Multicenter Randomized Trial Assessing MRI and Image-guided Biopsy for Suspected Prostate Cancer: The MULTIPROS Study.

Background The optimal diagnostic pathway for prostate cancer (PCa) is evolving, requiring further evaluation in a randomized controlled trial. Purpose To assess the diagnostic accuracy of prebiopsy multiparametric MRI in the identification of clinically significant PCa (csPCa) using radical prostatectomy (RP) specimens as the reference standard, and to test the diagnostic accuracy of combined US and MRI fusion-targeted biopsy with systematic biopsies. Materials and Methods In a prospective randomized controlled trial including university hospitals, men with suspected PCa were recruited between January 2015 and August 2020 to assess the diagnostic accuracy of multiparametric MRI before biopsy in detection of csPCa at biopsy and RP histopathologic structure (primary outcome). Men with lesions suspicious for cancer (Prostate Imaging and Reporting Data System [PI-RADS] ≥3) at multiparametric MRI were first randomized to either systematic random prostate biopsies alone (control group) or US and MRI fusion-targeted biopsies with systematic random prostate biopsies (intervention group) at a one-to-one ratio to compare the diagnostic accuracy of systematic random versus combined fusion with systematic random biopsies (secondary outcome). A subset of recruited participants (n = 89) underwent RP and histologic sectioning. Results There were 582 participants who were eligible to undergo multiparametric MRI (mean age, 65 years ± 6 [SD]). In total, 413 had a PI-RADS score of at least 3 and were randomized into either the intervention group (207 of 413; 50.1%) or control group (206 of 413; 49.9%). The csPCa detection rate in the intervention group was higher, with an adjusted odds ratio of 1.79 (95% CI: 1.14, 2.79; P = .01). A subgroup of 89 men underwent RP (21.5%; 89 of 413). Multiparametric MRI helped correctly identify 131 of 182 csPCa foci in 89 men (sensitivity, 72%; 95% CI: 65, 78). The specificity, positive predictive value, and negative predictive value were 71% (91 of 128), 78% (131 of 168), and 64% (91 of 142), respectively. Conclusion Prebiopsy multiparametric MRI was accurate in the depiction of clinically significant PCa. Combining US and MRI fusion-targeted biopsies with systematic biopsies helped detect more clinically significant lesions than did systematic biopsies alone. Clinical trial registration no. NCT02745496 © RSNA, 2023 Supplemental material is available for this article.

A Systematic Review of Focal Ablative Therapy for Clinically Localised Prostate Cancer in Comparison with Standard Management Options: Limitations of the Available Evidence and Recommendations for Clinical Practice and Further Research.

