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Although multiparametric magnetic resonance imaging (MRI) has high sensitivity, its lower specificity leads to a high prevalence of false-positive lesions requiring biopsy.To develop and externally validate a scoring system for MRI-detected Prostate Imaging Reporting and Data System (PIRADS)/Likert ≥3 lesions containing clinically significant prostate cancer (csPCa).The multicentre Rapid Access to Prostate Imaging and Diagnosis (RAPID) pathway included 1189 patients referred to urology due to elevated age-specific prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE); April 27, 2017 to October 25, 2019.Visual-registration or image-fusion targeted and systematic transperineal biopsies for an MRI score of ≥4 or 3 + PSA density ≥0.12 ng/ml/ml.Fourteen variables were used in multivariable logistic regression for Gleason ≥3 + 4 (primary) and Gleason ≥4 + 3, and PROMIS definition 1 (any ≥4 + 3 or ≥6 mm any grade; secondary). Nomograms were created and a decision curve analysis (DCA) was performed. Models with varying complexity were externally validated in 2374 patients from six international cohorts.The five-item Imperial RAPID risk score used age, PSA density, prior negative biopsy, prostate volume, and highest MRI score (corrected c-index for Gleason ≥3 + 4 of 0.82 and 0.80-0.86 externally). Incorporating family history, DRE, and Black ethnicity within the eight-item Imperial RAPID risk score provided similar outcomes. The DCA showed similar superiority of all models, with net benefit differences increasing in higher threshold probabilities. At 20%, 30%, and 40% of predicted Gleason ≥3 + 4 prostate cancer, the RAPID risk score was able to reduce, respectively, 11%, 21%, and 31% of biopsies against 1.8%, 6.2%, and 14% of missed csPCa (or 9.6%, 17%, and 26% of foregone biopsies, respectively).The Imperial RAPID risk score provides a standardised tool for the prediction of csPCa in patients with an MRI-detected PIRADS/Likert ≥3 lesion and can support the decision for prostate biopsy.In this multinational study, we developed a scoring system incorporating clinical and magnetic resonance imaging characteristics to predict which patients have prostate cancer requiring treatment and which patients can safely forego an invasive prostate biopsy. This model was validated in several other countries.

Background False positive multiparametric magnetic resonance imaging (mpMRI) phenotypes prompt unnecessary biopsies. The Prostate MRI Imaging Study (PROMIS) provides a unique opportunity to explore such phenotypes in biopsy-naïve men with raised prostate-specific antigen (PSA) and suspected cancer. Objective To compare mpMRI lesions in men with/without significant cancer on transperineal mapping biopsy (TPM). Design, setting, and participants PROMIS participants (n = 235) underwent mpMRI followed by a combined biopsy procedure at University College London Hospital, including 5-mm TPM as the reference standard. Patients were divided into four mutually exclusive groups according to TPM findings: (1) no cancer, (2) insignificant cancer, (3) definition 2 significant cancer (Gleason ≥3 + 4 of any length and/or maximum cancer core length ≥4 mm of any grade), and (4) definition 1 significant cancer (Gleason ≥4 + 3 of any length and/or maximum cancer core length ≥6 mm of any grade). Outcome measurements and statistical analysis Index and/or additional lesions present in 178 participants were compared between TPM groups in terms of number, conspicuity, volume, location, and radiological characteristics. Results and limitations Most lesions were located in the peripheral zone. More men with significant cancer had two or more lesions than those without significant disease (67% vs 37%; p, Take Home Message Significant cancer-associated magnetic resonance imaging lesions in biopsy-naïve men with suspected prostate cancer are larger, more conspicuous, and more diffusion restricted than false positives. Prostate-specific antigen density and apparent diffusion coefficient are predictors of significant disease, and could help guide decisions to biopsy men with indeterminate phenotypes.

