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Aim of the Study: To investigate the time points at which different major complications occur and their temporal distribution over the postoperative intervals., Patients and Methods: Patients who underwent RC between January 2003 and March 2024 at the university hospital Essen and had complete records regarding postoperative complications and their timing were included. All major complications with Clavian-Dindo (CD) grading III-V were identified and recorded according to a predefined morbidity catalog. The time to occurrence of complications, readmission and mortality, was plotted against the postoperative day over a 90-day period to illustrate the distribution of events in the postoperative period. For each complication group, the median timing and the interquartile range (IQR) as well as the incidence during the postoperative weeks were calculated., Results: Out of 757 patients, 282 (37.2%) suffered at least one major complication (CDC grade III-IV) with a total of 452 major complications. Most common complications were gastrointestinal, genitourinary and wound complications. Median (IQR) time to first major complication was 7 (4-17) days. Hospital readmission due to major complications was required in 68 (9%) patients at a median of 47 days. Most of cardiac, pulmonary, bleeding and gastrointestinal complications occurred very early in the first week, at a median of 3, 4, 4 and 5 days, respectively. Wound complications were more likely to occur within the second and third week, with a median time of 13 days. Thromboembolism developed at similar rates throughout the first 3 weeks. The other groups of complications including infectious, genitourinary and miscellaneous (mostly lymphocele) complications showed no specific pattern and occurred in a wide range over the 90 days and were considered intermediate and late events. Further analysis of the time to all complications (first major and secondary), showed an increase in median time to occurance for all complications except genitouranry and lymphocele, which occurred earlier. Deaths related to major complications were observed in 50 (6.6%) patients at a median time of 17 days., Conclusion: The current study shows the temporal patterns of the major complications within the RC morbidity catalog. Physicians should be aware of these patterns to facilitate anticipation and prevent fatal outcomes., Competing Interests: Declarations. Ethical approval: This study protocol was reviewed and approved by pproved by the local ethics committee at University Hospital Essen with approval number: 23-11582-BO. Informed consent was waived by the institutional review board in view of the retrospective nature of the study. All the procedures being performed were part of the routine care. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Detection of positive resection margins in surgical procedures of high-risk prostate cancer is key for minimizing the risk of recurrence. This study aimed at evaluating the accuracy of functional tumor-volume segmentation in intraoperative ex vivo PET/CT for margin assessment in prostate cancer patients undergoing radical prostatectomy. Methods: Seven high-risk prostate cancer patients received [ 18 F]PSMA-1007 before radical prostatectomy. After removal of the prostate gland, ex vivo imaging on the AURA 10 PET/CT system was performed, and functional tumor volume was segmented using 4 semiautomatic segmentation methods. Resection margins and volumes were compared with histopathology. Additionally, a supportive phantom study was conducted to assess segmentation accuracy at low radiopharmaceutical activity. Results: Clinically, 18 lesions were analyzed in intraoperative PET/CT. Sensitivity, specificity, and positive and negative predictive values of margin detection were 83%, 100%, 100%, and 92%, respectively, using an iterative thresholding method. In 1 patient, a biochemical recurrence was observed within 1 y of prostate-specific antigen follow-up, and 1 patient underwent adjuvant radiotherapy. The remaining 5 patients were still undergoing prostate-specific antigen follow-up with no evidence of biochemical recurrence. On the basis of a phantom-deduced minimal segmentable activity concentration of approximately 2 kBq/mL, we propose an administered [ 18 F]PSMA-1007 activity of at least 1.9 and 0.4 MBq/kg for preoperative and intraoperative injections, respectively. Conclusion: Intraoperative ex vivo PET/CT is a promising modality for intraoperative margin assessment. Prospective trials are needed to further investigate the value of specimen PET/CT-based radioguided surgery in high-risk prostate cancer., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: To investigate the expression patterns of Nectin-4, the target molecule of the antibody-drug conjugate enfortumab vedotin (EV), in relation to histological and molecular subtypes of urothelial bladder cancer (UBC)., Patients and Methods: We assessed the protein expression patterns of Nectin-4 in a spatially organised tissue microarray containing 1386 tissue cores from 314 consecutive patients with UBC who underwent radical cystectomy (2005-2018). Results were correlated with clinicopathological and follow-up data, as well as with different spatial locations (tumour central vs tumour-normal interface and primary tumour vs lymph node [LN] metastases). Additionally, we correlated Nectin-4 expression levels with histological and molecular subtypes. Finally, we assessed the value of Nectin-4 expression for predicting the efficacy of platinum therapy in the peri-operative