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Background/objectives: Radical prostatectomy (RP) may be considered for recurrent prostate cancer (PCa) following primary curative-intended local therapy. The effect of different prior therapies on patient-reported outcome measures (PROMs) after RP is not well defined., Methods: Validated PROMs (SF-12, EPIC-26, Decision Regret Scale) were used to compare health-related quality of life (HRQOL) and functional status changes following salvage RP after radiotherapy (RT-sRP) or focal therapy (FT-sRP), relative to primary RP., Results: Among 26,515 RP patients who underwent RP between 2014 and 2024, 107 (0.4%) previously received radiotherapy (RT-sRP) and 98 (0.4%) previously received focal therapy (FT-sRP). Compared with primary patients before RP, only the sexual function of RT-sRP patients was lower (EPIC score, 51 vs. 75, p < 0.001). One year after RP, RT-sRP patients exhibited lower functional status in all EPIC-26 domains compared to primary RP patients, whereas FT-sRP patients did not differ significantly. For instance, the median 1 yr EPIC-26 urinary incontinence scores were 46 (RT-sRP), 86 (FT-sRP), and 92 (primary RP). In adjusted mixed model analyses, the detrimental effects of RT-sRP vs. primary RP were further validated. In contrast, no such association was observed for FT-sRP. Decision regret and severe complications were low., Conclusions: Prior FT had only a marginal effect on HRQOL and functional status following RP, while urinary continence and sexual function were lower for RT-sRP patients as compared to primary RP patients. However, from an overall PROM perspective, prior therapies did not exert a prohibitive effect that would preclude RP as a treatment option in those patients.

We analyzed data for a cohort of 111 patients with EMBARK-like biochemical recurrence (BCR) of prostate cancer (prostate-specific antigen [PSA] doubling time ≤9 mo, PSA ≥1 ng/ml) after radical prostatectomy and localized oligorecurrence on prostate-specific membrane antigen (PSMA)-based imaging. All patients underwent PSMA-radioguided surgery (RGS). At PSMA-RGS, the median PSA was 1.95 ng/ml (interquartile range [IQR] 1.36-3.20) ng/ml and the median PSA doubling time was 4.0 mo (IQR 2.5-5.5). Clavien-Dindo grade >IIIa complications occurred in nine of 111 patients (8.1%). A complete biochemical response (cBR; PSA decline ≤0.2 ng/ml after PSMA-RGS) was observed in 53 patients (47.7%). In the cBR group (equivalent to the treatment suspension criterion in EMBARK), estimated survival rates at 2 yr were 49.9% (95% confidence interval [CI] 37.2-67.1%) for BCR-free survival and 65.2% (95% CI 52.2-81.4%) for treatment-free survival. A relevant proportion of our PSMA-RGS cohort with localized oligorecurrence on PSMA-based imaging fulfilled the EMBARK criteria. PSMA-RGS yielded meaningful biochemical responses that translated to long-lasting treatment-free periods. PATIENT SUMMARY: For some patients with prostate cancer and no evidence of metastasis on conventional imaging but high risk of metastatic progression, modern molecular imaging identifies small cancer deposits that can be removed via targeted surgery. This surgery led to a significant decrease in PSA (prostate-specific antigen) levels, which allowed a longer break from further treatment., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: To evaluate how prostate-specific antigen (PSA) levels decrease after removal of isolated prostate cancer (PCa) nodal metastases in relation to their diameter/volume ("PSA-density of PCa-metastases") and maximum standardized uptake value (SUV max )., Methods: A total of 83 consecutive patients with solitary nodal recurrence after radical prostatectomy who underwent prostate-specific membrane antigen-radioguided salvage surgery were retrospectively analyzed. Using multivariable linear regression models, the PSA-decrease after removal of each PCa-metastases (=PSA-contribution of each PCa-metastases) was correlated with the long axis diameter/estimated volume and the SUV max of each removed metastasis. Sizes were measured by imaging and histopathologic examination., Results: A total of 83 patients were included with a median (interquartile range [IQR]) PSA-decrease of 0.56 [0.22, 1.31] ng/mL after salvage surgery. The median [IQR] long axis diameters in imaging and histopathological examination were 8.0 [6.0, 11.0] mm and 8.4 [5.5, 11.1] mm, respectively. The median [IQR] estimated volumes were 0.13 [0.05, 0.32] cc (imaging) and 0.05 [0.02, 0.17] cc (pathology). In multivariable linear regression analyses, the estimated PSA-contribution ([95% confidence interval [CI]) of each millimeter of long axis diameter was 0.09 [0.03, 0.14] ng/mL (imaging) or 0.08 [0.03, 0.12] ng/mL (histology). The minimum diameter for biochemical recurrence (PSA ≥ 0.2 ng/mL) was >2.2 mm (imaging) or >2.5 mm (histology). The estimated PSA-contribution [95% CI] of each cc cancer volume was 1.23 [0.51, 1.94] ng/mL (imaging) or 1.46 [0.40, 2.52] ng/mL (histology). SUV max as surrogate parameter for tissue composition was associated with increased PSA-contribution of PCa-metastases (+0.03-0.05 ng/mL per unit increase)., Conclusions: The diameter/volume and SUV max of metastatic tissue correlate with its contribution to PSA levels. Therefore, very small metastases may produce too little PSA for biochemical recurrence., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

Background: To examine the feasibility and safety of the SENSEI ® drop-in gamma probe for robot-assisted, prostate-specific membrane antigen (PSMA)-radioguided salvage surgery (RGS) in lymph node or local oligorecurrent prostate cancer (PCa), detected via PSMA positron emission tomography/computed tomography (PET/CT)., Methods: The first thirteen patients with pelvic oligorecurrent PCa who underwent [ 99m Tc]Tc-PSMA-I&S RGS using the SENSEI ® drop-in gamma probe at the Martini-Klinik (February-June 2024) were retrospectively analyzed. Radioactivity measurements in counts per second (CPS) as absolute values or ratios (CPS of tumor specimens/mean CPS from the patients' benign tissues) were correlated with preoperative imaging and pathological findings (benign/malignant, lesion size). Postoperative complete biochemical response (cBR) was defined as prostate-specific antigen (PSA) levels of <0.2 ng/mL., Results: Fifty-four specimens were removed from 13 patients, with nineteen (35%) containing PCa. All patients had one PSMA PET/CT-positive lesion, which were all detected intraoperatively. These lesions showed higher ex vivo CPS, CPS ratios, and larger cancer diameters than PSMA PET/CT-negative lesions (all p < 0.05). Cancer-containing specimens exhibited higher CPS and CPS ratios than benign tissues (median values of 45 vs. 3, and 9.9 vs. 1.0, both p < 0.001). In total, 12/13 (92%) patients achieved cBR., Conclusions: This device yielded excellent detection rates with good correlation to preoperative imaging and histological results without adverse events.

