C, Miah S, Connor M, et al., 2020, A systematic review of salvage focal therapies for localised non-metastatic radiorecurrent prostate cancer, Translational andrology and urology, Vol: 9, Pages: S489-S499, ISSN: 2223-4691
Although radiotherapy to the prostate for cancer is effective, recurrence occurs in 10–15% within 5 years. Traditional salvage treatments for men with radiorecurrent prostate cancer comprise of watchful waiting (WW) with or without androgen deprivation therapy (ADT) or radical prostatectomy (RP). Neither strategy provides ideal therapeutic ratios. Salvage focal ablation is an emerging option. We performed a systematic review of the Medline and Embase databases for studies reporting outcomes of focal salvage brachytherapy (sBT), cryotherapy (sCT) or high-intensity focused ultrasound (sHIFU) for radiorecurrent prostate cancer (conception to April 2019). Results were screened for inclusion against predetermined eligibility criteria. Certain data were extracted, including rates of biochemical disease-free survival (BDFS), metastasis, conversion to second-line therapies and adverse events. Of a total 134 articles returned from the search, 15 studies (14 case series and 1 comparative study) reported outcomes after focal sBT [5], sCT [7] and sHIFU [3]. Cohort size varied depending on intervention, with eligible studies of sBT being small case series. Median follow-up ranged from 10 to 56 months. Although pre-salvage demographics were similar [median age range, 61–75 years; prostate-specific antigen (PSA) range, 2.8–5.5 ng/mL], there was heterogeneity in patient selection, individual treatment protocols and outcome reporting. At 3 years, BDFS ranged from 61% to 71.4% after sBT, 48.1–72.4% after sCT and 48% after sHIFU. Only studies of sCT reported 5-year BDFS, which ranged from 46.5% to 54.4%. Rates of metastasis were low after all salvage modalities, as were conversion to second-line therapies (although this was poorly reported). Grade 3 adverse events were rare. This systematic review indicates that salvage focal ablation of radiorecurrent prostate cancer provides acceptable oncological outcomes and is well tolerated. Unfortunately, there is hetero
Connor M, Saiful M, Rajiv J, et al., 2020, Value of systematic sampling in an mp-MRI targeted prostate biopsy strategy, Translational andrology and urology, Vol: 9, Pages: S455-S463, ISSN: 2223-4691
The clinical utility of systematic prostate biopsy in addition to multi-parametric magnetic resonance imagining (mp-MRI) targeted biopsy pathways remains unclear. Despite radiological advancements in mp-MRI and utilisation of international standardised reporting systems (i.e., PI-RADS, LIKERT), undetected clinically significant prostate cancer (csPCa) on imaging persists. This has prevented the widespread adoption of an exclusively targeted biopsy approach. The current evidence on csPCa cancer detection rates in mp-MRI targeted alone and combined with a non-targeted systematic sampling is presented. Arguments for and against routine limited systematic sampling as an adjunct to an mp-MRI targeted biopsy are discussed. Our review will report the clinical utility of a combined sampling strategy on csPCa detection rate. The available evidence suggests that we are yet to reach a stage where non-targeted systematic prostate biopsy can be routinely omitted in mp-MRI targeted prostate biopsy pathways. Research should focus on improving the accuracy of mp-MRI, prostate biopsy techniques, and in identifying those men that will most benefit from a combined prostate biopsy. Such strategies may help future urologists reduce the burden of non-targeted cores in modern mp-MRI prostate biopsy pathways.
Tam JO, Ahmed HU, 2020, Targeted and systematic biopsy for the diagnosis and management of prostate cancer — A case for lesion targeted-only biopsies, Clinical Oncology, Vol: 32, Pages: 136-143, ISSN: 0936-6555
For much of the 1990s, transrectal ultrasound systematic biopsy was the standard approach for prostate cancer diagnosis. However, in the past decade multiparametric magnetic resonance imaging, multiparametric ultrasound and image fusion targeting have come to the fore. Here we present the state-of-the-art diagnostic strategies in prostate cancer detection and examine the case for target-only biopsy, as well as the benefits and limitations.
