Interassay Variability and Clinical Implications of Five Different Prostate-specific Antigen Assays.

Background and objective: Prostate-specific antigen (PSA) remains a critical marker for prostate cancer (PCa) detection and monitoring. Recognising historical variability in PSA assays and the evolution of assay technology and calibration, this study aims to reassess interassay variability using the latest generation of five assays in a contemporary cohort of men undergoing prostate biopsy. Methods: Five different commercially available PSA assays were tested in a blood sample of 76 men before undergoing a prostate biopsy. Total PSA (tPSA) and free-to-total PSA ratio (%fPSA) were compared across assays, using Roche (Basel, Switzerland) as the benchmark, and correlated with biopsy outcome to analyse the impact on PCa diagnosis. The statistical analysis included Passing-Bablok regression and Bland-Altman plots, with a p value threshold of <0.05 for significance. Key findings and limitations: Among the 76 men, 28 (36.8%) were diagnosed with significant PCa (defined as International Society of Urological Pathology grade ≥2). A high correlation was observed between tPSA and %fPSA values among the different PSA assays tested (r2 ≥ 0.9). The Passing-Bablok analysis showed that tPSA results varied substantially among the assays, with slopes ranging between 0.78 and 1.04. Compared with the tPSA of Roche, tPSA values were on average 20.7% lower by Beckman (Oststeinbeck, Germany), 15.2% lower by Abbott (Chicago, IL, USA), 6.1% lower by Diasorin (Saluggia, Italy), and 9.6% higher by Brahms (Hennigsdorf, Germany; p < 0.001 for all). The %fPSA values by Abbott and Brahms were higher at 15.7% and 10.6%, respectively (p < 0.001), while the Beckman and Diasorin values had minimal differences of -0.3% and 2.3%, respectively (p > 0.05). The variability across assays would have resulted in discrepancies in both the sensitivity and the specificity for tPSA and %fPSA by at least 14%, depending on the cut-offs applied. Conclusions and clinical implications: Despite the use of the latest PSA assays, relevant variability of tPSA and %fPSA results can be observed among different assays. There is an urgent need for standardised calibration methods and greater awareness among practitioners concerning interassay variability. Clinicians should acknowledge that clinically relevant thresholds may depend on the specific PSA assay and that ideally the same assay is applied over time for better clinical decision-making. Patient summary: Prostate-specific antigen (PSA) is a critical marker for prostate cancer (PCa) detection and monitoring. However, significant variations were observed in the results of the latest PSA assays. Thus, standardised calibration methods and greater awareness among practitioners concerning interassay variability are needed.

BioPrev-C - development and validation of a contemporary prostate cancer risk calculator.

Objectives: To develop a novel biopsy prostate cancer (PCa) prevention calculator (BioPrev-C) using data from a prospective cohort all undergoing mpMRI targeted and transperineal template saturation biopsy. Materials and methods: Data of all men who underwent prostate biopsy in our academic tertiary care center between 11/2016 and 10/2019 was prospectively collected. We developed a clinical prediction model for the detection of high-grade PCa (Gleason score ≥7) based on a multivariable logistic regression model incorporating age, PSA, prostate volume, digital rectal examination, family history, previous negative biopsy, 5-alpha-reductase inhibitor use and MRI PI-RADS score. BioPrev-C performance was externally validated in another prospective Swiss cohort and compared with two other PCa risk-calculators (SWOP-RC and PBCG-RC). Results: Of 391 men in the development cohort, 157 (40.2%) were diagnosed with high-grade PCa. Validation of the BioPrev C revealed good discrimination with an area under the curve for high-grade PCa of 0.88 (95% Confidence Interval 0.82-0.93), which was higher compared to the other two risk calculators (0.71 for PBCG and 0.84 for SWOP). The BioPrev-C revealed good calibration in the low-risk range (0 - 0.25) and moderate overestimation in the intermediate risk range (0.25 - 0.75). The PBCG-RC showed good calibration and the SWOP-RC constant underestimation of high-grade PCa over the whole prediction range. Decision curve analyses revealed a clinical net benefit for the BioPrev-C at a clinical meaningful threshold probability range (≥4%), whereas PBCG and SWOP calculators only showed clinical net benefit above a 30% threshold probability. Conclusion: BiopPrev-C is a novel contemporary risk calculator for the prediction of high-grade PCa. External validation of the BioPrev-C revealed relevant clinical benefit, which was superior compared to other well-known risk calculators. The BioPrev-C has the potential to significantly and safely reduce the number of men who should undergo a prostate biopsy.

