Ashkan Mortezavi

Objective: To evaluate perioperative morbidity following robot‐assisted radical cystectomy with intracorporeal urinary diversion (iRARC) during the transition from open surgery at a single academic center, and to provide detailed complication profiles to guide surgical teams and patient counseling. Patients and Methods: We retrospectively analyzed 111 consecutive patients undergoing iRARC between 2017 and 2023. Perioperative outcomes and complications were assessed at 30 and 90 days, using the Clavien–Dindo (CD) classification. Complications were further categorized by etiology and severity. Detailed incidence rates and management strategies were recorded per patient. Results: A total of 163 complications occurred within 90 days, with 129 (79%) recorded within 30 days. Early complications were predominantly low‐grade ( n = 96, 74%), while 33 (26%) were high‐grade. Systemic complications 108 (84%) outnumbered primary surgical events 21 (16%). Among early high‐grade complications, cardiovascular and respiratory events were the most common ( n = 9, 27%), followed by infectious ( n = 7, 21%) and genitourinary complications ( n = 7, 21%). Incidence rates for events were calculated on a per‐patient basis: acute coronary syndrome 1.2%, pneumonia 2.7%, arrhythmias 2.7%, thrombosis 1.8%, pulmonary embolism 0.9%, insufficiency of the ileal anastomosis 0.9%, urinary tract infections 32.4%, and infected lymphoceles 8.1%. Genitourinary complications, including ureteral strictures (6.3%) and urinary leakage (3.6%), required frequent endourological interventions. Despite minimally invasive surgery and strict ERAS protocol implementation, paralytic ileus occurred in 19.8% of patients but was managed conservatively in all cases. Thirty‐four additional complications occurred between days 30 and 90, including 16 high‐grade events. The 90‐day mortality rate was 1.8%. In the multivariable analysis, no independent predictors of high‐grade complications were identified. Variables including BMI, clinical stage ≥ cT2, age, sex, and neoadjuvant chemotherapy showed no significant association (all p ≥ 0.20). Conclusion: iRARC is feasible and associated with an acceptable safety profile during the learning curve. Most complications were systemic and not directly related to the surgical technique, underscoring the need for multidisciplinary perioperative management. Detailed incidence data of specific complications provide valuable insights for realistic patient counseling and heightened awareness among care teams.

Patient-derived organoids (PDOs) offer new opportunities to model various cancers. However, their application in prostate cancer (PCa) has been hampered by poor success rates and overgrowth of cell types which are not representative of the patient samples. By exploiting a cohort of 164 PCa patient samples and tuning several culture parameters, we show that an extracellular matrix-free (ECM)-free culture system increases the take-rate of PDOs with luminal-like and PCa features. Single-cell RNA sequencing (scRNA-seq) reveals that ECM-free PDOs comprise cell populations associated with known PCa signatures and exhibit transcriptomic resemblance with their respective parental tumors. In addition, we define organoid-associated cell type signatures and identify markers discriminating tumors versus benign cells ex vivo and in situ . Furthermore, we generate the first prostate PDO single-cell atlas integrating previously-published scRNA-seq datasets and our newly- generated data. We show that Matrigel-based organoid cultures derived from primary PCa are essentially composed of benign-like epithelial cells, irrespective of the dataset or the malignant nature of the tissue of origin. In contrast, ECM-free conditions maintain heterogenous patient-specific luminal tumor cell populations and enrich in intermediate cell types. Ultimately, our work will significantly enhance the potential of PDOs in basic and translational PCa research.

Zusammenfassung: Auch nach mehr als 3 Dekaden ist der PSA-Test ungeschlagen in Sachen Kosteneffizienz als initialer Triagetest zur Früherkennung des Prostatakrebses. Überschreitet der PSA-Wert einen vordefinierten Grenzwert, haben die neuen Biomarker als Triggertest alle das Potenzial, die Anzahl der unnötigen MRT-Untersuchungen und Biopsien zu senken. Welcher Biomarker sich durchsetzt, ist davon abhängig, wie gut der Zugang zum Test ist (geografisch bedingt), wie belastbar die klinischen Studien sind (prospektiv, statistische Aussagekraft) und ob der Test auch im gewünschten Setting kalibriert ist (Screening vs. vor Biopsie). Der Stockholm3-Test erfüllt aktuell alle 3 Anforderungen für ein Screeningsetting, wobei zeitnahe auch Daten für den 4Kscore® erwartet werden.

