Concordance between Preoperative mpMRI and Pathological Stage and Its Influence on Nerve-Sparing Surgery in Patients with High-Risk Prostate Cancer.

BACKGROUND: We aimed to determine the concordance between the radiologic stage (rT), using multiparametric magnetic resonance imaging (mpMRI), and pathologic stage (pT) in patients with high-risk prostate cancer and its influence on nerve-sparing surgery compared to the use of the intraoperative frozen section technique (IFST). METHODS: The concordance between rT and pT and the rates of nerve-sparing surgery and positive surgical margin were assessed for patients with high-risk prostate cancer who underwent radical prostatectomy. RESULTS: The concordance between the rT and pT stages was shown in 66.4% (n = 77) of patients with clinical high-risk prostate cancer. The detection of patients with extraprostatic disease (≥pT3) by preoperative mpMRI showed a sensitivity, negative predictive value and accuracy of 65.1%, 51.7% and 67.5%. In addition to the suspicion of extraprostatic disease in mpMRI (≥rT3), 84.5% (n = 56) of patients with ≥rT3 underwent primary nerve-sparing surgery with IFST, resulting in 94.7% (n = 54) of men with at least unilateral nerve-sparing surgery after secondary resection with a positive surgical margin rate related to an IFST of 1.8% (n = 1). CONCLUSION: Patients with rT3 should not be immediately excluded from nerve-sparing surgery, as by using IFST some of these patients can safely undergo nerve-sparing surgery.

Multiparametric MRI may Help to Identify Patients With Prostate Cancer in a Contemporary Cohort of Patients With Clinical Bladder Outlet Obstruction Scheduled for Holmium Laser Enucleation of the Prostate (HoLEP).

Objective: To investigate the value of standard [digital rectal examination (DRE), PSA] and advanced (mpMRI, prostate biopsy) clinical evaluation for prostate cancer (PCa) detection in contemporary patients with clinical bladder outlet obstruction (BOO) scheduled for Holmium laser enucleation of the prostate (HoLEP). Material and Methods: We retrospectively analyzed 397 patients, who were referred to our tertiary care laser center for HoLEP due to BOO between 11/2017 and 07/2020. Of those, 83 (20.7%) underwent further advanced clinical PCa evaluation with mpMRI and/or prostate biopsy due to elevated PSA and/or lowered PSA ratio and/or suspicious DRE. Logistic regression and binary regression tree models were applied to identify PCa in BOO patients. Results: An mpMRI was conducted in 56 (66%) of 83 patients and revealed PIRADS 4/5 lesions in 14 (25%) patients. Subsequently, a combined systematic randomized and MRI-fusion biopsy was performed in 19 (23%) patients and revealed in PCa detection in four patients (5%). A randomized prostate biopsy was performed in 31 (37%) patients and revealed in PCa detection in three patients (4%). All seven patients (9%) with PCa detection underwent radical prostatectomy with 29% exhibiting non-organ confined disease. Incidental PCa after HoLEP (n = 76) was found in nine patients (12%) with advanced clinical PCa evaluation preoperatively. In univariable logistic regression analyses, PSA, fPSA ratio, and PSA density failed to identify patients with PCa detection. Conversely, patients with a lower International Prostate Symptom Score (IPSS) and PIRADs 4/5 lesion in mpMRI were at higher risk for PCa detection. In multivariable adjusted analyses, PIRADS 4/5 lesions were confirmed as an independent risk factor (OR 9.91, p = 0.04), while IPSS did not reach significance (p = 0.052). Conclusion: In advanced clinical PCa evaluation mpMRI should be considered in patients with elevated total PSA or low fPSA ratio scheduled for BOO treatment with HoLEP. Patients with low IPSS or PIRADS 4/5 lesions in mpMRI are at highest risk for PCa detection. In patients with a history of two or more sets of negative prostate biopsies, advanced clinical PCa evaluation might be omitted.