Longitudinal Tumor-informed Circulating Tumor DNA Status Predicts Disease Upstaging and Poor Prognosis for Patients Undergoing Radical Cystectomy.

BACKGROUND AND OBJECTIVE: Decision-making on the use of neoadjuvant and adjuvant treatment for patients with bladder cancer undergoing radical cystectomy (RC) currently depends on assessment of clinical and pathological features, which lack sensitivity. Circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. Our aim was to assess whether ctDNA status before RC is predictive of pathological and oncological outcomes. We also evaluated the dynamic changes in ctDNA status after RC in relation to recurrence-free survival (RFS). METHODS: We analyzed data for patients who underwent RC during 2021-2023 for whom prospective tumor-informed ctDNA analyses were conducted before and after RC. RFS was evaluated using the Kaplan-Meier method. Predictors for disease recurrence were assessed using Cox proportional-hazards models. Pathological outcomes associated with detectable ctDNA before RC were assessed in univariable and multivariable regression analyses. KEY FINDINGS AND LIMITATIONS: We included 112 patients in the analysis. Median follow-up was 8 mo (interquartile range 4-13). ctDNA was detected before RC in 59 patients (53%) and was associated with poor RFS (log-rank p < 0.0001). Detectable ctDNA before RC was associated with poor outcomes regardless of clinical stage (

Evaluation of Proclarix in the diagnostic work-up of prostate cancer.

Objectives: The use of multiparametric magnetic resonance imaging (mpMRI) has been widely adopted in the diagnostic work-up for suspicious prostate cancer (PCa) and is recommended in most current guidelines. However, mpMRI lesions are often indeterminate and/or turn out to be false-positive on prostate biopsy. The aim of this work was to evaluate Proclarix, a biomarker test for the detection of relevant PCa, regarding its diagnostic value in all men before biopsy and in men with indeterminate lesions on mpMRI (PI-RADS 3) during work-up for PCa. Materials and Methods: Men undergoing mpMRI-targeted and systematic biopsy of the prostate were prospectively enrolled. The Proclarix test was evaluated for the detection accuracy of clinically significant PCa (csPCa) defined as Grade Group ≥ 2 and its association to mpMRI results. Further, Proclarix's performance was also tested when adapted to prostate volume (Proclarix density) and performance compared to PSA density (PSAD). Results: A total of 150 men with a median age of 65 years and median PSA of 5.8 ng/mL were included in this study. CsPCa was diagnosed in 65 (43%) men. Proclarix was significantly associated with csPCa and higher PI-RADS score (p < 0.001). At the pre-defined cut-off of 10%, Proclarix's sensitivity for csPCa was 94%, specificity 19%, negative predictive value 80% and positive predictive value 47%. Proclarix density showed the highest AUC for the detection of csPCa of 0.77 (95%CI: 0.69-0.85) compared to PSA, PSAD and Proclarix alone. Proclarix was able to identify all six csPCa in men with PI-RADS 3 lesions (n = 28), whereas PSAD missed two out of six. At optimized cut-offs, Proclarix density outperformed PSAD by potentially avoiding 41% of unnecessary biopsies. Conclusion: Proclarix demonstrates high sensitivity in detecting csPCa but may still result in unnecessary biopsies. However, Proclarix density was able to outperform PSAD and Proclarix and was found to be useful in men with PI-RADS 3 findings by safely avoiding unnecessary biopsies without missing csPCa.

Validation of a Zero-shot Learning Natural Language Processing Tool to Facilitate Data Abstraction for Urologic Research.