Connor MJ, Shah TT, Horan G, et al., 2020, Cytoreductive treatment strategies for de novo metastatic prostate cancer, NATURE REVIEWS CLINICAL ONCOLOGY, Vol: 17, Pages: 168-182, ISSN: 1759-4774
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- Citations: 24
Eldred-Evans D, Neves JB, Simmons LAM, et al., 2020, The added value of diffusion-weighted images and dynamic contrast-enhancement in multi-parametric MRI for the detection of clinically significant prostate cancer in the PICTURE trial., BJU International, Vol: 125, Pages: 391-398, ISSN: 1464-4096
OBJECTIVE: To determine the additional diagnostic value of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging 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 following a previous non-MRI guided TRUS biopsy underwent a 3-Tesla mpMRI consisting of T2W, DWI and DCE followed by transperineal template prostate mapping (TPM) 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 (AUROC) fanalysis was performed to compare the diagnostic accuracy of each combination. The threshold for a positive mpMRI was set as 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, 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 at AUROC 0.74 (95% CI 0.68-0.80), T2W+DWI at 0.76 (95% CI 0.71-0.82) and T2W+DWI+DCE at 0.77 (95% CI 0.71-0.82) (p=0.55). The AUROCs remained comparable using other definitions of clinically significant disease including UCL/Ahmed 2 (p=0.79), Gleason >/=3+4 (p=0.53) and Gleason >/=4+3 (p=0.53). CONCLUSIONS: Using a 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.
Pye H, Ahmed H, Heavey S, et al., 2020, Evaluation of Proclarix, a prostate cancer risk score, used together with magnetic resonance imaging for the diagnosis of clinically significant prostate cancer, Genitourinary Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
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- Citations: 4
Lovegrove CE, Peters M, Guillaumier S, et al., 2020, Evaluation of functional outcomes following a second focal-HIFU in men with primary localised, non-metastatic prostate cancer; Results from the High Intensity Focused Ultrasound Evaluation and Assessment of Treatment (HEAT) Registry., BJU International, Vol: 125, Pages: 853-860, ISSN: 1464-4096
OBJECTIVES: To assess change in functional outcomes after second focal-HIFU compared to one focal-HIFU treatment. PATIENTS AND METHODS: In this multi-centre study (2005-2016), 821 men underwent focal-HIFU for localised non-metastatic prostate cancer. PROMS on IPSS, pad usage and erectile function (EF-score) were prospectively collected for up to 3 years. Inclusion criteria were men who had completed at least one follow-up questionnaire. The primary outcome was comparison of change in functional outcomes between baseline and follow-up after one focal-HIFU or second focal-HIFU using IPSS, EPIC and IIEF questionnaires. RESULTS: Of 821 men, 654 had one focal-HIFU and 167 had a second focal-HIFU. 355 (54.3%) men undergoing one focal-HIFU and 65 (38.9%) having second focal-HIFU returned follow-up questionnaires, respectively. Mean age and PSA were 66.4 and 65.6 years, and 7.9 and 8.4 ng/ml respectively. After one focal-HIFU, mean change in IPSS was -0.03 (p=0.02) and IIEF (EF-score) -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 compared to baseline IPSS prior to first focal-HIFU 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 second focal-HIFU. Mean change in EF-score after second focal-HIFU 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% new erectile dysfunction. 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 in urinary and erectile function. Data can be used to counsel patients with non-metastatic prostate cancer prior to considering HIFU therapy.