Effect of prostatic apex shape (Lee types) and urethral sphincter length in preoperative MRI on very early continence rates after radical prostatectomy.

PURPOSE: To test the effect of anatomic variants of the prostatic apex overlapping the membranous urethra (Lee type classification), as well as median urethral sphincter length (USL) in preoperative multiparametric magnetic resonance imaging (mpMRI) on the very early continence in open (ORP) and robotic-assisted radical prostatectomy (RARP) patients. METHODS: In 128 consecutive patients (01/2018-12/2019), USL and the prostatic apex classified according to Lee types A-D in mpMRI prior to ORP or RARP were retrospectively analyzed. Uni- and multivariable logistic regression models were used to identify anatomic characteristics for very early continence rates, defined as urine loss of ≤ 1 g in the PAD-test. RESULTS: Of 128 patients with mpMRI prior to surgery, 76 (59.4%) underwent RARP vs. 52 (40.6%) ORP. In total, median USL was 15, 15 and 10 mm in the sagittal, coronal and axial dimensions. After stratification according to very early continence in the PAD-test (≤ 1 g vs. > 1 g), continent patients had significantly more frequently Lee type D (71.4 vs. 54.4%) and C (14.3 vs. 7.6%, p = 0.03). In multivariable logistic regression models, the sagittal median USL (odds ratio [OR] 1.03) and Lee type C (OR: 7.0) and D (OR: 4.9) were independent predictors for achieving very early continence in the PAD-test. CONCLUSION: Patients' individual anatomical characteristics in mpMRI prior to radical prostatectomy can be used to predict very early continence. Lee type C and D suggest being the most favorable anatomical characteristics. Moreover, longer sagittal median USL in mpMRI seems to improve very early continence rates.

Implementation of Intraoperative Frozen Section During Radical Prostatectomy: Short-term Results from a German Tertiary-care Center.

BACKGROUND: Neurovascular bundle (NVB) preservation (NVBP) and surgical margin status are the main intraoperative factors influencing functional and oncologic outcomes in patients with prostate cancer undergoing radical prostatectomy (RP). OBJECTIVE: To test the impact of implementing the intraoperative frozen section technique (IFST) during NVBP on the frequency of NVB procedures and its effect on positive surgical margins (PSMs). DESIGN, SETTING, AND PARTICIPANTS: We relied on an institutional tertiary-care center database to identify patients who underwent RP (January 2014-October 2018). Until October 2017, decision for NVBP was taken based on preoperative magnetic resonance imaging, clinical characteristics, and nomograms, without the IFST. After November 2017, all patients received bilateral NVBP with the IFST, to check for a PSM in the area of the NVB. If a PSM occurred, a secondary resection of the respective NVB was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSM and NVB procedures were assessed. Subgroup analyses focused on pathologic tumor stages. RESULTS AND LIMITATIONS: Overall, 346 patients were identified. Of these patients, 54.9% (n=190) versus 45.1% (n=156) underwent RP without versus with the IFST. By using the IFST during NVBP, the PSM decreased from 29.5% to 15.4% (p=0.003) in the entire cohort (14.6% vs 8.6% in pT2; 47.1% vs 29.4% in pT3). Conversely, NVBP increased from 55.3% to 95.5% (p<0.001) in the entire cohort (68.9% vs 99.0% in pT2; 39.1% vs 88.2% in pT3). In multivariable logistic regressions, IFST use was an independent predictor of PSMs (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.30-0.98; p=0.047) and NVBP (OR: 5.60, 95% CI: 3.10-10.51; p<0.001) after controlling for patient and tumor characteristics. CONCLUSIONS: Implementation of the IFST during NVBP resulted in more frequent NVBP and was associated with a lower PSM, compared with RP without the IFST. Therefore, the IFST should be performed, if available. PATIENT SUMMARY: The intraoperative frozen section technique (IFST) during preservation of neurovascular bundles (NVBP) should be offered to patients who undergo radical prostatectomy. The IFST can reduce positive margin rates and increase the rate of NVBP.