CONTEXT: The clinical effectiveness of focal therapy (FT) for localised prostate cancer (PCa) remains controversial. OBJECTIVE: To analyse the evidence base for primary FT for localised PCa via a systematic review (SR) to formulate clinical practice recommendations. EVIDENCE ACQUISITION: A protocol-driven, PRISMA-adhering SR comparing primary FT (sub-total, focal, hemi-gland, or partial ablation) versus standard options (active surveillance [AS], radical prostatectomy [RP], or external beam radiotherapy [EBRT]) was undertaken. Only comparative studies with ≥50 patients per arm were included. Primary outcomes included oncological, functional, and quality-of-life outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Eligible SRs were reviewed and appraised (AMSTAR) and ongoing prospective comparative studies were summarised. EVIDENCE SYNTHESIS: Out of 1119 articles identified, four primary studies (1 randomised controlled trial [RCT] and 3 retrospective studies) recruiting 3961 patients and ten eligible SRs were identified. Only qualitative synthesis was possible owing to clinical heterogeneity. Overall, RoB and confounding were moderate to high. An RCT comparing vascular-targeted focal photodynamic therapy (PDT) with AS found a significantly lower rate of treatment failure at 2 yr with PDT. There were no differences in functional outcomes, although PDT was associated with worse transient adverse events. However, the external validity of the study was contentious. A retrospective study comparing focal HIFU with robotic RP found no significant differences in treatment failure at 3 yr, with focal HIFU having better continence and erectile function recovery. Two retrospective cohort studies using Surveillance, Epidemiology and End Results data compared focal laser ablation (FLA) against RP and EBRT, reporting significantly worse oncological outcomes for FLA. The overall data quality and applicability of the primary studies were limited because of clinical heterogeneity, RoB and confounding, lack of long-term data, inappropriate outcome measures, and poor external validity. Virtually all the SRs identified concluded that there was insufficient high-certainty evidence to make definitive conclusions regarding the clinical effectiveness of FT, with the majority of SRs judged to have a low or critically low confidence rating. Eight ongoing prospective comparative studies were identified. Ways of improving the evidence base are discussed. CONCLUSIONS: The certainty of the evidence regarding the comparative effectiveness of FT as a primary treatment for localised PCa was low, with significant uncertainties. Until higher-certainty evidence emerges from robust prospective comparative studies measuring clinically meaningful outcomes at long-term time points, FT should ideally be performed within clinical trials or well-designed prospective cohort studies. PATIENT SUMMARY: We examined the literature to determine the effectiveness of prostate-targeted treatment compared with standard treatments for untreated localised prostate cancer. There was no strong evidence showing that focal treatment compares favourably with standard treatments; consequently, focal treatment is not recommended for routine standard practice.

A Narrative Overview of Active Surveillance for Clinically Localised Prostate Cancer.

BACKGROUND: -Active surveillance (AS) is a strategy employed as an alternative to immediate standard active treatments for patients with low-risk localised prostate cancer (PCa). Active treatments such as radical prostatectomy and radiotherapy are associated with significant adverse effects which impair quality of life. The majority of patients with low-risk PCa undergo a slow and predictable course of cancer growth and do not require immediate curative treatment. AS provides a means to identify and monitor patients with low-risk PCa through regular PSA testing, imaging using MRI scans and regular repeat prostate biopsies. These measures enable the identification of progression, or increase in cancer extent or aggressiveness, which necessitates curative treatment. Alternatively, some patients may choose to leave AS to pursue curative interventions due to anxiety. The main benefit of AS is the avoidance of unnecessary radical treatments for patients at the early stages of the disease, hence avoiding over-treatment, whilst identifying those at risk of progression to be treated actively. The objective of this article is to provide a narrative summary of contemporary practice regarding AS based on a review of the available evidence base and clinical practice guidelines. Elements of discussion include the clinical effectiveness and harms of AS, what AS involves for healthcare professionals, and patient perspectives. The pitfalls and challenges for healthcare professionals are also discussed. DATA SOURCES: We consulted international guidelines, collaborative studies and seminal prospective studies on AS in the management of clinically localised PCa. CONCLUSION: AS is a feasible alternative to radical treatment options for low-risk PCa, primarily as a means of avoiding over-treatment, whilst identifying those who are at risk of disease progression for active treatment. There is emerging data demonstrating the long-term safety of AS as an oncological management strategy. Uncertainties remain regarding variation in definitions, criteria, thresholds and the most effective types of diagnostic interventions pertaining to patient selection, monitoring and reclassification. Efforts have been made to standardise the practice and conduct of AS. As data from high-quality prospective comparative studies mature, the practice of AS will continue to evolve. IMPLICATIONS FOR NURSING PRACTICE: The practice of AS involves a multi-disciplinary team of healthcare professionals consisting of nurses, urologists, oncologists, pathologists and radiologists. Nurses play a prominent role in managing AS programmes, and are closely involved in patient selection and recruitment, counselling, organising and administering diagnostic interventions including prostate biopsies, and ensuring patients' needs are being met throughout the duration of AS.

Predictive factors and oncological outcomes of persistently elevated prostate-specific antigen in patients following robot-assisted radical prostatectomy.

