Safety and Efficacy of Extended Therapy with [177Lu]Lu-PSMA: A German Multicenter Study.

Prospective results have demonstrated favorable safety and efficacy of [177Lu]Lu-PSMA radiopharmaceutical therapy for up to 6 cycles in men with metastatic castration-resistant prostate cancer. However, no systematic data are available outlining the feasibility of extended therapy beyond 6 cycles. We aim to evaluate the safety and efficacy of extended [177Lu]Lu-PSMA radiopharmaceutical therapy in patients who have received more than 6 cycles. Methods: In total, 111 patients were included in this multicenter retrospective analysis. Based on individual decisions, patients underwent uninterrupted continuation of therapy (continuous treatment) or reexposure after a therapy break (rechallenge treatment) between 2014 and 2023. Overall survival, 50% prostate-specific antigen (PSA) decline (measured 8-12 wk after treatment initiation or rechallenge), PSMA PET response, and grades per Common Terminology Criteria for Adverse Events were assessed. χ2 tests, multivariable Cox regression analysis, and log-rank tests were applied for statistical analyses. Results: Patients received extended treatment with [177Lu]Lu-PSMA, either as a continuous treatment (43/111, 38.7%) or as a rechallenge (68/111, 61.3%) treatment, with median cumulative doses of 57.4 or 60.8 GBq, respectively. Overall survival from the initiation of [177Lu]Lu-PSMA was 31.3, 23.2, and 40.2 mo for the entire cohort, the continuous treatment group, and the rechallenge treatment group, respectively. The initial 50% PSA decline was significantly higher in the retreated group than in the continuous group (57/63 [90.4%] vs. 26/42 [61.9%]; P = 0.006). A 50% PSA decline was observed in 23 of 62 patients (37.1%) after the first rechallenge. The rate of grades 3-4 toxicity was comparable between continuous and rechallenge treatments (anemia, 7/43 [16.3%] vs. 13/68 [19.1%)], P = 0.6; leukocytopenia, 1/43 [2.3%] vs. 2/67 [3.0%], P = 0.3; thrombocytopenia, 3/43 [7.0%] vs. 3/68 [4.4%], P = 0.3; renal, 2/43 [4.7%] vs. 5/68 [7.4%], P = 0.2). Conclusion: Extended therapy with [177Lu]Lu-PSMA is safe and has not been associated with increased grades 3-4 toxicity. Patient candidates for extended treatment experienced a favorable median survival of 31.3 mo from the first administration. Response under [177Lu]Lu-PSMA rechallenge demonstrated preserved efficacy of [177Lu]Lu-PSMA after a treatment break.

Influential Factors Impacting Treatment Decision-making and Decision Regret in Patients with Localized or Locally Advanced Prostate Cancer: A Systematic Literature Review.

CONTEXT: Treatment decision-making (TDM) for patients with localized (LPC) or locally advanced (LAPC) prostate cancer is complex, and post-treatment decision regret (DR) is common. The factors driving TDM or predicting DR remain understudied. OBJECTIVE: Two systematic literature reviews were conducted to explore the factors associated with TDM and DR. EVIDENCE ACQUISITION: Three online databases, select congress proceedings, and gray literature were searched (September 2022). Publications on TDM and DR in LPC/LAPC were prioritized based on the following: 2012 onward, ≥100 patients, journal article, and quantitative data. The Preferred Reporting Items Reviews and Meta-analyses guidelines were followed. Influential factors were those with p < 0.05; for TDM, factors described as "a decision driver", "associated", "influential", or "significant" were also included. The key factors were determined by number of studies, consistency of evidence, and study quality. EVIDENCE SYNTHESIS: Seventy-five publications (68 studies) reported TDM. Patient participation in TDM was reported in 34 publications; overall, patients preferred an active/shared role. Of 39 influential TDM factors, age, ethnicity, external factors (physician recommendation most common), and treatment characteristics/toxicity were key. Forty-nine publications reported DR. The proportion of patients experiencing DR varied by treatment type: 7-43% (active surveillance), 12-57% (radical prostatectomy), 1-49% (radiotherapy), 28-49% (androgen-deprivation therapy), and 21-47% (combination therapy). Of 42 significant DR factors, treatment toxicity (sexual/urinary/bowel dysfunction), patient role in TDM, and treatment type were key. CONCLUSIONS: The key factors impacting TDM were physician recommendation, age, ethnicity, and treatment characteristics. Treatment toxicity and TDM approach were the key factors influencing DR. To help patients navigate factors influencing TDM and to limit DR, a shared, consensual TDM approach between patients, caregivers, and physicians is needed. PATIENT SUMMARY: We looked at factors influencing treatment decision-making (TDM) and decision regret (DR) in patients with localized or locally advanced prostate cancer. The key factors influencing TDM were doctor's recommendation, patient age/ethnicity, and treatment side effects. A shared, consensual TDM approach between patients and doctors was found to limit DR.