Performance of Combined Magnetic Resonance Imaging/Ultrasound Fusion-guided and Systematic Biopsy of the Prostate in Biopsy-naïve Patients and Patients with Prior Biopsies.

BACKGROUND: As recent prospective studies showed targeted biopsies (TBs) to be superior to systematic biopsies (SBs), magnetic resonance imaging (MRI) is gaining wider acceptance in the diagnostic setup of prostate cancer (PCa). OBJECTIVE: To examine the performance of MRI/ultrasound fusion-guided TB in combination with SB in the detection of PCa in patients with and without prior biopsy. DESIGN, SETTING, AND PARTICIPANTS: A total of 219 men undergoing combined transrectal TB and 12-core SB from February 2014 to November 2018 were analysed. For all patients showing a suspicion of PCa in multiparametric MRI, TB was performed using fusion imaging with real-time virtual sonography. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cancer detection rates (CDRs) and significant CDRs for TB, SB, and TB+SB were analysed. Further stratification was performed for a number of previous biopsy sessions and Prostate Imaging Reporting and Data System (PI-RADS) score. Significant PCa was defined as any PCa with Gleason score ≥3+4. RESULTS AND LIMITATIONS: Of all, 141 patients were biopsy naïve, while 78 patients had at least one prior biopsy. Median prostate-specific antigen (PSA) level prior to biopsy was 8.4ng/ml (interquartile range 5.5-11.8ng/ml). The overall CDR was 63.5% (139/219), while the PI-RADS-dependent CDRs for the combination of TB+SB were 29.1%, 67.7%, and 86.2% for patients with PI-RADS 3, 4, and 5, respectively. Looking at TB or SB alone, CDRs were 55.7% and 57.5%. The overall CDR for significant PCa was 51.6%. (18.2%, 50.5%, and 81.5% for PI-RADS 3, 4, and 5, respectively). CDRs were significantly higher for biopsy-naïve patients (65.2% vs 67.4% vs 71.6% for TB vs SB vs TB+SB) than for patients with one previous negative biopsy (38.2% vs 43.6% vs 50.9% for TB vs SB vs TB+SB; all p<0.01). CONCLUSIONS: Multiparametric MRI can raise the CDR in patients with and without biopsies performed earlier. With higher PI-RADS lesions, the risk of harbouring PCa increases. Combining TB with SB further improved the diagnostic accuracy in biopsy-naïve patients and after one previous negative biopsy. PATIENT SUMMARY: Multiparametric magnetic resonance imaging before prostate biopsy increases cancer detection rates in biopsy-naïve patients and patients with a previous negative biopsy. The combination of targeted biopsy with systematic biopsy improved the diagnostic accuracy in biopsy-naïve patients and after one previous negative biopsy.

Comparison of Complication Rates with Antibiotic Prophylaxis with Cefpodoxime Versus Fluoroquinolones After Transrectal Prostate Biopsy.