setting., Results: Nectin-4 expression was observed in 63% of primary tumours and 87% of LN metastases, with significantly higher levels in LNs. Of the histological subtypes, the micropapillary (58%) and pure urothelial histologies (30%) were associated with the highest Nectin-4 positivity, while the sarcomatoid (17%), squamous (15%) and small/cell-neuroendocrine (0%) subtypes exhibited the lowest. Nectin-4 immunopositivity rates were significantly higher in luminal (urothelial-like [42%] and genomically unstable [34%] Lund subtypes) compared to the basal (5%) or mesenchymal (0%) molecular subtypes. Higher Nectin-4 expression levels were associated with lower tumour stage but showed no association with overall survival. Finally, patients with low Nectin-4 expression tended to derive more benefit from platinum-based chemotherapy in both adjuvant and neoadjuvant settings (P < 0.001, P = 0.067)., Conclusion: Our results revealed a low spatial heterogeneity of Nectin-4 expression within the primary tumour. In contrast, differential Nectin-4 expression was found in the context of histological and molecular subtypes. Nectin-4-expressing tumours may show varying sensitivity to both EV and platinum-based chemotherapy., (© 2025 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Distinct molecular subtypes of muscle-invasive bladder cancer (MIBC) may show different platinum sensitivities. Currently available data were mostly generated at transcriptome level and have limited comparability to each other. We aimed to determine the platinum sensitivity of molecular subtypes by using the protein expression-based Lund Taxonomy. In addition, we assessed the tumor heterogeneity within the primary tumor and between the primary and lymph node (LN) metastatic sites. Thirteen immunohistochemical markers were stained in a tissue microarray with an overall number of 1,508 cores. Statistical evaluation was performed in 199 patients divided into three chemo-naïve MIBC cohorts: (1) pT3/4 and/or LN+ patients who received radical cystectomy without platinum treatment, (2) patients who received adjuvant chemotherapy (AC), and (3) patients who underwent palliative platinum treatment for metastatic disease or postoperative progression. Overall survival (OS) was used as the primary endpoint. Patients with the genomically unstable (GU) subtype had significantly better OS in the AC group compared to the radical cystectomy group (HR: 0.395, 95% CI: 0.205-0.795, p = 0.005). In contrast, no such association was observed for the basal/squamous (Ba/Sq) subtype. Intratumor heterogeneity was present in 19% of cases, with the lowest level in the Ba/Sq and GU tumors (14% each) and the highest level of 43% in small-cell/neuroendocrine-like tumors. There was greater subtype heterogeneity between primary tumors and LN metastases. In conclusion, immunohistochemistry-based Lund Taxonomy subtypes remain stable within the same primary tumor, with the GU subtype deriving the greatest OS benefit from AC. However, high tumor heterogeneity between the primary tumor and metastatic sites can impact the effectiveness of therapies., (© 2025 The Author(s). The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Introduction: The impact of surgical therapy on selected patients with limited metastatic/recurrence burden has not yet been well studied. We investigated the outcome of surgical resection for patients with local recurrence only or oligometastatic urothelial carcinoma (UC) of the bladder., Methods: We identified patients with oligometastatic UC or local recurrence only after radical cystectomy who underwent surgical resection with curative intent between 2003 and 2022 at our center. Oligometastatic UC was defined as three or fewer resectable lesions, regardless of the number of organs involved. We studied the surgical outcome, progression-free survival (PFS) and overall survival (OS) in this selected group of patients., Results: A total of 39 patients were selected, including 18 (46%) with local recurrence and 21 (54%) with oligometastatic UC. Nine patients (23%) experienced intraoperative complications, all of whom belonged to the local recurrence group, while 8 patients (20.5%) experienced major postoperative complications, including 6 patients from the local recurrence group and 2 patients with oligometastatic disease. The median PFS following surgery was 19 months (95% CI; 2.5-35.5) with 1- and 3-year progression rates of 47% and 29%, while the median OS was 24 months (95% CI; 8.6-39.3) with 1- and 3-year survival rates of 51% and 30%. A significantly better median PFS was observed in the metastatic versus local recurrence group (35 vs. 8 months, p = 0.01). Similarly, a median OS of 41 months was observed in the metastatic group compared to only 12 months for the local recurrence group (p = 0.12). Overall, a better survival time of 30 months was observed in the metachronous group compared to 6 months in the synchronous group (p = 0.046). In a further analysis of the metastatic group, metachronous oligometastasis was associated with a longer survival of 43 months compared to 9 months for synchronous metastasis (p = 0.18). Some differences were not significant, which may be due to sample size., Conclusion: Our study shows reasonable surgical and survival outcomes of metastasectomy, especially in the metachronous subgroup, for UC without risk of higher perioperative morbidity. On the other hand, resection of local recurrence is associated with a higher risk of incomplete resection and higher intraoperative and postoperative morbidity without offering a survival benefit., (© 2024 S. Karger AG, Basel.)