Predictors of Early Continence Recovery Following Radical Prostatectomy, Including Transperineal Ultrasound to Evaluate the Membranous Urethra Length (CHECK-MUL Study).

INTRODUCTION: To predict early continence recovery following radical prostatectomy (RP) using baseline demographic and clinical data, as well as dynamic transperineal ultrasound (TPUS) parameters of membranous urethral length (MUL). PATIENTS AND METHODS: A retrospective CHECK-MUL (check of membranous urethral length) study was conducted. We evaluated 154 patients who underwent RP between August 2018 and April 2023. All patients underwent pre- and postoperative dynamic TPUS to measure MUL. Urinary continence was defined as the use of one safety pad or less 3 months post surgery. The International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) was used to assess urinary incontinence (UI). We used logistic regression to assess the association between MUL and early continence recovery. A multivariable logistic regression model was then constructed for the prediction of early continence recovery based on the MUL. RESULTS: The median MUL observed pre- and postoperatively in this study were similar (14.6 mm and 12.9 mm). In the univariable logistic regression analysis, the pre- and postoperative MUL measured by TPUS (odds ratio (OR): 1.12; 95%-CI: 1.02-1.79; p = 0.05 and OR: 1.01; 95%-CI: 1.02-1.12; p < 0.01) directions were independent predictors of early continence recovery 3 months post surgery. In addition, age (OR: 1.23; 95%-CI: 1.11-1.42; p = 0.03), BMI (OR: 1.44; 95%-CI: 1.18-2.92; p = 0.05), and bilateral nerve sparing (OR: 1.24; 95%-CI: 1.02-1.9; p = 0.05) were independent predictors of urinary continence in univariable logistic regression models. Preoperative MUL >15 mm (95% CI 1.28-1.33; p = 0.03) and postoperative MUL >14 mm (95% CI 1.2-1.16; p = 0.05) were significantly associated with early continence recovery at 3 months post surgery. CONCLUSIONS: The likelihood of continence recovery increases with membranous urethral length and decreases with age, BMI, and lack of nerve sparing. Preoperative MUL >15 mm and postoperative MUL >14 mm were significantly associated with early continence recovery at 3 months post surgery.

Randomized Trial of Prostate-Specific Membrane Antigen PET/CT Before Definitive Radiotherapy for Unfavorable Intermediate- and High-Risk Prostate Cancer (PSMA-dRT Trial).

This multicenter randomized phase III trial (NCT04457245) evaluated the effect of performing prostate-specific membrane antigen (PSMA) PET/CT before definitive radiotherapy. Methods: Men with unfavorable intermediate- or high-risk prostate cancer were randomized 1.08:1 between receiving and not receiving a PSMA PET/CT scan before definitive radiotherapy. All other imaging modalities were allowed in the control arm. The primary endpoint was 5-y progression-free survival. Results: Fifty-four men were randomized between November 2020 and December 2021 (PSMA PET/CT, n = 25; control, n = 29). The trial closed early after approval and insurance coverage of PSMA PET/CT. In the PSMA PET/CT arm, 14 patients had localized disease (miT2b-cN0M0), 6 had locally advanced disease (miT3a-bN0M0), 3 had regional metastasis (miN1M0), and 1 had distant metastasis (miM1b). Four patients were upstaged. Conclusion: PSMA PET/CT upstaged 17% of patients, which allowed for more accurate radiotherapy planning. Unfortunately, this trial closed early before completion of target enrollment (54/316, 17%) and was underpowered to assess the effect of PSMA PET/CT on progression-free survival.