BACKGROUND: Urologic research often requires data abstraction from unstructured text contained within the electronic health record. A number of natural language processing (NLP) tools have been developed to aid with this time-consuming task; however, the generalizability of these tools is typically limited by the need for task-specific training. OBJECTIVE: To describe the development and validation of a zero-shot learning NLP tool to facilitate data abstraction from unstructured text for use in downstream urologic research. DESIGN, SETTING, AND PARTICIPANTS: An NLP tool based on the GPT-3.5 model from OpenAI was developed and compared with three physicians for time to task completion and accuracy for abstracting 14 unique variables from a set of 199 deidentified radical prostatectomy pathology reports. The reports were processed in vectorized and scanned formats to establish the impact of optical character recognition on data abstraction. INTERVENTION: A zero-shot learning NLP tool for data abstraction. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The tool was compared with the human abstractors in terms of superiority for data abstraction speed and noninferiority for accuracy. RESULTS AND LIMITATIONS: The human abstractors required a median (interquartile range) of 93 s (72-122 s) per report for data abstraction, whereas the software required a median of 12 s (10-15 s) for the vectorized reports and 15 s (13-17 s) for the scanned reports (p < 0.001 for all paired comparisons). The accuracies of the three human abstractors were 94.7% (95% confidence interval [CI], 93.8-95.5%), 97.8% (95% CI, 97.2-98.3%), and 96.4% (95% CI, 95.6-97%) for the combined set of 2786 data points. The tool had accuracy of 94.2% (95% CI, 93.3-94.9%) for the vectorized reports and was noninferior to the human abstractors at a margin of -10% (α = 0.025). The tool had slightly lower accuracy of 88.7% (95% CI 87.5-89.9%) for the scanned reports, making it noninferior to two of three human abstractors. CONCLUSIONS: The developed zero-shot learning NLP tool offers urologic researchers a highly generalizable and accurate method for data abstraction from unstructured text. An open access version of the tool is available for immediate use by the urologic community. PATIENT SUMMARY: In this report, we describe the design and validation of an artificial intelligence tool for abstracting discrete data from unstructured notes contained within the electronic medical record. This freely available tool, which is based on the GPT-3.5 technology from OpenAI, is intended to facilitate research and scientific discovery by the urologic community.

Saline-assisted fascial exposure (SAFE) technique to improve nerve-sparing in robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: To provide a summary of our initial experience and assess the impact of the Saline-Assisted Fascial Exposure (SAFE) technique on erectile function (EF), urinary continence, and oncological outcomes after Robot-Assisted Laparoscopic Radical Prostatectomy (RALP). PATIENTS AND METHODS: From January 2021 to July 2022, we included patients with a baseline Sexual Health Inventory for Men (SHIM) score of ≥17 and a high probability of extracapsular extension (ECE), ranging from 21% to 73%, as per the Martini et al. nomogram. A propensity score matching was carried out at a ratio of 1:2 between patients who underwent RALP + SAFE (33) and RALP alone (66). The descriptive statistical analysis is presented. The SAFE technique was performed using two approaches, transrectal guided by micro-ultrasound or transperitoneal. Its principle entails a low-pressure injection of saline solution in the periprostatic fascia to achieve an atraumatic dissection of the neural hammock. Potency was defined as a SHIM score of ≥17 and continence as no pads per day. RESULTS: At follow-up intervals of 6, 13, 26, and 52 weeks, the SHIM score differed significantly between the two groups, favouring the RALP + SAFE (P = 0.01, P < 0.001, P < 0.001, and P = 0.01, respectively). These results remained significant when the mean SHIM score was assessed. As shown by the cumulative incidence curve, EF rates were higher in the RALP + SAFE compared to the RALP alone group (log-rank P < 0.001). The baseline SHIM and use of the SAFE technique were independent predictors of EF recovery. CONCLUSIONS: The use of the SAFE technique led to better SHIM scores at 6, 13, 26, and 52 weeks after RALP in patients at high risk of ECE who underwent a partial NS procedure.

Intraoperative Fluorescent Image Guidance for Nerve-Sparing Prostatectomy: A Review of Historical Context and Current Research.