Objectives: To determine the surgical and oncologic outcomes of salvage radical prostatectomy (sRP) after FT failure., Materials and Methods: Patients who consecutively underwent primary RP or sRP after FT failure between 2008 and 2022 were retrospectively selected. Primary or sRP were performed with either a robot-assisted or open approach. All surgeries were performed by surgeons with experience of ≥ 500 cases. Biochemical recurrence-free survival (BFS), intra- and postoperative surgical and functional outcomes were assessed. To evaluate the impact of surgical setting, propensity score (PS) matching was performed., Results: 80 patients received sRP. Outcomes were analyzed using PS-matched cohorts (203 RPs vs. 68 sRPs). After a median follow-up of 25.4 months, sRP and RP had equal BFS (24mo-BFS: 72.4% vs. 76.0% (p = 0.8)). No statistically significant differences were found between sRP and RP in terms of median operative time (OT) (171 min vs. 168 min), estimated blood loss (EBL) (500 ml vs. 500 ml), length of hospital stay (LOS) (7 days vs. 7 days) and time to catheter removal (11 days vs. 11 days) and 1-year continence rates (all standardized mean differences ≤ 0.1). The main limitation is the retrospective study design., Conclusion: In the hands of experienced surgeons, sRP after FT offered comparable surgical and oncologic outcomes as RP in a primary setting., Competing Interests: Declaration. Conflict of interest: The authors declare that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To explore the detection rates of clinically significant prostate cancer (csPCa; ISUP ≥2) in patients with a single MRI lesion that is visible or invisible on transrectal ultrasound (TRUS) during biopsy., Methods: Retrospective analyses of patients who underwent targeted and systematic biopsy of the prostate for one MRI-visible lesion (PI-RADS score ≥ 3) between 2017 and 2022. TRUS-visibility, PI-RADS score, and clinical parameters were recorded prospectively. Univariable and multivariable logistic regression models were used to identify predictors of csPCa., Results: 277 consecutive patients with one MRI-visible lesion were identified. A correlating lesion on TRUS was present in 147/277 (53%). The median age, PSA level, and prostate volume were 68.0 years (IQR: 62.0-73.0), 7.3 ng/ml (IQR: 5.4-10.8) and 45.0 cc (IQR: 32.0-68.0), respectively. Baseline parameters were not significantly different between the two groups. CsPCa was detected in 59/130 (45%) without and in 102/147 (69%) patients with a corresponding TRUS lesion. In multivariable logistic regression analysis predicting csPCa, TRUS-visibility (OR: 2.13, CI: 1.14-4.03, p = 0.02) and PI-RADS score (PI-RADS 4: OR: 7.28, CI: 3.33-17.19; PI-RADS 5: OR: 13.39, CI: 5.27-36.83, p < 0.001) achieved independent predictor status., Conclusions: Bimodal-visible lesions more often harbored csPCa and were easier to target. TRUS-visibility of MRI lesions is an independent predictor of csPCa. Therefore, education in both modalities is essential. Despite MRI, the ultrasound should still be diligently examined., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

Purpose: The aim of our study was to investigate the impact of the time interval between prostate biopsy and radical prostatectomy (RP) on postoperative urinary continence (UC)/erectile function (EF). From a clinical point of view, an interval of several weeks seems to facilitate surgical preparation., Materials and Methods: We retrospectively analyzed patients who underwent RP for localized prostate cancer (PCa) in a tertiary care center between 2011 and 2020. We evaluated the influence of the following variables on UC and EF 1 year after RP: time from biopsy to RP, age, BMI, pathological T-stage, EF and intraoperative nerve sparing (unilateral vs. bilateral). For this purpose, we performed linear regression analyses as well as manual grouping and cluster analyses to identify possible temporal cutoff ranges. The EPIC-26 and the IIEF questionnaires were used for the assessment of UC and EF., Results: We identified 6202 consecutive patients who underwent RP. Neither manual grouping nor cluster analyses showed a significant difference in continence or potency after RP. According to linear regression models, only age was an independent predictor of incontinence (95%-CI 0.006-0.01), and EF before RP (95%-CI 0.22-0.26), age (95%-CI - 0.68 to - 0.5), BMI (95%-CI - 0.66 to - 0.29) and bilateral NS (95%-CI 5.5-2.1) had significant impacts on postoperative EF (all p < 0.001)., Conclusion: In the selected patient population, the time interval between prostate biopsy and RP did not seem to have an effect on postoperative functional outcomes (UC and EF)., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflicts of interest., (© 2024. The Author(s).)

Background and Objective: In patients with oligorecurrent prostate cancer (PCa), prostate-specific membrane antigen-targeted radioguided surgery (PSMA-RGS) prolongs treatment-free survival. Data on patient-reported outcome measures (PROMs) are lacking., Methods: A retrospective assessment of validated PROMs (12-item Short Form Health Survey [SF-12], 26-item Expanded Prostate Index Composite, and Decision Regret Scale [DRS]) was performed before and after PSMA-RGS for oligorecurrent PCa. Mixed models were used., Key Findings and Limitations: A total of 373 patients were analyzed at a median (interquartile range [IQR]) age of 66 (61, 70) yr and prostate-specific antigen of 0.8 (0.4, 1.5) ng/ml. Six months after PSMA-RGS, the median (IQR) scores for the PROMs were as follows: SF-12 physical 54 (49, 56), SF-12 mental 53 (43, 56), urinary incontinence 86 (52, 100), urinary irritation 94 (88, 100), sexual 27 (9, 57), hormonal 90 (79, 100), and bowel 96 (83, 100). Only the sexual score decreased in a significant fashion from baseline over time (median [IQR], 17 [8,38]) after 3 yr vs 37 [13, 63] at baseline, p  = 0.01). The decision regret remained low (median [IQR] DRS at 1 yr: 5 [0, 20]). More than 90% of the patients reported that PSMA-RGS was the correct decision after 1 yr., Conclusions and Clinical Implications: We recorded no significant decrease in quality of life or any functional status domain, except sexual. While decision regret was low, sexual functioning might deteriorate further., Patient Summary: No significant deterioration in health-related quality of life was reported after removing early prostate cancer metastases. Very few patients expressed remorse about their decision for salvage surgery., (© 2024 The Author(s).)

Introduction: Leukemia history affects some radical prostatectomy (RP) patients. Although its prevalence and effect as an adverse risk factor are well known in cardiac surgery, the number of RP patients with a leukemia history, as well as their rate of adverse in-hospital outcomes, are unknown., Methods: We identified RP patients (National Inpatient Sample 2000-2019), stratified according to the presence or absence of a leukemia history. Descriptive analyses, propensity score matching (PSM, ratio 1:10), and multivariable logistic regression models were used., Results: Of 259,939 RP patients, 416 (0.2%) had a leukemia history. Their proportion increased from 0.1 to 0.2% covering the study span ( p < 0.01). Leukemia history patients were older (median age, 64 vs. 62 years, p < 0.001). After PSM for age, insurance status, ethnicity, pelvic lymph node dissection, and Charlson Comorbidity Index, leukemia history RP patients exhibited higher rates of acute kidney injury (<2.6 vs. 0.9%; Odds Ratio [OR] 2.0, p = 0.02), more frequently underwent dialysis (3.6 vs. 1.9%; OR 1.9, p = 0.03), and more frequently had a length of stay exceeding one week (4.8 vs. 2.5%; OR 2.0, p = 0.006)., Conclusions: Although leukemia history RP patients are rare, their numbers have increased. Renal complications and extended hospital stays are more frequent in those individuals.

Purpose: To compare the oncological and surgical outcomes of patients with recurrent prostate cancer (PCa) who underwent either open or newly established robot-assisted salvage prostate-specific membrane antigen-radioguided surgery (PSMA-RGS)., Materials and Methods: Patients who consecutively underwent PSMA-RGS for PCa recurrence between January 2021 and December 2022 were identified. The rate of complete biochemical response, biochemical recurrence-free survival [BFS], and the rate of salvage therapy were evaluated. Univariable and multivariable regression models tested the association between the surgical approach and surgical outcomes., Results: Overall, 85 patients were selected, with 61 patients (72%) undergoing open PSMA-RGS and 24 patients (28%) receiving a robot-assisted approach. The oncological outcomes of the two groups were comparable (12-month BFS: 41% (Confidence interval (CI): 29-58%) vs. 39% (CI: 19-79%), p = 0.9, respectively). According to multivariable regression models, the robotic approach did not significantly influence estimated blood loss (EBL) (β = -40, 95% CI: -103, 22; p = 0.2) and significantly increased operative time (OT) (β = 28, 95% CI: 10, 46; p = 0.002). No Clavien-Dindo III-V complications were reported in the robotic group., Conclusion: Both, the open as well as the robot-assisted approach for PSMA-RGS had comparable oncological outcomes. No safety concerns arose for the robotic-assisted approach offering a potentially improved quality of life for patients., (© 2023. The Author(s).)

