Artificial intelligence and radiologists in prostate cancer detection on MRI (PI-CAI): an international, paired, non-inferiority, confirmatory study.

BACKGROUND: Artificial intelligence (AI) systems can potentially aid the diagnostic pathway of prostate cancer by alleviating the increasing workload, preventing overdiagnosis, and reducing the dependence on experienced radiologists. We aimed to investigate the performance of AI systems at detecting clinically significant prostate cancer on MRI in comparison with radiologists using the Prostate Imaging-Reporting and Data System version 2.1 (PI-RADS 2.1) and the standard of care in multidisciplinary routine practice at scale. METHODS: In this international, paired, non-inferiority, confirmatory study, we trained and externally validated an AI system (developed within an international consortium) for detecting Gleason grade group 2 or greater cancers using a retrospective cohort of 10 207 MRI examinations from 9129 patients. Of these examinations, 9207 cases from three centres (11 sites) based in the Netherlands were used for training and tuning, and 1000 cases from four centres (12 sites) based in the Netherlands and Norway were used for testing. In parallel, we facilitated a multireader, multicase observer study with 62 radiologists (45 centres in 20 countries; median 7 [IQR 5-10] years of experience in reading prostate MRI) using PI-RADS (2.1) on 400 paired MRI examinations from the testing cohort. Primary endpoints were the sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC) of the AI system in comparison with that of all readers using PI-RADS (2.1) and in comparison with that of the historical radiology readings made during multidisciplinary routine practice (ie, the standard of care with the aid of patient history and peer consultation). Histopathology and at least 3 years (median 5 [IQR 4-6] years) of follow-up were used to establish the reference standard. The statistical analysis plan was prespecified with a primary hypothesis of non-inferiority (considering a margin of 0·05) and a secondary hypothesis of superiority towards the AI system, if non-inferiority was confirmed. This study was registered at ClinicalTrials.gov, NCT05489341. FINDINGS: Of the 10 207 examinations included from Jan 1, 2012, through Dec 31, 2021, 2440 cases had histologically confirmed Gleason grade group 2 or greater prostate cancer. In the subset of 400 testing cases in which the AI system was compared with the radiologists participating in the reader study, the AI system showed a statistically superior and non-inferior AUROC of 0·91 (95% CI 0·87-0·94; p<0·0001), in comparison to the pool of 62 radiologists with an AUROC of 0·86 (0·83-0·89), with a lower boundary of the two-sided 95% Wald CI for the difference in AUROC of 0·02. At the mean PI-RADS 3 or greater operating point of all readers, the AI system detected 6·8% more cases with Gleason grade group 2 or greater cancers at the same specificity (57·7%, 95% CI 51·6-63·3), or 50·4% fewer false-positive results and 20·0% fewer cases with Gleason grade group 1 cancers at the same sensitivity (89·4%, 95% CI 85·3-92·9). In all 1000 testing cases where the AI system was compared with the radiology readings made during multidisciplinary practice, non-inferiority was not confirmed, as the AI system showed lower specificity (68·9% [95% CI 65·3-72·4] vs 69·0% [65·5-72·5]) at the same sensitivity (96·1%, 94·0-98·2) as the PI-RADS 3 or greater operating point. The lower boundary of the two-sided 95% Wald CI for the difference in specificity (-0·04) was greater than the non-inferiority margin (-0·05) and a p value below the significance threshold was reached (p<0·001). INTERPRETATION: An AI system was superior to radiologists using PI-RADS (2.1), on average, at detecting clinically significant prostate cancer and comparable to the standard of care. Such a system shows the potential to be a supportive tool within a primary diagnostic setting, with several associated benefits for patients and radiologists. Prospective validation is needed to test clinical applicability of this system. FUNDING: Health~Holland and EU Horizon 2020.

Robot-assisted vs open retropubic radical prostatectomy: a propensity score-matched comparative analysis based on 15 years and 18,805 patients.

PURPOSE: To compare oncological, functional, and surgical outcomes of a large cohort of patients who underwent open retropubic radical prostatectomy (ORP) or robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Data from 18,805 RPs performed with either the open or the robot-assisted approaches at a single tertiary referral center between 2008 and 2022 were analyzed. The impact of surgical approach on biochemical recurrence-free survival, salvage radiotherapy-free survival, and metastasis-free survival was analyzed by log-rank test and Kaplan-Meier analysis in a propensity score (PS)-based matched cohort. Intraoperative and postoperative surgical outcomes were assessed. One-week, 3-month, and 12-month continence rates and 12-month erectile function (EF) were analyzed. RESULTS: No statistically significant differences in oncological outcomes were found between ORP and RARP. A slight statistically significant difference in favor of RARP was noted in urinary continence at 3 months (RARP vs. ORP: 81% vs. 77%, p = 0.007) and 12 months (91% vs. 89.3%, p = 0.008), respectively. The rate of EF was statistically significantly higher (60%) after RARP than after ORP (45%, p < 0.001). CONCLUSION: Both RARP and ORP yielded similar oncological outcomes. RARP offered a slight advantage in terms of continence recovery, but its clinical significance may be less meaningful. RARP resulted in significantly improved postoperative EF, suggesting a potential influence of both surgical experience and minimally invasive approach.