Activity of Lutetium-177 Prostate-specific Membrane Antigen and Determinants of Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer Previously Treated with Cabazitaxel: The PACAP Study.

BACKGROUND: Both cabazitaxel and lutetium-177 prostate-specific membrane antigen (Lu-PSMA) improve survival in metastatic castration-resistant prostate cancer (mCRPC) after an androgen receptor pathway inhibitor and docetaxel, but there are limited data regarding Lu-PSMA activity after cabazitaxel. OBJECTIVE: To assess the activity of Lu-PSMA and determinants of outcomes after cabazitaxel in mCRPC. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was conducted of consecutive mCRPC patients from eight European centers treated with Lu-PSMA after cabazitaxel. INTERVENTION: Lu-PSMA every 6-8 wk at a dose of 6-7.6 GBq. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was radiographic progression-free survival (rPFS). The secondary endpoints included time to prostate-specific antigen (PSA) progression (TTPSA), overall survival (OS), PSA decline, objective response rate (ORR), clinical benefit, and safety. RESULTS AND LIMITATIONS: Of 126 patients, 68% had International Society of Urological Pathology (ISUP) grade 4-5 disease, 21% had visceral metastases, and 7% had lymph node disease only. DNA damage repair (DDR) alterations were detected in 11/50 (22%) patients with available testing. Patients received a median number of 3 Lu-PSMA cycles (interquartile range 2-4). With a median follow-up of 12.0 mo, the median rPFS was 4.4 mo (95% confidence interval [CI] 3.2-5.4), TTPSA 3.5 mo (95% CI 3.0-4.6), and OS 8.9 mo (95% CI 6.5-12.7). The ORR was 35%, and 55 patients (44%) experienced a PSA decline of ≥50%. The time to castration resistance of <12 mo was associated with shorter rPFS (p = 0.01). A similar trend was observed for ISUP grade 4-5 (p = 0.08), and baseline positron-emission tomography parameters including PSMA mean standardized uptake value (SUV) and maximum SUV (respectively, p = 0.06 and 0.05). The duration of previous cabazitaxel or DDR status did not impact outcomes. Patients experiencing a PSA decline of ≥ 50% on therapy demonstrated longer rPFS, TTPSA, and OS (all p < 0.0001). Limitations include retrospective data collection and investigator-based rPFS assessment. CONCLUSIONS: Lu-PSMA demonstrated a substantial PSA decline but limited rPFS after cabazitaxel in a real-life setting. Adverse baseline characteristics, baseline positron-emission tomography parameters, and quality of PSA response may help identify patients less likely to benefit from Lu-PSMA. PATIENT SUMMARY: Lutetium-177 prostate-specific membrane antigen (Lu-PSMA) improved outcomes in patients with castration-resistant prostate cancer, but there are limited data about its activity after cabazitaxel, a chemotherapy that is also the standard of care in this setting. We conducted a study across eight European centers and showed substantial responses on Lu-PSMA after cabazitaxel, although activity was short lived in a heavily pretreated population. Our findings prompt for real-life evaluation of Lu-PSMA in earlier settings to define the best therapeutic sequence.

Bricker versus Wallace ureteroileal anastomosis: A multi-institutional propensity score-matched analysis.

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.

RECIP 1.0 Predicts Progression-Free Survival After [177Lu]Lu-PSMA Radiopharmaceutical Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer.