Background: Despite constant improvements, incontinence is one of the most relevant and quality-of-life-reducing side effects of radical prostatectomy (RP) and, in addition to patient-specific factors such as age, the experience of the surgeon/center and the surgical technique used play an important role., Aims: To present current real-world data on short-term incontinence after RP from one of the largest German rehabilitation centers in 2022 and to compare it to the results from the same institution in 2016., Methods and Results: Retrospective, unicentric, univariate analysis of data from 1394 men after RP in 2022 on admission and discharge from the rehabilitation clinic. Incontinence defined as ≥ 1 pad/day was evaluated by quantitative measuring all day incontinence under a defined graduation and compared to the results of 2016. Totally, 1393 men were available for analysis in 2022 compared to 1390 in 2016. Median age for both cohorts was 66 years with minor differences in preoperative PSA levels. Despite different surgical approaches, no significant change in short-term incontinence rates in 2016 and 2022 were noted at discharge (76.9% vs. 77.9%, p = 0.56). A notable increase in patients with ISUP grade Group 2 and a shift towards robotic surgery were observed in 2022 (45.5%-71%). While nerve sparing led to a significant improvement in continence (p < 0.01), lymphadenectomy and T-stage were not related to any significant increase in short-term incontinence rates. Comparing age groups within the cohort, patients > 69 years exhibited the highest risk of short-term incontinence and least likelihood of regaining continence during rehabilitation (p < 0.01). Men treated at a certified prostate cancer center had significantly (p < 0.01) lower short-term incontinence rates., Conclusion: Our study shows little improvement in short-term postoperative incontinence rates after RP in Germany in the last 6 years and known risk factors for postoperative incontinence like age, nerve-sparing surgery, and level of experience were reproduced in our analyses. We conclude not only to carefully select but also to counsel patients before being treated for prostate cancer and to strongly advice treatment at certified centers., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Male germ cell tumors (GCT) have excellent survival. Long-term sequelae in cancer survivors are an evolving field. We evaluated the risk of patients with GCT to develop primary hypogonadism and adherence to guideline-recommended therapy in a real-world cohort. Monocentric study at a tertiary cancer centre to evaluate treated GCT-patients (2001-2019). Post therapeutic male endocrine function, International Index of Erectile Function (IIEF)-5 and The aging males' symptoms rating scale (AMS) questionnaires were assessed. The overall response rates were low, with 44 of 402 contacted patients participating in the study. From these, 32(73%) underwent blood analysis, 42(95%) answered the IIEF-5 and 43(98%) the AMS. Latent hypogonadism (serum testosterone 8-12 nmol/l) was found in n = 9 (28%) and manifest hypogonadism (testosterone < 8 nmol/l) in n = 8 (25%). 50% (n = 21) indicated erectile dysfunction on IIEF-5 (cut off ≤ 21 pts.) and 62.8% (n = 27) reported symptomatic affection on AMS (cut off ≥ 27 pts.). Majority of tested patients revealed different degrees of hypogonadism. Standard instruments were able to detect gonadal damage in > 50%, which underscored the clinical need to evaluate endocrine function in cancer survivors. We further indicated the difficulties of today's research and provided starting points to assess barriers for study participations., Competing Interests: Competing interests CD has advisory roles for Janssen and IPSEN and has received travel compensation from Janssen, IPSEN and BayerB.H. has had advisory roles for ABX, AAA/Novartis, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen R&D, Lightpoint Medical, Inc., and Pfizer; has received research funding from Astellas, Bristol Myers Squibb, AAA/Novartis, German Research Foundation, Janssen R&D, and Pfizer; and has received compensation for travel from Astellas, AstraZeneca, Bayer and Janssen R&D. A.H, MGvB, AI, MN, UK, LP declare no conflicts of interest.VG: receiving grant support, lecture fees, consulting fees, and travel support from AstraZeneca, BMS, Ipsen, and Pfizer, consulting fees and travel support from Bayer, grant support, lecture fees, and consulting fees from MSD, consulting fees from Roche, Eli Lilly, Onkowissen, and EUSA Pharma, consulting fees and lecture fees from Janssen– Cilag, PharmaMar, Merck Serono, and Eisai, lecture fees from Asklepios Clinic, Diakonie Clinic, Dortmund Hospital, andClinic of Oldenburg, and grant support and consulting fees from Novartis. Ethical approval This study protocol was reviewed and approved by the local ethics committee of University Duisburg-Essen (21-9860-BO) and conducted in accordance with the ethical standards of the Declaration of Helsinki. The participants provided informed written consent before participating in the study., (© 2024. The Author(s).)

Background: It is controversial whether the use of a double-J stent (DJ) in patients with bladder cancer before radical cystectomy (RC) increases the risk of tumour seeding in the upper tract and thus the risk of metachronous upper tract urothelial carcinoma (UTUC). The aim of our study is to investigate the risk of upper tract recurrence after RC in patients previously managed with a DJ stent., Methods: A total of 699 patients who had undergone RC between January 2003 and March 2022 with complete perioperative data and pathological outcome were included in our study. Patients treated preoperatively with a DJ stent were identified and compared for development of metachronous UTUC with those who did not receive prior internal stenting. Multivariable Cox regression analysis was used to determine predictors of UTUC occurrence among the possible pathological features; risk factors for mortality after RC were also examined., Results: Of 699 patients, 117 (16.7%) were managed preoperatively with a DJ stent. The overall probability of metachronous UTUC was 1%, 4% and 6% at 1, 3 and 5 years, respectively. The groups with and without DJ stenting were comparable regarding their clinicopathologic features, except for the higher incidence of hydronephrosis in the DJ group. At similar follow-up periods (median follow-up 32 months), metachronous UTUC was detected in four (3.4%) patients in the DJ group and in 13 (2.2%) in the non-stented group (P=0.44). The median interval (IQR) from cystectomy to UTUC was 40.5 (20-49) months in the DJ group and 37 (24-82) in the non-stented group (P=0.7). In the multivariable analysis, only presence of CIS (HR 3.83, 95% CI 1.19-12.29, P=0.024) and positive ureteral margin (HR=5.2, 95% CI 1.38-19.57, P=0.015) were predictors of metachronous UTUC. The study is limited by the retrospective nature and relatively short follow-up., Conclusions: Ureteral stenting for management of hydronephrosis in patients with bladder cancer undergoing RC is a viable option, without higher risk for UTUC or mortality. Patients with positive ureteral margin and CIS are considered high-risk groups for upper tract recurrence and should receive long-term, rigorous follow-up.