Connor MJ, Winkler M, Ahmed HU, 2020, Survival in Oligometastatic Prostate Cancer-A New Dawn or the Will Rogers Phenomenon?, JAMA ONCOLOGY, Vol: 6, Pages: 185-186, ISSN: 2374-2437
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- Citations: 14
Antonelli M, Johnston EW, Dikaios N, et al., 2020, Machine learning classifiers can predict Gleason pattern 4 prostate cancer with greater accuracy than experienced radiologists (vol 29, pg 4754, 2019), EUROPEAN RADIOLOGY, Vol: 30, Pages: 1295-1295, ISSN: 0938-7994
Cadeddu JA, 2020, Re: Robot-Assisted Radical Prostatectomy after Focal Therapy: Oncological, Functional Outcomes and Predictors of Recurrence., J Urol, Vol: 203
Watson V, McCartan N, Krucien N, et al., 2020, Evaluating the trade-offs men with localised prostate cancer make between the risks and benefits of treatments: the COMPARE study., The Journal of Urology, ISSN: 0022-5347
PURPOSE: COMPARE (COMparing treatment options for ProstAte cancer) aimed to evaluate and quantify the trade-offs patients make between different aspects of active surveillance and definitive therapy. METHODS: A Discrete Choice Experiment (DCE) tool was used to elicit patients' preferences for different treatment characteristics in 34 urology departments. Patients with localised prostate cancer completed the DCE within one week of being diagnosed and before they made treatment decisions. The DCE was pre-tested (N=5) and piloted (n=106) with patients. Patients chose their preferred treatment profile based on six characteristics: treatment type (active surveillance, focal therapy, radical therapy), return to normal activities, erectile function, urinary function, not needing more cancer treatment and 10-15 year cancer-specific survival. Different tools were designed for low-intermediate (n=468) and high-risk (n=166) patients. An error-components conditional logit model was used to estimate preferences and trade-offs between treatment characteristics. RESULTS: Low-intermediate risk patients were willing to trade 6.99% absolute decrease in survival to have active surveillance over definitive therapy. They were willing to trade 0.75%, 0.46% and 0.19% absolute decrease in survival for a one-month reduction in time-to-return to normal activities, and 1% absolute improvements in urinary and sexual function, respectively. High-risk patients were willing to trade 3.10%, 1.04% and 0.41% absolute decrease in survival for a one-month reduction in time-to-return to normal activities and 1% absolute improvements in urinary and sexual function, respectively. CONCLUSIONS: Patients with low-intermediate risk prostate cancer preferred active surveillance to definitive therapy. Patients of all risks were willing to trade-off cancer-specific survival for improved quality-of-life.Registration:clinicaltrials.gov Registration Identifier NCT01177865Funding:Medical Research Council (UK) (gran
Lovegrove C, Miah S, El-Shater Bosaily A, et al., 2020, Comparison of TRUS-Biopsy to transperineal template mapping biopsies stratified by multi-parametric MRI score within the PROMIS trial., The Journal of Urology, Vol: 203, Pages: 100-107, ISSN: 0022-5347
INTRODUCTION: We evaluated performance of transrectal ultrasound-guided systematic (TRUS) biopsy compared to transperineal template mapping (TPM) with a 5mm sampling frame, stratified by MP-MRI Likert score within the PROMIS study. METHODS: Biopsy-naïve men due prostate biopsy for elevated PSA and/or abnormal digital rectal examination underwent MP-MRI, TPM and TRUS biopsies, conducted and reported blind to other test results. Clinically significant prostate cancer (csPCa) was primarily defined as Gleason >/=4+3 or maximum cancer core length (MCCL) >/=6mm of any grade, and secondarily Gleason >/=3+4 or MCCL >/=4mm of any grade. RESULTS: In 41 months, 740 men at 11 centres were recruited; 576 underwent all three tests. Of 150 with MRI score 1-2, 8 (5.1%) had any Gleason >/=3+4 disease on TRUS-biopsy. In 75 where TRUS-biopsy showed Gleason 3+3 of any MCCL, 61/75 (81%) had Gleason 3+4, 8/75 (11%) Gleason 4+3 and 0/75 (0%) Gleason >/=4+5. For definition1 csPCa, TRUS-biopsy sensitivity remained stable and low across MP-MRI Likert scores (35%-52%). For definition2 csPCa and any cancer, sensitivity increased with higher MP-MRI score. Negative predictive value varied due to varying disease prevalence but for all cancer thresholds declined with increasing MP-MRI score. CONCLUSIONS: TRUS-biopsy in the setting of MP-MRI Likert scores 1-2 finds Gleason 3+4 disease in only 1 in 20 men. Further, for any csPCa definition, TRUS-biopsy had poor sensitivity and variable but low NPV across MP-MRI scores. Men undergoing TRUS-biopsy without targeting in the setting of MP-MRI score 3 to 5 should be advised to undergo a repeat (targeted) biopsy.
