Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy. METHODS: At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes). RESULTS: Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P = 0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis. CONCLUSIONS: After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.).

Patient-Reported Outcomes 12 Years after Localized Prostate Cancer Treatment.

Outcomes after Localized Prostate Cancer TreatmentDonovan et al. present the long-term patient-reported outcomes of 1643 randomly assigned participants in the ProtecT (Prostate Testing for Cancer and Treatment) trial. Functional and quality-of-life impacts of prostatectomy, radiotherapy with neoadjuvant androgen deprivation, and active monitoring are described. Over the trial period from 7 to 12 years, generic quality-of-life scores were similar among all groups, with varying degrees of impact on urinary leakage, sexual function, and fecal leakage depending on the treatment group.

Active monitoring, radical prostatectomy and radical radiotherapy in PSA-detected clinically localised prostate cancer: the ProtecT three-arm RCT.

BACKGROUND: Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments. OBJECTIVES: To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50-69 years. DESIGN: A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up. SETTING: Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK. PARTICIPANTS: Between 2001 and 2009, 228,966 men aged 50-69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring (n = 545), radical prostatectomy (n = 553) or radical radiotherapy (n = 545) and 997 chose a treatment. INTERVENTIONS: The interventions were active monitoring, radical prostatectomy and radical radiotherapy. TRIAL PRIMARY OUTCOME MEASURE: Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants. SECONDARY OUTCOME MEASURES: Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes. RESULTS: There were no statistically significant differences between the groups for 17 prostate cancer-specific (p = 0.48) and 169 all-cause (p = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, n = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, n = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, n = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; p = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring (n = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy (n = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy (n = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; p < 0.001). Radical prostatectomy had the greatest impact on sexual function/urinary continence and remained worse than radical radiotherapy and active monitoring. Radical radiotherapy's impact on sexual function was greatest at 6 months, but recovered somewhat in the majority of participants. Sexual and urinary function gradually declined in the active monitoring group. Bowel function was worse with radical radiotherapy at 6 months, but it recovered with the exception of bloody stools. Urinary voiding and nocturia worsened in the radical radiotherapy group at 6 months but recovered. Condition-specific quality-of-life effects mirrored functional changes. No differences in anxiety/depression or generic or cancer-related quality of life were found. At the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year, the probabilities that each arm was the most cost-effective option were 58% (radical radiotherapy), 32% (active monitoring) and 10% (radical prostatectomy). LIMITATIONS: A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed. CONCLUSIONS: At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years. TRIAL REGISTRATION: Current Controlled Trials ISRCTN20141297. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information.

Prostate cancer is the most common cancer in men and is often found through a blood test called a prostate-specific antigen test and through biopsies of the prostate. Over the years, these tests led to the detection of many small cancers that do not cause harm. Some prostate cancers are harmful, but it is difficult to recognise them early. When cancer is still inside the prostate, the conventional treatments are surgery or radiotherapy, which carry side effects including leaking urine and difficulty getting an erection, so another option is repeat investigations at regular intervals (active monitoring), with treatments given if the cancer progresses. These options needed to be compared in a study called a 'randomised trial' in which men agree to be allocated to one of the three treatments. In the Prostate testing for cancer and Treatment (ProtecT) study, 200,000 men aged 50­69 years were invited to have a prostate-specific antigen test. Of the 82,849 men who agreed to be tested, 1643 of whom had prostate cancer that was still contained in the prostate agreed to be allocated to one of the three treatments. After an average of 10 years of follow-up, 99% of men were alive in each of the treatment groups. However, when compared with active monitoring, surgery and radiotherapy reduced the risk of disease spreading outside the prostate by half. Patients reported that urinary leakage and sexual function were worst with surgery, and sexual and bowel functions were affected by radiotherapy. Men on active monitoring had a gradual decline in their urinary and sexual function, particularly as around half of them later had surgery or radiotherapy. Radiotherapy was the treatment that seemed to be the best value for money. The findings from the Prostate testing for cancer and Treatment (ProtecT) study can help men make decisions about being tested and which treatment to have if they are found to have cancer within the prostate. We now need to find out the longer-term effects of these treatments on how long men live and their quality of life.

Diagnostic evaluation of magnetization transfer and diffusion kurtosis imaging for prostate cancer detection in a re-biopsy population.