PI-QUAL version 2: an update of a standardised scoring system for the assessment of image quality of prostate MRI.

Multiparametric MRI is the optimal primary investigation when prostate cancer is suspected, and its ability to rule in and rule out clinically significant disease relies on high-quality anatomical and functional images. Avenues for achieving consistent high-quality acquisitions include meticulous patient preparation, scanner setup, optimised pulse sequences, personnel training, and artificial intelligence systems. The impact of these interventions on the final images needs to be quantified. The prostate imaging quality (PI-QUAL) scoring system was the first standardised quantification method that demonstrated the potential for clinical benefit by relating image quality to cancer detection ability by MRI. We present the updated version of PI-QUAL (PI-QUAL v2) which applies to prostate MRI performed with or without intravenous contrast medium using a simplified 3-point scale focused on critical technical and qualitative image parameters. CLINICAL RELEVANCE STATEMENT: High image quality is crucial for prostate MRI, and the updated version of the PI-QUAL score (PI-QUAL v2) aims to address the limitations of version 1. It is now applicable to both multiparametric MRI and MRI without intravenous contrast medium. KEY POINTS: High-quality images are essential for prostate cancer diagnosis and management using MRI. PI-QUAL v2 simplifies image assessment and expands its applicability to prostate MRI without contrast medium. PI-QUAL v2 focuses on critical technical and qualitative image parameters and emphasises T2-WI and DWI.

Histopathological results of radical prostatectomy specimen of men younger than 50 years of age at the time of surgery: possible implications for prostate cancer screening programs?

INTRODUCTION: Prostate cancer (PCa) detection is usually achieved by PSA measurement and, if indicated, further diagnostics. The recent EAU guidelines recommend a first PSA test at the age of 50 years, if no family history of PCa or BRCA2 mutation exists. However, some men might harbor significant PCa at younger age; thus we evaluated the histopathological results of men treated with radical prostatectomy (RP) in their 40 s at our institution. MATERIALS AND METHODS: We relied on the data of all patients who underwent RP in our institution between 1992 and 2020 and were younger than 50 years at the time of surgery. The histopathological results are descriptively presented. Moreover, we tested the effect of a positive family history on the descriptive results. RESULTS: Overall, 1225 patients younger than 50 years underwent RP at our institution. Median age was 47 years. Most patients showed favorable histopathological characteristics. However, 20% of patients had extraprostatic disease (≥ pT3a), 15% had ISUP Gleason grade group ≥ 3, and 7% had positive lymph nodes (pN1). Patients with a known positive family history did not have a higher rate of adverse disease as their counterparts with a negative family history. DISCUSSION: Our data show that the majority of patients who were diagnosed with PCa at a very young age had favorable histopathological RP characteristics. However, a non-negligible proportion of patients already showed locally advanced disease and would have probably benefited from earlier PCa detection. This should be kept in mind when PCa screening recommendations are proposed.

Contemporary patterns of local ablative therapies for prostate cancer at United States cancer centers: results from a national registry.

PURPOSE: To describe the national-level patterns of care for local ablative therapy among men with PCa and identify patient- and hospital-level factors associated with the receipt of these techniques. METHODS: We retrospectively interrogated the National Cancer Database (NCDB) for men with clinically localized PCa between 2010 and 2017. The main outcome was receipt of local tumor ablation with either cryo- or laser-ablation, and "other method of local tumor destruction including high-intensity focused ultrasound (HIFU)". Patient level, hospital level, and demographic variables were collected. Mixed effect logistic regression models were fitted to identify separately patient- and hospital-level predictors of receipt of local ablative therapy. RESULTS: Overall, 11,278 patients received ablative therapy, of whom 78.8% had cryotherapy, 15.6% had laser, and 5.7% had another method including HIFU. At the patient level, men with intermediate-risk PCa were more likely to be treated with local ablative therapy (OR 1.05; 95% CI 1.00-1.11; p = 0.05), as were men with Charlson Comorbidity Index > 1 (OR 1.36; 95% CI 1.29-1.43; p < 0.01), men between 71 and 80 years (OR 3.70; 95% CI 3.43-3.99; p < 0.01), men with Medicare insurance (OR 1.38; 95% 1.31-1.46; p < 0.01), and an income < $47,999 (OR 1.16; 95% CI 1.06-1.21; p < 0.01). At the hospital-level, local ablative therapy was less likely to be performed in academic/research facilities (OR 0.45; 95% CI 0.32-0.64; p < 0.01). CONCLUSIONS: Local ablative therapy for PCa treatment is more commonly offered among older and comorbid patients. Future studies should investigate the uptake of these technologies in non-hospital-based settings and in light of recent changes in insurance coverage.