Ahmed HU, Berge V, Bottomley D, et al., 2020, Correction: Corrigendum: Can we deliver randomized trials of focal therapy in prostate cancer? (Nature Reviews Clinical Oncology, (2014), 11, 8, (482-491), 10.1038/nrclinonc.2014.44), Nature Reviews Clinical Oncology, ISSN: 1759-4774
Nature Reviews Clinical Oncology 11, 482–491 (2014) In the published version of this article, the affiliation and position held by Dr Viktor Berge was incorrectly stated as Professor of Urology and Director of Research at the University Hospital Oslo. Dr Berge is a Consultant Urologist at the Department of Urology, at the Oslo University Hospital.
Khoo CC, Eldred-Evans D, Peters M, et al., 2020, Likert vs PI-RADS v2: a comparison of two radiological scoring systems for detection of clinically significant prostate cancer, 114th Annual Meeting of the American-Urological-Association (AUA), Publisher: WILEY, Pages: 49-55, ISSN: 1464-4096
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- Citations: 25
Mehta P, Antonelli M, Ahmed H, et al., 2020, Decision fusion of 3D convolutional neural networks to triage patients with suspected prostate cancer using volumetric biparametric MRI, Conference on Medical Imaging - Computer-Aided Diagnosis, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, ISSN: 0277-786X
Paliashvili K, Di Maggio F, Ho HMK, et al., 2019, A novel adjuvant drug-device combination tissue scaffold for radical prostatectomy, Drug Delivery, Vol: 26, Pages: 1115-1124, ISSN: 1071-7544
Prostate cancer is a leading cause of death in men and despite improved surgical procedures that aid tumor resection, the risk of recurrence after surgery as a result of positive resection margins remains significant. Adjuvant chemotherapy is often required but this is associated with toxicity. Improved ways of delivering highly toxic chemotherapeutic drugs in a more controlled and targeted manner after the prostate has been removed during surgery could reduce the risk of recurrence and avoid systemic toxicity. The aim of this study was to develop a novel drug-device combination tissue scaffold that can be used to deliver the chemotherapeutic agent, docetaxel, into the tissue cavity that is created following radical prostatectomy. The device component investigated consisted of highly porous, poly(dl-lactide-co-glycolide) microparticles made using thermally induced phase separation. A facile method was established for loading docetaxel with high efficiency within one hour. Sustained drug release was observed from the microparticles when placed into a dynamic system simulating tissue perfusion. The drug released from the microparticles into perfusates collected at regular time intervals inhibited colony formation and exhibited sustained cytotoxicity against 3D spheroids of PC3 prostate cancer cells over 10 days. In conclusion, this study demonstrates the concept of combining docetaxel with the biodegradable microparticles at the point of care is technically feasible for achieving an effective drug-device combination tissue scaffold. This approach could provide an effective new approach for delivering adjuvant chemotherapy following radical prostatectomy.
Adeleke S, Latifoltojar A, Sidhu H, et al., 2019, 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, BMC Medical Imaging, Vol: 19, Pages: 1-11, ISSN: 1471-2342
BackgroundAccurate 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/designThe 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 signif
van Luijtelaar A, Greenwood BM, Ahmed HU, et al., 2019, Focal laser ablation as clinical treatment of prostate cancer: Report from a Delphi consensus project, World Journal of Urology, Vol: 37, Pages: 2147-2153, 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.
Bass EJ, Orczyk C, Grey A, et 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, Vol: 124, Pages: 643-648, 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.