Background Multiparametric magnetic resonance imaging (MP-MRI) is established in the diagnosis of prostate cancer, but the need for enhanced sequences has recently been questioned. Objective To assess whether dynamic contrast-enhanced imaging (DCE) improves accuracy over T2 and diffusion sequences. Design, setting, and participants PROMIS was a multicentre, multireader trial, with, in this part, 497 biopsy-naive men undergoing standardised 1.5T MP-MRI using T2, diffusion, and DCE, followed by a detailed transperineal prostate mapping (TPM) biopsy at 5 mm intervals. Likert scores of 1–5 for the presence of a significant tumour were assigned in strict sequence, for (1) T2 + diffusion and then (2) T2 + diffusion + dynamic contrast-enhanced images. Outcome measurements and statistical analysis For the primary analysis, the primary PROMIS outcome measure (Gleason score ≥4 + 3 or ≥6 mm maximum cancer length) on TPM was used, and an MRI score of ≥3 was considered positive. Results and limitations Sensitivity without and with DCE was 94% and 95%, specificity 37% and 38%, positive predictive value 51% and 51%, and negative predictive value 90% and 91%, respectively (p > 0.05 in each case). The number of patients avoiding biopsy (scoring 1–2) was similar (123/497 vs 121/497, p = 0.8). The number of equivocal scores (3/5) was slightly higher without DCE (32% vs 28% p = 0.031). The proportion of MRI equivocal (3/5) and positive (4–5) cases showing significant tumours were similar (23% and 71% vs 20% and 69%). No cases of dominant Gleason 4 or higher were missed with DCE, compared with a single case with T2 + diffusion-weighted imaging. No attempt was made to correlate lesion location on MRI and histology, which may be considered a limitation. Radiologists were aware of the patient’s prostate-specific antigen. Conclusions Contrast adds little when MP-MRI is used to exclude significant prostate cancer. Patient summary An intravenous injection of contrast may not be necessary when magnetic resonance imaging is used as a test to rule out significant tumours in the prostate.

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

BACKGROUND: Recurrent prostate cancer after radiotherapy occurs in one in five patients. The efficacy of prostate magnetic resonance imaging (MRI) in recurrent cancer has not been established. Furthermore, high-quality data on new minimally invasive salvage focal ablative treatments are needed. OBJECTIVE: To evaluate the role of prostate MRI in detection of prostate cancer recurring after radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: The FORECAST trial was both a paired-cohort diagnostic study evaluating prostate multiparametric MRI (mpMRI) and MRI-targeted biopsies in the detection of recurrent cancer and a cohort study evaluating focal ablation at six UK centres. A total of 181 patients were recruited, with 155 included in the MRI analysis and 93 in the focal ablation analysis. INTERVENTION: Patients underwent choline positron emission tomography/computed tomography and a bone scan, followed by prostate mpMRI and MRI-targeted and transperineal template-mapping (TTPM) biopsies. MRI was reported blind to other tests. Those eligible underwent subsequent focal ablation. An amendment in December 2014 permitted focal ablation in patients with metastases. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes were the sensitivity of MRI and MRI-targeted biopsies for cancer detection, and urinary incontinence after focal ablation. A key secondary outcome was progression-free survival (PFS). RESULTS AND LIMITATIONS: Staging whole-body imaging revealed localised cancer in 128 patients (71%), with involvement of pelvic nodes only in 13 (7%) and metastases in 38 (21%). The sensitivity of MRI-targeted biopsy was 92% (95% confidence interval [CI] 83–97%). The specificity and positive and negative predictive values were 75% (95% CI 45–92%), 94% (95% CI 86–98%), and 65% (95% CI 38–86%), respectively. Four cancer (6%) were missed by TTPM biopsy and six (8%) were missed by MRI-targeted biopsy. The overall MRI sensitivity for detection of any cancer was 94% (95% CI 88–98%). The specificity and positive and negative predictive values were 18% (95% CI 7–35%), 80% (95% CI 73–87%), and 46% (95% CI 19–75%), respectively. Among 93 patients undergoing focal ablation, urinary incontinence occurred in 15 (16%) and five (5%) had a grade ≥3 adverse event, with no rectal injuries. Median follow-up was 27 mo (interquartile range 18–36); overall PFS was 66% (interquartile range 54–75%) at 24 mo. CONCLUSIONS: Patients should undergo prostate MRI with both systematic and targeted biopsies to optimise cancer detection. Focal ablation for areas of intraprostatic recurrence preserves continence in the majority, with good early cancer control. PATIENT SUMMARY: We investigated the role of magnetic resonance imaging (MRI) scans of the prostate and MRI-targeted biopsies in outcomes after cancer-targeted high-intensity ultrasound or cryotherapy in patients with recurrent cancer after radiotherapy. Our findings show that these patients should undergo prostate MRI with both systematic and targeted biopsies and then ablative treatment focused on areas of recurrent cancer to preserve their quality of life.

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.