Introduction: Extended pelvic lymph node dissection (ePLND) in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) is a widely used procedure. However, little is known about anatomical site-specific yields and subsequent metastatic patterns in these patients. Patients and methods: Data on a consecutive series of 1107 patients undergoing RARP at our centre between 2004 and 2018 were analysed. In men undergoing LN dissection, the internal, external and obturator nodes were removed and sent in separately. We performed an analysis of LN yields in total and for each anatomical zone, patterns of LN metastases and complications. Oncological outcome in pN+ disease was assessed including postoperative PSA persistence and survival. Results: A total of 823 ePLNDs were performed in the investigated cohort resulting in 98 men being diagnosed as pN+ (8.9%). The median (IQR) LN yield was 19 (14–25), 10 (7–13) on the right and 9 (6–12) on the left side (P < 0.001). A median of six (4–8) LNs were retrieved from the external, three (1–6) from the internal iliac artery, and eight (6–12) from the obturator fossa. More men had metastatic LNs on the right side compared to the left (41 vs. 19). Symptomatic lymphoceles occurred exclusively in the ePLND group (2.3% vs. 0%, p = 0.04). Postoperatively, 47 (47.9%) of men with pN+ reached a PSA of < 0.1μg/ml. There was no association between a certain pN+ region and postoperative PSA persistence or BCRFS. The estimated cancer specific survival rate at 5 years was 98.5% for pN+ disease. Conclusion: Robot-assisted laparoscopic ePLND with a high LN yield and low complication rate is feasible. However, we observed an imbalance in more removed and positive LNs on the right side compared to the left. A high rate of postoperative PSA persistence and early recurrence in pN+ patients might indicate a possibly limited therapeutical value of the procedure in already spread disease. Yet, these men demonstrated an excellent survival.

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

Background: To investigate the clinical implications of magnetic resonance imaging (MRI) negative prostate cancer (PCa) in a cohort of men undergoing transperineal prostate biopsy.Methods: We included all men without prior diagnosis of PCa undergoing transperineal template saturation ± fusion‐guided targeted biopsy of the prostate between November 2014 and March 2018. Before biopsy, all patients underwent MRI and biopsies were performed irrespective of imaging results. Baseline characteristics, imaging, biopsy results, and follow‐up information were retrieved from the patient charts. Patients were classified as either MRI negative (Prostate Imaging Reporting and Data System [PIRADS] ≤ 2) or positive (PIRADS ≥ 3). ISUP grade group 1 was defined as clinically nonsignificant (nsPCa) and ≥2 as clinically significant PCa (csPCa). Primary outcome was the individual therapeutic decision after diagnosis of PCa stratified according to MRI visibility. Secondary outcomes were the sensitivity and specificity of MRI, and the urooncological outcomes after radical prostatectomy (RP).Results: From 515 patients undergoing prostate biopsy, 171 (33.2%) patients had a negative and 344 (66.8%) a positive MRI. Pathology review stratified for MRI negative and positive cases revealed nsPCa in 27 (15.8%) and 32 (9.3%) and csPCa in 26 (15.2%) and 194 (56.4%) of the patients, respectively. The rate of active treatment in the MRI negative was lower compared with the MRI positive cohort (12.3% vs. 53.2%; odd ratio [OR] = 0.12; p < 0.001). While men with negative MRI were more likely to undergo active surveillance (AS) than MRI positive patients (18.1% vs. 10.8%; OR = 1.84; p = 0.027), they rarely underwent RP (6.4% vs. 40.7%, OR = 0.10; p < 0.001). Logistic regression revealed that a negative MRI was independently protective for active treatment (OR = 0.32, p = 0.014). The specificity, sensitivity, negative, and positive predictive value of MRI for detection of csPCa were 49.2%, 88.2%, 56.4%, and 84.8%, respectively. The rate of adverse clinicopathological outcome features (pT3/4, ISUP ≥4, or prostate‐specific antigen [PSA]‐persistence) following RP was 4.7% for men with MRI negative compared to 17.4% for men with MRI positive PCa (OR = 3.1, p = 0.19).Conclusion: Only few men with MRI negative PCa need active cancer treatment at the time of diagnosis, while the majority opts for AS. Omitting prostate biopsies and performing a follow‐up MRI may be a safe alternative to reduce the number of unnecessary interventions.