BACKGROUND: After recommended restriction of the use of fluoroquinolones, the optimal antibiotic prophylaxis for transrectal prostate biopsy is still under debate. OBJECTIVE: To test the effectiveness of cefpodoxime as oral antibiotic prophylaxis for transrectal prostate biopsies and the complication rates relative to fluoroquinolones. DESIGN, SETTING, AND PARTICIPANTS: Antibiotic prophylaxis for transrectal prostate biopsies at the Department of Urology at University Hospital Frankfurt was fluoroquinolones for 342 consecutive patients in January 2018 and December 2019 and cefpodoxime for 100 patients from January 2020 to July 2020. Data were prospectively evaluated and retrospectively analyzed. Patients were followed up according to clinical routine at 6 wk after biopsy at the earliest. Patients without follow-up (n = 98) and those receiving antibiotic prophylaxis other than cefpodoxime or fluoroquinolones (n = 15) were excluded. INTERVENTION: Use of cefpodoxime or fluoroquinolones as antibiotic prophylaxis for transrectal prostate biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression models were used to predict biopsy-related complications according to antibiotic prophylaxis. RESULTS AND LIMITATIONS: Of 442 patients, 100 (22.6%) received cefpodoxime as antibiotic prophylaxis. Patient baseline and biopsy characteristics were comparable between the cefpodoxime and fluoroquinolone groups. Moreover, there were no differences in the number of prior prostate biopsies or the proportions of systematic vs. fusion biopsies (p > 0.05). There were no differences between the groups in infectious complications such as epididymitis and prostatitis after biopsy. Infectious complication rates were very low, at 2.0% in the cefpodoxime and0.9%fluoroquinolone group. Moreover, there were no differences between the groups in patient-reported complications, such as gross hematuria occurring at more than 5 d after biopsy, hematospermia, or rectal bleeding. In multivariable analyses, after adjustment for patient and prostate biopsy characteristics, cefpodoxime was not associated with higher complication rates than fluoroquinolones (p > 0.05). CONCLUSIONS: Complications after transrectal prostate biopsies are rare and cefpodoxime might be a sufficient choice as oral antibiotic prophylaxis and noninferior compared to fluoroquinolones. PATIENT SUMMARY: Cefpodoxime might be a sufficient choice as an easily applicable oral antibiotic prophylaxis for transrectal prostate biopsy. The safety profile of cefpodoxime is comparable to the safety profile of fluoroquinolones.

The Effect of Adverse Patient Characteristics on Perioperative Outcomes in Open and Robot-Assisted Radical Prostatectomy.

Objective: To analyze the effect of adverse preoperative patient and tumor characteristics on perioperative outcomes of open (ORP) and robot-assisted radical prostatectomy (RARP). Material and Methods: We retrospectively analyzed 656 patients who underwent ORP or RARP according to intraoperative blood loss (BL), operation time (OR time), neurovascular bundle preservation (NVBP) and positive surgical margins (PSM). Univariable and multivariable logistic regression models were used to identify risk factors for impaired perioperative outcomes. Results: Of all included 619 patients, median age was 66 years. BMI (<25 vs. 25-30 vs. ≥30) had no influence on blood loss. Prostate size >40cc recorded increased BL compared to prostate size ≤ 40cc in patients undergoing ORP (800 vs. 1200 ml, p < 0.001), but not in patients undergoing RARP (300 vs. 300 ml, p = 0.2). Similarly, longer OR time was observed for ORP in prostates >40cc, but not for RARP. Overweight (BMI 25-30) and obese ORP patients (BMI ≥30) showed longer OR time compared to normal weight (BMI <25). Only obese patients, who underwent RARP showed longer OR time compared to normal weight. NVBP was less frequent in obese patients, who underwent ORP, relative to normal weight (25.8% vs. 14.0%, p < 0.01). BMI did not affect NVPB at RARP. No differences in PSM were recorded according to prostate volume or BMI in ORP or RARP. In multivariable analyses, patient characteristics such as prostate volume and BMI was an independent predictor for prolonged OR time. Moreover, tumor characteristics (stage and grade) predicted worse perioperative outcome. Conclusion: Patients with larger prostates and obese patients undergoing ORP are at risk of higher BL, OR time or non-nervesparing procedure. Conversely, in patients undergoing RARP only obesity is associated with increased OR time. Patients with larger prostates or increased BMI might benefit most from RARP compared to ORP.

Complication Rates After TRUS Guided Transrectal Systematic and MRI-Targeted Prostate Biopsies in a High-Risk Region for Antibiotic Resistances.