Concordance of biopsy and pathologic ISUP grading in salvage radical prostatectomy patients for recurrent prostate cancer.

PURPOSE: To investigate the concordance of biopsy and pathologic International Society of Urological Pathology (ISUP) grading in salvage radical prostatectomy (SRP) patients for recurrent prostate cancer. METHODS: Within a high-volume center database, we identified patients who underwent SRP for recurrent prostate cancer (PCa) between 2004 and 2020. Upgrading, downgrading, concordance, and any discordance between posttreatment biopsy ISUP and ISUP at SRP were tested. Logistic regression models were used to predict ISUP upgrading and ISUP discordance. Models were adjusted for prostatic specific antigen before SRP, age at surgery, initial prostatic specific antigen (PSA), type of primary treatment, time from primary PCa diagnosis to SRP, number of positive cores at biopsy, and original Gleason score. RESULTS: Overall, 184 patients with available biopsy and pathologic ISUP grading were identified. Of those, 17.4% (n = 32), 40.8% (n = 75), 19.6% (n = 36), and 22.2% (n = 41) harbored biopsy ISUP 1, ISUP 2, ISUP 3, and ISUP 4-5 grading, respectively. Pathologic ISUP 1, ISUP 2, ISUP 3, and ISUP 4-5 grading was recorded in 6.0% (n = 11), 40.8% (n = 75), 32.1% (n = 59), and 21.2% (n = 39), respectively. Median PSA before SRP was 5.5 ng/ml (interquartile range [IQR]: 3.1-8.1 ng/ml), median age at SRP was 65.1 years (IQR:60.7-69.4 years) and median time from original PCa diagnosis to SRP was 47 months (IQR: 27.3-85.2 months). Concordance of biopsy and pathologic ISUP was identified in 45.1% (n = 83). Conversely, any ISUP discordance, upgrading and downgrading of at least one ISUP group was identified in 54.9% (n = 101), 35.3% (n = 65), and 19.6% (n = 36). In logistic models, none of the preoperative characteristics was associated with upgrading or ISUP discordance (all p > 0.1). CONCLUSION: Discordance between biopsy and pathologic ISUP grading is common at SRP. However, in 45% of SRP cases biopsy ISUP is capable to predict pathologic ISUP. Further studies are necessary to identify characteristics for ISUP upgrading at SRP.

68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography-Based Primary Staging and Histological Correlation after Extended Pelvic Lymph Node Dissection in Intermediate-Risk Prostate Cancer.

OBJECTIVE: The objective of this study is to evaluate prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA PET/CT)-based primary staging in exclusively D'Amico intermediate-risk prostate cancer (PCa) patients. PATIENTS AND METHODS: We relied on the Braunschweig institutional database and retrospectively identified D'Amico intermediate-risk PCa patients who were administered to 68Ga-PSMA PET/CT-based primary staging prior to consecutive radical prostatectomy and extended lymph node dissection. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of lymph node metastases were analyzed per-patient (n = 39), per-pelvic side (n = 78), and per-anatomic-region (external iliac artery and vein left/right vs. obturator fossa left/right vs. internal iliac artery left/right) (n = 203), respectively. RESULTS: Sensitivity, specificity, PPV, and NPV per-patient were 20.0, 94.1, 33.3, and 88.9%, respectively. Sensitivity, specificity, PPV, and NPV per-pelvic-side were 16.7, 97.2, 33.3, and 93.3%, respectively. Sensitivity, specificity, PPV, and NPV per-anatomic-region were 16.7, 99.0, 33.3, and 97.5%, respectively. CONCLUSIONS: We recorded high rates of specificity and NPV for 68Ga-PSMA PET/CT-based primary staging in D'Amico intermediate-risk PCa patients. Conversely, the sensitivity and PPV were lower than anticipated. Larger and favorably prospective trials are needed to verify our results and to unravel possible bias from such smaller studies.

Moving away from systematic biopsies: image-guided prostate biopsy (in-bore biopsy, cognitive fusion biopsy, MRUS fusion biopsy) -literature review.