Objectives: To evaluate the long-term oncological outcomes and functional results of the neurovascular structure-adjacent frozen-section examination (NeuroSAFE) during nerve-sparing (NS) radical prostatectomy (RP)., Materials and Methods: A 10-yr survival analysis on 11069 RPs performed with or without the NeuroSAFE, between January 2002 to June 2011 was carried out. In the NeuroSAFE cohort, the neurovascular structure-adjacent prostatic margins are removed and stained for cryo-sectioning during RP. In case of a PSM, partial or full removal of the neurovascular bundle was performed. The impact of NeuroSAFE on biochemical recurrence-free survival (BFS), salvage radiation therapy-free survival, metastasis-free survival, and prostate cancer-specific survival at 10 years was analyzed. 1-year (1-yr) erectile function (EF), 1-yr, and 2-yr continence rates were assessed in propensity score-based matched cohorts., Results: Median follow-up was 121 (IQR: 73, 156) months. No differences in BFS between NeuroSAFE and non-NeuroSAFE were recorded (10-yr BFS: NeuroSAFE vs non-Neurosafe, pT2: 81% vs 84%, p = 0.06; pT3a: 58% vs. 63%, p = 0.6; ≥pT3b: 22% vs. 27%, p = 0.99). No differences were found between the two groups in terms of sRFS (pT2: p = 0.1; pT3a: p = 0.4; ≥pT3b: p = 0.4) (Fig. 1B, Table 2), and MTS (pT2: p = 0.3; pT3a: p = 0.6; ≥pT3b: p = 0.9). The NeuroSAFE-navigated patients reported a better 1-yr EF than non-NeuroSAFE (68% vs. 58%, p = 0.02) and no differences in 1-yr and 2-yr continence rates (92.4% vs. 91.8%, and 93.4% vs. 93%, respectively). The main limitation is the retrospective study design., Conclusions: While the NeuroSAFE approach did not show significant improvements in long-term oncologic or continence outcomes, it did provide an opportunity for a higher proportion of patients to improve postoperative functional results, possibly through increased nerve-sparing procedures., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: In a subset of patients with oligorecurrent prostate cancer (PCa), salvage surgery with prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) seems to be of value., Objective: To evaluate whether a lower level of postoperative prostate-specific antigen (PSA; <0.1 ng/ml) is predictive of therapy-free survival (TFS) following salvage PSMA-RGS., Design, Setting, and Participants: This cohort study evaluated patients with biochemical recurrence after radical prostatectomy and oligorecurrent PCa on PSMA positron emission tomography treated with PSMA-RGS in three tertiary care centers (2014-2022)., Intervention: PSMA-RGS., Outcome Measurements and Statistical Analysis: Postsalvage surgery PSA response was categorized as <0.1, 0.1-<0.2, or >0.2 ng/ml. Kaplan-Meier and multivariable Cox regression models evaluated TFS according to PSA response., Results and Limitations: Among 553 patients assessed, 522 (94%) had metastatic soft tissue lesions removed during PSMA-RGS. At 2-16 wk after PSMA-RGS, 192, 62, and 190 patients achieved PSA levels of <0.1, 0.1-<0.2, and >0.2 ng/ml, respectively. At 2 yr of follow-up, TFS rate was 81.1% versus 56.1% versus 43.1% (p < 0.001) for patients with PSA <0.1 versus 0.1-<0.2 versus >0.2 ng/ml. In multivariable analyses, PSA levels of 0.1-0.2 ng/ml (hazard ratio [HR]: 1.9, confidence interval [CI]: 1.1-3.1) and ≥0.2 ng/ml (HR: 3.2, CI: 2.2-4.6, p < 0.001) independently predicted the need for additional therapy after PSMA-RGS. The main limitation is the lack of a control group., Conclusions: For patients after salvage PSMA-RGS, a lower biochemical response (PSA <0.1 ng/ml) seems to predict longer TFS. This insight may help in counseling patients postoperatively as well as guiding the timely selection of additional therapy., Patient Summary: We studied what happened to prostate cancer patients in three European centers who had salvage surgery using a special method called prostate-specific membrane antigen-targeted radioguidance. We found that patients who had low prostate-specific antigen levels soon after surgery were less likely to need further treatment for a longer time., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: In contrast to other malignancies, histologic confirmation prior treatment in patients with a high suspicion of clinically significant prostate cancer (csPCA) is common. To analyze the impact of extracapsular extension (ECE), cT-stage defined by digital rectal examination (DRE), and PSA-density (PSA-D) on detection of csPCA in patients with at least one PI-RADS 5 lesion (hereinafter, "PI-RADS 5 patients")., Materials and Methods: PI-RADS 5 patients who underwent MRI/Ultrasound fusion biopsy (Bx) between 2016 and 2020 were identified in our institutional database. Uni- and multivariable logistic-regression models were used to identify predictors of csPCA-detection (GGG ≥ 2). Risk models were adjusted for ECE, PSA-D, and cT-stage. Corresponding Receiver Operating Characteristic (ROC) curves and areas under the curve (AUC) were calculated., Results: Among 493 consecutive PI-RADS 5 patients, the median age and PSA was 69 years (IQR 63-74) and 8.9 ng/ml (IQR 6.0-13.7), respectively. CsPCA (GGG ≥ 2) was detected in 405/493 (82%); 36/493 patients (7%) had no cancer. When tabulating for PSA-D of > 0.2 ng/ml/cc and > 0.5 ng/ml/cc, csPCA was found in 228/253 (90%, PI-RADS5 + PSA-D > 0.2 ng/ml/cc) and 54/54 (100%, PI-RADS5 + PSA-D > 0.5 ng/ml/cc). Finally, a model incorporating PSA-D and cT-stage achieved an AUC of 0.79 (CI 0.74-0.83)., Conclusion: In PI-RADS 5 patients, PSA-D and cT-stage emerged as strong predictors of csPCA at biopsy. Moreover, when adding the threshold of PSA-D > 0,5 ng/ml/cc, all PI-RADS 5 patients were diagnosed with csPCA. Therefore, straight treatment for PCA can be considered, especially if risk-factors for biopsy-related complications such as obligatory dual platelet inhibition are present., (© 2024. The Author(s).)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Despite modern imaging modalities, lymph-node staging before radical prostatectomy (RP) remains challenging in patients with prostate cancer (PCa). The visibility of lymph-node metastases (LNMs) is critically influenced by their size., Objective: This study aims to describe the distribution of maximal tumor diameters (i.e., size) in LNMs of pN1-PCa at RP and its consequences on visibility in preoperative imaging and oncological outcomes., Design, Setting, and Participants: A total of 2705 consecutive patients with pN1-PCa at RP, harboring a cumulative 7510 LNMs, were analyzed. Descriptive and multivariable analyses addressed the risk of micrometastases (MM)-only disease and the visibility of LNMs. Kaplan-Meier curves and Cox analyses were used for biochemical recurrence-free survival (BCRFS) stratified for MM-only disease., Results: The median LNM size was 4.5mm (interquartile range (IQR): 2.0-9.0 mm). Of 7510 LNMs, 1966 (26%) were MM (≤ 2mm). On preoperative imaging, 526 patients (19%) showed suspicious findings (PSMA-PET/CT: 169/344, 49%). In multivariable analysis, prostate-specific antigen (PSA) (OR 0.98), age (OR 1.01), a Gleason score greater than 7 at biopsy (OR 0.73), percentage of positive cores at biopsy (OR 0.36), and neoadjuvant treatment (OR 0.51) emerged as independent predictors for less MM-only disease (p < 0.05). Patients with MM-only disease compared to those harboring larger LNMs had a longer BCRFS (median 60 versus 29 months, p < 0.0001)., Conclusion: Overall, 26% of LNMs were MM (≤ 2mm). Adverse clinical parameters were inversely associated with MM at RP. Consequently, PSMA-PET/CT did not detect a substantial proportion of LNMs. LNM size and count are relevant for prognosis., (© 2024. The Author(s).)