Background Focal cryotherapy can be used to treat patients with clinically significant nonmetastatic prostate cancer to reduce side effects. Objective Early-medium-term cancer control and functional outcomes. Design, setting, and participants A 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 27.8mo [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. Intervention Focal cryoablation of MR-visible tumours. Outcome measurements and statistical analysis Follow-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 limitations A 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 68.7yr (IQR 64.9–73.8) and preoperative PSA 10.8ng/ml (IQR 7.8–15.6). Overall FFS at 3yr 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. Conclusions Focal cryotherapy primarily for anterior intermediate and high-risk prostate cancer results in good rates of cancer control and low rates of treatment-related side effects. Patient summary In this multicentre study of 122 patients undergoing focal cryotherapy for medium- to high-risk prostate cancer, at 3yr, no patient died from their cancer whilst failure-free survival, was approximately 90%. None of the patients needed pads for managing urine leakage, although 16% had erection problems.

ReIMAGINE represents the first efforts to define prostate cancer risk using the full spectrum of emerging diagnostics (both commercial and academic). The outputs will provide image-based data sets that will replace, or adjust, historical and flawed risk calculators.

Focal therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment.To report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer.An analysis of 1379 patients with ≥6 mo of follow-up prospectively recorded in the HIFU Evaluation and Assessment of Treatment (HEAT) registry from 13 UK centres (2005-2020) was conducted. Five or more years of follow-up was available for 325 (24%) patients. Focal HIFU therapy used a transrectal ultrasound-guided device (Sonablate; Sonacare Inc., Charlotte, NC, USA).Failure-free survival (FFS) was primarily defined as avoidance of no evidence of disease to require salvage whole-gland or systemic treatment, or metastases or prostate cancer-specific mortality. Differences in FFS between D'Amico risk groups were determined using a log-rank analysis. Adverse events were reported using Clavien-Dindo classification.The median (interquartile range) age was 66 (60-71) yr and prostate-specific antigen was 6.9 (4.9-9.4) ng/ml with D'Amico intermediate risk in 65% (896/1379) and high risk in 28% (386/1379). The overall median follow-up was 32 (17-58) mo; for those with ≥5 yr of follow-up, it was 82 (72-94). A total of 252 patients had repeat focal treatment due to residual or recurrent cancer; overall 92 patients required salvage whole-gland treatment. Kaplan-Meier 7-yr FFS was 69% (64-74%). Seven-year FFS in intermediate- and high-risk cancers was 68% (95% confidence interval [CI] 62-75%) and 65% (95% CI 56-74%; p = 0.3). Clavien-Dindo2 adverse events occurred in 0.5% (7/1379). The median 10-yr follow-up is lacking.Focal HIFU in carefully selected patients with clinically significant prostate cancer, with six and three of ten patients having, respectively, intermediate- and high-risk cancer, has good cancer control in the medium term.Focal high-intensity focused ultrasound treatment to areas of prostate with cancer can provide an alternative to treating the whole prostate. This treatment modality has good medium-term cancer control over 7 yr, although 10-yr data are not yet available.

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Background All risk stratification strategies in cancer overlook a spectrum of disease. The Prostate MR Imaging Study (PROMIS) provides a unique opportunity to explore cancers that are overlooked by multiparametric magnetic resonance imaging (mpMRI). Objective To summarise attributes of cancers that are systematically overlooked by mpMRI. Design, setting, and participants PROMIS tested performance of mpMRI and transrectal ultrasonography (TRUS)-guided biopsy, using 5 mm template mapping (TPM) biopsy as the reference standard. Outcome measurements and statistical analysis Outcomes were overall and maximum Gleason scores, maximum cancer core length (MCCL), and prostate-specific antigen density (PSAD). Cancer attributes were compared between cancers that were overlooked and those that were detected. Results and limitations Of men with cancer, 7% (17/230; 95% confidence interval [CI] 4.4–12%) had significant disease overlooked by mpMRI according to definition 1 (Gleason ≥ 4 + 3 of any length or MCCL ≥ 6 mm of any grade) and 13% (44/331; 95% CI 9.8–17%) according to definition 2 (Gleason ≥ 3 + 4 of any length or MCCL ≥ 4 mm). In comparison, TRUS-guided biopsy overlooked 52% (119/230; 95% CI 45–58%) of significant disease by definition 1 and 40% (132/331; 95% CI 35–45%) by definition 2. Prostate cancers undetected by mpMRI had significantly lower overall and maximum Gleason scores (p = 0.0007; p 3 + 4 (Gleason Grade Groups 3–5; 95% CI 0–6.4%) or maximum Gleason score > 4 + 3 (Gleason Grade Groups 4–5; 95% CI 0–8.0%) on TPM biopsy were undetected by mpMRI. Application of a PSAD threshold of 0.15 reduced the proportion of men with undetected cancer to 5% (12/230; 95% CI 2.7–8.9%) for definition 1 and 9% (30/331; 95% CI 6.2–13%) for definition 2. Application of a PSAD threshold of 0.10 reduced the proportion of men with undetected disease to 3% (6/230; 95% CI 1.0–5.6%) for definition 1 cancer and to 3% (11/331; 95% CI 1.7–5.9%) for definition 2 cancer. Limitations were post hoc analysis and uncertain significance of undetected lesions. Conclusions Overall, a small proportion of cancers are overlooked by mpMRI, with estimates ranging from 4.4% (lower boundary of 95% CI for definition 1) to 17% (upper boundary of 95% CI for definition 2). Prostate cancers undetected by mpMRI are of lower grade and shorter length than cancers that are detected. Patient summary Prostate cancers that are undetected by magnetic resonance imaging (MRI) are smaller and less aggressive than those that are detected, and none of the most aggressive cancers are overlooked by MRI.