OBJECTIVE: To evaluate diffusion kurtosis imaging (DKI) and magnetisation transfer imaging (MTI) compared to standard MRI for prostate cancer assessment in a re-biopsy population. METHODS: Thirty-patients were imaged at 3 T including DKI (Kapp and Dapp) with b-values 150/450/800/1150/1500 s/mm2 and MTI performed with and without MT saturation. Patients underwent transperineal biopsy based on prospectively defined MRI targets. Receiver-operating characteristic (ROC) analyses assessed the parameters and Wilcoxon-signed ranked test assessed relationships between metrics. RESULTS: Twenty patients had ≥ 1 core positive for cancer in a total of 26 MRI targets (Gleason 3+3 in 8, 3+4 in 12, ≥ 4+3 in 6): 13 peripheral (PZ) and 13 transition zone (TZ). The apparent diffusion coefficient (ADC) and Dapp were significantly lower and the Kapp and MT ratio (MTR) significantly higher in tumour versus benign tissue (all p ≤ 0.005); ROC values 0.767-1.000. Normal TZ had: lower ADC and Dapp and higher Kapp and MTR compared to normal PZ. MTR showed a moderate correlation to Kapp (r = 0.570) and Dapp (r = -0.537) in normal tissue but a poor correlation in tumours. No parameter separated low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease for either PZ (p = 0.414-0.825) or TZ (p = 0.148-0.825). CONCLUSION: ADC, Dapp, Kapp and MTR all distinguished benign tissue from tumour, but none reliably differentiated low- from high-grade disease. KEY POINTS: • MTR was significantly higher in PZ and TZ tumours versus normal tissue • K app was significantly lower and D app higher for PZ and TZ tumours • There was no incremental value for DKI/MTI over mono-exponential ADC parameters • No parameter could consistently differentiate low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease • Divergent MTR/DKI values in TZ tumours suggests they offer different functional information.

Aiming for a holistic integrated service for men diagnosed with prostate cancer - Definitions of standards and skill sets for nurses and allied healthcare professionals.

PURPOSE: To establish a comprehensive set of recommendations for the service structure and skill set of nurses and allied healthcare professionals in prostate cancer care. METHODS: Using components of formal consensus methodology, a 30-member multidisciplinary panel produced 53 items for discussion relating to the provision of care for prostate cancer patients by specialist nurses and allied healthcare professionals. Items were developed by two rounds of email correspondence in which, first, items were generated and, second, items refined to form the basis of a consensus meeting which constituted the third round of review. The fourth and final round was an email review of the consensus output. RESULTS: The panel agreed on 33 items that were appropriate for recommendations to be made. These items were grouped under categories of "Environment" and "Patient Pathway" and included comments on training, leadership, communication and quality assessment as well as specific items related to prostate diagnosis clinics, radical treatment clinics and follow-up survivor groups. CONCLUSIONS: Specialist nurses and allied healthcare professionals play a vital role alongside urologists and oncologists to provide care to men with prostate cancer and their families. We present a set of standards and consensus recommendations for the roles and skill-set required for these practitioners to provide gold-standard prostate cancer care. These recommendations could form the basis for development of comprehensive integrated prostate cancer pathways in prostate cancer centres as well as providing guidance for any units treating men with prostate cancer.

Transperineal prostate biopsies for diagnosis of prostate cancer are well tolerated: a prospective study using patient-reported outcome measures.

We aimed to determine short-term patient-reported outcomes in men having general anesthetic transperineal (TP) prostate biopsies. A prospective cohort study was performed in men having a diagnostic TP biopsy. This was done using a validated and adapted questionnaire immediately post-biopsy and at follow-up of between 7 and 14 days across three tertiary referral hospitals with a response rate of 51.6%. Immediately after biopsy 43/201 (21.4%) of men felt light-headed, syncopal, or suffered syncope. Fifty-three percent of men felt discomfort after biopsy (with 95% scoring <5 in a 0-10 scale). Twelve out of 196 men (6.1%) felt pain immediately after the procedure. Despite a high incidence of symptoms (e.g., up to 75% had some hematuria, 47% suffered some pain), it was not a moderate or serious problem for most, apart from hemoejaculate which 31 men suffered. Eleven men needed catheterization (5.5%). There were no inpatient admissions due to complications (hematuria, sepsis). On repeat questioning at a later time point, only 25/199 (12.6%) of men said repeat biopsy would be a significant problem despite a significant and marked reduction in erectile function after the procedure. From this study, we conclude that TP biopsy is well tolerated with similar side effect profiles and attitudes of men to repeat biopsy to men having TRUS biopsies. These data allow informed counseling of men prior to TP biopsy and a benchmark for tolerability with local anesthetic TP biopsies being developed for clinical use.