OBJECTIVE: To compare the detection rate of clinically significant cancer (CSCa) by magnetic resonance imaging-targeted biopsy (MRI-TB) with that by standard systematic biopsy (SB) and to evaluate the role of MRI-TB as a replacement from SB in men at clinical risk of prostate cancer. METHODS: The non-systematic literature was searched for peer-reviewed English-language articles using PubMed, including the prospective paired studies, where the index test was MRI-TB and the comparator text was SB. Also the randomized clinical trials (RCTs) are included if one arm was MRI-TB and another arm was SB. RESULTS: Eighteen prospective studies used both MRI-TB and TRUS-SB, and eight RCT received one of the tests for prostate cancer detection. In most prospective trials to compare MRI-TB vs. SB, there was no significant difference in any cancer detection rate; however, MRI-TB detected more men with CSCa and fewer men with CISCa than SB. CONCLUSION: MRI-TB is superior to SB in detection of CSCa. Since some significant cancer was detected by SB only, a combination of SB with the TB technique would avoid the underdiagnosis of CSCa.

A systematic review and meta-analysis of Histoscanning™ in prostate cancer diagnostics.

CONTEXT: The value of Histoscanning™ (HS) in prostate cancer (PCa) imaging is much debated, although it has been used in clinical practice for more than 10 years now. OBJECTIVE: To summarize the data on HS from various PCa diagnostic perspectives to determine its potential. MATERIALS AND METHODS: We performed a systematic search using 2 databases (Medline and Scopus) on the query "Histoscan*". The primary endpoint was HS accuracy. The secondary endpoints were: correlation of lesion volume by HS and histology, ability of HS to predict extracapsular extension or seminal vesicle invasion. RESULTS: HS improved cancer detection rate "per core", OR = 16.37 (95% CI 13.2; 20.3), p < 0.0001, I2 = 98% and "per patient", OR = 1.83 (95% CI 1.51; 2.21), p < 0.0001, I2 = 95%. The pooled accuracy was markedly low: sensitivity - 0.2 (95% CI 0.19-0.21), specificity - 0.12 (0.11-0.13), AUC 0.12. 8 of 10 studiers showed no additional value for HS. The pooled accuracy with histology after RP was relatively better, yet still very low: sensitivity - 0.56 (95% CI 0.5-0.63), specificity - 0.23 (0.18-0.28), AUC 0.4. 9 of 12 studies did not show any benefit of HS. CONCLUSION: This meta-analysis does not see the incremental value in comparing prostate Histoscanning with conventional TRUS in prostate cancer screening and targeted biopsy. HS proved to be slightly more accurate in predicting extracapsular extension on RP, but the available data does not allow us to draw any conclusions on its effectiveness in practice. Histoscanning is a modification of ultrasound for prostate cancer visualization. The available data suggest its low accuracy in screening and detecting of prostate cancer.

ESUR/ESUI position paper: developing artificial intelligence for precision diagnosis of prostate cancer using magnetic resonance imaging.

Artificial intelligence developments are essential to the successful deployment of community-wide, MRI-driven prostate cancer diagnosis. AI systems should ensure that the main benefits of biopsy avoidance are delivered while maintaining consistent high specificities, at a range of disease prevalences. Since all current artificial intelligence / computer-aided detection systems for prostate cancer detection are experimental, multiple developmental efforts are still needed to bring the vision to fruition. Initial work needs to focus on developing systems as diagnostic supporting aids so their results can be integrated into the radiologists' workflow including gland and target outlining tasks for fusion biopsies. Developing AI systems as clinical decision-making tools will require greater efforts. The latter encompass larger multicentric, multivendor datasets where the different needs of patients stratified by diagnostic settings, disease prevalence, patient preference, and clinical setting are considered. AI-based, robust, standard operating procedures will increase the confidence of patients and payers, thus enabling the wider adoption of the MRI-directed approach for prostate cancer diagnosis. KEY POINTS: • AI systems need to ensure that the benefits of biopsy avoidance are delivered with consistent high specificities, at a range of disease prevalence. • Initial work has focused on developing systems as diagnostic supporting aids for outlining tasks, so they can be integrated into the radiologists' workflow to support MRI-directed biopsies. • Decision support tools require a larger body of work including multicentric, multivendor studies where the clinical needs, disease prevalence, patient preferences, and clinical setting are additionally defined.

Automated multiparametric localization of prostate cancer based on B-mode, shear-wave elastography, and contrast-enhanced ultrasound radiomics.