Purpose: To identify reasons for negative histopathology of specimens from prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) in recurrent prostate cancer (PCa) after prostatectomy., Methods: Of 302 patients who underwent PSMA-RGS, 17 (5.6%) demonstrated a negative histopathology. Preoperative data, PSMA PET, PSMA SPECT, and follow-up information were analyzed retrospectively to differentiate true/false positive (TP/FP) from true/false negative (TN/FN) lesions., Results: The median prostate-specific antigen at PET was 0.4 ng/ml (interquartile range [IQR] 0.3-1.2). Twenty-five index lesions (median short axis 7 mm, IQR 5-8; median long-axis 12 mm, IQR 8-17) had a median SUVmax of 4 (IQR 2.6-6; median PSMA expression score 1, IQR 1-1). Six lesions were TP, twelve were FP, one was TN, and six remained unclear. All TP lesions were in the prostatic fossa or adjacent to the internal iliac arteries. Three suspected local recurrences were FP. All FP lymph nodes were located at the distal external iliac arteries or outside the pelvis. A low PSMA-expressing TN node was identified next to a common iliac artery. Unclear lesions were located next to the external iliac arteries or outside the pelvis., Conclusion: In most cases with a negative histopathology from PSMA-RGS, lesions were FP on PSMA PET. Unspecific uptake should be considered in low PSMA-expressing lymph nodes at the distal external iliac arteries or outside the pelvis, especially if no PSMA-positive lymph nodes closer to the prostatic fossa are evident. Rarely, true positive metastases were missed by surgery or histopathology., (© 2023. The Author(s).)

Objective: To assess the influence of biochemical recurrence (BCR) risk groups and PSA kinetics on the outcomes of radioguided surgery against prostate-specific membrane antigen (PSMA-RGS). Currently, neither BCR risk group nor PSA doubling time (PSA-DT), or PSA velocity (PSA-V) are actively assigned or relevant for counseling prior to PSMA-RGS., Methods: We retrospectively analyzed PSMA-RGS cases for oligorecurrent prostate cancer between 2014 and 2023. BCR risk groups, PSA-DT, and PSA-V were analyzed as predictors for complete biochemical response (cBR, PSA < 0.2 ng/mL), BCR-free, and therapy-free survival (BCRFS, TFS)., Results: Of 374 included patients, only 21/374 (6%) and 201/374 (54%) were classified as low- and high-risk BCR (no group assignment possible in 152/374, 41%). A total of 13/21 (62%) patients with low- and 120/201 (60%) with high-risk BCR achieved cBR ( p = 1.0). BCR classification was no predictor for BCRFS (HR:1.61, CI: 0.70-3.71, p = 0.3) or subsequent TFS (HR:1.07, CI: 0.46-2.47, p = 0.9). A total of 47/76 (62%) patients with PSA-DT ≤ 6 mo and 50/84 (60%) with PSA-DT > 6 mo achieved cBR ( p = 0.4). PSA-DT was not associated with cBR (OR: 0.99, CI: 0.95-1.03, p = 0.5), BCRFS (HR: 1.00, CI: 0.97-1.03, p = 0.9), or TFS (HR: 1.02, CI: 0.99-1.04, p = 0.2). Consistent negative findings were recorded for PSA-V., Conclusions: The BCR risk groups and PSA kinetics do not predict the oncological success of PSMA-RGS performed at low absolute PSA values. Indolent low-risk BCR is rarely treated by PSMA-RGS.

Background and Objective: Metastasis-directed therapy is a feasible option for low PSA, recurrent locoregional metastatic prostate cancer. After initial salvage surgery, patients with good response might consider a repeat salvage surgery in case of recurrent, isolated, and PSMA-positive metastases. This analysis aimed to evaluate the oncological outcome and safety of repeat PSMA-targeted radioguided surgery (RGS) after either prior RGS or "standard" salvage lymph node dissection (SLND)., Materials and Methods: We identified 37 patients undergoing repeat RGS after prior SLND (n = 21) (SLND-RGS) or prior RGS (n = 16) (RGS-RGS) between 2014 and 2021 after initial radical prostatectomy with or without pelvic radiation therapy at two German tertiary referral centers. Kaplan-Meier analyses and uni-/multivariable Cox regression models were used to investigate factors associated with biochemical recurrence-free survival (BRFS) and treatment-free survival (TFS) after repeat salvage surgery., Results and Limitations: Complete Biochemical Response (cBR, PSA < 0.2 ng/ml) was observed in 20/32 patients (5 NA). Median overall BRFS [95% confidence interval (CI)] after repeat salvage surgery was 10.8 months (mo) (5.3-22). On multivariable regression, only age (HR 1.09, 95% CI 1.01-1.17) and preoperative PSA (HR 1.23, 95% CI 1.01-1.50) were associated with shorter BRFS, although PSA (HR 1.16, 95% CI 0.99-1.36) did not achieve significant predictor status in univariable analysis before (p value = 0.07). Overall, one year after second salvage surgery, 89% of the patients (number at risk: 19) did not receive additional treatment and median TFS was not reached. Clavien-Dindo grade > 3a complications were observed in 8% (3/37 patients). Limitations are the retrospective evaluation, heterogeneous SLND procedures, lack of long-term follow-up data, and small cohort size., Conclusion: In this study, repeat RGS was safe and provided clinically meaningful biochemical recurrence- and treatment-free intervals for selected cases. Patients having low preoperative PSA seemed to benefit most of repeat RGS, irrespective of prior SLND or RGS or the time from initial RP/first salvage surgery., (© 2023. The Author(s).)

Background: Quantitative Gleason grading appears to be a reliable prognostic parameter and provides broader risk stratification then the traditional Gleason grading in patients with prostate cancer (PCa) treated with radical prostatectomy (RP)., Objective: To determine if quantification of Gleason pattern (GP) 4 for targeted and systematic biopsy (TBx + SBx) cores together with further clinical variables can identify the lowest quantitative GP 4 fraction on RP., Design, Setting, and Participants: A total of 548 patients underwent TBx + SBx of the prostate and then RP, with pathology revealing Gleason score 3 + 4, 4 + 3, or 4 + 4 disease., Intervention: TBx + SBx of the prostate followed by RP., Outcome Measurements and Statistical Analysis: GP 4 fraction thresholds of ≤5%, ≤10%, ≤15%, ≤20%, and ≤25% were compared between the TBx + SBx and RP specimens. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy for predicting the GP 4 fraction in the RP specimen were determined. Logistic regression models were used to establish a probabilistic relationship between various combinations of clinical and biopsy variables and the GP 4 fraction in the RP specimen., Results and Limitations: GP 4 fractions of ≤5%, ≤10%, ≤15%, ≤20%, and ≤25% was observed in 33%, 49%, 58%, 65%, and 70% of patients on TBx, and 18%, 41%, 53%, 63%, and 70% of patients on RP, respectively. The sensitivity, specificity, NPV, PPV, and accuracy were 75%, 67%, 91%, 39%, and 74% for a TBx GP 4 fraction of ≤5%, and 65%, 85%, 65%, 85%, and 79% for a TBx GP 4 fraction of ≤25%, respectively. A model combining quantified TBx + SBx GP 4 with clinical parameters demonstrated the highest diagnostic accuracy. Limitations include the retrospective study design., Conclusions: Our results demonstrate that the combination of MRI-TBx + SBx and GP 4 quantification allowed precise detection of a low fraction of GP 4 when using RP specimens as the reference standard. Moreover, we found that clinical variables including Prostate Imaging-Reporting and Data System score without biopsy are limited in detection of low GP 4 fractions., Patient Summary: Combination of targeted biopsy alone as well as combined with systematic biopsy and quantitative Gleason grading of biopsy specimen showed high agreement with pathology findings after surgical removal of the prostate. This could help in identifying patients who are suitable for active surveillance., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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., (© 2023. The Author(s).)