The influence of prostate-specific antigen density on positive and negative predictive values of multiparametric magnetic resonance imaging to detect Gleason score 7-10 prostate cancer in a repeat biopsy setting.

OBJECTIVES: To evaluate the influence of prostate-specific antigen density (PSAD) on positive (PPV) and negative (NPV) predictive values of multiparametric magnetic resonance imaging (mpMRI) to detect Gleason score ≥7 cancer in a repeat biopsy setting. PATIENTS AND METHODS: Retrospective study of 514 men with previous prostate biopsy showing no or Gleason score 6 cancer. All had mpMRI, graded 1-5 on a Likert scale for cancer suspicion, and subsequent targeted and 24-core systematic image-fusion guided transperineal biopsy in 2013-2015. The NPVs and PPVs of mpMRIs for detecting Gleason score ≥7 cancer were calculated (±95% confidence intervals) for PSAD ≤0.1, 0.1-0.2, ≤0.2 and >0.2 ng/mL/mL, and compared by chi-square test for linear trend. RESULTS: Gleason score ≥7 cancer was detected in 31% of the men. The NPV of Likert 1-2 mpMRI was 0.91 (±0.04) with a PSAD of ≤0.2 ng/mL/mL and 0.71 (±0.16) with a PSAD of >0.2 ng/mL/mL (P = 0.003). For Likert 3 mpMRI, PPV was 0.09 (±0.06) with a PSAD of ≤0.2 ng/mL/mL and 0.44 (±0.19) with a PSAD of >0.2 ng/mL/mL (P = 0.002). PSAD also significantly affected the PPV of Likert 4-5 mpMRI lesions: the PPV was 0.47 (±0.08) with a PSAD of ≤0.2 ng/mL/mL and 0.66 (±0.10) with a PSAD of >0.2 ng/mL/mL (P < 0.001). CONCLUSION: In a repeat biopsy setting, a PSAD of ≤0.2 ng/mL/mL is associated with low detection of Gleason score ≥7 prostate cancer, not only in men with negative mpMRI, but also in men with equivocal imaging. Surveillance, rather than repeat biopsy, may be appropriate for these men. Conversely, biopsies are indicated in men with a high PSAD, even if an mpMRI shows no suspicious lesion, and in men with an mpMRI suspicious for cancer, even if the PSAD is low.

Comparison of initial and tertiary centre second opinion reads of multiparametric magnetic resonance imaging of the prostate prior to repeat biopsy.

OBJECTIVES: To investigate the value of second-opinion evaluation of multiparametric prostate magnetic resonance imaging (MRI) by subspecialised uroradiologists at a tertiary centre for the detection of significant cancer in transperineal fusion prostate biopsy. METHODS: Evaluation of prospectively acquired initial and second-opinion radiology reports of 158 patients who underwent MRI at regional hospitals prior to transperineal MR/untrasound fusion biopsy at a tertiary referral centre over a 3-year period. Gleason score (GS) 7-10 cancer, positive predictive value (PPV) and negative (NPV) predictive value (±95 % confidence intervals) were calculated and compared by Fisher's exact test. RESULTS: Disagreement between initial and tertiary centre second-opinion reports was observed in 54 % of cases (86/158). MRIs had a higher NPV for GS 7-10 in tertiary centre reads compared to initial reports (0.89 ± 0.08 vs 0.72 ± 0.16; p = 0.04), and a higher PPV in the target area for all cancer (0.61 ± 0.12 vs 0.28 ± 0.10; p = 0.01) and GS 7-10 cancer (0.43 ± 0.12 vs 0.2 3 ± 0.09; p = 0.02). For equivocal suspicion, the PPV for GS 7-10 was 0.12 ± 0.11 for tertiary centre and 0.11 ± 0.09 for initial reads; p = 1.00. CONCLUSIONS: Second readings of prostate MRI by subspecialised uroradiologists at a tertiary centre significantly improved both NPV and PPV. Reporter experience may help to reduce overcalling and avoid overtargeting of lesions. KEY POINTS: • Multiparametric MRIs were more often called negative in subspecialist reads (41 % vs 20 %). • Second readings of prostate mpMRIs by subspecialist uroradiologists significantly improved NPV and PPV. • Reporter experience may reduce overcalling and avoid overtargeting of lesions. • Greater education and training of radiologists in prostate MRI interpretation is advised.

Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial.

BACKGROUND: Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. OBJECTIVE: To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. DESIGN, SETTING, AND PARTICIPANTS: Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression. RESULTS AND LIMITATIONS: Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0=5, M1=32) and 305 had locally advanced disease (62%). The median PSA was 17µg/l. Treatments included radical prostatectomy (RP; n=54; 11%), radiotherapy (RT; n=245; 50%), androgen deprivation therapy (ADT; n=122; 25%), other treatments (n=11; 2%), and unknown (n=60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38-0.83; p=0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation. CONCLUSIONS: Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding. PATIENT SUMMARY: Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease.

Robotic assisted laparoscopic radical prostatectomy following transrectal compared to transperineal prostate biopsy: surgical, oncological and functional outcomes.

BACKGROUND: To assess if transperineal prostate (TP) biopsy affects th e outcome of robotic-assisted laparoscopic prostatectomy (RALP), with particular reference to perioperative complications, oncological results and functional outcomes in the early postoperative setting. METHODS: We identified 61 men who had undergone RALP after TP biopsies, from June 2012 to June 2014 and a control group of 120 men who had undergone RALP after conventional TRUS biopsy in the same period. Data was compared from the pre-operative biopsy, peri- and postoperative period, procedural outcomes including histological, oncological and functional outcomes between the groups. RESULTS: The groups had comparable demographics, with matched median ages and PSA levels. There was a higher incidence of Gleason 6 disease detected in the TRUS group (P=0.01). Mean operative time (146 minutes TRUS vs. 158 minutes TP, P=0.133), blood loss (250 mL TRUS vs. 288 mL TP, P=0.462) and intraoperative complications were not significantly different between groups. Median length of stay (1 day) and median catheter duration (7 days) were identical in both cohorts. PSA failure rate at 6 months was similar (11.7% TRUS vs. 9.8% TP, P=0.904). There were no differences in functional outcomes (potency or continence) between groups at 6 month s follow-up. CONCLUSIONS: RALP is safe after TP biopsy with no adverse impact on oncological or short-term functional outcomes.

10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer.

BACKGROUND: The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. METHODS: We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. RESULTS: There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). CONCLUSIONS: At a median of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

Multiparametric Prostate Magnetic Resonance Imaging and Cognitively Targeted Transperineal Biopsy in Patients With Previous Abdominoperineal Resection and Suspicion of Prostate Cancer.

OBJECTIVE: To report our experience with a combination of prostate magnetic resonance imaging (MRI) and transperineal ultrasound biopsy for evaluating the prostate in patients with elevated prostate-specific antigen (PSA) who have previously undergone abdominoperineal resection (APR). PATIENTS AND METHODS: We reviewed the records of 11 patients with a history of APR and clinical suspicion of prostate cancer due to elevated PSA levels over a 5-year period. All patients underwent multiparametric MRI at our institution prior to biopsy. MR diagnoses were validated either by transperineal ultrasound biopsy (Likert 3-5) guided by visual registration or clinical follow-up >6 months (Likert 1-2). RESULTS: All 7 cases with highly suspicious lesions (Likert 4-5) on MRI demonstrated cancer-1 case of Gleason 3 + 3 and 6 cases of Gleason ≥3 + 4 disease. Two cases with Likert 3 MR lesions revealed benign tissue upon biopsy. Two patients with no suspicious lesions on MRI were followed-up clinically, with PSA levels remaining stable over a mean period of 17.5 months (range 7-28 months). CONCLUSION: The use of prebiopsy multiparametric prostate MRI and subsequent cognitively targeted transperineal biopsy guided by visual registration can aid in the diagnostic pathway of patients with APR and a suspicion of prostate cancer.

Magnetic Resonance and Ultrasound Image Fusion Supported Transperineal Prostate Biopsy Using the Ginsburg Protocol: Technique, Learning Points, and Biopsy Results.