OBJECTIVES: The aim of this study was to assess the potential of machine learning based on B-mode, shear-wave elastography (SWE), and dynamic contrast-enhanced ultrasound (DCE-US) radiomics for the localization of prostate cancer (PCa) lesions using transrectal ultrasound. METHODS: This study was approved by the institutional review board and comprised 50 men with biopsy-confirmed PCa that were referred for radical prostatectomy. Prior to surgery, patients received transrectal ultrasound (TRUS), SWE, and DCE-US for three imaging planes. The images were automatically segmented and registered. First, model-based features related to contrast perfusion and dispersion were extracted from the DCE-US videos. Subsequently, radiomics were retrieved from all modalities. Machine learning was applied through a random forest classification algorithm, using the co-registered histopathology from the radical prostatectomy specimens as a reference to draw benign and malignant regions of interest. To avoid overfitting, the performance of the multiparametric classifier was assessed through leave-one-patient-out cross-validation. RESULTS: The multiparametric classifier reached a region-wise area under the receiver operating characteristics curve (ROC-AUC) of 0.75 and 0.90 for PCa and Gleason > 3 + 4 significant PCa, respectively, thereby outperforming the best-performing single parameter (i.e., contrast velocity) yielding ROC-AUCs of 0.69 and 0.76, respectively. Machine learning revealed that combinations between perfusion-, dispersion-, and elasticity-related features were favored. CONCLUSIONS: In this paper, technical feasibility of multiparametric machine learning to improve upon single US modalities for the localization of PCa has been demonstrated. Extended datasets for training and testing may establish the clinical value of automatic multiparametric US classification in the early diagnosis of PCa. KEY POINTS: • Combination of B-mode ultrasound, shear-wave elastography, and contrast ultrasound radiomics through machine learning is technically feasible. • Multiparametric ultrasound demonstrated a higher prostate cancer localization ability than single ultrasound modalities. • Computer-aided multiparametric ultrasound could help clinicians in biopsy targeting.

ESUR/ESUI consensus statements on multi-parametric MRI for the detection of clinically significant prostate cancer: quality requirements for image acquisition, interpretation and radiologists' training.

OBJECTIVES: This study aims to define consensus-based criteria for acquiring and reporting prostate MRI and establishing prerequisites for image quality. METHODS: A total of 44 leading urologists and urogenital radiologists who are experts in prostate cancer imaging from the European Society of Urogenital Radiology (ESUR) and EAU Section of Urologic Imaging (ESUI) participated in a Delphi consensus process. Panellists completed two rounds of questionnaires with 55 items under three headings: image quality assessment, interpretation and reporting, and radiologists' experience plus training centres. Of 55 questions, 31 were rated for agreement on a 9-point scale, and 24 were multiple-choice or open. For agreement items, there was consensus agreement with an agreement ≥ 70% (score 7-9) and disagreement of ≤ 15% of the panellists. For the other questions, a consensus was considered with ≥ 50% of votes. RESULTS: Twenty-four out of 31 of agreement items and 11/16 of other questions reached consensus. Agreement statements were (1) reporting of image quality should be performed and implemented into clinical practice; (2) for interpretation performance, radiologists should use self-performance tests with histopathology feedback, compare their interpretation with expert-reading and use external performance assessments; and (3) radiologists must attend theoretical and hands-on courses before interpreting prostate MRI. Limitations are that the results are expert opinions and not based on systematic reviews or meta-analyses. There was no consensus on outcomes statements of prostate MRI assessment as quality marker. CONCLUSIONS: An ESUR and ESUI expert panel showed high agreement (74%) on issues improving prostate MRI quality. Checking and reporting of image quality are mandatory. Prostate radiologists should attend theoretical and hands-on courses, followed by supervised education, and must perform regular performance assessments. KEY POINTS: • Multi-parametric MRI in the diagnostic pathway of prostate cancer has a well-established upfront role in the recently updated European Association of Urology guideline and American Urological Association recommendations. • Suboptimal image acquisition and reporting at an individual level will result in clinicians losing confidence in the technique and returning to the (non-MRI) systematic biopsy pathway. Therefore, it is crucial to establish quality criteria for the acquisition and reporting of mpMRI. • To ensure high-quality prostate MRI, experts consider checking and reporting of image quality mandatory. Prostate radiologists must attend theoretical and hands-on courses, followed by supervised education, and must perform regular self- and external performance assessments.

Multiparametric Ultrasound for Prostate Cancer Detection and Localization: Correlation of B-mode, Shear Wave Elastography and Contrast Enhanced Ultrasound with Radical Prostatectomy Specimens.