Fluorescent probes in the near-infrared (NIR) range have immense potential to improve observation of positive margins, lymph nodes, and nerves in prostatectomy. Development of fluorescent dyes and mechanisms of cellular uptake paved the way for the current emerging technologies. However, intracellular transport of fluorophores proved to be logistically challenging with respect to intraoperative deployment. Peptide-based probes with high specificity for nerves enabled broader and more rapid labeling. Key features of the ideal probe include selectivity, minimal background noise, safety, and low cost. Human neuropeptide 401 (HNP401) and oxazine-based probes perform well in these categories. As for tumor-specific labeling, prostate specific membrane antigen is relatively selective for the prostate and can be conjugated to a fluorophore. NIR spectrum emission is an ideal range for clinical imaging use, as fluorescence occurs outside the field of visible light, and tissue optical properties diverge significantly at the visible-NIR transition. Indocyanine, carbocyanine, and fluorescein derivatives are common fluorophore conjugates for the probes. Finally, to harness the power of fluorescence intraoperatively, the surgeon must look through a specialized lens. Multiphoton microscopy, optical coherence tomography, and confocal laser endomicroscopy have emerged as frontrunners in this arena. As with any evolving technology, ongoing research is expanding the applications of fluorescent intraoperative imaging in prostate surgery. Innovations in camera technology, dye selection, and image processing are refining the technique's capabilities. A core challenge of these technologies translating into the operating room relates to size and the ability to view objects at vastly different magnifications. Dual modality zoom settings are promising solutions. Furthermore, interdisciplinary collaboration between surgeons, imaging specialists, and researchers continues to drive advancements. In conclusion, fluorescent intraoperative imaging has the potential to usher in a new era of precision and safety in prostate surgery.

Focal therapy with high-intensity focused ultrasound for prostate cancer: 3-year outcomes from a prospective trial.

OBJECTIVE: To assess the oncological and functional outcomes of focal high-intensity focused ultrasound (HIFU) in treating localised prostate cancer (PCa), a 3-year prospective study was undertaken using periodic post-ablation saturation biopsies. PATIENTS AND METHODS: Men with two or fewer lesions of grade group (GG) ≤3 PCa were eligible for participation. Additional criteria included a prostate-specific antigen (PSA) level of ≤15 ng/mL, clinical T1c-T2, and a life expectancy of ≥10 years. The primary endpoint was failure-free survival (FFS), defined as absence of clinically significant PCa (csPCa) in- or out-of-field on protocol-mandated saturation biopsy, no whole-gland or systemic salvage treatment, PCa metastasis, or PCa-related death. Results are reported using two distinct definitions of csPCa: (i) the presence of any GG ≥2 and (ii) any GG ≥3 or core involvement of ≥6 mm. Secondary endpoints were functional patient-reported outcome measures addressing urinary, sexual, and bowel function. RESULTS: A total of 91 patients were included: six (7%) with GG1 and 85 (93%) with GG ≥2. In all, 83 (91%) underwent at least one follow-up biopsy. Biopsy attendance at 6, 12, and 36 months was 84%, 67%, and 51%, respectively. The FFS at these time points for any GG ≥2 PCa was 79% (95% confidence interval [CI] 80-88%), 57% (95% CI 48-69%) and 44% (95% CI 34-56%), respectively. Using the second definition, FFS were 88% (95% CI 81-95%), 70% (95% CI 61-81%) and 65% (95% CI 55-77%), respectively. The 3-year cancer-specific survival was 100%, and freedom from metastasis was 99%. Magnetic resonance imaging (MRI) (negative predictive value of up to 89%, 95% CI 84-93%) and relative decrease of PSA values (P = 0.4) performed poorly in detecting residual disease. Urinary and bowel assessment returned to baseline questionnaire scores within 3 months. In all, 17 (21%) patients reported meaningful worsening in erectile function. A significant decrease of PCa related anxiety was observed. CONCLUSIONS: Focal HIFU treatment for localised PCa shows excellent functional outcomes with half of the patients remaining cancer-free after 3 years. Whole-gland treatment was avoided in 81%. Early follow-up biopsies are crucial to change or continue the treatment modality at the right time, while the use of MRI and PSA in detecting PCa recurrence is uncertain.

Atherosclerosis of the iliac arteries for the prediction of erectile dysfunction and epistaxis in men undergoing abdominal CT scan.