BACKGROUND: Prostate biopsy supported by transperineal image fusion has recently been developed as a new method to the improve accuracy of prostate cancer detection. OBJECTIVE: To describe the Ginsburg protocol for transperineal prostate biopsy supported by multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound (TRUS) image fusion, provide learning points for its application, and report biopsy results. The article is supplemented by a Surgery in Motion video. DESIGN, SETTING, AND PARTICIPANTS: This single-centre retrospective outcome study included 534 patients from March 2012 to October 2015. A total of 107 had no previous prostate biopsy, 295 had benign TRUS-guided biopsies, and 159 were on active surveillance for low-risk cancer. SURGICAL PROCEDURE: A Likert scale reported mpMRI for suspicion of cancer from 1 (no suspicion) to 5 (cancer highly likely). Transperineal biopsies were obtained under general anaesthesia using BiopSee fusion software (Medcom, Darmstadt, Germany). All patients had systematic biopsies, two cores from each of 12 anatomic sectors. Likert 3-5 lesions were targeted with a further two cores per lesion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Any cancer and Gleason score 7-10 cancer on biopsy were noted. Descriptive statistics and positive predictive values (PPVs) and negative predictive values (NPVs) were calculated. RESULTS AND LIMITATIONS: The detection rate of Gleason score 7-10 cancer was similar across clinical groups. Likert scale 3-5 MRI lesions were reported in 378 (71%) of the patients. Cancer was detected in 249 (66%) and Gleason score 7-10 cancer was noted in 157 (42%) of these patients. PPV for detecting 7-10 cancer was 0.15 for Likert score 3, 0.43 for score 4, and 0.63 for score 5. NPV of Likert 1-2 findings was 0.87 for Gleason score 7-10 and 0.97 for Gleason score ≥4+3=7 cancer. Limitations include lack of data on complications. CONCLUSIONS: Transperineal prostate biopsy supported by MRI/TRUS image fusion using the Ginsburg protocol yielded high detection rates of Gleason score 7-10 cancer. Because the NPV for excluding Gleason score 7-10 cancer was very high, prostate biopsies may not be needed for all men with elevated prostate-specific antigen values and nonsuspicious mpMRI. PATIENT SUMMARY: We present our technique to sample (biopsy) the prostate by the transperineal route (the area between the scrotum and the anus) to detect prostate cancer using a fusion of magnetic resonance and ultrasound images to guide the sampling.

Defining the learning curve for multiparametric magnetic resonance imaging (MRI) of the prostate using MRI-transrectal ultrasonography (TRUS) fusion-guided transperineal prostate biopsies as a validation tool.

OBJECTIVES: To determine the accuracy of multiparametric magnetic resonance imaging (mpMRI) during the learning curve of radiologists using MRI targeted, transrectal ultrasonography (TRUS) guided transperineal fusion biopsy (MTTP) for validation. PATIENTS AND METHODS: Prospective data on 340 men who underwent mpMRI (T2-weighted and diffusion-weighted MRI) followed by MTTP prostate biopsy, was collected according to Ginsburg Study Group and Standards for Reporting of Diagnostic Accuracy standards. MRI data were reported by two experienced radiologists and scored on a Likert scale. Biopsies were performed by consultant urologists not 'blinded' to the MRI result and men had both targeted and systematic sector biopsies, which were reviewed by a dedicated uropathologist. The cohorts were divided into groups representing five consecutive time intervals in the study. Sensitivity and specificity of positive MRI reports, prostate cancer detection by positive MRI, distribution of significant Gleason score and negative MRI with false negative for prostate cancer were calculated. Data were sequentially analysed and the learning curve was determined by comparing the first and last group. RESULTS: We detected a positive mpMRI in 64 patients from Group A (91%) and 52 patients from Group E (74%). The prostate cancer detection rate on mpMRI increased from 42% (27/64) in Group A to 81% (42/52) in Group E (P < 0.001). The prostate cancer detection rate by targeted biopsy increased from 27% (17/64) in Group A to 63% (33/52) in Group E (P < 0.001). The negative predictive value of MRI for significant cancer (>Gleason 3+3) was 88.9% in Group E compared with 66.6% in Group A. CONCLUSION: We demonstrate an improvement in detection of prostate cancer for MRI reporting over time, suggesting a learning curve for the technique. With an improved negative predictive value for significant cancer, decision for biopsy should be based on patient/surgeon factors and risk attributes alongside the MRI findings.

Targeted transperineal biopsy of the prostate has limited additional benefit over background cores for larger MRI-identified tumors.