Background Multiparametric magnetic resonance imaging (mpMRI) has improved risk stratification for suspected prostate cancer in patients following prior biopsy. However, not all significant cancers are detected by mpMRI. The PICTURE study provides the ideal opportunity to investigate cancer undetected by mpMRI owing to the use of 5 mm transperineal template mapping (TTPM) biopsy. Objective To summarise attributes of cancers systematically undetected by mpMRI in patients with prior biopsy. Design, setting, and participants PICTURE was a paired-cohort confirmatory study in which men requiring repeat biopsy underwent mpMRI followed by TTPM biopsy. Outcome measurements and statistical analysis Attributes were compared between cancers detected and undetected by mpMRI at the patient level. Four predefined histopathological thresholds were used as the target condition for TTPM biopsy. Application of prostate-specific antigen density (PSAD) was explored. Results and limitations When nonsuspicious mpMRI was defined as Likert score 1–2, 2.9% of patients (3/103; 95% confidence interval [CI] 0.6–8.3%) with definition 1 disease (Gleason ≥ 4 + 3 of any length or maximum cancer core length [MCCL] ≥ 6 mm of any grade) had their cancer not detected by mpMRI. This proportion was 6.5% (11/168; 95% CI 3.3–11%) for definition 2 disease (Gleason ≥ 3 + 4 of any length or MCCL ≥ 4 mm of any grade), 4.8% (7/146; 95% CI 2.0–9.6%) for any amount of Gleason ≥ 3 + 4 cancer, and 9.3% (20/215; 95% CI 5.8–14%) for any cancer. Definition 1 cancers undetected by mpMRI had lower overall Gleason score (p = 0.02) and maximum Gleason score (p = 0.01) compared to cancers detected by mpMRI. Prostate cancers undetected by mpMRI had shorter MCCL than cancers detected by mpMRI for every cancer threshold: definition 1, 6 versus 8 mm (p = 0.02); definition 2, 5 versus 6 mm (p = 0.04); any Gleason ≥ 3 + 4, 5 versus 6 mm (p = 0.03); and any cancer, 3 versus 5 mm (p = 0.0009). A theoretical PSAD threshold of 0.15 ng/ml/ml reduced the proportion of patients with undetected disease on nonsuspicious mpMRI to 0% (0/105; 95% CI 0–3.5%) for definition 1, 0.58% (1/171; 95% CI 0.01–3.2%) for definition 2, and 0% (0/146) for any Gleason ≥ 3 + 4. Conclusions Few significant cancers are undetected by mpMRI in patients requiring repeat prostate biopsy. Undetected tumours are of lower overall and maximum Gleason grade and shorter cancer length compared to cancers detected by mpMRI. Patient summary In patients with a previous prostate biopsy, magnetic resonance imaging (MRI) overlooks few prostate cancers, and these tend to be smaller and less aggressive than cancer that is detected., Take Home Message In men with previous prostate biopsy, few prostate cancers are not detected by multiparametric magnetic resonance imaging (mpMRI), and these are lower in size and grade than prostate cancer that is detected by mpMRI. This further reinforces the role that mpMRI should play in assessment of suspected prostate cancer.