BACKGROUND: To investigate the association between erectile dysfunction (ED) as well as epistaxis (ES) in relation to the extent of iliac atherosclerosis. METHODS: In this retrospective cross-sectional study, all consecutive male patients treated at our institution from 01/2016 to 12/2020 undergoing abdominal CT scan were evaluated. Patients (n = 1272) were invited by mail to participate in the study in returning two questionnaires for the evaluation of ED (IIEF-5) and ES. Patients who returned filled-in questionnaires within a 3-month deadline were included in the study. The extent of atherosclerosis in the common iliac artery (CIA) and the internal iliac artery (IIA) was assessed by calcium scoring on unenhanced CT. Stratification of results was performed according to reported IIEF-5 scores and consequential ED groups. RESULTS: In total, 437 patients (34.4% of contacted) met the inclusion criteria. Forty-two patients did not fulfill predefined age requirements (< 75 years) and 120 patients had to be excluded as calcium scoring on nonenhanced CT was not feasible. Finally, 275 patients were included in the analysis and stratified into groups of "no-mild" (n = 146) and "moderate-severe" (n = 129) ED. The calcium score (r=-0.28, p < 0.001) and the number of atherosclerotic lesions (r=-0.32, p < 0.001) in the CIA + IIA showed a significant negative correlation to the IIEF-5 score, respectively. Patients differed significantly in CIA + IIA calcium score (difference: 167.4, p < 0.001) and number of atherosclerotic lesions (difference: 5.00, p < 0.001) when belonging to the "no-mild" vs. "moderate-severe" ED group, respectively. A multivariable regression model, after adjusting for relevant baseline characteristics, showed that the number of atherosclerotic CIA + IIA lesions was an independent predictor of ED (OR = 1.05, p = 0.036), whereas CIA + IIA calcium score was not (OR = 1.00031, p = 0.20). No relevant correlation was found between ES episodes and IIEF-5 scores (r=-0.069, p = 0.25), CIA + IIA calcium score (r=-0.10, p = 0.87) or number of atherosclerotic CIA + IIA lesions (r=-0.032, p = 0.60), respectively. CONCLUSIONS: The number of atherosclerotic lesions in the iliac arteries on nonenhanced abdominal CT scans is associated with the severity of ED. This may be used to identify subclinical cardiovascular disease and to quantify the risk for cardiovascular hazards in the future. TRIAL REGISTRATION: BASEC-Nr. 2020 - 01637.

Biopsy and Erectile Functional Outcomes of Partial Prostate Ablation: A Systematic Review and Meta-analysis of Prospective Studies.

OBJECTIVE: To provide a systematic summary of prospectively performed studies evaluating ablative therapies for the treatment of prostate cancer (PCa) that included protocol-mandated assessment of (1) residual disease by post-treatment biopsy and/or (2) erectile functional outcomes. MATERIALS AND METHODS: We performed a comprehensive literature search in September 2022. Studies were evaluated according to a predefined and registered plan in PROSPERO (CRD42022302777). Only prospective trials with protocol-mandated post-treatment prostate biopsies or functional assessments were included. Targeted focal therapy was the only ablation pattern with sufficient data to perform meta-analyses (29 studies, 1079 patients). RESULTS: At baseline, 65.0% of patients treated with targeted focal therapy harbored grade group (GG) ≥2 PCa. One year after treatment, in-field treatment failure with ≥GG1 and ≥GG2 PCa occurred in 25.7% (range 11.1%-66.7%) and 8.8% (range 0%-27.8%) of men, respectively. In patients that received whole-gland biopsies 1year after ablation, residual ≥GG1 and ≥GG2 PCa was detected anywhere in the prostate in 43.7% (range 19.4%-71.7%) and 13.0% (range 0%-35.9%) of men. Erectile function was negatively affected by treatment, but 78.7% were potent 1year after targeted focal therapy (7 studies, 197 patients), and the average decrease in erectile function scores was 8.8% at 1year (21 studies, 760 patients). CONCLUSION: Though long-term data after targeted focal therapy are limited, oncologic and treatment failure occurred in 13% and 9% (≥GG2 at 6-12months after treatment). Most men were able to maintain potency. This work can help benchmark new techniques and power future trials.

Retrospective analysis of the uptake of active surveillance for low-risk prostate cancer in Zurich, Switzerland.