Aim of the Study: The aim of our study is to evaluate the difference in stricture rate between matched groups of Bricker and Wallace techniques for ureteroileal anastomosis., Patients and Methods: A retrospective analysis of patients undergoing urinary diversion (UD) with Bricker and Wallace ureteroileal anastomosis at two university hospitals. Two groups of Bricker and Wallace patients were matched in a 1:1 ratio based on the age, sex, body mass index (BMI), Charlson comorbidity index (CCI), preoperative hydronephrosis, prior radiation therapy or abdominal surgery, pathologic T and N stages and 30-days-Clavien grade complications≥III. A multivariable Cox regression analysis was conducted to identify predictors of ureteroenteric stricture (UES) in all patients., Results: Overall, 740 patients met the inclusion criteria and 209 patients in each group were propensity matched. At a similar median follow-up of 25 months, UES was detected in 25 (12%) and 30 (14.4%) patients in Bricker and Wallace groups, respectively (p = 0.56). However, only one patient in the Bricker group developed a bilateral stricture compared to 15 patients in the Wallace group, resulting in a significantly higher number of affected renal units in the Wallace group: 45 (10.7%) versus only 26 (6.2%) in the Bricker group (p = 0.00). On multivariable extended Cox analysis, prior radiotherapy, presence of T4 pelvic malignancy and nodal positive disease were independent predictor of UES formation., Conclusion: The technique of ureteroileal anastomosis itself does not increase the rate of stricture; however, conversion of two renal units into one is associated with a higher incidence of bilateral upper tract involvement., (© 2024 The Japanese Urological Association.)

Background: The extent of pelvic lymphadenectomy (PLND) as part of radical cystectomy (RC) for bladder cancer (BC) remains unclear. Sentinel-based and lymphangiographic approaches could lead to reduced morbidity without sacrificing oncologic safety., Objective: To evaluate the feasibility and diagnostic value of fluorescence-guided template sentinel region dissection (FTD) using a handheld near-infrared fluorescence (NIRF) camera in open radical cystectomy., Design, Setting, and Participants: After peritumoral cystoscopic injection of indocyanine green (ICG) 21 patients underwent open RC with FTD due to BC between June 2019 and June 2021. Intraoperatively, the FIS-00 Hamamatsu Photonics® NIRF camera was used to identify and resect fluorescent template sentinel regions (FTRs) followed by extended pelvic lymphadenectomy (ePLND) as oncological back-up., Outcome Measurement and Statistical Analysis: Descriptive analysis of positive and negative results per template region., Results and Limitations: FTRs were identified in all 21 cases. Median time (range) from ICG injection to fluorescence detection was 75 (55-125) minutes. On average (SD), 33.4 (9.6) lymph nodes were dissected per patient. Considering template regions as the basis of analysis, 67 (38.3%) of 175 resected regions were NIRF-positive, with 13 (7.4%) regions harboring lymph node metastases. We found no metastatic lymph nodes in NIRF-negative template regions. Outside the standard template, two NIRF-positive benign nodes were identified., Conclusion: The concept of NIRF-guided FTD proved for this group all lymph node metastases to be found in NIRF-positive template regions. Pending validation in a larger collective, resection of approximately 40% of standard regions may be sufficient and may result in less morbidity., (© 2024 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Clinical trials revealed significant antitumor activity for immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma (mUC). Due to their strict eligibility criteria, clinical trials include selected patient cohorts, and thus do not necessarily represent real-world population outcomes. In this multicentric, retrospective study, we investigated real-world data to assess the effectiveness of pembrolizumab and atezolizumab and to evaluate the prognostic value of routinely available clinicopathological and laboratory parameters. Clinical and follow-up data from mUC patients who received ICIs (01/2017-12/2021) were evaluated. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and duration of response (DOR) were used as endpoints. Patients' (n = 210, n = 76 atezolizumab and 134 pembrolizumab) median OS and PFS were 13.6 and 5.9 months, respectively. Impaired ECOG-PS, the presence of visceral, liver or bone metastases, and hemoglobin levels were independently associated with poor OS and DCR. Furthermore, Bellmunt risk factors and the enhanced Bellmunt-CRP score were shown to be prognostic for OS, PFS and DCR. In conclusion, ICIs are effective treatments for a broad range of mUC patients. Our results confirmed the prognostic value of numerous risk factors and showed that Bellmunt risk scores can further be improved when adding CRP to the model., (© 2023. Springer Nature Limited.)

Online adaptive radiotherapy (ART) allows adaptation of the dose distribution to the anatomy captured by with pre-adaptation imaging. ART is time-consuming, and thus intra-fractional deformations can occur. This prospective registry study analyzed the effects of intra-fraction deformations of clinical target volume (CTV) on the equivalent uniform dose (EUD CTV ) of focal bladder cancer radiotherapy. Using margins of 5-10 mm around CTV on pre-adaptation imaging, intra-fraction CTV-deformations found in a second imaging study reduced the 10th percentile of EUD CTV values per fraction from 101.1% to 63.2% of the prescribed dose. Dose accumulation across fractions of a series was determined with deformable-image registration and worst-case dose accumulation that maximizes the correlation of cold spots. A strong fractionation effect was demonstrated-the EUD CTV was above 95% and 92.5% as determined by the two abovementioned accumulation methods, respectively, for all series of dose fractions. A comparison of both methods showed that the fractionation effect caused the EUD CTV of a series to be insensitive to EUD CTV -declines per dose fraction, and this could be explained by the small size and spatial variations of cold spots. Therefore, ART for each dose fraction is unnecessary, and selective ART for fractions with large inter-fractional deformations alone is sufficient for maintaining a high EUD CTV for a radiotherapy series.