Lovegrove C, Brown L, Miah S, et al., 2019, Comparison of TRUS-biopsy to Transperineal Template Mapping Biopsies Stratified by MRI Score Within the PROMIS trial, International Surgical Conference of the Association-of-Surgeons-in-Training (ASIT), Publisher: WILEY, Pages: 9-10, ISSN: 0007-1323
Shah TT, Peters M, Arya M, et al., 2019, Reply to Zhipeng Mai's Letter to the Editor re: Taimur T. Shah, Max Peters, David Eldred-Evans, et al. Early-Medium-Term Outcomes of Primary Focal Cryotherapy to Treat Nonmetastatic Clinically Significant Prostate Cancer from a Prospective Multicentre Registry. Eur Urol 2019; 76: 98-105, EUROPEAN UROLOGY, Vol: 76, Pages: E63-E64, ISSN: 0302-2838
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Stabile A, Orczyk C, Hosking-Jervis F, et al., 2019, Medium‐term oncological outcomes in a large cohort of men treated with either focal or hemi‐ablation using high‐intensity focused ultrasonography for primary localized prostate cancer, BJU International, Vol: 124, Pages: 431-440, 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
Lovegrove C, Miah S, Servian P, et al., 2019, A Prospective Analysis of Robotic Targeted MRI-US Fusion Prostate Biopsy Using the Centroid Targeting Approach, BRITISH JOURNAL OF SURGERY, Vol: 106, Pages: 154-154, ISSN: 0007-1323
Peters M, van Son MJ, Moerland MA, et 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, Vol: 104, Pages: 1045-1053, ISSN: 0360-3016
PurposeFor the treatment of localized prostate cancer, focal therapy has the potential to cure with fewer side effects than traditional whole-gland treatments. We report an update on toxicity, quality of life (QoL), and tumor control in our magnetic resonance imaging (MRI)-guided ultrafocal high-dose-rate brachytherapy cohort.Methods and MaterialsDisease status was evaluated by systematic biopsies and 3T multiparametric MRI. The brachytherapy implant procedure under fused transrectal ultrasound/MRI guidance was followed by a 1.5 T MRI for contour adjustments and catheter position verification. A single dose of 19 Gy was delivered to the tumor with a margin of 5 mm. Genitourinary (GU) toxicity, gastrointestinal (GI) toxicity, and erectile dysfunction (ED) were graded with the Common Terminology Criteria for Adverse Events version 4.0. QoL was measured with RAND-36, European Organisation for Research and Treatment of Cancer QLQ-C30 and PR25. International Prostate Symptom Scores and International Index of Erectile Function scores were obtained. Prostate-specific antigen level was monitored, with biochemical recurrence defined as nadir + 2 ng/mL (Phoenix).ResultsThirty patients with National Comprehensive Cancer Network low- (13%) to intermediate-risk (87%) 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) and median initial prostate-specific antigen level was 7.3 ng/mL (5.2-8.1). Maximum Gleason score was 4 + 3 = 7 (in 2 patients). All tumors were radiologic (MRI) stage T2. No grade >2 GU or >1 GI toxicity occurred. International Prostate Symptom Scores only deteriorated temporarily. Mild pretreatment ED deteriorated to moderate/severe ED in 50% of patients. Long-term clinically relevant QoL deterioration was seen in sexual activity and tiredness, whereas emotional and cognitive functioning improved. At 4 years, biochemical disease–free survival was 70% (95% conf
Dikaios N, Giganti F, Sidhu HS, et al., 2019, Multi-parametric MRI zone-specific diagnostic model performance compared with experienced radiologists for detection of prostate cancer, European Radiology, Vol: 29, Pages: 4150-4159, 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
Marconi L, Stonier T, Tourinho-Barbosa R, et al., 2019, Robot-assisted radical prostatectomy after focal therapy: oncological, functional outcomes and predictors of recurrence, European Urology, Vol: 76, Pages: 27-30, 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.
Shah TT, Peters M, Eldred-Evans D, et al., 2019, Early-medium medium-term outcomes of primary focal cryotherapy to treat nonmetastatic clinically significant prostate cancer from a prospective multicentre registry, European Urology, Vol: 76, Pages: 98-105, 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
Antonelli M, Johnston EW, Dikaios N, et al., 2019, Machine learning classifiers can predict Gleason pattern 4 prostate cancer with greater accuracy than experienced radiologists, European Radiology, Vol: 29, Pages: 4754-4764, 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
Johnston EW, Latifoltojar A, Sidhu HS, et al., 2019, 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, Vol: 29, Pages: 3159-3169, 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
Johnston EW, Bonet-Carne E, Ferizi U, et al., 2019, VERDICT MRI for prostate cancer: intracellular volume fraction versus apparent diffusion coefficient, Radiology, Vol: 291, Pages: 391-397, ISSN: 0033-8419
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
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