PURPOSE: Similar to multiparametric magnetic resonance imaging, multiparametric ultrasound represents a promising approach to prostate cancer imaging. We determined the diagnostic performance of B-mode, shear wave elastography and contrast enhanced ultrasound with quantification software as well as the combination, multiparametric ultrasound, for clinically significant prostate cancer localization using radical prostatectomy histopathology as the reference standard. MATERIALS AND METHODS: From May 2017 to July 2017, 50 men with biopsy proven prostate cancer underwent multiparametric ultrasound before radical prostatectomy at 1 center. Three readers independently evaluated 12 anatomical regions of interest for the likelihood of clinically significant prostate cancer on a 5-point Likert scale for all separate ultrasound modalities and multiparametric ultrasound. A logistic linear mixed model was used to estimate diagnostic performance for the localization of clinically significant prostate cancer (any tumor with Gleason score 3 + 4 = 7 or greater, tumor volume 0.5 ml or greater, extraprostatic extension or stage pN1) using a Likert score of 3 or greater and 4 or greater as the threshold. To detect the index lesion the readers selected the 2 most suspicious regions of interest. RESULTS: A total of 48 men were included in the final analysis. The region of interest specific sensitivity of multiparametric ultrasound (Likert 3 or greater) for clinically significant prostate cancer was 74% (95% CI 67-80) compared to 55% (95% CI 47-63), 55% (95% CI 47-63) and 59% (95% CI 51-67) for B-mode, shear wave elastography and contrast enhanced ultrasound, respectively. Multiparametric ultrasound sensitivity was significantly higher for Likert thresholds and all different clinically significant prostate cancer definitions (all p <0.05). Multiparametric ultrasound improved the detection of index lesion prostate cancer. CONCLUSIONS: Multiparametric ultrasound of the prostate, consisting of B-mode, shear wave elastography and contrast enhanced ultrasound with parametric maps, improved localization and index lesion detection of clinically significant prostate cancer compared to single ultrasound modalities, yielding good sensitivity.

Radical Prostatectomy after Vascular Targeted Photodynamic Therapy with Padeliporfin: Feasibility, and Early and Intermediate Results.

PURPOSE: Vascular targeted photodynamic therapy with TOOKAD® is a new therapeutic option for localized prostate cancer management. The objectives of this study were to assess the feasibility of radical prostatectomy after vascular targeted photodynamic therapy and describe functional and oncologic outcomes. MATERIALS AND METHODS: We retrospectively included in study 45 patients who underwent salvage radical prostatectomy after vascular targeted photodynamic therapy for recurrent prostate cancer at a total of 14 surgical centers in Europe between October 2008 and March 2017. Of the 42 radical prostatectomies performed 16 were robot-assisted, 6 were laparoscopic and 20 were open surgery. Primary end points were morbidity and technical difficulties. Secondary end points were early and intermediate postoperative functional and oncologic outcomes. RESULTS: Median operative time was 180 minutes (IQR 150-223). Median blood loss was 200 ml (IQR 155-363). According to the surgeons the surgery was easy in 29 patients (69%) and difficult in 13 (31%). Nerve sparing was feasible in 14 patients (33%). Five postoperative complications (12%) were found, including 2 Clavien I, 2 Clavien II and 1 Clavien IIIB complications. Of the cases 13 (31%) were pT3 and 21 (50%) were pT2c. Surgical margins were positive in 13 patients (31%). Prostate specific antigen was undetectable at 6 to 12 months in 37 patients (88%). Nine patients underwent complementary radiotherapy. Four patients had final prostate specific antigen greater than 0.2 ng/ml at a median followup of 23 months (IQR 12-36). At 1 year 27 patients (64%) were completely continent (no pads) and 10 (24%) had low incontinence (1 pad). Four patients (11%) recovered potency without treatment and 23 (64%) recovered potency with appropriate treatment. CONCLUSIONS: Salvage radical prostatectomy after vascular targeted photodynamic therapy treatment was feasible and safe without difficulty for most of the surgeons.

A comparative study of robot-assisted and open radical prostatectomy in 10 790 men treated by highly trained surgeons for both procedures.

OBJECTIVE: To compare oncological, functional and surgical outcomes of open retropubic radical prostatectomy (ORP) vs robot-assisted laparoscopic radical prostatectomy (RARP). PATIENTS AND METHODS: We identified 10 790 consecutive treated patients within our prospective database (2008-2016) who underwent either ORP (7007 patients) or RARP (3783). All procedures were performed by seven highly trained surgeons performing both surgical approaches regularly. Oncological (48-month biochemical recurrence [BCR] rate), functional (urinary continence, erectile function), and surgical outcomes (rate of nerve-sparing [NS] procedures, lymph node yield, surgical margin [SM] status, length of hospital stay [LOS], operation time, blood loss, transfusion rate, time to catheter removal) were assessed. Kaplan-Meier, multivariable Cox and logistic regression models were used to test for BCR and functional outcome differences. RESULTS: No statistically significant difference regarding oncological outcome distinguished between ORP vs RARP. For functional outcomes, the 1-week continence rates were higher in the ORP group (25.8% vs 21.8%, P < 0.001). At 3 months, no statistically significant differences were observed. At 12 months, continence rates were modestly higher in the RARP group (90.3% vs 88.8%, P = 0.01). This effect was no longer observed after stratification for age-groups. The 12-month potency rates were similar in ORP vs RARP (80.3% vs 83.6%, P = 0.33). For surgical outcomes, there was no significant difference in the rates of NS procedures, lymph node yield, SM status, and LOS. Conversely, operation time was shorter in ORP, and blood loss, transfusion rates and time to catheter removal were significantly lower in RARP. CONCLUSIONS: Both surgical approaches, performed in a high-volume centre by the same surgeons, achieve excellent, comparable oncological and functional outcomes. However, a modest advantage for RARP for surgical outcomes was observed, most likely attributable to its minimally invasive nature, and better teaching capabilities. Consequently, more than the surgical approach itself, the well-trained surgeon remains the most important factor to achieve satisfactory outcomes.