Robotic-assisted laparoscopic partial nephrectomy (RALPN) is becoming a standard treatment for localized renal tumors worldwide. Data on the learning curve (LC) of RALPN are still insufficient. In the present study, we have attempted to gain further insight in this area by evaluating the LC using cumulative summation analysis (CUSUM). A series of 127 robotic partial nephrectomies were performed by two surgeons at our center between January 2018 and December 2020. CUSUM analysis was used to evaluate LC for operative time (OT). The different phases of surgical experience were compared in terms of perioperative parameters and pathologic outcomes. In addition, multivariate linear regression analysis was used to confirm the results of the CUSUM analysis by adjusting the phases of surgical experience for the other confounding factors that may affect OT. The median age of patients was 62 years, mean BMI was 28, and mean tumor size was 32 mm. Tumor complexity was classified as low, intermediate, and high risk according to the PADUA score in 44%, 38%, and 18%, respectively. The mean OT was 205 min, and trifecta was achieved in 72.4%. According to the CUSUM diagram, the LC of OT was divided into three phases: initial learning phase (18 cases), plateau phase (20 cases), and mastery phase (subsequent cases). The mean OT was 242, 208, and 190 min in the first, second, and third phases, respectively (P < 0.001). Surgeon experience phases were significantly associated with OT in multivariate analysis considering other preoperative and operative parameters. Surgical outcome was comparable between the three phases in terms of complications and achievement of trifecta; hospital stay was shorter in the mastery phase than in the first 2 phases (4 days vs 5 days, P = 0.02). The LC for RALPN is divided into 3 performance phases with CUSUM. Mastery of surgical technique was achieved after performing 38 cases. The initial learning phase of RALPN has no negative impact on surgical and oncologic outcomes ., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Introduction: Ureteroenteric stricture (UES) is the leading cause of renal function deterioration after radical cystectomy (RC) and urinary diversion (UD). The aim of the present review is to summarize studies that discussed the risk factors associated with UES development. Identifying the responsible factors is of importance to help surgeons to modify their treatment or follow-up strategies to reduce this serious complication., Materials and Methods: A comprehensive search of the literature using the PubMed database was conducted. The target of the search was only studies that primarily aimed to identify risk factors of UES after RC and UD. References of searched papers were also checked for potential inclusion., Results: The search originally yielded a total of 1357 articles, of which only 15 met our inclusion criteria, comprising 13, 481 patients. All the studies were observational, and retrospective published between 2013 and 2022. The natural history of UES and the reported risk factors varied widely across the studies. In 13 studies, a significant association between some risk factors and UES development was demonstrated. High body mass index (BMI) was the most frequently reported stricture risk factor, followed by perioperative urinary tract infection (UTI), robotic-assisted radical cystectomy (RARC), occurrence of post-operative Clavian grade ≥ 3 complications and urinary leakage. Otherwise, many other risk factors were reported only once., Conclusion: The literature is still lacking well-designed prospective studies investigating predisposing factors of UES. The available data suggest that the high BMI, RARC and complicated postoperative course are the main risk factors for stricture formation., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

In this prospective two-center feasibility study, we evaluate the diagnostic value of intraoperative ex vivo specimenPET/CT imaging of radical prostatectomy (RP) and lymphadenectomy specimens. Ten patients with high-risk prostate cancer underwent clinical prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) preoperatively on the day of surgery. Six patients received 68 Ga-PSMA-11 and four 18 F-PSMA-1007. Radioactivity of the resected specimen was measured again using a novel specimenPET/CT device (AURA10; XEOS Medical, Gent, Belgium) developed for intraoperative margin assessment. All index lesions of staging multiparametric magnetic resonance imaging could be visualized. Overall, specimenPET/CT correlated well with conventional PET/CT regarding detection of suspicious tracer foci (Pearson coefficient 0.935). In addition, specimenPET/CT demonstrated all lymph node metastases detected on conventional PET/CT ( n  = 3), as well as three previously undetected lymph node metastases. Importantly, all positive or close (<1 mm) surgical margins could be visualized in agreement with histopathology. In conclusion, specimenPET/CT enables detection of PSMA-avid lesions and warrants further investigation to tailor RP, based on a good correlation with final pathology. Future trials will prospectively compare ex vivo specimenPET/CT with a frozen section analysis for the detection of positive surgical margins and assessment of biochemical recurrence-free survival., Patient Summary: In this report, we examined prostatectomy and lymphadenectomy specimens for suspicious positron emission tomography (PET) signals after preoperative tracer injection. It was found that in all cases, a good signal could be visualized, with a promising correlation of surface assessment compared with histopathology. We conclude that specimenPET imaging is feasible and may help improve oncological outcomes in the future., (© 2023 The Author(s).)