OBJECTIVES: Active surveillance for low-risk prostate cancer closely monitors patients conservatively instead of the pursuit of active treatment to reduce overtreatment of insignificant disease. Since 2009, active surveillance has been recommended as the primary management option in the European Association of Urology guidelines for low-risk disease. The present study aimed to investigate the use and uptake of active surveillance over 10 years in our certified prostate cancer centre (University Hospital of Zurich) compared with those derived from the cancer registry of the canton of Zurich, Switzerland. MATERIALS AND METHODS: We retrospectively identified all men diagnosed with low-risk prostate cancer at our institution and from the cancer registry of the canton of Zurich from 2009 to 2018. The primary treatment of each patient was recorded. Descriptive statistics were used to analyze the use of different treatments in our centre. The results were compared with those derived from the cancer registry. RESULTS: A total of 3393 men with low-risk prostate cancer were included in this study (University Hospital of Zurich: n = 262; cancer registry: n = 3131). In the University Hospital of Zurich and cancer registry cohorts, 146 (55.7%) and 502 (16%) men underwent active surveillance, respectively. The proportions of local treatment [115 (43.9%) vs 2220 (71%)] and androgen deprivation therapy [0 (0%) vs 43 (1.4%)] were distinctly lower in the University Hospital of Zurich cohort than in the cancer registry cohort. The uptake of active surveillance over the years was high in the University Hospital of Zurich cohort (35.4% in 2009 and 88.2% in 2018) but only marginal in the cancer registry cohort (12.2% in 2009 and 16.2% in 2018). CONCLUSION: Despite clear guideline recommendations, active surveillance for low-risk prostate cancer is still widely underused. Our analysis showed that access to a certified interdisciplinary tumour board significantly increases the use of active surveillance.

Limited Value of Bladder Wash Cytology During Follow-Up of Patients With Non-muscle Invasive Bladder Cancer.

Aims We aimed to assess the performance of bladder wash cytology (BWC) in daily clinical practice in a pure follow-up cohort of patients previously diagnosed with non-muscle invasive bladder cancer (NMIBC). Materials and methods We analyzed 2064 BWCs derived from 314 patients followed for NMIBC (2003-2016). Follow-up investigations were performed using cystoscopy (CS) in combination with BWC. Patients with suspicious CS and/or positive BWC underwent bladder biopsy or transurethral resection. BWC was considered positive if malignant or suspicious cells were reported. Sensitivity (Sn) and specificity (Sp) were calculated for the entire cohort and separately for low-grade (LG) and high-grade (HG) tumors, and carcinoma in situ (CIS) subgroups. Results A total of 95 recurrences were detected, of which only three were detected by BWC alone. Overall, Sn and Sp of BWC were 17.9% and 99.5%, respectively. For LG disease, these numbers were 14.0% and 100%, and for HG disease, these were 22.2% and 99.1%, respectively. For patients with CIS at initial diagnosis, Sn and Sp were 11.0% and 71.4%, respectively. For isolated primary CIS, Sn was 50.0%, and Sp was 98.2%. Conclusion Routine use of BWC in the follow-up for NMIBC is of limited value even in HG tumors. In the presence of isolated primary CIS, adjunct BWC might be justified.

Is Regular Radiographic Upper Urinary Tract Imaging for Surveillance of Non-Muscle Invasive Bladder Cancer Justified?

Patients with non-muscle invasive (NMI) urothelial bladder cancer (BC) are at increased risk for the development of a secondary upper-urinary-tract urothelial carcinoma (UTUC). We aimed to assess the usefulness of routine upper-tract imaging surveillance during NMIBC follow-up in a patient cohort of a tertiary academic center. All routine upper-tract-imaging scans using computerized tomography urography (CTU) between 2003 and 2016 were assessed for UTUC detection. A total of 315 patients were analyzed. Initial tumor stage was Ta in 207 patients (65.7%), T1 in 98 patients (31.1%) and pure CIS in 10 patients (3.2%). A total of 149 (47.3%) presented with low-grade (LG), and 166 (52.7%) with high-grade (HG) disease. Median follow-up was 48 months (IQR: 55). Four patients (1.2%) were diagnosed with UTUC during follow-up. All four patients presented with initial Ta HG BC. Two of the patients (50%) were diagnosed by routine upper tract imaging. The other two patients were diagnosed after development of symptoms. The 5- and 10-year UTUC-free survival was 98.5% (standard error (SE) 0.9) and 97.6% (SE 1.3), respectively. UTUCs were detected exclusively in patients with initial HG disease, indicating that upper-tract surveillance might only be necessary in these patients.

Prostate cancer detection rate in men undergoing transperineal template-guided saturation and targeted prostate biopsy.