Response Evaluation Criteria in Prostate-Specific Membrane Antigen Imaging (RECIP) 1.0 is an evidence-based framework to evaluate therapeutic efficacy in metastatic prostate cancer using prostate-specific membrane antigen (PSMA) PET/CT. This study aimed to evaluate the associations of interim PSMA PET/CT by RECIP 1.0 with short-term outcome after radiopharmaceutical treatment. Methods: This multicenter retrospective study included patients with metastatic castration-resistant prostate cancer who underwent [177Lu]Lu-PSMA radiopharmaceutical therapy at 3 academic centers and received PSMA PET/CT at baseline and at 12 wk. Pairs of PSMA PET/CT images were assessed by 5 readers for visual RECIP 1.0. The primary outcome was the association of RECIP with prostate-specific antigen progression-free survival (PSA-PFS) by Kaplan-Meier analysis. Results: In total, 124 of 287 screened patients met the inclusion criteria, with 0 (0%), 29 (23%), 54 (44%), and 41 (33%) of those 124 patients having complete response, partial response, stable disease, or progressive disease (PD) by visual RECIP 1.0, respectively. Patients with visual RECIP PD had a significantly shorter PSA-PFS than those with RECIP stable disease or with RECIP partial response (2.6 vs. 6.4 vs. 8.4 mo; P < 0.001). The median PSA-PFS among patients with RECIP PD versus those with non-RECIP PD was 2.6 versus 7.2 mo (hazard ratio, 13.0; 95% CI, 7.0-24.1; P < 0.001). Conclusion: PSMA PET/CT by RECIP 1.0 after 2 cycles of [177Lu]Lu-PSMA is prognostic for PSA-PFS. PSMA PET/CT by RECIP 1.0 may be used in earlier stages of prostate cancer to evaluate drug efficacy and to predict progression-free survival.

[Rare tumors and tumor types of the urinary system in the 5th edition of the WHO classification 2022]. / Seltenere Tumoren und Tumortypen des ableitenden Harnsystems in der 5. Aufl. der WHO-Klassifikation 2022.

The 5th edition of the World Health Organization (WHO) classification of tumors of the urinary tract and male genital organs introduced both general and specific changes in structure, classification, and nomenclature. This also applies to rarer tumors and tumor subtypes of the urinary system. Knowledge of these changes is relevant for routine histopathological work. This article provides an overview of the main new features of the rarer tumors and tumor subtypes of the urinary system in the new edition of the WHO classification.

Near-infrared fluorescence lymph node template region dissection plus backup lymphadenectomy in open radical cystectomy for bladder cancer using an innovative handheld device: A single center experience.

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.

Prostate-specific Membrane Antigen Positron Emission Tomography-detected Disease Extent and Overall Survival of Patients with High-risk Nonmetastatic Castration-resistant Prostate Cancer: An International Multicenter Retrospective Study.

Previously, we demonstrated that prostate-specific membrane antigen positron emission tomography (PSMA-PET) revealed distant metastases in 109/200 patients (39% distant nodes, 24% bone, and 6% visceral organ) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and high-risk features (International Society of Urological Pathology score ≥4 and/or prostate-specific antigen doubling time ≤10 mo) without metastases by conventional imaging. However, the impact of disease extent determined by PSMA-PET on patient outcomes is unknown. We followed these 200 patients for a median of 43 mo after PSMA-PET and retrospectively assessed the association between patient characteristics, PSMA-PET findings, treatment management, and outcomes using a Kaplan-Meier model and Cox multivariable regressions. Among assessed disease characteristics, polymetastatic disease (five or more distant lesions on PET) was independently associated with shorter overall survival (OS; median 61 mo vs not reached; hazard ratio [95% confidence interval], 1.81 [1.00-3.27]; p = 0.050) and time to new metastases (median 38 vs 60 mo; 1.80 [1.10-2.96]; p = 0.019), and initial pN1 status with shorter OS (55 mo vs not reached; 1.94 [1.12-3.37]; p = 0.019). Following PSMA-PET, locoregional salvage therapies were used most commonly in no/local disease (58%), and androgen receptor signaling inhibitors were used in distant metastatic disease (51%). PSMA-PET provides additional risk stratification for patients with nmCRPC. Polymetastatic disease (five or more distant lesions) is associated with worse outcomes. PATIENT SUMMARY: A novel sensitive imaging technology, called prostate-specific membrane antigen positron emission tomography (PSMA-PET), allows doctors to detect the spread of prostate cancer, known as distant metastases, earlier and more accurately than in the past. In our study, PSMA-PET detected none to many metastases in patients who were considered free of distant metastasis by conventional imaging. These findings predicted outcomes and were used to select appropriate treatment.

Safety and quality of cystectomy and pelvic lymph node dissection after neoadjuvant durvalumab and cisplatin/gemcitabine.