Background High-intensity focused ultrasound (HIFU) is a minimally-invasive treatment for nonmetastatic prostate cancer. Objective To report medium-term outcomes in men receiving primary whole-gland HIFU from a national multi-centre registry cohort. Design, setting, and participants Five-hundred and sixty-nine patients at eight hospitals were entered into an academic registry. Intervention Whole-gland HIFU (Sonablate 500) for primary nonmetastatic prostate cancer. Redo-HIFU was permitted as part of the intervention. Outcome measurements and statistical analysis Our primary failure-free survival outcome incorporated no transition to any of the following: (1) local salvage therapy (surgery or radiotherapy), (2) systemic therapy, (3) metastases, or (4) prostate cancer-specific mortality. Secondary outcomes included adverse events and genitourinary function. Results and limitations Mean age was 65 yr (47–87 yr). Median prostate-specific antigen was 7.0 ng/ml (interquartile range 4.4–10.2). National Comprehensive Cancer Network low-, intermediate-, and high-risk disease was 161 (28%), 321 (56%), and 81 (14%), respectively. One hundred and sixty three of 569 (29%) required a total of 185 redo-HIFU procedures. Median follow-up was 46 (interquartile range 23–61) mo. Failure-free survival at 5 yr after first HIFU was 70% (95% confidence interval [CI]: 64–74). This was 87% (95% CI: 78–93), 63% (95% CI: 56–70), and 58% (95% CI: 32–77) for National Comprehensive Cancer Network low-, intermediate-, and high-risk groups, respectively. Fifty eight of 754 (7.7%) had one urinary tract infection, 22/574 (2.9%) a recurrent urinary tract infection, 22/754 (3%) epididymo-orchitis, 227/754 (30%) endoscopic interventions, 1/754 (0.13%) recto-urethral fistula, and 1/754 (0.13%) osteitis pubis. Of 206 known to be pad-free pre-HIFU, 183/206 (88%) remained pad free, and of 236 with good baseline erectile function, 91/236 (39%) maintained good function. The main limitation is lack of long-term data. Conclusions Whole-gland HIFU is a repeatable day-case treatment that confers low rates of urinary incontinence. Disease control at a median of just under 5 yr of follow-up demonstrates its potential as a treatment for nonmetastatic prostate cancer. Endoscopic interventions and erectile dysfunction rates are similar to other whole-gland treatments. Patient summary In this report we looked at the 5-yr outcomes following whole-gland high-intensity focused ultrasound treatment for prostate cancer and found that cancer control was acceptable with a low risk of urine leakage. However, risk of erectile dysfunction and further operations was similar to other whole-gland treatments like surgery and radiotherapy.

Background Tissue preservation by means of focal therapy offers some men with clinically significant prostate cancer an alternative to standard care that appears to confer favourable genito-urinary outcomes. The precise estimates of these outcomes have so far been based on small series. Objective This analysis pools the sexual domain related patient reported outcomes from three prospective, registered studies that represent a range of inclusion criteria. Design, setting, and participants One-hundred and eighteen men with localised prostate cancer (prostate specific antigen ≤ 15ng/ml, Gleason ≤ 4+3, stage ≤ T3aN0M0) treated in a tissue-preserving manner using high intensity focused ultrasound from three registered studies were included. Data on International Index of Erectile Function (IIEF-5) scores and use of phosphodiesterase-5-inhibitors were collected at baseline, and 1 mo, 3 mo, 6 mo, 9 mo, and 12 mo postoperatively. The IIEF-15 total and individual domain scores were used to assess overall sexual function. Urinary function was assessed with the International Prostate Symptom Score (IPSS), IPSS quality-of-life, and UCLA-Expanded Prostate Cancer Index Composite continence questionnaires. General health status was derived by means of the Charlson score. Multiple linear regression was used to assess whether age, grade, stage, qualitative scores (IIEF, IPSS, Expanded Prostate Cancer Index Composite, Charlson), or focal therapy type duration were associated with IIEF-5 and IIEF-15 scores at 12 mo. Results and limitations Median age was 63 yr (interquartile range [IQR] 52–70 yr). Median IIEF-erectile score at baseline was 23 (IQR 11–28). This declined significantly to 9 (IQR 3–22, p p =0.30) at 1 yr posttreatment. Changes in total IIEF and other IIEF domains were only significantly different from preoperative values at 1 mo and 3 mo postoperatively. In the same period, the proportion of men using phosphodiesterase-5-inhibitors was 10% preoperatively, reaching 43% and 42% at 6 mo and 9 months before declining to 37% at 1 yr. The only baseline determinants of postoperative erectile function were total IIEF and IIEF-erectile function scores ( p =0.002). The primary limitation of our study is the relatively short follow-up of 1 yr. Conclusion Men who received a range of tissue preserving therapies from the three pertinent studies experienced small decreases in total IIEF, erectile, and individual sexual domain scores that are not significantly different to those recorded at baseline. The only determinant of erectile dysfunction after tissue preserving therapy was preoperative erectile dysfunction status. Tissue preservation confers a high probability of maintaining erectile function that appears independent of all perioperative factors with the exception of baseline status. Patient summary In this report, the largest prospectively collected and published set of patients with erectile dysfunction outcomes post–focal therapy for prostate cancer, we have found a return to baseline International Index of Erectile Function–erectile and total International Index of Erectile Function scores by 6 mo post–focal therapy which was maintained at 1 yr, with the majority of patients not on any form of medical treatment for their erectile dysfunction at that point. Focal therapy may represent a suitable alternative for men of any age or comorbidity wishing to maintain erectile function.