Perioperative management of direct oral anticoagulants in patients undergoing radical prostatectomy: results of a prospective assessment.

INTRODUCTION AND OBJECTIVES: In the perioperative setting, temporary interruption of direct oral anticoagulants (DOACs) is recommended. However, the safety of these recommendations is based on non-urological surgical experiences. Our objective was to verify the safety of these recommendations in patients undergoing radical prostatectomy (RP). MATERIALS AND METHODS: Patients regularly receiving a DOAC and scheduled for RP at our institution were prospectively assessed. DOAC intake was usually stopped 48 h before surgery without any preoperative bridging therapy. Postoperatively, patients received risk-adapted low-molecular weight heparin (LMWH). On the third day after unremarkable RP, DOAC intake was restarted and the administration of LMWH was stopped. We assessed perioperative outcomes and 30-day morbidity. RESULTS: Thirty-two consecutive patients receiving DOAC underwent RP at our institution between 12/2017 and 07/2018. Time of surgery (median, 177 min) and intraoperative blood loss (median, 500 mL) were unremarkable. DOACs were restarted on the third postoperative day in 30 patients (94%). No patient had a significant hemoglobin level reduction after DOAC restart. Overall, 28% of patients experienced complications within 30 days after surgery. Most of which were minor (Clavien ≤ 2), three patients (9%), however, had Clavien ≥ 3 complications. CONCLUSION: Our report is the first to prospectively assess current guideline recommendations regarding DOAC restarting after major urological surgery. RP can safely be performed, if DOACs are correctly paused before surgery. Moreover, in case of an uneventful postoperative clinical course, DOACs can be safely restarted on the third postoperative day. A 9% Clavien ≥ 3 30-day morbidity warrants attention and should be further explored in future studies.

Prostate cancer rates in patients with initially negative elastography-targeted biopsy vs. systematic biopsy.

PURPOSE: To assess whether real-time elastography-targeted biopsy (RTE-bx) is superior to the standard systematic transrectal ultrasound (TRUS)-guided biopsy in predicting subsequent prostate cancer (PCa) rates in patients with initially negative biopsy and to specifically reveal differences in the occurrence of high-grade (Gleason ≥ 4 + 3) PCa by comparing both biopsy methods. PATIENTS AND METHODS: Overall, 630 patients had an initially negative prostate biopsy between 2007 and 2015, either RTE targeted (n = 213) or systematically (n = 417). Follow-up data, ascertained by a questionnaire, of patients receiving RTE-bx were compared to data of patients receiving systematic biopsy (sbx) using Mann-Whitney-U test and Chi-square test. We performed logistic regression analyses to assess any association with PCa or high-grade PCa occurrence. RESULTS: In total, 258 (41%) patients were diagnosed with PCa at repeat biopsy whereof 54 (8.6%) harboured high-grade PCa. PCa occurred in 95 (44.6%) patients with initially negative RTE-bx and in 163 (39.1%) patients with initially negative sbx (p = 0.003). 24 (11.3%) patients receiving RTE-bx and 30 (7.2%) patients receiving sbx were diagnosed with high-grade PCa (p = 0.095). Logistic regression analyses showed that patients with the initial RTE-bx vs. those with the initial sbx neither resulted in a significant higher risk for PCa occurrence (OR 1.35 [CI 0.87-2.1]; p = 0.2) nor for high-grade PCa occurrence (OR 1.52 [CI 0.66-3.35]; p = 0.3). CONCLUSIONS: We found no statistically significant association of prior biopsy method to subsequent PCa or high-grade PCa occurrence. Referring to our analyses, RTE is not superior to sbx in predicting subsequent PCa rates and, therefore, not eligible to decide on repeat biopsy.

Antimicrobial lubricant reduces rectal bacteria at transrectal prostate biopsy: results from a prospective randomized trial.