Introduction: There is still an ongoing debate whether a transrectal ultrasound (TRUS) approach for prostate biopsies is associated with higher (infectious) complications rates compared to transperineal biopsies. This is especially of great interests in settings with elevated frequencies of multidrug resistant organisms (MDRO). Materials and Methods: Between 01/2018 and 05/2019 230 patients underwent a TRUS-guided prostate biopsy at the department of Urology at University Hospital Frankfurt. Patients were followed up within the clinical routine that was not conducted earlier than 6 weeks after the biopsy. Among 230 biopsies, 180 patients took part in the follow-up. No patients were excluded. Patients were analyzed retrospectively regarding complications, infections and underlying infectious agents or needed interventions. Results: Of all patients with follow up, 84 patients underwent a systematic biopsy (SB) and 96 a targeted biopsy (TB) after MRI of the prostate with additional SB. 74.8% of the patients were biopsy-naïve. The most frequent objective complications (classified by Clavien-Dindo) lasting longer than one day after biopsy were hematuria (17.9%, n = 32), hematospermia (13.9%, n = 25), rectal bleeding (2.8%, n = 5), and pain (2.2%, n = 4). Besides a known high MDRO prevalence in the Rhine-Main region, only one patient (0.6%) developed fever after biopsy. One patient each (0.6%) consulted a physician due to urinary retention, rectal bleeding or gross hematuria. There were no significant differences in complications seen between SB and SB + TB patients. The rate of patients who consulted a physician was significantly higher for patients with one or more prior biopsies compared to biopsy-naïve patients. Conclusion: Complications after transrectal prostate biopsies are rare and often self-limiting. Infections were seen in <1% of all patients, regardless of an elevated local prevalence of MDROs. Severe complications (Clavien-Dindo ≥ IIIa) were only seen in 3 (1.7%) of the patients. Repeated biopsy is associated with higher complication rates in general.

Performance and Impact of Prostate Specific Membrane Antigen-Based Diagnostics in the Management of Men with Biochemical Recurrence of Prostate Cancer and its Role in Salvage Lymph Node Dissection.

Up to 50% of patients initially treated for prostate cancer in a curative intent experience biochemical recurrence, possibly requiring adjuvant treatment. However, salvage treatment decisions, such as lymph node dissection or radiation therapy, are typically based on prostate specific antigen (PSA) recurrence. Importantly, common imaging modalities (e.g., computed tomography [CT], magnetic resonance imaging, and bone scan) are limited and the detection of recurrent disease is particularly challenging if PSA is low. Prostate specific membrane antigen (PSMA) positron-emission tomography/computed tomography (PET/CT) is a novel and promising imaging modality which aims to overcome the incapability of early identification of distant and regional metastases. Within this review, we summarize the current evidence related to PSMA-PET/CT in prostate cancer men diagnosed with biochemical recurrence after local treatment with curative intent. We discuss detection rates of PSMA-PET/CT stratified by PSA-levels and its impact on clinical decision making. Furthermore, we compare different image-fusion techniques such as PSMA-PET vs. F-/C-Choline-PET scans vs. PSMA-single photon emission computed tomography/CT. Finally, we touch upon the contemporary role of radio-guided-PSMA salvage lymphadenectomy.

Very Early Continence After Radical Prostatectomy and Its Influencing Factors.

Introduction and Objectives: Surgical techniques such as preservation of the full functional-length of the urethral sphincter (FFLU) have a positive impact on postoperative continence rates. Thereby, data on very early continence rates after radical prostatectomy (RP) are scarce. The aim of the present study was to analyze very early continence rates in patients undergoing FFLU during RP. Materials and Methods: Very early-continence was assessed by using the PAD-test within 24 h after removal of the transurethral catheter. The PAD-test is a validated test that measures the amount of involuntary urine loss while performing predefined physical activities within 1 h (e.g., coughing, walking, climbing stairs). Full continence was defined as a urine loss below 1 g. Mild, moderate, and severe incontinence was defined as urine loss of 1-10 g, 11-50 g, and >50 g, respectively. Results: 90 patients were prospectively analyzed. Removal of the catheter was performed on the 6th postoperative day. Proportions for no, mild, moderate and severe incontinence were 18.9, 45.5, 20.0, and 15.6%, respectively. In logistic regression younger age was associated with significant better continence (HR 2.52, p = 0.04), while bilateral nerve-sparing (HR 2.56, p = 0.057) and organ-confined tumor (HR 2.22, p = 0.078) showed lower urine loss, although the effect was statistically not significant. In MVA, similar results were recorded. Conclusion: Overall, 64.4% of patients were continent or suffered only from mild incontinence at 24 h after catheter removal. In general, reduced urine loss was recorded in younger patients, patients with organ-confined tumor and in patients with bilateral nerve sparing. Severe incontinence rates were remarkably low with 15.6%.