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.

Background Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field. Objective To gather expert opinion on patient selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design. Design, setting, and participants Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health. Outcome measurements and statistical analysis Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level. Results and limitations Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging–targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5 mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3 + 3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus. Conclusions The landscape of PCa treatment is rapidly evolving with new treatment technologies. This consensus meeting provides guidance to clinicians on current expert thinking in the field of focal therapy. Patient summary In this report we present expert opinion on patient selection, interventions, and meaningful outcomes for clinicians working in focal therapy for prostate cancer., Take Home Message Focal therapy as an active treatment for prostate cancer is rapidly evolving. Expert opinion gathered in this report using robust consensus methodology captures current thinking and can help direct future research and clinical care.

Clinically significant nonmetastatic prostate cancer (PCa) is currently treated using whole-gland therapy. This approach is effective but can have urinary, sexual, and rectal side effects.To report on 5-yr PCa control following focal high-intensity focused ultrasound (HIFU) therapy to treat individual areas of cancer within the prostate.This was a prospective study of 625 consecutive patients with nonmetastatic clinically significant PCa undergoing focal HIFU therapy (Sonablate) in secondary care centres between January 1, 2006 and December 31, 2015. A minimum of 6-mo follow-up was available for599 patients. Intermediate- or high-risk PCa was found in 505 patients (84%).Disease was localised using multiparametric magnetic resonance imaging (mpMRI) combined with targeted and systematic biopsies, or transperineal mapping biopsies. Areas of significant disease were treated. Follow-up included prostate-specific antigen (PSA) measurement, mpMRI, and biopsies.The primary endpoint, failure-free survival (FFS), was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality.The median follow-up was 56 mo (interquartile range [IQR] 35-70). The median age was 65 yr (IQR 61-71) and median preoperative PSA was 7.2 ng/ml (IQR 5.2-10.0). FFS was 99% (95% confidence interval [CI] 98-100%) at 1 yr, 92% (95% CI 90-95%) at 3 yr, and 88% (95% 85-91%) at 5 yr. For the whole patient cohort, metastasis-free, cancer-specific, and overall survival at 5 yr was 98% (95% CI 97-99%), 100%, and 99% (95% CI 97-100%), respectively. Among patients who returned validated questionnaires, 241/247 (98%) achieved complete pad-free urinary continence and none required more than 1 pad/d. Limitations include the lack of long-term follow-up.Focal therapy for select patients with clinically significant nonmetastatic prostate cancer is effective in the medium term and has a low probability of side effects.In this multicentre study of 625 patients undergoing focal therapy using high-intensity focused ultrasound (HIFU), failure-free survival, metastasis-free survival, cancer-specific survival, and overall survival were 88%, 98%, 100%, and 99%, respectively. Urinary incontinence (any pad use) was 2%. Focal HIFU therapy for patients with clinically significant prostate cancer that has not spread has a low probability of side effects and is effective at 5 yr.

Item does not contain fulltext BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) may have a role in detecting clinically significant prostate cancer in men with raised serum prostate-specific antigen levels. Variations in technique and the interpretation of images have contributed to inconsistency in its reported performance characteristics. OBJECTIVE: Our aim was to make recommendations on a standardised method for the conduct, interpretation, and reporting of prostate mpMRI for prostate cancer detection and localisation. DESIGN, SETTING, AND PARTICIPANTS: A consensus meeting of 16 European prostate cancer experts was held that followed the UCLA-RAND Appropriateness Method and facilitated by an independent chair. MEASUREMENT: Before the meeting, 520 items were scored for "appropriateness" by panel members, discussed face to face, and rescored. RESULTS AND LIMITATIONS: Agreement was reached in 67% of 260 items related to imaging sequence parameters. T2-weighted, dynamic contrast-enhanced, and diffusion-weighted MRI were the key sequences incorporated into the minimum requirements. Consensus was also reached on 54% of 260 items related to image interpretation and reporting, including features of malignancy on individual sequences. A 5-point scale was agreed on for communicating the probability of malignancy, with a minimum of 16 prostatic regions of interest, to include a pictorial representation of suspicious foci. Limitations relate to consensus methodology. Dominant personalities are known to affect the opinions of the group and were countered by a neutral chairperson. CONCLUSIONS: Consensus was reached on a number of areas related to the conduct, interpretation, and reporting of mpMRI for the detection, localisation, and characterisation of prostate cancer. Before optimal dissemination of this technology, these outcomes will require formal validation in prospective trials.