Introduction: Immune checkpoint inhibitors (ICI) such as anti-PD-L1 and anti-PD-1 agents have been proven to be effective in various cancers. However, the rate of non-responders is still high in all cancer entities. Therefore, the identification of biomarkers that could help to optimize therapeutic decision-making is of great clinical importance. Soluble PD-L1 (sPD-L1) and PD-1 (sPD-1) are emerging blood-based biomarkers and were previously shown to be prognostic in various clinical studies., Objective: We aimed to evaluate the prognostic relevance of sPD-L1 and sPD-1 in patients with different tumor entities who underwent ICI therapy., Methods: We searched for articles in PubMed via Medline, Embase, Scopus, and Cochrane databases. The primary outcome was overall survival (OS) and progression-free survival (PFS); furthermore, we analyzed on-treatment serum level changes of sPD-L1 and sPD-1 during ICI therapy., Results: We synthesized the data of 1,054 patients with different cancer types from 15 articles. Pooled univariate analysis showed that elevated levels of sPD-L1 were significantly associated with inferior OS (HR = 1.67; CI:1.26-2.23, I 2  = 79%, p < 0.001). The strongest association was found in non-small cell lung cancer, whereas weaker or no association was observed in melanoma as well as in renal cell and esophageal cancers. Pooled multivariate analysis also showed that elevated levels of sPD-L1 correlated with worse OS (HR = 1.62; CI: 1.00-2.62, I 2  = 84%, p = 0.05) and PFS (HR = 1.71; CI:1.00-2.94, I 2  = 82%, p = 0.051). Furthermore, we observed that one or three months of anti-PD-L1 treatment caused a strong (27.67-fold) elevation of sPD-L1 levels in malignant mesothelioma and urothelial cancer., Conclusions: We found significantly inferior OS in ICI-treated cancer patients with elevated pre-treatment sPD-L1 levels, but this association seems to be tumor type dependent. In addition, sPD-L1 increases during anti-PD-L1 therapy seems to be therapy specific., (© 2022. The Author(s).)

Intraoperative identification of positive resection margins (PRMs) in high-risk prostate cancer (PC) needs improvement. Cerenkov luminescence imaging (CLI) with 68 Ga-PSMA-11 is promising, although limited by low residual activity and artificial signals. Here, we aimed to assess the value of CLI and flexible autoradiography (FAR) with 18 F-PSMA-1007. Methods: Mice bearing subcutaneous PSMA-avid RM1-PGLS tumors were administered 18 F-PSMA-1007, and PET/CT was performed. After the animals had been killed, organs were excised and measured signals in CLI and FAR CLI were correlated with tracer activity concentrations (ACs) obtained from PET/CT. For clinical assessment, 7 high-risk PC patients underwent radical prostatectomy immediately after preoperative 18 F-PSMA PET/CT. Contrast-to-noise ratios (CNRs) were calculated for both imaging modalities in intact specimens and after incision above the index lesion. Results: In the heterotopic in vivo mouse model ( n = 5), CLI did not detect any lesion. FAR CLI detected a distinct signal in all mice, with a lowest AC of 7.25 kBq/mL (CNR, 5.48). After incision above the index lesion of the prostate specimen, no increased signal was observed at the cancer area in CLI. In contrast, using FAR CLI, a signal was detectable in 6 of 7 patients. The AC in the missed index lesion was 1.85 kBq/mL, resulting in a detection limit of at least 2.06 kBq/mL. Histopathology demonstrated 2 PRMs, neither of which was predicted by CLI or FAR CLI. Conclusion: 18 F-PSMA FAR CLI was superior to CLI in tracer-related signal detectability. PC was could be visualized in radical prostatectomy down to 2.06 kBq/mL. However, the detection of PRMs was limited. Direct anatomic correlation of FAR CLI is challenging because of the scintillator overlay., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: Although targeted approaches have become available in second- and third-line settings, platinum-based chemotherapy remains the standard first-line treatment for advanced muscle-invasive bladder cancer (MIBC). Therefore, the prediction of platinum resistance is of utmost clinical importance., Methods: In this study, we established a routine compatible method for the molecular classification of MIBC samples according to various classification systems and applied this method to evaluate the impact of subtypes on survival after adjuvant chemotherapy. This retrospective study included 191 patients with advanced MIBC (pT≥3 or pN+) who underwent radical cystectomy, with or without adjuvant chemotherapy. A 48-gene panel and classifier rule set were established to determine molecular subtypes according to TCGA, MDA, LundTax, and Consensus classifications. Additionally, 12 single platinum-predictive candidate genes were assessed. The results were correlated with patients' clinicopathological and follow-up data and were validated using independent data sets., Results: Our final evaluation of 159 patients demonstrated better survival in the luminal groups for those who received chemotherapy compared with those who did not. In contrast, no such differences were observed in basal subtypes. The use of chemotherapy was associated with better survival in patients with high APOBEC3G expression (p < 0.002). This association was confirmed using an independent data set of patients who received neoadjuvant platinum therapy., Conclusions: The proposed method robustly replicates the most commonly used transcriptome-based subtype classifications from paraffin-embedded tissue samples. The luminal, but not basal, molecular subtypes had the greatest benefit from adjuvant platinum therapy. We identified and validated APOBEC3G as a novel predictive marker for platinum-treated patients., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Multiparametric magnetic resonance imaging (mpMRI) and targeted biopsy (TB) facilitate accurate detection of clinically significant prostate cancer (csPC). However, it