PURPOSE: To compare histological outcomes in patients undergoing MRI-transrectal ultrasound fusion transperineal (MTTP) prostate biopsy and determine the incremental benefit of targeted cores. METHODS: Seventy-six consecutive patients with 89 MRI-identified targets underwent MTTP biopsy. Separate targeted biopsies and background cores were obtained according to a standardized protocol. Target biopsies were considered of added diagnostic value if these cores showed a higher Gleason grade than non-targeted cores taken from the same sector (Group 1, n = 41). Conversely, where background cores demonstrated an equal or higher Gleason grade, target cores were considered to be non-beneficial (Group 2, n = 48). RESULTS: There was no significant difference in age, PSA, prostate volume, time-to-biopsy, and number of cores obtained between the groups. A greater proportion of target cores were positive for cancer (158/228; 69.3 %) compared to background (344/1881; 18.38 %). The median target volume was 0.54 cm(3) for Group 1 (range 0.09-2.79 cm(3)) and 1.65 cm(3) for Group 2 (0.3-9.07 cm(3)), p < 0.001. The targets in Group 1 had statistically lower diameters for short and long axes, even after correction for gland size. The highest area under the receiver operating characteristic curve was demonstrated when a lesion cutoff value of 1.0 cm in short axis was applied, resulting in a sensitivity of 83.3 % and a specificity of 82.9 %. CONCLUSIONS: When a combined systematic and targeted transperineal prostate biopsy is performed, there is limited benefit in acquiring additional cores from larger-volume targets with a short axis diameter >1.0 cm.

Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline.

OBJECTIVES: To improve awareness and recognition of chronic bacterial prostatitis (CBP) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) among non-specialists and patients. To provide guidance to healthcare professionals treating patients with CBP and CP/CPPS, in both non-specialist and specialist settings. To promote efficient referral of care between non-specialists and specialists and the involvement of the multidisciplinary team (MDT). PATIENTS AND METHODS: The guideline population were men with CBP or CP/CPPS (persistent or recurrent symptoms and no other urogenital pathology for ≥3 of the previous 6 months). Consensus recommendations for the guidelines were based on a search to identify literature on the diagnosis and management of CBP and CP/CPPS (published between 1999 and February 2014). A Delphi panel process was used where high-quality, published evidence was lacking. RESULTS: CBP and CP/CPPS can present with a wide range of clinical manifestations. The four main symptom domains are urogenital pain, lower urinary tract symptoms (LUTS - voiding or storage symptoms), psychological issues and sexual dysfunction. Patients should be managed according to their individual symptom pattern. Options for first-line treatment include antibiotics, α-adrenergic antagonists (if voiding LUTS are present) and simple analgesics. Repeated use of antibiotics, such as quinolones, should be avoided if there is no obvious symptomatic benefit from infection control or cultures do not support an infectious cause. Early use of treatments targeting neuropathic pain and/or referral to specialist services should be considered for patients who do not respond to initial measures. An MDT approach (urologists, pain specialists, nurse specialists, specialist physiotherapists, general practitioners, cognitive behavioural therapists/psychologists, and sexual health specialists) is recommended. Patients should be fully informed about the possible underlying causes and treatment options, including an explanation of the chronic pain cycle. CONCLUSION: Chronic prostatitis can present with a wide variety of signs and symptoms. Identification of individual symptom patterns and a symptom-based treatment approach are recommended. Further research is required to evaluate management options for CBP and CP/CPPS.

Investigating the ability of multiparametric MRI to exclude significant prostate cancer prior to transperineal biopsy.

INTRODUCTION: We characterized false negative prostate magnetic resonance imaging (MRI) reporting by using histology derived from MRI-transrectal ultrasound (TRUS)-guided transperineal (MTTP) fusion biopsies. METHODS: In total, 148 consecutive patients were retrospectively reviewed. Men underwent multiparametric MRI (mpMRI), reported by a consultant/attending radiologist in line with European Society of Urogenital Radiology (ESUR) standards. MTTP biopsy of the lesions was performed according to the Ginsburg recommendations. Cases with an MRI-histology mismatch were identified and underwent a second read by an experienced radiologist. A third review was performed with direct histology comparison to determine a true miss from an MRI-occult cancer. Statistical analysis was performed with McNemar's test. RESULTS: False negative lesions were identified in 29 MRI examinations (19.6%), with a total of 46 lesions. Most false negative lesions (21/46) were located in the anterior sectors of the prostate. The second read led to a significant decrease of false-negative lesions with 7/29 further studies identified as positive on a patient-by-patient basis (24.1% of studies, p = 0.016) and 11/46 lesions (23.9%; p = 0.001). Of these, 30 lesions following the first read and 23 lesions after the second read were considered significant cancer according to the University College London criteria. However, on direct comparison with histology, most lesions were MRI occult. CONCLUSION: We demonstrate that MRI can fail to detect clinically relevant lesions. Improved results were achieved with a second read but despite this, a number of lesions remain MRI-occult. Further advances in imaging are required to reduce false negative results.