This case series evaluated the feasibility of prostate-specific membrane antigen (PSMA)-radioguided surgery (RGS) with 99m Tc-MIP-1404 in recurrent prostate cancer. Methods: Nine patients with PSMA-positive lesions on PET/CT received 99m Tc-MIP-1404 (median, 747 MBq; interquartile range [IQR], 710-764 MBq) 17.2 h (IQR, 16.9-17.5 h) before SPECT/CT and 22.3 h (IQR, 20.8-24.0 h) before RGS. Results: Seventeen PSMA-positive lesions were detected on PET/CT (median short-axis diameter, 4 mm; IQR, 3-6 mm; median SUV max , 8.9; IQR, 5.2-12.6). Nine of 17 (52.9%) were visible on SPECT/CT (median SUV max , 13.8; IQR, 8.0-17.9). Except for 2 foci, all PET/CT-positive findings demonstrated intraoperative count rates above the background level (median count, 31; IQR, 17-89) and were lymph node metastases. Moreover, PSMA-RGS identified 2 additional metastases compared with PET/CT. Prostate-specific antigen values decreased after RGS in 6 of 9 patients (67%). Conclusion: PSMA-RGS with 99m Tc-MIP-1404 identified lymph node metastases in all patients, including 2 additional lesions compared with PET/CT., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: In a subset of patients with recurrent oligometastatic prostate cancer (PCa) salvage surgery with prostate-specific membrane antigen (PSMA)-targeted radioguidance (PSMA-RGS) might be of value., Objective: To evaluate the oncological outcomes of salvage PSMA-RGS and determine the predictive preoperative factors of improved outcomes., Design, Setting, and Participants: A cohort study of oligorecurrent PCa patients with biochemical recurrence (BCR) after radical prostatectomy and imaging with PSMA positron emission tomography (PET), treated with PSMA-RGS in two tertiary care centers (2014-2020), was conducted., Intervention: PSMA-RGS., Outcome Measurements and Statistical Analysis: Kaplan-Meier and multivariable Cox regression models were used to assess BCR-free (BFS) and therapy-free (TFS) survival. Postoperative complications were classified according to Clavien-Dindo., Results and Limitations: Overall, 364 patients without concomitant treatment were assessed. At PSMA-RGS, metastatic soft-tissue PCa lesions were removed in 343 (94%) patients. At 2-16 wk after PSMA-RGS, 165 patients reached a prostate-specific antigen (PSA) level of <0.2 ng/ml. Within 3 mo, 24 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. At 2 yr, BFS and TFS rates were 32% and 58%, respectively. In multivariable analyses, higher preoperative PSA (hazard ratio [HR]: 1.07, 95% confidence interval [CI]: 1.02-1.12), higher number of PSMA-avid lesions (HR: 1.23, CI: 1.08-1.40), multiple (pelvic plus retroperitoneal) localizations (HR: 1.90, CI: 1.23-2.95), and retroperitoneal localization (HR: 2.04, CI: 1.31-3.18) of lesions in preoperative imaging were independent predictors of BCR after PSMA-RGS. The main limitation is the lack of a control group., Conclusions: As salvage surgery in oligorecurrent PCa currently constitutes an experimental treatment approach, careful patient selection is mandatory based on life expectancy, low PSA values, and low number of PSMA PET-avid lesions located in the pelvis., Patient Summary: We looked at the outcomes from prostate cancer patients with recurrent disease after radical prostatectomy. We found that surgery may be an opportunity to prolong treatment-free survival, but patient selection criteria need to be very narrow., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: We assessed the diagnostic yield of consecutive transperineal targeted biopsy of multiparametric magnetic resonance imaging index lesion and secondary lesion and additive systematic biopsy in patients who received combined targeted biopsy+systematic biopsy of prostate., Materials and Methods: Of 1,467 patients with targeted biopsy+systematic biopsy, analyses were restricted to 571 patients with index lesion+secondary lesion, Prostate Imaging-Reporting and Data System score ≥3. Index lesion was defined as having the greatest Prostate Imaging-Reporting and Data System score and/or lesion volume as opposed to secondary lesion. We retrospectively compared clinically significant prostate cancer rates (ie, Gleason Grade Group ≥2) between index lesion+secondary lesion and index lesion+secondary lesion+systematic biopsy. Subgroup analyses in men with ipsilateral index lesion+secondary lesion focused on contralateral systematic biopsy. Multivariable logistic regression analyses to predict any clinically significant prostate cancer included age, previous biopsies, prostate specific antigen density, respective index lesion/secondary lesion volumes, side relation, Prostate Imaging-Reporting and Data System strata, and number of targeted biopsy and systematic biopsy cores., Results: Clinically significant prostate cancer rates for index lesion+secondary lesion vs index lesion+secondary lesion+systematic biopsy were 38% vs 42% ( P = .2) at expense of significantly higher median number of biopsy cores (9 vs 25, P < .001). In the subgroup with ipsilateral index lesion+secondary lesion (n = 236), contralateral systematic biopsy detected clinically significant prostate cancer in 17%. In the narrower subgroup with ipsilateral index lesion+secondary lesion (n = 131) without any clinically significant prostate cancer, contralateral systematic biopsy detected clinically significant prostate cancer in 3.8%. Multivariable logistic regression analyses confirmed contralateral systematic biopsy as independent predictor, but performed similarly without systematic biopsy information (area under the curve 87.1% vs 86.6%)., Conclusions: Targeted biopsy of secondary lesion should be included in targeted biopsy protocols due to added diagnostic information. However, for targeted biopsy of index lesion+secondary lesion additional systematic biopsy is of limited informative value in terms of overall clinically significant prostate cancer detection. However, when index lesion+secondary lesion are ipsilateral, contralateral systematic biopsy should be recommended for purpose of prostate lobe information. Our results indicate great potential to reduce systematic biopsy cores and associated potential morbidity, and warrant prospective evaluation.

Objectives: To assess if systematic (SBx) vs. transrectal or transperineal mpMRI-ultrasound targeted combined with systematic (TBx + SBx) biopsy confer different effects on treatment delay to radical prostatectomy measured as Gleason grade group (GGG) upgrade of prostate cancer (PCa)., Materials and Methods: We relied on a multi-institutional cohort of localized PCa patients who underwent RP in Martini-Klinik, Hamburg, or Prostate Center Northwest, Gronau, between 2014 and 2022. Analyses were restricted to PCa GGG 1-3 diagnosed at SBx (n = 4475) or TBx + SBx (n = 1282). Multivariable logistic regression modeling (MVA) predicting RP GGG upgrade of ≥ 1 was performed separately for SBx and TBx + SBx., Results: Treatment delay to RP of < 90, 90-180 and 180-365 days was reported in 59%, 35% and 6.2% of SBx and in 60%, 34% and 5.9% of the TBx + SBx patients, respectively. Upgrade to GGG ≥ 4 at RP was detected in 15% of SBx patients and 0.86% of TBx patients. In MVA performed for SBx, treatment delay yielded independent predictor status (OR 1.17 95% CI 1.02-1.39, p = 0.028), whereas for TBx + SBx MVA, statistical significance was not achieved., Conclusion: Treatment delay remained independently associated with radical prostatectomy GGG upgrade after adjustment for clinical variables in the patients diagnosed with SBx alone, but not in those who received combined TBx + SBx. These findings can be explained through inherent misclassification rates of SBx, potentially obfuscating historical observations of natural PCa progression and potential dangers of treatment delay. Thus, mpMRI-guided combined TBx + SBx appears mandatory for prospective delay-based examinations of PCa., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Structured implementation of robot-assisted surgery in the field of medical education is lacking. We assessed students' interest in robot-assisted surgery and tested if the implementation of a hands-on robotic course into the curriculum could increase the interest to join a surgical discipline in general and especially in female students, since women are clearly underrepresented in surgical disciplines., Methods: After a prostate cancer focused seminar, 100 students were 1:1 randomized into two groups. Group B: Baseline characteristics and professional interest were assessed prior and after a hands-on robotic course, using a da Vinci® console with simulator (da Vinci® Surgical training, Intuitive Surgical Inc., USA). Group A served as post-interventional consistency control group, received the questionnaire only once after the hands-on training., Results: The male to female ratio of students was 54% and 46%. The interest to turn into urology/surgery, categorized as yes", "no", "maybe" changed from 18 to 16%, 36 to 30% and 46 to 54% respectively after the hands-on robotic course ( p  < 0.001). Also, the positive attitude towards the surgical field significantly increased (20 vs. 48%; p  < 0.001). Comparing male and female students, virtually identical proportions (23 vs. 23%) opted for joining urology or surgery as a discipline, whereas rejection (45 vs. 25%) and perchance (32 vs. 50%) of that notion differed between genders ( p  = 0.12)., Conclusion: Our results demonstrate great demand for implementing robotic training into medical education for an up-to-date curriculum. Although the decision process on career choice is widely multifactorial, stereotypes associated with surgical disciplines should be eliminated. This could have a particularly positive effect on the recruitment of female medical students since women are clearly underrepresented in surgical disciplines although currently and with increasing proportions, more female students are enrolled in medical schools then male., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Ekrutt, Leyh-Banurrah, Knipper, Schramm, Beyer, Maurer, Graefen and Budäus.)