remains unclear how targeted cores should be applied for accurate diagnosis of csPC., Objective: To assess csPC detection rates for two target-directed MRI/transrectal ultrasonography (TRUS) fusion biopsy approaches, conventional TB and target saturation biopsy (TS)., Design, Setting, and Participants: This was a prospective single-center study of outcomes for transperineal MRI/TRUS fusion biopsies for 170 men. Half of the men (n = 85) were randomized to conventional TB with four cores per lesion and half (n = 85) to TS with nine cores. Biopsies were performed by three experienced board-certified urologists., Outcome Measurements and Statistical Analysis: PC and csPC (International Society of Urological Pathology grade group ≥2) detection rates for systematic biopsy (SB), TB, and TS were analyzed using McNemar's test for intrapatient comparisons and Fisher's exact test for TS versus TB. A combination of targeted biopsy (TS or TB) and SB served as the reference., Results and Limitations: According to the reference, csPC was diagnosed for 57 men in the TS group and 36 men in the TB group. Of these, TS detected 57/57 csPC cases and TB detected 33/36 csPC cases (p = 0.058). Detection of Gleason grade group 1 disease was 10/12 cases with TS and 8/17 cases with TB (p = 0.055). In addition, TS detected 97% of 63 csPC lesions, compared to 86% with TB (p = 0.1). Limitations include the single-center design, the limited generalizability owing to the transperineal biopsy route, the lack of central review of pathology and radical prostatectomy correlation, and uneven distributions of csPC prevalence, Prostate Imaging-Reporting and Data System (PI-RADS) 5 lesions, men with two or more PI-RADS ≥3 lesions, and prostate-specific antigen density between the groups, which may have affected the results., Conclusions: In our study, rates of csPC detection did not significantly differ between TS and TB., Patient Summary: In this study, we investigated two targeted approaches for taking prostate biopsy samples after observation of suspicious lesions on prostate scans. We found that the rates of detection of prostate cancer did not significantly differ between the two approaches., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Programmed death ligand-1 (PD-L1) is an immune checkpoint molecule and a widely used therapeutic target in urothelial cancer. Its circulating, soluble levels (sPD-L1) were recently suggested to be associated with the presence and prognosis of various malignancies but have not yet been investigated in upper tract urothelial carcinoma (UTUC). In this study, we assessed sPD-L1 levels in 97 prospectively collected serum samples from 61 UTUC patients who underwent radical nephroureterectomy (RNU), chemotherapy (CTX), or immune checkpoint inhibitor (ICI) therapy. In addition to pretreatment samples, postoperative and on-treatment sPD-L1 levels were determined in some patients by using ELISA. In the RNU group, elevated preoperative sPD-L1 was associated with a higher tumor grade (p = 0.019), stage (p < 0.001) and the presence of metastasis (p = 0.002). High sPD-L1 levels were significantly associated with worse survival in both the RNU and CTX cohorts. sPD-L1 levels were significantly elevated in postoperative samples (p = 0.011), while they remained unchanged during CTX. Interestingly, ICI treatment caused a strong, 25-fold increase in sPD-L1 (p < 0.001). Our results suggest that elevated preoperative sPD-L1 level is a predictor of higher pathological tumor stage and worse survival in UTUC, which therefore may help to optimize therapeutic decision-making. The observed characteristic sPD-L1 flare during immune checkpoint inhibitor therapy may have clinical significance.

Cerenkov luminescence imaging (CLI) was successfully implemented in the intraoperative context as a form of radioguided cancer surgery, showing promise in the detection of surgical margins during robot-assisted radical prostatectomy. The present study was designed to provide a quantitative description of the occupational radiation exposure of surgery and histopathology personnel from CLI-guided robot-assisted radical prostatectomy after the injection of 68 Ga-PSMA-11 in a single-injection PET/CT CLI protocol. Methods: Ten patients with preoperative 68 Ga-PSMA-11 administration and intraoperative CLI were included. Patient dose rate was measured before PET/CT ( n  = 10) and after PET/CT ( n  = 5) at a 1-m distance for 4 patient regions (head [A], right side [B], left side [C], and feet [D]). Electronic personal dosimetry (EPD) was used for intraoperative occupational exposure ( n  = 10). Measurements included the first surgical assistant and scrub nurse at the operating table and the CLI imager/surgeon at the robotic console and encompassed the whole duration of surgery and CLI image acquisition. An estimation of the exposure of histopathology personnel was performed by measuring prostate specimens ( n  = 8) with a germanium detector. Results: The measured dose rate value before PET/CT was 5.3 ± 0.9 (average ± SD) μSv/h. This value corresponds to a patient-specific dose rate constant for positions B and C of 0.047 μSv/h⋅MBq. The average dose rate value after PET/CT was 1.04 ± 1.00 μSv/h. The patient-specific dose rate constant values corresponding to regions A to D were 0.011, 0.026, 0.024, and 0.003 μSv/h⋅MBq, respectively. EPD readings revealed average personal equivalent doses of 9.0 ± 7.1, 3.3 ± 3.9, and 0.7 ± 0.7 μSv for the first surgical assistant, scrub nurse, and CLI imager/surgeon, respectively. The median germanium detector-measured activity of the prostate specimen was 2.96 kBq (interquartile range, 2.23-7.65 kBq). Conclusion: Single-injection 68 Ga-PSMA-11 PET/CT CLI procedures are associated with a reasonable occupational exposure level, if kept under 110 procedures per year. Excised prostate specimen radionuclide content was below the exemption level for 68 Ga. Dose rate-based calculations provide a robust estimation for EPD measurements., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