Objectives: We review important aspects of nanotechnology, and discuss the wide range of research and clinical applications of nanomedicine in the field of urology. There is particular emphasis on key clinical and pre-clinical studies to provide an update on recent and potential applications in the care of urological patients. Methods: A directed Medline literature review of nanotechnology was performed. Important publications that have shaped our understanding of nanotechnology were selected for review and were augmented by manual searches of reference lists. Results: Nanotechnology is the study, design, creation, synthesis, manipulation, and application of functional materials, devices, and systems through control of matter at the nanometer scale. Studies demonstrate a number of important concepts. These include nanovectors, nanotubes, and nanosensors for targeted drug delivery; nanowires and nanocantilever arrays for early detection of precancerous and malignant lesions; and nanopores for DNA sequencing. These advances will lead to significant applications relevant to the diagnosis, management, and treatment of all urological conditions. Conclusions: This review is designed for the urologist to provide an overview and update on nanotechnology and its applications in the field of urology. In the future, it is widely expected that nanotechnology and nanomedicine will have a significant impact on urological research and clinical practice, allowing urologists to intervene at the cellular and molecular level. With structured, safe implementation, nanotechnologies have the potential to revolutionise urological practice in our lifetime.

Background Although localised prostate cancer is multifocal in most instances, the index lesion might be responsible for disease progression. Objective To determine the early genitourinary functional and cancer control outcomes of index lesion ablation. Design, setting, and participants This was a single-centre prospective development study in which 56 men were treated (July 2009–January 2011). The mean age was 63.9 yr (standard deviation 5.8) and median prostate-specific antigen (PSA) was 7.4 ng/ml (interquartile range [IQR] 5.6–9.5). There were seven (12.5%) low-risk, 47 (83.9%) intermediate-risk, and two (3.6%) high-risk cancers. Intervention Multiparametric magnetic resonance imaging (mpMRI) and prostate biopsies to localise disease, followed by index lesion ablation using high-intensity focused ultrasound. Outcome measurements and statistical analysis Primary outcomes were genitourinary side effects measured using validated questionnaires. Secondary outcomes included absence of clinically significant disease at 12 mo. Results and limitations The composite of leak-free, pad-free continence, and erections sufficient for penetration decreased from a baseline frequency of 40/56 (71.4%) to 33/56 (58.9%) at 12 mo. Pad-free and leak-free, pad-free continence was preserved in 48/52 (92.3%) and 46/50 (92.0%) patients, respectively. Erections sufficient for intercourse were preserved in 30/39 (76.9%) patients. The median PSA nadir decreased to 2.4 ng/ml (IQR 1.6–4.1). At 12 mo, 42/52 (80.8%) patients had histological absence of clinically significant cancer and 85.7% (48/56) had no measurable prostate cancer (biopsy and/or mpMRI). Two (3.6%) patients had clinically significant disease in untreated areas not detected at baseline. The main study limitation is the short follow-up duration. Conclusions Index lesion ablation had low rates of genitourinary side effects and acceptable short-term absence of clinically significant cancer. Comparative effectiveness trials are required to assess cancer control outcomes against radical therapy. Patient summary In this study we looked at whether it is possible to treat the largest and highest-grade tumour in men who have more than one known prostate tumour. We show that the side effects of targeted ablation were low, with acceptable rates of early cancer control. Larger studies with longer follow-up are needed. Trial registration NCT00988130