OBJECTIVES: To compare prostate cancer (PCa) detection rate of transperineal template-guided saturation prostate biopsy (SBx) and multiparametric magnetic resonance imaging (mpMRI)/transrectal ultrasound fusion guided targeted biopsy (TBx). MATERIALS AND METHODS: We prospectively enrolled 392 men who underwent SBx and TBx in case of suspicious lesions from November 2016 to October 2019. Triggers for a biopsy were an elevated prostate-specific antigen (PSA) and/or positive digital rectal examination and only treatment naïve patients without a previous diagnosis of PCa were included. Study inclusion occurred before biopsy and a prebiopsy mpMRI was available in all men. SBx were taken from 20 different locations according to the modified Barzell zones. The primary endpoint was the detection rate of clinically significant PCa (csPCa) and insignificant PCa (ciPCa) by SBx and/or TBx by comparing the two methods alone and in combination. Additional TBx were taken for any prostate imaging-reporting and data system (PI-RADS) lesion ≥3 seen on the mpMRI. csPCa was defined as any Gleason score ≥7 and ciPCa as Gleason score 6. RESULTS: A total of 392 men with a median age of 64 years (interquartile range [IQR]: 58-69), a median PSA of 7.0 ng/ml (IQR: 4.8-10.1) were enrolled. Overall, PCa was found in 200 (51%) of all biopsied men, with 158 (79%) being csPCa and 42 (21%) ciPCa. A total of 268 (68%) men with a suspicious mpMRI and underwent a combined TBx and SBx, of whom csPCa was found in 139 (52%). In this subgroup, 116/139 (83%) csPCa would have been detected by TBx alone, and an additional 23 (17%) were found by SBx. Men with a negative mpMRI (PI-RADS < 3, n = 124, 32%) were found to have csPCa in 19 (15%) cases. In patients with a negative mpMRI in combination with a PSA density <0.1 ng/ml2 , only 8% (3/36) had csPCa. If only TBx would have been performed and all men with a negative mpMRI would not have been biopsed, 42/158 (27%) of csPCa would have been missed, and 38/42 (90%) ciPCa would have not been detected. On multivariable analysis, significant predictors of csPCa were increasing PSA (odds ratio, OR: 1.07 [95% confidence interval, CI: 1.03-1.11]), increasing age (OR: 1.07 [95% CI: 1.03-1.11]), PI-RADS score ≥ 3 (OR: 6.49 [95% CI: 3.55-11.89]), and smaller prostate volume (OR: 0.96 [95% CI: 0.95 -0.97] (p < 0.05 for all parameters). CONCLUSION: In comparison to SBx, TBx alone detects csPCa in only ¾ of all men with a positive mpMRI lesion. Thus, systematic biopsies in addition to TBx have to be considered at least in some who undergo a prostate biopsy. In men with a negative mpMRI, SBx still detects 15% csPCa, but similarly overdetecting ciPCa. According to our results, low PSA density and negative mpMRI findings could be used to decide which men can safely avoid biopsy.

Tumor Stent for Chronic Ureteral Obstruction: Which Are Predictors of Stent Failure?

Purpose: To identify predictors of UROSOFT® tumor stent failure. According to the manufacturer, this reinforced ureteral stent has a maximal dwell time of 6 months. Nonetheless, stent failure may reduce this maximal dwell time. Methods: All patients undergoing first-time UROSOFT tumor stent insertion in our institution between 2010 and 2018 were considered for this retrospective analysis. Primary endpoint was stent failure and defined as premature stent exchange or percutaneous nephrostomy insertion. The local ethics committee approved the study protocol (study ID: BASEC 2020-00175). Results: In total, 182 patients were available for analysis. Median age was 68 years. Causes for tumor stent placement were extrinsic ureteral obstruction in 144 patients (79%) and intrinsic obstruction in 38 patients (21%). Tumor stent failure-free survival estimates at 1, 2, 3, 4, and 5 months were 89%, 83%, 76%, 65%, and 52%, respectively. Patients with stent failure had significantly higher grade of hydronephrosis, higher urinary culture bacterial growth, higher serum white blood cell count, higher C-reactive protein, and lower estimated glomerular filtration rate at the time of reintervention, compared with patients who underwent regular stent exchange. Of all baseline and perioperative parameters, we found bilateral insertion, intrinsic ureteral obstruction, and urinary tract infection (UTI) at time of tumor stent insertion to be significant and independent predictors of stent failure (all p < 0.05). Conclusion: Despite a theoretical maximal dwell time of 6 months, ∼50% of all cases are subject to premature stent failure. Predictors of stent failure are bilateral insertion, intrinsic ureteral obstruction, and UTI at the time of tumor stent insertion. Preoperative antibiotic therapy may impact on stent failure rate.