MRI-Fusion Targeted vs. Systematic Prostate Biopsy-How Does the Biopsy Technique Affect Gleason Grade Concordance and Upgrading After Radical Prostatectomy?

Introduction: MRI-targeted biopsy (TB) increases overall prostate-cancer (PCa) detection-rates and decreases the risk of insignificant PCa detection. However, the impact of these findings on the definite pathology after radical prostatectomy (RP) is under debate. Materials and Methods: Between 01/2014 and 12/2018, 366 patients undergoing prostate biopsy and RP were retrospectively analyzed. The correlation between biopsy Gleason-score (highest Gleason-score in a core) and the RP Gleason-score in patients undergoing systematic biopsy (SB-group) (n = 221) or TB+SB (TB-group, n = 145) was tested using the ISUP Gleason-group grading (GGG, scale 1-5). Sub analyses focused on biopsy GGG 1 and GGG ≥ 2. Results: Proportions of biopsy GGG 1-5 in the SB-group and TB-group were 24.4, 37.6, 19, 10.9, 8.1% and 13.8, 43.4, 24.2, 13.8, 4.8%, respectively (p = 0.07). Biopsy and pathologic GGG were concordant in 108 of 221 (48.9%) in SB- and 74 of 145 (51.1%) in TB-group (p = 0.8). Gleason upgrading was recorded in 33.5 and 31.7% in SB- vs. TB-group (p = 0.8). Patients with biopsy GGG 1 undergoing RP showed an upgrading in 68.5%(37/54) in SB- and 75%(15/20) in TB-group (p = 0.8). In patients with biopsy GGG ≥ 2 concordance increased for both biopsy approaches (54.5 vs. 55.2% for SB- vs. TB-group, p = 0.9). Discussion: Irrespective of differences in PCa detection-rates between TB- and SB-groups, no significant differences in GGG concordance and upgrading between patients of both groups undergoing biopsy, followed by RP, were recorded. Concordance rates increased in men with biopsy GGG ≥ 2. TB seems to detect more patients with PCa without a difference in concordance with final pathology.

The number decision task: Investigation of the representation of multi-digit numbers.

The ability to process multi-digit numbers is an essential skill which we investigated using a number decision task. Subjects were asked to decide whether a target number (e.g., 649) is too small or too large to be the mean between two delimiter numbers that constituted the interval (e.g., 567 and 715). Three-digit numbers were presented vertically with (1) growing interval sizes (i.e., distance between the two delimiters; e.g., interval size between 567 and 715 is 148) and target gap to the mean (e.g., the gap between the 'real' mean 641 and the target 649 is 8) and (2) growing interval sizes with constant gap to the mean (i.e., for each interval size the gap between target and mean was held constant). The results showed that target gap to the mean "masked" the influence of interval sizes, i.e., subjects' performance improved with increasing interval sizes (distance effect). This effect was reversed when constant target gaps to the mean and growing interval sizes were presented. These results were replicated presenting the numbers horizontally and with two-digit numbers. Additionally, a significant influence of decade but no effect of unit compatibility on reaction times and error rates, on number magnitude (size effect) and response format was found. Overall, we showed that the number decision task is an efficient tool to investigate multidigit number representation and the results from the experiments revealed evidence for a hybrid model of multi-digit number representation in which numbers are represented as a whole but also on separate mental number lines that interact with each other.