OBJECTIVE: To report on the surgical safety and quality of pelvic lymph node dissection (PLND) in patients treated with radical cystectomy (RC) and PLND for muscle-invasive bladder cancer (MIBC) after neoadjuvant chemo-immunotherapy. PATIENTS AND METHODS: The Swiss Group for Clinical Cancer Research (SAKK) 06/17 was an open-label single-arm phase II trial including 61 cisplatin-fit patients with clinical stage (c)T2-T4a cN0-1 operable urothelial MIBC or upper urinary tract cancer. Patients received neoadjuvant cisplatin/gemcitabine and durvalumab followed by surgery. Prospective quality assessment of surgeries was performed via central review of intraoperative photographs. Postoperative complications were assessed using the Clavien-Dindo Classification. Data were analysed descriptively. RESULTS: A total of 50 patients received RC and PLND. All patients received neoadjuvant chemo-immunotherapy. The median (interquartile range) number of lymph nodes removed was 29 (23-38). No intraoperative complications were registered. Grade ≥III postoperative complications were reported in 12 patients (24%). Complete nodal dissection (100%) was performed at the level of the obturator fossa (bilaterally) and of the left external iliac region; in 49 patients (98%) at the internal iliac region and at the right external iliac region; in 39 (78%) and 38 (76%) patients at the right and left presacral level, respectively. CONCLUSION: This study supports the surgical safety of RC and PLND following neoadjuvant chemo-immunotherapy in patients with MIBC. The extent and completeness of protocol-defined PLND varies between patients, highlighting the need to communicate and monitor the surgical template.

Diagnostic Accuracy of 68Ga-FAPI Versus 18F-FDG PET in Patients with Various Malignancies.

To assess the diagnostic accuracy of 68Ga-labeled fibroblast activation protein inhibitor (FAPI) and 18F-labeled FDG PET for the detection of various tumors, we performed a head-to-head comparison of both imaging modalities across a range of tumor entities as part of our ongoing 68Ga-FAPI PET observational trial. Methods: The study included 115 patients with 8 tumor entities who received imaging with 68Ga-FAPI for tumor staging or restaging between October 2018 and March 2022. Of those, 103 patients received concomitant imaging with 68Ga-FAPI and 18F-FDG PET and had adequate lesion validation for accuracy analysis. Each scan was evaluated for the detection of primary tumor, lymph nodes, and visceral and bone metastases. True or false positivity and negativity to detected lesions was assigned on the basis of histopathology from biopsies or surgical excision, as well as imaging validation. Results: 68Ga-FAPI PET revealed higher accuracy than 18F-FDG PET in the detection of colorectal cancer (n = 14; per-patient, 85.7% vs. 78.6%; per-region, 95.6% vs. 91.1%) and prostate cancer (n = 22; per-patient, 100% vs. 90.9%; per-region, 96.4% vs. 92.7%). 68Ga-FAPI PET and 18F-FDG PET had comparable per-patient accuracy in detecting breast cancer (n = 16, 100% for both) and head and neck cancers (n = 10, 90% for both modalities). 68Ga-FAPI PET had lower per-patient accuracy than 18F-FDG PET in cancers of the bladder (n = 12, 75% vs. 100%) and kidney (n = 10, 80% vs. 90%), as well as lymphoma (n = 9, 88.9% vs. 100%) and myeloma (n = 10, 80% vs. 90%). Conclusion: 68Ga-FAPI PET demonstrated higher diagnostic accuracy than 18F-FDG PET in the diagnosis of colorectal cancer and prostate cancer, as well as comparable diagnostic performance for cancers of the breast and head and neck. Accuracy and impact on management will be further assessed in an ongoing prospective interventional trial (NCT05160051).

Magnetic Resonance Imaging-guided Active Surveillance Without Annual Rebiopsy in Patients with Grade Group 1 or 2 Prostate Cancer: The Prospective PROMM-AS Study.