Prognostic value of unifocal and multifocal positive surgical margins in a large series of robot-assisted radical prostatectomy for prostate cancer.

PURPOSE: To evaluate the prognostic value of positive surgical margins (PSM) focality for the prediction of biochemical recurrence (BCR) in patients undergoing robotic-assisted radical prostatectomy (RARP) for prostate cancer. METHODS: All men with clinically localized prostate cancer undergoing RARP in our tertiary referral centre between May 2005 and August 2016 were retrospectively identified. Patients with neoadjuvant therapy were excluded. Comparisons were made between cases with negative surgical margins (NSM), unifocal PSM (uPSM), and multifocal PSM (mPSM). RESULTS: From a total of 973 patients available for analysis, 315 (32%) had a PSM. In these patients, 190 had uPSM and 125 had mPSM. Focality of PSM was significantly associated with tumour stage and grade, preoperative PSA, and postoperative PSA persistence (all p < 0.001), but not with nerve sparing (NS) (p = 0.15). PSA persistence was found in 120 (12%) patients, resulting in 853 patients available for survival analyses with a median follow-up of 52 months. Both uPSM and mPSM were found to be independent predictors of BCR, conferring a hazard ratio of 1.9 (95% CI 1.3-3.0; p = 0.002) and 3.4 (95% CI 2.1-5.6; p < 0.001), respectively, when compared to NSM. In subgroup analyses, PSM was particularly predictive for BCR when patients underwent unilateral or bilateral NS (p ≤ 0.003). CONCLUSIONS: Based on a large case series of RARP, we found PSM focality to be an independent predictor of BCR, with a 1.9- and 3.4-fold risk increase for BCR in case of uPSM and mPSM, respectively. PSM seems to be of particular prognostic relevance when NS has been performed.

Long-term prognostic performance of low-dose coronary computed tomography angiography with prospective electrocardiogram triggering.

OBJECTIVES: To assess long-term prognosis after low-dose 64-slice coronary computed tomography angiography (CCTA) using prospective electrocardiogram-triggering. METHODS: We included 434 consecutive patients with suspected or known coronary artery disease referred for low-dose CCTA. Patients were classified as normal, with non-obstructive or obstructive lesions, or previously revascularized. Coronary artery calcium score (CACS) was assessed in 223 patients. Follow-up was obtained regarding major adverse cardiac events (MACE): cardiac death, myocardial infarction and elective revascularization. We performed Kaplan-Meier analysis and Cox regressions. RESULTS: Mean effective radiation dose was 1.7 ± 0.6 mSv. At baseline, 38% of patients had normal arteries, 21% non-obstructive lesions, 32% obstructive stenosis and 8% were revascularized. Twenty-nine patients (7%) were lost to follow-up. After a median follow-up of 6.1 ± 0.6 years, MACE occurred in 0% of patients with normal arteries, 6% with non-obstructive lesions, 30% with obstructive stenosis and 39% of those revascularized. MACE occurrence increased with increasing CACS (P < 0.001), but 4% of patients with CACS = 0 experienced MACE. Multivariate Cox regression identified obstructive stenosis, lesion burden in CCTA and CACS as independent MACE predictors (P ≤ 0.001). CONCLUSION: Low-dose CCTA with prospective electrocardiogram-triggering has an excellent long-term prognostic performance with a warranty period >6 years for patients with normal coronary arteries. KEY POINTS: • Coronary CT angiography (CCTA) has an excellent long-term prognostic performance. • CCTA can accurately stratify cardiac risk according to coronary lesion severity. • A normal CCTA predicts freedom from cardiac events for >6 years. • Patients with a coronary calcium score of 0 may experience cardiac events. • CCTA allows for reclassification of cardiac risk compared with ESC SCORE.