In this prospective single-center feasibility study, we demonstrate that the use of three-dimensional (3D)-printed prostate models support nerve-sparing radical prostatectomy (RP) and intraoperative frozen sectioning (IFS) in ten men suffering from intermediate- and high-risk prostate cancer (PC), of whom seven harbored pT3 disease. Patient-specific 3D resin models were printed based on preoperative multiparametric magnetic resonance imaging (mpMRI) to provide an exact 3D impression of significant tumor lesions. RP and IFS were planned in a patient-tailored fashion. The 36-region Prostate Imaging Reporting and Data System (PI-RADS) v2.0 scheme was used to compare the MRI/3D print with whole-mount histopathology. In all cases, localization of the index lesion was correctly displayed by MRI and the 3D model. Localization of significant PC lesions correlated significantly (Pearson`s correlation coefficient of 0.88; p <  0.001). In addition, a significant correlation of the width, length, and volume of the tumor and prostate gland, derived from the printed model and histopathology, was found, using Pearson's correlation analyses and Bland-Altman plots. In conclusion, 3D-printed prostate models correlate well with final pathology and can be used to tailor RP. PATIENT SUMMARY: The use of three-dimensional (3D)-printed prostate models based on preoperative magnetic resonance imaging (MRI) may improve prostatectomy outcome. This study confirmed the accuracy of 3D-printed prostates compared with pathology from radical prostatectomy specimens. Thus, MRI-derived 3D-printed prostate models can assist in prostate cancer surgery., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Upper tract urothelial carcinoma (UTUC) is a rare cancer with a barely predictable clinical behaviour. Serum MMP-7 is a validated prognostic marker in urothelial bladder cancer, a tumour entity with large clinical, histological, and molecular similarity to UTUC. The serum MMP-7 levels have not yet been investigated in UTUC. In the present study, we determined MMP-7 concentrations in an overall number of 103 serum samples from 57 UTUC patients who underwent surgical or systemic (platinum or immune checkpoint inhibitor) therapy by using the ELISA method. In addition to pre-treatment samples, the serum samples collected at predefined time points after or during therapy were also investigated. Serum MMP-7 concentrations were correlated with clinicopathological and follow-up data. Our results revealed significantly, two-fold elevated pre-treatment serum MMP-7 levels in metastatic cases of UTUC in both the radical surgery- and the chemotherapy-treated cohorts ( p = 0.045 and p = 0.040, respectively). In addition, high serum MMP-7 levels significantly decreased after radical surgery, and high pre-treatment MMP-7 concentrations were associated with shorter survival both in the surgery- and chemotherapy-treated cohorts ( p = 0.029 and p = 0.001, respectively). Our results revealed pre-treatment serum MMP-7 as a prognostic marker for UTUC, which may help to improve preoperative risk-stratification and thereby improve therapeutic decision-making.

Objective: Patients with bladder cancer (BC) are at risk of developing upper tract urothelial carcinoma (UTUC). Therefore, CT urography is recommended for follow-up. To avoid intravenous contrast agents, retrograde pyelography (RPG) is an alternative. However, it is still unclear whether RPG increases the incidence of UTUC. The aim of this study was to investigate the impact of RPG in the presence of BC on the risk of developing UTUC., Patients and Methods: Retrospectively analysing a total of 3,680 RPGs between 2009 and 2016, all patients with simultaneous BC (group 1) and those without synchronous BC (group 2) during RPG were compared. All patients were risk stratified according to the EORTC bladder calculator. In patients without BC during RPG, risk stratification was based on the worst prior tumour characteristics., Results: A total of 145 patients with a history of BC were analysed. Of these, 112 patients underwent RPG with simultaneous BC. UTUC developed in 6 of 112 patients (5.4%) and 58.9% (66/112) had high-risk BC according to the EORTC bladder calculator. In the control group, one out of 33 (3%) patients with metachronous high-risk BC developed UTUC., Conclusions: Using RPG in the presence of BC did not increase the risk of UTUC. Due to the predominant number of high-risk/high-grade tumours, individual tumour biology appears to be the primary driver for the development of UTUC., (© 2021 S. Karger AG, Basel.)

Purpose: To evaluate fibroblast-activation-protein (FAP) expression in different clinical stages of prostate cancer (PC) with regards to utility of [ 68  Ga]Ga-FAPI-04 PET/CT imaging in patients with castration-resistant PC (CRPC)., Methods: Tissue microarrays (TMAs) were constructed from prostatic tissue from 94 patients at different stages of PC (primary PC, patients undergoing neoadjuvant androgen deprivation therapy, CRPC, and neuroendocrine PC (NEPC)) and were stained with anti-FAP monoclonal antibody. A positive pixel count algorithm (H-Index) was used to compare FAP expression between the groups. Additionally, three men with advanced CRPC or NEPC underwent [ 68  Ga]Ga-FAPI-04 PET/CT, and PET positivity was analyzed., Results: The mean H-index for benign tissue, primary PC, neoadjuvant androgen deprivation therapy before radical prostatectomy, CRPC, and NEPC was 0.018, 0.031, 0.042, 0.076, and 0.051, respectively, indicating a significant rise in FAP expression with advancement of disease. Corroborating these findings [ 68  Ga]Ga-FAPI-04 PET/CT was highly positive in men with advanced CRPC., Conclusion: Increased FAP tissue expression supports the use of FAP inhibitor (FAPI)-molecular theranostics in CRPC., (© 2021. The Author(s).)