Context The current standard for diagnosing prostate cancer in men at risk relies on a transrectal ultrasound–guided biopsy test that is blind to the location of the cancer. To increase the accuracy of this diagnostic pathway, a software-based magnetic resonance imaging–ultrasound (MRI-US) fusion targeted biopsy approach has been proposed. Objective Our main objective was to compare the detection rate of clinically significant prostate cancer with software-based MRI-US fusion targeted biopsy against standard biopsy. The two strategies were also compared in terms of detection of all cancers, sampling utility and efficiency, and rate of serious adverse events. The outcomes of different targeted approaches were also compared. Evidence acquisition We performed a systematic review of PubMed/Medline, Embase (via Ovid), and Cochrane Review databases in December 2013 following the Preferred Reported Items for Systematic reviews and Meta-analysis statement. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Evidence synthesis Fourteen papers reporting the outcomes of 15 studies ( n =2293; range: 13–582) were included. We found that MRI-US fusion targeted biopsies detect more clinically significant cancers (median: 33.3% vs 23.6%; range: 13.2–50% vs 4.8–52%) using fewer cores (median: 9.2 vs 37.1) compared with standard biopsy techniques, respectively. Some studies showed a lower detection rate of all cancer (median: 50.5% vs 43.4%; range: 23.7–82.1% vs 14.3–59%). MRI-US fusion targeted biopsy was able to detect some clinically significant cancers that would have been missed by using only standard biopsy (median: 9.1%; range: 5–16.2%). It was not possible to determine which of the two biopsy approaches led most to serious adverse events because standard and targeted biopsies were performed in the same session. Software-based MRI-US fusion targeted biopsy detected more clinically significant disease than visual targeted biopsy in the only study reporting on this outcome (20.3% vs 15.1%). Conclusions Software-based MRI-US fusion targeted biopsy seems to detect more clinically significant cancers deploying fewer cores than standard biopsy. Because there was significant study heterogeneity in patient inclusion, definition of significant cancer, and the protocol used to conduct the standard biopsy, these findings need to be confirmed by further large multicentre validating studies. Patient summary We compared the ability of standard biopsy to diagnose prostate cancer against a novel approach using software to overlay the images from magnetic resonance imaging and ultrasound to guide biopsies towards the suspicious areas of the prostate. We found consistent findings showing the superiority of this novel targeted approach, although further high-quality evidence is needed to change current practice.

Prostate biopsy is commonly performed for cancer detection and management. The benefits and risks of prostate biopsy are germane to ongoing debates about prostate cancer screening and treatment.To perform a systematic review of complications from prostate biopsy.A literature search was performed using PubMed and Embase, supplemented with additional references. Articles were reviewed for data on the following complications: hematuria, rectal bleeding, hematospermia, infection, pain, lower urinary tract symptoms (LUTS), urinary retention, erectile dysfunction, and mortality.After biopsy, hematuria and hematospermia are common but typically mild and self-limiting. Severe rectal bleeding is uncommon. Despite antimicrobial prophylaxis, infectious complications are increasing over time and are the most common reason for hospitalization after biopsy. Pain may occur at several stages of prostate biopsy and can be mitigated by anesthetic agents and anxiety-reduction techniques. Up to 25% of men have transient LUTS after biopsy, and2% have frank urinary retention, with slightly higher rates reported after transperineal template biopsy. Biopsy-related mortality is rare.Preparation for biopsy should include antimicrobial prophylaxis and pain management. Prostate biopsy is frequently associated with minor bleeding and urinary symptoms that usually do not require intervention. Infectious complications can be serious, requiring prompt management and continued work into preventative strategies.

Background Prostate biopsy parameters are commonly used to attribute cancer risk. A targeted approach to lesions found on imaging may have an impact on the risk attribution given to a man. Objective To evaluate whether, based on computer simulation, targeting of lesions during biopsy results in reclassification of cancer risk when compared with transrectal ultrasound (TRUS) guided biopsy. Design, setting, and participants A total of 107 reconstructed three-dimensional models of whole-mount radical prostatectomy specimens were used for computer simulations. Systematic 12-core TRUS biopsy was compared with transperineal targeted biopsies using between one and five cores. All biopsy strategies incorporated operator and needle deflection error. A target was defined as any lesion ≥0.2 ml. A false-positive magnetic resonance imaging identification rate of 34% was applied. Outcome measurements and statistical analysis Sensitivity was calculated for the detection of all cancer and clinically significant disease. Cases were designated as high risk based on achieving ≥6 mm cancer length and/or ≥50% positive cores. Statistical significance (p values) was calculated using both a paired Kolmogorov-Smirnov test and the t test. Results and limitations When applying a widely used biopsy criteria to designate risk, 12-core TRUS biopsy classified only 24% (20 of 85) of clinically significant cases as high risk, compared with 74% (63 of 85) of cases using 4 targeted cores. The targeted strategy reported a significantly higher proportion of positive cores (44% vs 11%; p, Take Home Message Image-directed prostate biopsy results in an increase in risk attribution if traditional criteria (maximum cancer core length, proportion of positive cores) are applied. Targeted biopsy strategies will require new risk stratification models accounting for the increased likelihood of sampling the tumour.