Our aim was to evaluate factors associated with persistently elevated prostate-specific antigen (PSA) and biochemical recurrence following robotic-assisted radical prostatectomy (RARP). The study population (N = 5300) consisted of consecutive patients who underwent RARP for localized prostate cancer by a single surgeon (VP) from January 2008 through July 2013. A query of our Institutional Review Board-approved registry identified 162 men with persistently elevated PSA (group A), defined as PSA level ≥0.1 ng/ml at 6 weeks after surgery, who were compared with rest of the cohort group having undetectable PSA, group B (<0.1 ng/ml). A univariate and multivariate logistic regression analysis was used to evaluate the significant association between various variables and the following: (1) persistently elevated PSA, (2) BCR (PSA value ≥0.2 ng/ml) on follow-up in the persistent PSA group. On multivariate analysis, only the following parameters were significantly associated with persistent PSA after RARP-preoperative [PSA >10 ng/ml (p = 0.01), Gleason Score ≥8 (p = 0.001) and clinical stage(p = 0.001)]; postoperative [pathologic stage (p = 0.001), extraprostatic extension (EPE, p = 0.01), lymph node positivity (p = 0.001), positive surgical margin (PSM, p = 0.02), Gleason score (p = 0.01) and tumor volume percent (p < 0.001)]. The mean follow-up was 38.1 months. The BCR was significantly higher in group A as compared to group B(52.47 vs 7.9 %) respectively; p = 0.01). The mean time to BCR was significantly lesser in group A as compared to group B(8.9 vs 21.1 months respectively; p = 0.01). The BCR-free survival rates at 1 year and 3 years were significantly lower statistically in the persistent PSA group in comparison to other groups (69.7 vs 97.3 % and 48.5 vs 92.1 %, respectively; p = 0.01). On multivariate logistic regression analysis in patients with persistent PSA on follow-up, preoperative PSA >10 ng/ml, postoperative Gleason score ≥8, postoperative stage ≥pT3, positive pelvic lymph nodes, PSM >3 mm and post-RARP PSA doubling time (DT) <10 months (p < 0.001) were significantly associated with BCR. In patients after RARP, factors associated with aggressive disease (high preoperative PSA, Gleason score ≥8, stage ≥T3, PSM, high tumor volume percent and EPE) predict PSA persistence. Although these patients with persistent PSA after RARP are more likely to have BCR and that too earlier than those patients with undetectable PSA after RARP, a significant proportion of these patients (47.53 %) remain free of BCR. This subset of patients is associated with these favorable parameters (preoperative PSA <10 ng/ml, post-RARP PSA DT ≥10 months, postoperative Gleason score <8, pathologic stage 

Safety of selective nerve sparing in high risk prostate cancer during robot-assisted radical prostatectomy.