Objective: When considering increased morbidity of apical biopsies, the added diagnostic value of separate targeting of mid-gland and apical segment of the pan-segmental mid-apical mpMRI prostate cancer (PCa) suspicious lesions was assessed., Materials and Methods: A total of 420 patients with a single mpMRI PCa-suspicious PI-RADS ≥ 3 intraprostatic lesion extending from the mid-gland to the apical segment of the gland underwent transrectal MRI-targeted (TBx) and systematic prostate biopsy. Clinically significant PCa (CsPCa) was defined as Gleason Score (GS) ≥ 3 + 4. PCa detection rates of TBx cores were assessed according to targeted anatomical segments. Finally, the diagnostic values of two theoretical TBx protocols utilizing 1-core (A) vs. 2-cores (B) per anatomical segment were compared., Results: TBx within the pan-segmental mid-apical lesions yielded 44% of csPCa. After stratification into mid- vs. apical segment of the lesion, csPCa was detected in 36% (mid-gland) and 32% (apex), respectively. Within the patients who had no csPCa detection by mid-gland sampling (64%, n = 270), extreme apical TBx yielded additional 8.1% of csPCa. Comparison of extreme apical TBx strategy B vs. overall PCa detection in our cohort revealed corresponding similar rates of 49 vs.50% and 31 vs.32%, respectively., Conclusion: Separate analyses of both segments, mid-gland and apex, clearly revealed the diagnostic contribution of apical TBx. Our findings strongly suggest to perform extreme apical TBx even within pan-segmental lesions. Moreover, our results indicate that a higher number of cores sampled from the mid-gland segment might be avoided if complemented with a two-core extreme apical TBx., (© 2022. The Author(s).)

Purpose: Positive surgical margins (PSM) represent a poor prognostic factor at radical prostatectomy (RP). To investigate the impact of PSM, its length, the focality and the Gleason grade at the PSM, on the oncologic outcomes in nonorgan-confined RP patients., Methods: Within a high-volume center database, we identified patients who harbored non-organ-confined (pT3) prostate cancer (PCa) at RP between 2010 and 2016. Only patients without lymph node invasion were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of PSM on biochemical recurrence (BCR), metastasis, and cancer-specific death after RP in patients without adjuvant radiotherapy., Results: Overall, 3705 patients were identified. Of those, 27.2% (n = 1007) harbored PSM. At 96 months after RP, BCR-free, metastasis-free and cancer-specific survival was 41.6 versus 57.5%, 82.7 versus 88.6%, and 94.7 versus 98.5% for patients with versus without PSM (all p < 0.001). BCR-free, metastasis-free and cancer-specific survival rates at 96 months were 56.7 versus 26.5% (p < 0.001), 94.4 versus 67.4% (p < 0.001), and 100.0 versus 87.1% (p < 0.01) for Gleason pattern 3 versus ≥ 4 at the margin and 45.0 versus 27.8% (p < 0.01), 83.3 versus 82.3% (p = 0.2), and 95.2 versus 92.7% (p = 0.3) for <4 mm versus ≥4 mm length of margin. In multivariable Cox models PSM was an independent predictor for BCR (hazard ratio [HR]:1.53, p < 0.001) and cancer-specific death (HR:2.75, p = 0.02). In subgroups of patients with PSM only, Gleason ≥ 4 at the margin (HR:1.60, p < 0.01) and length of PSM (HR:1.02, p < 0.05) was an independent predictor of BCR., Conclusion: PSM represents an independent predictor for worse oncologic outcome in nonorgan-confined PCa at RP. Gleason ≥ 4 at the margin was associated with the development of BCR, metastasis, and with cancer-specific death after RP. Next to margin status, Gleason at the margin and its length carry important information that should be reported for the specimen., (© 2022 The Authors. The Prostate published by Wiley Periodicals LLC.)

Purpose: We assessed whether sampling of the transitional zone can be spared in patients with exclusively peripheral prostate cancer (PCa)-suspicious multiparametric magnetic resonance imaging (mpMRI) lesions who undergo combined mpMRI targeted (TBx) and systematic prostate biopsies (SBx)., Materials and Methods: Of 1,685 patients who underwent extended SBx including transitional zone sampling and had TBx of ≥1 lesion in the peripheral and/or transitional zone, we selected 863 patients with exclusively peripheral PCa-suspicious lesions and negative transitional zone mpMRI. Clinically significant PCa (csPCa) was defined as Gleason score (GS) ≥3+4. Within the selected cohort we performed a retrospective head-to-head comparison of csPCa detection rates between biopsy protocols: A) combination of peripheral TBx plus extended SBx including transitional zone sampling vs B) peripheral TBx plus SBx without any transitional zone sampling. Analyses were complemented with multivariable logistic regression models (LRMs) in the total cohort for predicting csPCa in SBx transitional zone sampling., Results: Compared to the extended protocol (A), omission of systematic transitional zone sampling (B) yielded similar PCa detection for csPCa (48% vs 47%) and GS 3+3 (21% vs 20%). Only 2.0% csPCa was additionally detected with transitional zone SBx sampling (A). LRM confirmed that intraprostatic zonal distribution of mpMRI lesions independently influences csPCa detection rates of transitional zone SBx sampling., Conclusions: A peripheral TBx plus SBx without any transitional zone sampling protocol (B) yields similar csPCa detection rates as the standard extended protocol (A) but may reduce biopsy-related morbidity. This zone-dependent biopsy strategy warrants prospective evaluation to optimize the extent of systematic biopsies in presence of suspicious mpMRI lesions.

Aim: Few small-scaled studies performed systematic analysis of the benefits of extending prostate specific membrane antigen positron-emission tomography/ computed tomography ( 68 Ga-PSMA I&T PET/CT) to the lower extremities in prostate cancer (PCa) patients. We hypothesized that 68 Ga-PSMA I&T PET/CT positive lesions are rare in lower extremities of prostate cancer (PCa) patients, the clinical implication is negligible and may therefore be omitted., Methods: We retrospectively analyzed 1,068 PCa patients who received 68 Ga-PSMA I&T PET/CT in a single institution (2016-2018). Of those, 285 (26.7%) were newly diagnosed, 529 (49.5%) had biochemical recurrence (BCR) and 254 (23.8%) were castration-resistant prostate cancer (CRPC) patients., Results: Of 1,068 68 Ga-PSMA I&T PET/CTs, positive lesions in the lower extremities were identified in 6.9% patients (n=74). Positive lesions in the lower extremities were most common in CRPC patients (19.7%; n=50), followed by newly diagnosed (3.2%; n=9) and BCR (2.8%; n=15) PCa patients. Only 3 patients presented with exclusive lesions in the lower extremities, respectively 0.8% (n=2) in CRPC and 0.4% (n=1) in newly diagnosed PCa. Both CRPC (94.1%, n=47) and BCR (80.0%, n=12) patients with PSMA-positive lesions predominantly received systemic therapy., Conclusion: Identification of lower extremities lesions with PSMA PET/CT is uncommon and exclusive lesions are rare. PSMA PET/CT findings of the lower extremities did not change therapy management. Thus, scanning of the lower extremities can be omitted in standard protocols., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The detection of a pathogenic variant in the BRCA1 or BRCA2 gene has medical and psychological consequences for both, affected mutation carriers and their relatives. A two-phase study with explanatory sequential mixed methods design examined the psychological impact of genetic testing and associated family communication processes. Analyzing a survey data of 79 carriers of a BRCA1 or BRCA2 mutation, the majority had general psychological distress independent of cancer diagnosis in the patients' history. The point prevalence of depression was 16.9%. Contrary to their subjective perception, the respondents' knowledge about those mutations was moderate. Despite the high rate of information transfer to relatives at risk (100%), their reported uptake of genetic testing was low (45.6%). Communication about the mutation detection was more frequent with female than with male relatives. In-depth focus group interviews revealed significant barriers to accessing genetic counseling including anxiety, uncertainty about the benefits of testing and about the own cancer risk, particularly among males. This study suggests that an adequate knowledge of the genetic background and psychological support is required to reduce emotional distress, to support familial communication and to facilitate genetic testing., (© 2021. The Author(s).)