Background: Multiparametric magnetic resonance imaging (mpMRI) may allow patients with prostate cancer (PC) on active surveillance (AS) to avoid repeat prostate biopsies during monitoring. Objective: To assess the ability of mpMRI to reduce guideline-mandated biopsy and to predict grade group upgrading in patients with International Society of Urological Pathology grade group (GG) 1 or GG 2 PC using Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scores. The hypothesis was that the AS disqualification rate (ASDQ) rate could be reduced to 15%. Design setting and participants: PROMM-AS was a prospective study assessing 2-yr outcomes for an mpMRI-guided AS protocol. A 12 mo after AS inclusion on the basis of MRI/transrectal ultrasound fusion-guided biopsy (FBx), all patients underwent mpMRI. For patients with stable mpMRI (PRECISE 1-3), repeat biopsy was deferred and follow-up mpMRI was scheduled for 12 mo later. Patients with mpMRI progression (PRECISE 4-5) underwent FBx. At the end of the study, follow-up FBx was indicated for all patients. Outcome measurements and statistical analysis: We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for upgrading to GG 2 in the GG 1 group, and to GG 3 in the GG 2 group on MRI. We performed regression analyses that included clinical variables. Results and limitations: The study included 101 patients with PC (60 GG 1 and 41 GG 2). Histopathological progression occurred in 31 patients, 18 in the GG 1 group and 13 in the GG 2 group. Thus, the aim of reducing the ASDQ rate to 15% was not achieved. The sensitivity, specificity, PPV, and NPV for PRECISE scoring of MRI were 94%, 64%, 81%, and 88% in the GG 1 group, and 92%, 50%, 92%, and 50%, respectively, in the GG 2 group. On regression analysis, initial prostate-specific antigen (p < 0.001) and higher PRECISE score (4-5; p = 0.005) were significant predictors of histological progression of GG 1 PC. Higher PRECISE score (p = 0.009), initial Prostate Imaging-Reporting and Data System score (p = 0.009), previous negative biopsy (p = 0.02), and percentage Gleason pattern 4 (p = 0.04) were significant predictors of histological progression of GG 2 PC. Limitations include extensive MRI reading experience, the small sample size, and limited follow-up. Conclusions: MRI-guided monitoring of patients on AS using PRECISE scores avoided unnecessary follow-up biopsies in 88% of patients with GG 1 PC and predicted upgrading during 2-yr follow-up in both GG 1 and GG 2 PC. Patient summary: We investigated whether MRI (magnetic resonance imaging) scores can be used to guide whether patients with lower-risk prostate cancer who are on active surveillance (AS) need to undergo repeat biopsies. Follow-up biopsy was deferred for 1 year for patients with a stable score and performed for patients whose score progressed. After 24 months on AS, all men underwent MRI and biopsy. Among patients with grade group 1 cancer and a stable MRI score, 88% avoided biopsy. For patients with MRI score progression, AS termination was correctly recommended in 81% of grade group 1 and 92% of grade group 2 cases.

Surface CD52, CD84, and PTGER2 mark mature PMN-MDSCs from cancer patients and G-CSF-treated donors.

Precise molecular characterization of circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is hampered by their mixed composition of mature and immature cells and lack of specific markers. Here, we focus on mature CD66b+CD10+CD16+CD11b+ PMN-MDSCs (mPMN-MDSCs) from either cancer patients or healthy donors receiving G-CSF for stem cell mobilization (GDs). By RNA sequencing (RNA-seq) experiments, we report the identification of a distinct gene signature shared by the different mPMN-MDSC populations under investigation, also validated in mPMN-MDSCs from GDs and tumor-associated neutrophils (TANs) by single-cell RNA-seq (scRNA-seq) experiments. Analysis of such a gene signature uncovers a specific transcriptional program associated with mPMN-MDSC differentiation and allows us to identify that, in patients with either solid or hematologic tumors and in GDs, CD52, CD84, and prostaglandin E receptor 2 (PTGER2) represent potential mPMN-MDSC-associated markers. Altogether, our findings indicate that mature PMN-MDSCs distinctively undergo specific reprogramming during differentiation and lay the groundwork for selective immunomonitoring, and eventually targeting, of mature PMN-MDSCs.

Differences and Common Ground in 177Lu-PSMA Radioligand Therapy Practice Patterns: International Survey of 95 Theranostic Centers.