D'Amico high risk prostate cancer is associated with higher incidence of extra prostatic disease. It is recommended to avoid nerve sparing in high risk patients to avoid residual cancer. We report our intermediate term oncologic and functional outcomes in patients with preoperative D'Amico high risk prostate cancer, who underwent selective nerve sparing robot-assisted radical prostatectomy (RARP). Between Jan 2008 till June 2013, 557 patients underwent RARP for D'Amico high risk prostate cancer. The criteria for nerve sparing were as follows-complete: non palpable disease with <3 cores involvement on prostate biopsy; partial: non palpable disease with <4 cores involvement on prostate biopsy; none: clinically palpable disease with ≥4 cores involvement on prostate biopsy and intraoperative visual cues of locally advanced disease (loss of dissection planes, focal bulge of prostatic capsule). Degree of nerve sparing (NS) was graded intraoperatively by the surgeon independently at either side as side specific margins were assessed to predict subjectivity of the intraoperative judgment. Various data were collected and analyzed. Of 557 patients who underwent RARP 140 underwent complete (group 1), 358 patients underwent partial (group 2), and 59 patients underwent non-nerve-sparing procedure (group 3). There were no difference in preoperative characteristic between the groups (p = 0.678), but group 3 had higher Gleason score sum (p = 0.001), positive cores on biopsy (p = 0.001) and higher t stage (p = 0.001). Postoperatively Extra prostatic extension (p = 0.001), seminal vesicle invasion (p = 0.001), and tumor volume (p < 0.001) were higher in Group 3. Side specific positive surgical margins (PSMs) rates were higher for non-nerve-sparing compared to partial and complete nerve sparing RARP (p < 0.001; overall PSMs = 25.2 %). On univariate and multivariate analysis, nerve sparing did not affect PSMs (p > 0.05). The overall biochemical recurrence (BCR) rate at mean follow-up of 24.3 months was 19.21 %. The continence rate at 3 month was significantly higher in complete NS group in comparison to non-NS group (p = 0.020), however, this difference was not statistically significant at 1 year. Similarly, mean time to continence was significantly lower in complete NS group in comparison to non-NS group (p = 0.030). The potency rate was significantly higher and mean time to potency was significantly lower in complete NS group in comparison to non-NS group (p = 0.010 and 0.020, respectively). In high risk prostate cancer patients, selective nerve sparing during RARP, using the preoperative clinical variables (clinical stage and positive cores on biopsy) and surgeon's intraoperative perception, could provide reasonable intermediate term oncologic, functional outcomes (continence and potency) with acceptable perioperative morbidity and positive surgical margins rate. Use of these preoperative factors and surgeon's intraoperative judgment can appropriately evaluate high risk prostate cancer patients for nerve sparing RARP.

Applications of indocyanine green in robotic urology.

Indocyanine green is a fluorescent molecule with wide ranging applications in minimally invasive urological surgery. This article explores the utility of ICG assisted intraoperative fluorescence in robotic urology.

Current status of various neurovascular bundle-sparing techniques in robot-assisted radical prostatectomy.

Nerve-sparing procedures during robot-assisted radical prostatectomy (RARP) have demonstrated improved postoperative functional outcomes. This article provides an overview of clinically applied prostatic neuro-anatomy, various techniques of nerve sparing (NS), and recent innovations in NS and potency outcomes of NS RARP. We retrieved and reviewed all listed publications within PubMed using keywords: nerve sparing, robotic radical prostatectomy, prostate cancer, outcomes, pelvic neuroanatomy and potency. Studies reporting potency outcomes of NS RARP (comparative and non-comparative) were analysed using the Delphi method with an expert panel of urological robotic surgeons. Herein, we outline the published techniques of NS during RARP. Potency and continence outcomes of individual series are discussed in light of the evidence provided by case series and published trials. The potency outcomes of various comparative and non-comparative series of NS RARP have also been mentioned. There are numerous NS techniques reported for RARP. Each method is complimented with benefits and constrained by idiosyncratic caveats, and thus, careful patient selection, a wise intraoperative clinical judgment and tailored approach for each patient is required, when decision for nerve sparing is made. Further large prospective multi-institutional randomized controlled trials are required to evaluate potency and continence outcomes of these techniques, using a rigid standard patient selection criteria and definition of potency are warranted in the new era of functional outcome-driven research.

Continence outcomes of robot-assisted radical prostatectomy in patients with adverse urinary continence risk factors.