Competing Interests: The authors declare that they have no conflict of interest.

Background: A trend towards inverse stage migration in prostate cancer (PCa) was reported. However, previous analyses did not take into account potential differences in sampling strategies (number of biopsy cores), which might have confounded these reports., Material and Methods: Within our single-institutional database we identified PCa patients treated with radical prostatectomy (RP) between 2000 and 2020 (n = 21,646). We calculated the estimated annual percentage change (EAPC) for D'Amico risk groups, biopsy Gleason Grade Group (GGG), PSA and cT stage as well as postoperative RP GGG and pT stage relying on log linear regression methodology. Subsequently, we repeated the analyses after adjustment for number of cores obtained at biopsy., Results: Absolute rates of D'Amico low risk decreased (-30.1%), while intermediate and high risk increased (+21.2% and +9.0%, respectively). Rates of GGG I decreased (-50.0%), while GGG II-V increased, with the largest increase in GGG II (+22.5%). This trend, albeit less pronounced, was also recorded after adjusted EAPC analyses (p < .05). Specifically, EAPC values for D'Amico low vs intermediate vs high risk were -1.07%, +0.37%, +0.45%, respectively, and EAPC values for GGG ranged between -0.71% (GGG I) and +0.80% (GGG IV). Finally, an increase in ≥cT2 (EAPC: +3.16%) was displayed (all p < .001). These trends were confirmed in EAPC calculations in RP GGG and pT stages (p < .001)., Conclusion: Our findings confirm the trend towards less frequent treatment of low risk PCa and more frequent treatment of high risk PCa, also after adjustment for number of biopsy cores., (© 2021 The Authors. The Prostate Published by Wiley Periodicals LLC.)

Purpose: We sought to address the impact of preoperative prostate specific membrane antigen (PSMA) positron emission tomography (PET) findings prior to radical prostatectomy and pelvic lymph node dissection on biochemical recurrence and time to adjuvant or salvage treatment., Materials and Methods: Between 2013 and 2017, 64 intermediate and 166 high risk (230) prostate cancer patients received 68 Ga-PSMA-11 PET followed by radical prostatectomy and pelvic lymph node dissection. Biochemical recurrence-free and therapy-free survivalwere determined. For all time-to-event analyses, univariable and multivariable Cox proportional hazards models and univariable Kaplan-Meier analyses were applied, with a significance threshold of p <0.05., Results: The overall sensitivity, specificity, positive predictive value and negative predictive value of PSMA PET for pN1 disease was 48.5%, 95.7%, 82.1% and 82.2%, respectively. Median followup was 30.2 months. Biochemical recurrence occurred in 50.4% (116) of patients and adjuvant or salvage treatment was performed in 46.5% (107). Worst biochemical recurrence-free and therapy-free survival was observed in pN1 patients who also exhibited PSMA PET positive lymph node, followed by pN1 patients without PSMA PET positive lymph node and patients without evidence of lymph node metastasis on histology and PSMA PET (median biochemical recurrence-free survival 1.7 vs. 7.5 vs. >36 months, median therapy-free survival 2.6 vs. 8.9 vs. >36 months)., Conclusions: Patients with positive lymph node on PSMA PET prior to radical prostatectomy have to expect early biochemical recurrence and adjuvant/salvage therapy, despite thorough pelvic lymph node dissection. Therefore, results from PSMA PET can be used for patients' consultation and more stringent followup as well as for planning of neoadjuvant/adjuvant therapy.

Introduction and Objective:  Multiparametric MRI (mpMRI) represents the current gold standard for the detection of primary prostate cancer (PC) after a negative biopsy. PSMA PET imaging has been introduced in the diagnostic work-up of PC with high accuracy, but is currently mainly utilised in the setting of biochemical recurrence. This study aimed to determine the efficacy of combined 68 Ga-PSMA-11 PET/mpMRI imaging to detect PC in patients with previously negative prostate biopsies., Methods:  A total of 57 patients who had undergone at least one prior negative prostate biopsy were included in this retrospective analysis. All patients underwent 68 Ga-PSMA-11 PET/mpMRI imaging of the prostate. mpMRI was evaluated according to the PIRADS classification system and 68 Ga-PSMA-11 PET was rated on a 5-point Likert scale (1: PC highly unlikely; 2: PC unlikely; 3: presence of PC is equivocal; 4: PC likely; 5: PC highly likely). All patients received a systematic random biopsy as well as a targeted transrectal biopsy of lesions suspicious on imaging. Imaging and histological biopsy outcomes were compared on a per-patient basis., Results:  In the histological analysis, 35/57 (61.4 %) patients harboured PC lesions. In patients with biopsy-proven PC, 21/35 (60.0 %) had a PI-RADS 4 or 5 lesion on mpMRI and 28 /35 (80.0 %) had a PET rating of 4 or 5. Combined 68 Ga-PSMA-11 PET/mpMRI missed only one patient with a Gleason score (GS) 7a tumour (rating of 1 or 2 in both PET and mpMRI). Limitations include the retrospective analysis as well as possible false negative biopsy results even in a fusion biopsy setting., Conclusion:  In this initial analysis, the combined 68 Ga-PSMA-11 PET/mpMRI proved to be a valuable imaging tool to guide prostate biopsies for the detection of PC in patients with a negative prior biopsy. In this approach, 68 Ga-PSMA-11 PET and mpMRI show partially complementary findings that enhance the detection of PC lesions., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Prostate-specific membrane antigen (PSMA)-based radioguidance for salvage lymph node dissection (sLND) in recurrent prostate cancer has shown promising early oncological outcomes. However, long-term outcomes are still undetermined. Future studies are needed before introducing PSMA positron emission tomography-based sLND into routine clinical practice outside of clinical trials or registries., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: Based on unfavorable oncological and functional outcomes of non-organ-confined (NOC) prostate cancer (PCa), defined as ≥ pT3, pN1 or both, we aimed to develop a NOC prediction tool based on multiparametric MRI-guided targeted fusion biopsy (TBx)., Materials and Methods: Analyses were restricted to 594 patients with simultaneous PCa detection at systematic biopsy (SBx), TBx and subsequent radical prostatectomy (RP) at our institution. Development (n = 396; cohort 1) and validation cohorts (n = 198; cohort 2) were used to develop and validate the NOC nomogram. A head-to-head comparison was performed between stand-alone TBx model and combined TBx/SBx model. Second validation was performed in patients with positive TBx, but negative SBx (n = 193; cohort 3)., Results: The most parsimonious TBx model included three independent predictors of NOC: pretreatment PSA (OR 1.05 95% CI: 1.01-1.08), highest TBx-detected Gleason pattern (3 + 3 [REF] vs. ≥ 4 + 5; OR 9.3 95% CI 3.8-22) and presence of TBx-detected perineural invasion (OR 2.2 95% CI: 1.3-3.6). The combined TBx/SBx model had the same predictors. For the stand-alone TBx and combined TBx/SBx model, external validation yielded accuracy of 76.5% (95% CI: 69.3-83.1) and 76.6% (95% CI: 69.4-83.6) within cohort 2. The external validation of the stand-alone TBx model yielded 72.4% (95% CI: 65.0-79.6) accuracy within cohort 3., Conclusion: Our stand-alone TBx-based nomogram can identify PCa patients at the risk of NOC, using three simple variables, with the similar accuracy as the TBx/SBx-based model. It is non-inferior to combined TBx/SBx-based model and performs with sufficient accuracy in specific patients with positive TBx, but negative SBx.