PURPOSE: Antibiotic resistance may lead to increasing infection rates at transrectal prostate biopsy. Local antimicrobial agents might help to reduce bacterial load. The aim of this study was to test the potency of antimicrobial lubricants to reduce local bacterial loads and specifically fluoroquinolone-resistant strains. PATIENTS AND METHODS: Overall, 384 prostate biopsy (PBx) patients of a larger prospective randomized trial (n = 1000) were included. Patients were randomized for biopsy with pre-interventional instillation of an antimicrobial lubricant (intervention group n = 256) or with the standard lubricant (control group n = 128). Bacteria were recovered on pre- and post-biopsy rectal swab cultures from both patient groups. Bacterial colonization was semi-quantitatively recorded and analyzed for the presence of ciprofloxacin-resistant isolates. RESULTS: Within the intervention group, where antimicrobial lubricant was instilled for PBx, the post-biopsy bacterial count was statistically significantly lower compared to prior biopsy bacterial count (p < 0.001), while in the control group, no statistically significant difference was shown. Moreover, our results demonstrated the tendency for reduction in ciprofloxacin-resistant bacteria growth when instillation of antimicrobial lubricant was used (9.4% versus 5.9%, p = 0.5 prior- and post-biopsy). No reduction in ciprofloxacin-resistant bacterial growth was demonstrated for the control group. Ciprofloxacin-resistance was shown in overall 30 (7.8%) patients. CONCLUSION: Our data demonstrated that the antimicrobial lubricant prior biopsy leads to reduced bacterial load. Moreover, our data show the tendency for reduced ciprofloxacin-resistant bacteria growth when antimicrobial lubricant was instilled prior biopsy. However, the incidence of ciprofloxacin-resistant bacteria is low in our patient population. Rectal swabs should assess fluoroquinolone-resistance rates at prostate biopsy.

Validation of the current eligibility criteria for focal therapy in men with localized prostate cancer and the role of MRI.

PURPOSE: To validate current eligibility criteria for focal therapy (FT) in prostate cancer men undergoing radical prostatectomy (RP) and to assess the role of magnetic resonance imaging (MRI). METHODS: Retrospective analysis of 217 RP patients (2009-2016) with preoperative MRI (almost all in external institutions) and fulfillment of different FT eligibility criteria: unilateral tumor, clinical tumor stage ≤ cT2a, prostate volume ≤ 60 mL and either biopsy Gleason 3 + 3 or ≤ 3 + 4 and PSA ≤ 10 or ≤ 15 ng/mL. Multivariable logistic regression analyses (MVA) assessed the role of MRI to predict the presence of significant contralateral tumor or extracapsular extension (ECE), including seminal vesicle invasion. To quantify model accuracy, Receiver Operating Characteristics-derived area under the curve (AUC) was used. RESULTS: Of 217 patients fulfilling widest biopsy criteria and 113 fulfilling additional MRI criteria, 64 (29.7%) and 37 (32.7%) remained eligible for FT according to histopathological results. In MVA, fulfillment of MRI criteria reached independent predictor status for prediction of contralateral tumor but not for ECE. Addition of MRI resulted in AUC gain (57.5-64.6%). Sensitivity, specificity, PPV and NPV for MRI to predict contralateral tumor were: 41.8, 71.6, 70.9 and 42.6%, respectively. Virtually the same results were recorded for Gleason 3 + 3 and/or PSA ≤ 10 ng/mL. CONCLUSIONS: Patient eligibility criteria for FT using biopsy criteria remained insufficient with respect to contralateral tumor disease. Although, MRI improves accuracy, it cannot safely exclude or minimize chance of significant cancer on contralateral prostate side. To date, stricter eligibility criteria are needed to provide more diagnostic reliability.

Obesity paradox in prostate cancer: increased body mass index was associated with decreased risk of metastases after surgery in 13,667 patients.

INTRODUCTION: Obesity might negatively affect prostate cancer (PCa) outcomes. However, evidence according to the associations between obesity and metastases-free survival after radical prostatectomy (RP) is still inconsistent. METHODS: We relied on PCa patients treated with RP at the Martini-Klinik Prostate Cancer Center between 2004 and 2015. First, multivariable Cox regression analyses examined the impact of obesity on metastases after RP. Last, in a propensity score matched cohort, Kaplan-Meier analyses assessed metastases-free survival according to body mass index (kg/m2) (BMI) strata (≥ 30 vs. < 25). RESULTS: Of 13,667 individuals, 1990 (14.6%) men were obese (BMI ≥ 30). Median follow-up was 36.4 month (IQR 13.3-60.8). Obese patients were less likely to exhibit metastases after RP (HR 0.7, 95% CI 0.5-0.97, p = 0.03). Similarly, after propensity score adjustment, obesity was associated with increased metastases-free survival (log rank p = 0.001). CONCLUSION: We recorded the obesity paradox phenomenon in PCa patients. In particular, high BMI (≥ 30) was associated with decreased risk of metastases after RP, despite an increased risk being anticipated. Whether statin use might have affected the results was not assessed. Further research is needed to unravel the controversially debated association between obesity and PCa.