OBJECTIVE: To analyse the continence outcomes of robot-assisted radical prostatectomy (RARP) in suboptimal patients that have challenging continence recovery factors such as enlarged prostates, elderly patients, higher body mass index (BMI), salvage prostatectomy, and bladder neck procedures before RARP. PATIENTS AND METHODS: From January 2008 through November 2012, 4,023 patients underwent RARP by a single surgeon at our institution. Retrospective analysis of prospectively collected data identified 3,362 men who had minimum of 1-year follow-up. This cohort of patients was stratified into six groups: Group I, aged ≥70 years (451 patients); Group II, BMI ≥35 kg/m(2) (197); Group III, prior bladder neck procedures (103); Group IV, prostate weight ≥80 g (280); and Group V, salvage prostatectomy (41). Group VI consisted of patients (2 447) with none of these risk factors. Continence outcomes at follow-up were analysed for all groups. RESULTS: The continence rate at 1 year and mean (sd) time to continence in different groups were: for patients aged ≥70 years, 85.6% and 3.2 (4.5) months; BMI of ≥35 kg/m(2) , 87.8% and 3.1 (4.5) months; prior bladder neck treatment, 82.4% and 3.4 (4.7) months; prostate weight of ≥80 g, 85.8% and 3.3 (4.4) months; salvage procedures, 51.3% and 6.6 (8.3) months; and in Group VI (none of the risk factors), 95.1% and 2.4 (3.2) months. The continence rate was significantly higher in group VI compared with the salvage group (group V) at the different follow-up intervals (P < 0.001). When compared with the other groups (I-IV), the continence rate, although higher, was not statistically significant at the different intervals in group VI (no risk). The mean time to continence was significantly lower in group VI compared with the other groups (I-V; P < 0.001). CONCLUSIONS: This study has shown that selected risk factors adversely affect the time to return of continence after RARP, yet aside from salvage patients, there was no statistically significant difference demonstrated between the adverse-risk groups included. Patients undergoing salvage RP had significantly lower continence rates at the various intervals compared with the other groups. Patients with the risk factors identified should be counselled concerning expectations for achieving urinary continence.

Dehydrated Human Amnion/Chorion Membrane Allograft Nerve Wrap Around the Prostatic Neurovascular Bundle Accelerates Early Return to Continence and Potency Following Robot-assisted Radical Prostatectomy: Propensity Score-matched Analysis.

We present a propensity-matched analysis of patients undergoing placement of dehydrated human amnion/chorion membrane (dHACM) around the neurovascular bundle (NVB) during nerve-sparing (NS) robot-assisted laparoscopic prostatectomy (RARP). From March 2013 to July 2014, 58 patients who were preoperatively potent (Sexual Health Inventory for Men [SHIM] score >19) and continent (no pads) underwent full NS RARP. Postoperative outcomes were analyzed between propensity-matched graft and no-graft groups, including time to return to continence, potency, and biochemical recurrence. dHACM use was not associated with increased operative time or blood loss or negative oncologic outcomes (p>0.500). Continence at 8 wk returned in 81.0% of the dHACM group and 74.1% of the no-dHACM group (p=0.373). Mean time to continence was enhanced in group 1 patients (1.21 mo) versus (1.83 mo; p=0.033). Potency at 8 wk returned in 65.5% of the dHACM patients and 51.7% of the no-dHACM group (p=0.132). Mean time to potency was enhanced in group 1, (1.34 mo), compared to group 2 (3.39 mo; p=0.007). Graft placement enhanced mean time to continence and potency. Postoperative SHIM scores were higher in the dHACM group at maximal follow-up (mean score 16.2 vs 9.1). dHACM allograft use appears to hasten the early return of continence and potency in patients following RARP.

Complications following artificial urinary sphincter placement after radical prostatectomy and radiotherapy: a meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of artificial urinary sphincter (AUS) placement after radical prostatectomy (RP) and external beam radiotherapy (EBRT). PATIENTS AND METHODS: There were 1 886 patients available for analysis of surgical revision outcomes and 949 for persistent urinary incontinence (UI) outcomes from 15 and 11 studies, respectively. The mean age (sd) was 66.9 (1.4) years and the number of patients per study was 126.6 (41.7). The mean (sd, range) follow-up was 36.7 (3.9, 18-68) months. A systematic database search was conducted using keywords, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Published series of AUS implantations were retrieved, according to the inclusion criteria. The Newcastle-Ottawa Score was used to ascertain the quality of evidence for each study. Surgical results from each case series were extracted. Data were analysed using CMA statistical software. RESULTS: AUS revision was higher in RP + EBRT vs RP alone, with a random effects risk ratio of 1.56 (95% confidence interval [CI] 1.02-2.72; P < 0.050; I(2) = 82.0%) and a risk difference of 16.0% (95% CI 2.05-36.01; P < 0.080). Infection/erosion contributed to the majority of surgical revision risk compared with urethral atrophy (P = 0.020). Persistent UI after implantation was greater in patients treated with EBRT (P < 0.001). CONCLUSIONS: Men receiving RP + EBRT appear at increased risk of infection/erosion and urethral atrophy, resulting in a greater risk of surgical revision compared with RP alone. Persistent UI is more common with RP + EBRT.