Background: The prognostic value of circulating tumor cells (CTCs) in patients with hormone-naïve oligometastatic prostate cancer (HNoMPC) undergoing cytoreductive radical prostatectomy (CRP) is unknown., Objective: To determine the pre- and postoperative prognostic value of CTC enumeration in patients undergoing CRP., Design, Setting, and Participants: Thirty-three patients with HNoMPC from the prospective, single-arm ProMPT trial who underwent CRP between 2014 and 2015 at the Martini-Klinik were evaluated. Follow-up visits for all patients were conducted every 6 mo up to 36 mo after CRP and included serial detection of CTCs in 7.5 ml blood samples using the CellSearch system., Intervention: CRP., Outcome Measurements and Statistical Analysis: CTC enumerations before and after CRP, and their prognostic value on metastatic castration-resistant prostate cancer-free survival and overall survival (OS) were analyzed using Kaplan-Meier plots and univariable Cox-regression analysis., Results and Limitations: Sixteen patients (48.5%) had positive CTCs prior to CRP. A CTC count of ≥2 before or 6 mo after CRP was a prognostic factor for worse oncologic outcome. Compared with other biomarkers (prostate-specific antigen, lactate dehydrogenase, and bone-specific alkaline phosphatase), the prognostic value of CTCs was highest using Harrell's C for OS (0.69), while the highest C-index could be achieved for a combination of conventional markers and CTC count (0.74). After progression to metastatic castration-resistant prostate cancer, CTC enumeration of ≥5 was prognostic for OS. The main limitation is the small sample size., Conclusions: CTC enumeration contributes to prognostic information, which might help select HNoMPC patients who might benefit most from CRP., Patient Summary: In this report, we looked at the value of circulating tumor cell (CTC) determination in patients undergoing radical prostatectomy for oligometastatic prostate cancer. We could show that the number of CTCs was a prognostic factor at all analyzed time points and was more closely associated with prognosis than other biomarkers commonly used in daily clinical practice., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: The purpose of this study was to investigate adherence to recommended adjuvant radiotherapy (aRT) in radical prostatectomy (RP) patients with adverse pathologic features and to analyse the outcome of patients who followed or denied this recommendation., Patients and Methods: We included 1140 consecutive RP patients (2006-2015) with non-organ confined (pT3) prostate cancer and either positive surgical margins (R1) and/or lymph node involvement (pN1) and non-detectable postoperative prostate-specific antigen who received multidisciplinary aRT recommendations. Patients were stratified into adherence versus non-adherence to recommendations. Additionally, subgroups within pathologic criteria (pT3R1N0, pT3R0N1, pT3R1N1) were analyzed. Kaplan-Meier, as well as multivariable Cox regression analyses were used to assess biochemical recurrence (BCR)-free survival, metastasis-free survival, cancer-specific survival, and overall survival., Results: Overall, 508 (44.6%) patients were non-adherent. Of those, 273 (53.6%) did not receive any RT, and 235 (46.4%) received salvage RT. At 8 years, BCR-free survival was 57.7 versus 20.1%, metastasis-free survival was 76.5 versus 75.4%, cancer-specific survival was 91.7 versus 87.4%, and overall survival was 80.4 versus 75.8% in adherent versus non-adherent patients, respectively (P < .001). In multivariable Cox regression predicting BCR, metastatic progression, cancer-specific mortality, and overall mortality, non-adherence to aRT recommendation represented an independent predictor (hazard ratio [HR], 3.8; 95% confidence interval [CI], 3.1-4.5; HR, 1.6; 95% CI, 1.2-2.2; HR, 2.8; 95% CI, 1.5-5.3; and HR, 1.8; 95% CI, 1.2-2.8, respectively)., Conclusions: Only about 55% of patients followed our multidisciplinary recommendations. Adherent patients were significantly less likely to experience BCR, metastatic progression, cancer-specific mortality, and overall mortality. Thus, patients with high risk of recurrence may be advised about the possibility of improved oncologic outcomes in case of adherence to aRT recommendations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

Purpose: We analyzed the number of multiparametric magnetic resonance imaging targeted biopsy cores per lesion needed to detect prostate cancer in patients treated with radical prostatectomy., Materials and Methods: Analyses focused on targeted biopsy of magnetic resonance imaging lesions suspicious for prostate cancer with a PI-RADS® (Prostate Imaging Reporting and Data System) score of 3 or greater and consecutive radical prostatectomy. Descriptive statistics included the frequency/proportion and IQR. Multivariable logistic regression analyses on the per lesion level were used to predict the number of targeted biopsies with prostate cancer., Results: In the total cohort of 771 radical prostatectomy cases 437 (57%) and 334 (43%) were systematic transrectal ultrasound guided biopsy naïve or had 1 or more prior negative systematic transrectal ultrasound guided biopsies, respectively. A maximum PI-RADS score of 3, 4 and 5 was present in 67 (8.7%), 567 (74%) and 137 patients (18%), respectively. A total of 1,459 multiparametric magnetic resonance imaging lesions suspicious for prostate cancer were identified for analysis. Prostate cancer was detected based on an initial, second, third, or fourth or greater targeted biopsy in 79%, 92%, 98% and 100% of cases, respectively. The rate of prostate cancer detection on the first targeted biopsy core increased with higher PI-RADS scores of 3, 4 and 5 (67%, 79% and 87%, respectively). The number of prior negative systematic transrectal ultrasound guided biopsies and pathological tumor stage emerged as independent predictors on multivariate analysis, addressing the need for 2 or more targeted biopsy cores to detect clinically significant prostate cancer., Conclusions: Radical prostatectomy based analyses demonstrated that most cancers could be detected by 2 targeted biopsies only while in a minority of cases 3 or more targeted biopsies were necessary. Such findings might indicate that the targeted biopsy procedure and the related technology have improved, especially in patients with intermediate/high risk prostate cancer.

Objective: To assess the prevalence of fluoroquinolone resistant (QR) bacteria, multidrug resistant (MDR) bacteria and Enterococcus faecalis (E. faecalis) in rectal swabs of patients undergoing transrectal prostate biopsy and for evaluating if risk factor assessment is reliable for prediction of QR bacteria, MDR bacteria, or E. faecalis., Patients and Methods: Two hundred consecutive patients received a rectal swab examination prior to transrectal magnetic resonance imaging-guided fusion biopsy, for evaluating the prevalence of QR bacteria, MDR bacteria, and E. faecalis. The results of a standardized risk factor questionnaire, assessing known prognosticators for higher prevalence of resistant bacteria in rectal flora were correlated with the occurrence of QR bacteria, MDR bacteria, and E. faecalis in rectal swabs., Results: QR E. coli was detected in 12 patients (6%). Regarding MDR bacteria, extended spectrum β- lactamase- producing E. coli occurred in 8 patients (4%). E. faecalis was found in 15 patients (7.5%). A total of 193 patients completed the risk factor questionnaire. Of those, 107 (53.2%) patients harbored no risk factors, while 86 (42.8%) had at least 1 risk factor, of which the most common was repeat biopsy. No association was found between any risk factor and occurrence of QR bacteria, MDR bacteria, or E. faecalis (P >.05)., Conclusion: The prevalence of resistant germs in our cohort was lower compared to other series. Moreover, the rate of QR bacteria, MDR bacteria, or E. faecalis in rectal swabs was not reliably associated with risk factor assessment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Imaging modalities with high accuracy are essential for proper selection of patients for salvage lymph node dissection (sLND). Unlike nodal staging before radical prostatectomy, data on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) before sLND are scarce. We analyzed 23 patients undergoing 68 Ga-PSMA-PET before sLND and compared the imaging findings with histopathology at sLND. Altogether, 29/109 resected lymph node (LN) fields harbored histologically confirmed LN metastases (26.6%)., The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 89.5%, 74.1%, 70.8%, 90.9%, and 80.4% in side-based analysis, and 75.9%, 87.5%, 68.8%, 90.9%, and 84.4%, respectively, in LN field-based analysis. In contrast to existing studies, sensitivity in particular was lower. This might be because of referral for sLND on the basis of PSMA-PET from 13 different nuclear medicine centers. However, this could still provide more realistic data if sLND should become widely used. Second, our pathologists routinely used immunohistochemistry, resulting in a higher yield of smaller metastases, increasing the accuracy of histopathology. Despite its acceptable accuracy in a real-world scenario, sLND should not only focus on PSMA-PET-positive fields, as small PSMA-PET-negative metastases may be present. PATIENT SUMMARY: We analyzed the accuracy of prostate-specific membrane antigen positron emission tomography (PSMA-PET) before salvage lymph node dissection in a real-world situation. Although the accuracy is reasonable, resection should not exclusively focus on PSMA-PET-positive fields., (Copyright © 2018. Published by Elsevier B.V.)

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.