Evolution of repeat prostate biopsy strategies incorporating transperineal and MRI-TRUS fusion techniques.

PURPOSE: To test the hypothesis that MRI-TRUS fusion technique can increase the detection rate of prostate cancer (PC) in patients with previously negative biopsy. METHODS: Patient records of men with persisting suspicion for PC after previous negative biopsy having undergone either extensive transrectal prostate biopsies (MD Anderson protocol; MDA), transperineal saturation (STP) or magnetic resonance imaging (MRI)/transrectal ultrasound (TRUS) fusion transperineal biopsies (MTTP) in three consecutive time intervals were reviewed retrospectively. The respective approach was the standard for the above indication at these episodes. In Cambridge, 70 patients underwent MDA biopsies, 75 STP underwent biopsies and 74 patients underwent MTTP biopsies. In total, 164 MTTP patients with the same indication from Heidelberg were analysed as reference standard. In total, 383 men were included into analysis. Low-grade PC was defined as Gleason score 7 (3 + 4) or lower. RESULTS: Even though MTTP patients had significantly larger prostates, the overall cancer detection rate for PC was the highest in MTTP (24.2 % MDA, 41.3 % STP, 44.5 % MTTP, p = 0.027, Kruskal-Wallis test). The detection rate for clinically relevant high-grade PC was highest in MTTP; however, this did not reach statistical significance compared with MDA (23.5 % MDA, 12.9 % STP, 27.2 % MTTP, p = 0.25, Fischer's exact test). Comparing MTTP between Cambridge and Heidelberg, detection rates did not differ significantly (44.5 vs. 48 %, p = 0.58). There was a higher detection rate of high-grade cancer in Heidelberg. (36.3 vs. 27.2 %, p = 0.04). CONCLUSION: Patients whom are considered for repeat biopsies may benefit from undergoing MRI-targeted TRUS fusion technique due to higher cancer detection rate of significant PC.

Prostate cancer: performance characteristics of combined T2W and DW-MRI scoring in the setting of template transperineal re-biopsy using MR-TRUS fusion.

OBJECTIVES: To measure the performance characteristics of combined T2-weighted (T2W) and diffusion-weighted (DW) magnetic resonance imaging (MRI) suspicion scoring prior to MR-transrectal ultrasound (TRUS) fusion template transperineal (TTP) re-biopsy. METHODS: Thirty-nine patients referred for prostate re-biopsy, with prior MRI examinations, were retrospectively included. The MR images, including T2W and DW-MRI, had been independently evaluated prospectively by two radiologists using a structured scoring system. An MR-TRUS fusion TTP re-biopsy was used for MR target and non-targeted biopsy cores. Targeting performance and correlation with disease status were evaluated on a per-patient and per-region basis. RESULTS: The cancer yield was 41% (16/39 patients). MR targeting accurately detected the disease in 12/16 (75%) cancerous patients and missed the disease in 4/16 (25%) patients, all with Gleason 3 + 3 disease. There was a significant relationship (P < 0.01) between MR suspicion score and the significance of cancer. Reader 1 had significantly higher sensitivity in the transition zone (TZ; 0.84) compared with the peripheral zone (PZ; 0.32) (P = 0.04). Inter-reader agreement was moderate for the PZ and substantial for the TZ. CONCLUSIONS: MRI targeting is beneficial in the setting of TTP MR-TRUS fusion re-biopsy and MR suspicion score relates to prostate cancer clinical significance. A T2W and DW-MRI structured scoring system results in good inter-reader agreement in this setting. KEY POINTS: • Pre-biopsy MRI aids the detection of high significance cancer during prostate re-biopsy. • MRI suspicion level correlates with the clinical significance of prostate cancer detected. • T2W and DW-MRI structured scoring of pre-biopsy MRI permits good inter-reader agreement.