Surgical and procedural skills training at medical school - a national review.

This national study quantifies procedural and surgical skills training at medical schools in the United Kingdom (UK), a stipulated requirement of all graduates by the General Medical Council (GMC). A questionnaire recorded basic procedural and surgical skills training provided by medical schools and surgical societies in the UK. Skills were extracted from (1) GMC Tomorrows Doctors and (2) The Royal College of Surgeons Intercollegiate Basic Surgical Skills (BSS) course. Data from medical school curricula and extra-curricular student surgical societies were compared against the national GMC guidelines and BSS course content. Data were analysed using Mann-Whitney U tests. Representatives from 23 medical schools completed the survey (71.9% response). Thirty one skills extracted from the BSS course were split into 5 categories, with skills content cross referenced against GMC documentation. Training of surgical skills by medical schools was as follows: Gowning and gloving (72.8%), handling instruments (29.4%), knot tying (17.4%), suturing (24.7%), other surgical techniques (4.3%). Surgical societies provided significantly more training of knot tying (64.4%, P = 0.0013) and suturing (64.5%, P = 0.0325) than medical schools. Medical schools provide minimal basic surgical skills training, partially supplemented by extracurricular student surgical societies. Our findings suggest senior medical students do not possess simple surgical and procedural skills. Newly qualified doctors are at risk of being unable to safely perform practical procedures, contradicting GMC Guidelines. We propose a National Undergraduate Curriculum in Surgery and Surgical Skills to equip newly qualified doctors with basic procedural skills to maximise patient safety.

Surgical Safety Training of World Health Organization Initiatives.

Undergraduate training in surgical safety is essential to maximize patient safety. This national review quantified undergraduate surgical safety training. Training of 2 international safety initiatives was quantified: (1) World Health Organization (WHO) "Guidelines for Safe Surgery" and (2) Department of Health (DoH) "Principles of the Productive Operating Theatre." Also, 13 additional safety skills were quantified. Data were analyzed using Mann-Whitney U tests. In all, 23 universities entered the study (71.9% response). Safety skills from WHO and DoH documents were formally taught in 4 UK medical schools (17.4%). Individual components of the documents were taught more frequently (47.6%). Half (50.9%) of the additional safety skills identified were taught. Surgical societies supplemented safety training, although the total amount of training provided was less than that in university curricula (P < .0001). Surgical safety training is inadequate in UK medical schools. To protect patients and maximize safety, a national undergraduate safety curriculum is recommended.

Human anatomy: let the students tell us how to teach.

Anatomy teaching methods have evolved as the medical undergraduate curriculum has modernized. Traditional teaching methods of dissection, prosection, tutorials and lectures are now supplemented by anatomical models and e-learning. Despite these changes, the preferences of medical students and anatomy faculty towards both traditional and contemporary teaching methods and tools are largely unknown. This study quantified medical student and anatomy faculty opinion on various aspects of anatomical teaching at the Department of Anatomy, University of Bristol, UK. A questionnaire was used to explore the perceived effectiveness of different anatomical teaching methods and tools among anatomy faculty (AF) and medical students in year one (Y1) and year two (Y2). A total of 370 preclinical medical students entered the study (76% response rate). Responses were quantified and intergroup comparisons were made. All students and AF were strongly in favor of access to cadaveric specimens and supported traditional methods of small-group teaching with medically qualified demonstrators. Other teaching methods, including e-learning, anatomical models and surgical videos, were considered useful educational tools. In several areas there was disharmony between the opinions of AF and medical students. This study emphasizes the importance of collecting student preferences to optimize teaching methods used in the undergraduate anatomy curriculum.