177Lu-labeled prostate-specific membrane antigen (PSMA) radioligand therapy effectively treats metastatic castration-resistant prostate cancer. Patients requiring treatment, and consequently the number of theranostic centers, are expected to increase significantly after Food and Drug Administration and European Medicines Agency approval. This requires standardization or harmonization among theranostic centers. The aim of this study was to assess operational differences and similarities among 177Lu-PSMA treatment centers. Methods: A questionnaire comprising 62 items, designed by a core team of 5 physicians and externally reviewed by international experts, was developed. Study participants were asked to provide answers about their center, patient selection, radiopharmaceuticals, clinical assessment before and after 177Lu-PSMA treatments, laboratory values, treatment discontinuation, posttreatment imaging, and general information. An invitation e-mail to participate in the study was sent in June 2022. Duplicates were removed to allow for only one valid response per center. Results: Ninety-five of 211 (45%) contacted centers completed the questionnaire. Most participating centers were in Europe (51%), followed by America (22%) and Asia (22%). During the 12 mo before this study, a total of 5,906 patients received 177Lu-PSMA therapy at the 95 participating centers. Most of these patients were treated in Europe (2,840/5,906; 48%), followed by Asia (1,313/5,906; 22%) and Oceania (1,225/5,906; 21%). PSMA PET eligibility for 177Lu-PSMA was determined most frequently using 68Ga-PSMA-11 (77%). Additional pretherapy imaging included 18F-FDG PET/CT, CT, renal scintigraphy, and bone scintigraphy at 41 (49%), 27 (32%), 25 (30%), and 13 (15%), respectively, of the 84 centers for clinical standard of care, compassionate care, or local research protocols and 11 (26%), 25 (60%), 9 (21%), and 28 (67%), respectively, of the 42 centers for industry-sponsored trials. PSMA PET eligibility criteria included subjective qualitative assessment of PSMA positivity at 33% of centers, VISION criteria at 23%, and TheraP criteria at 13%. The mean standard injected activity per cycle was 7.3 GBq (range, 5.5-11.1 GBq). Sixty-two (65%) centers applied standardized response assessment criteria, and PSMA PET Progression Criteria were the most applied (37%). Conclusion: Results from this international survey revealed interinstitutional differences in several aspects of 177Lu-PSMA radionuclide therapy, including patient selection, administered activity, and the response assessment strategy. Standardization or harmonization of protocols and dedicated training are desirable in anticipation of increasing numbers of patients and theranostic centers.

Risk factors for ureteroenteric stricture after radical cystectomy and urinary diversion: A systematic review.

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.

[Urinary incontinence after radical prostatectomy for prostate cancer-data from 17,149 patients from 125 certified centers]. / Harninkontinenz nach radikaler Prostatektomie beim Prostatakarzinom ­ aktuelle Daten von 17.149 Patienten aus 125 zertifizierten Zentren.

BACKGROUND: In addition to erectile dysfunction, urinary incontinence is the most common functional limitation after radical prostatectomy (RPE) for prostate cancer (PCa). The German S3 guideline recommends informing patients about possible effects of the therapy options, including incontinence. However, only little data on continence from routine care in German-speaking countries after RPE are currently available, which makes it difficult to inform patients. OBJECTIVE: The aim of this work is to present data on the frequency and severity of urinary incontinence after RPE from routine care. MATERIALS AND METHODS: Information from the PCO (Prostate Cancer Outcomes) study is used, which was collected between 2016 and 2022 in 125 German Cancer Society (DKG)-certified prostate cancer centers in 17,149 patients using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26). Changes in the "incontinence" score before (T0) and 12 months after RPE (T1) and the proportion of patients who used pads, stratified by age and risk group, are reported. RESULTS: The average score for urinary incontinence (value range: 0-worst possible to 100-best possible) was 93 points at T0 and 73 points 12 months later. At T0, 97% of the patients did not use a pad, compared to 56% at T1. 43% of the patients who did not use a pad before surgery used at least one pad a day 12 months later, while 13% use two or more. The proportion of patients using pads differs by age and risk classification. CONCLUSION: The results provide a comprehensive insight into functional outcome 12 months after RPE and can be taken into account when informing patients.