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Background and Objective: Patients with muscle-invasive bladder cancer (MIBC) who develop a recurrence after radical cystectomy (RC) have poor outcomes. This study aims to evaluate the safety and efficacy of adjuvant radiotherapy (ART) in mitigating pelvic recurrences in high-risk MIBC patients. We report on survival outcomes, health-related quality of life (HRQoL), and hematological toxicity for these patients., Methods: A multicentric phase 2 trial was conducted from August 2014 to October 2020, in which 72 high-risk MIBC patients received ART after RC. High risk was defined by the presence of one or more of the following criteria: pT3 stage and lymphovascular invasion, pT4 stage, fewer than ten lymph nodes removed, positive lymph nodes, and positive surgical margins. Using intensity-modulated radiotherapy, patients with pelvic lymph nodes ± cystectomy bed (in case of a positive surgical margin) received 50 Gy in 25 fractions. Outcomes were local relapse-free rate (LRFR), clinical relapse-free survival (CRFS), overall survival (OS) (Kaplan-Meier statistics), HRQoL (European Organisation for Research and Treatment of Cancer QLQ-C30/QLQ-BLM30 surveys), and hematological toxicity (Common Terminology Criteria for Adverse Events grading)., Key Findings and Limitations: The median follow-up of patients without a recurrence was 39 mo. At 2 and 5 yr, LRFRs were 81% (95% confidence interval [CI] 71-91%) and 79% (95% CI 68-89%), CRFS rates were 32% (95% CI 21-42%) and 20% (95% CI 11-30%), and OS rates were 48% (95% CI 36-59%) and 34% (95% CI 22-45%), respectively. At the end of ART, several symptoms worsened, most returning to baseline within the first few months. Diarrhea showed the greatest deterioration, recovering to baseline score only partially. Hematological toxicity of incidence grade ≥2 included lymphopenia (75%), neutropenia (2%), thrombopenia (2%), and anemia (17%). Limitations include the single-arm design and the limited availability of blood samples and surveys., Conclusions and Clinical Implications: ART after RC is well tolerated and leads to a favorable local control rate, supporting its use in clinical practice., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objective: Oligometastatic castration-sensitive prostate cancer (omCSPC) represents an early state in the progression of metastatic disease for which patients experience better outcomes in comparison to those with higher disease burden. Despite the generally more indolent nature, there is still much heterogeneity, with some patients experiencing a more aggressive clinical course unexplained by clinical features alone. Our aim was to investigate correlation of tumor genomics with the mode of progression (MOP) and pattern of failure (POF) following first treatment (metastasis-directed and/or systemic therapy) for omCSPC., Methods: We performed an international multi-institutional retrospective study of men treated for metachronous omCSPC who underwent tumor next-generation sequencing with at least 1 yr of follow-up after their first treatment. Descriptive MOP and POF results are reported with respect to the presence of genomic alterations in pathways of interest. MOP was defined as class I, long-term control (LTC; no radiographic progression at last follow-up), class II, oligoprogression (1-3 lesions), or class III, polyprogression (≥4 lesions). POF included the location of lesions at first failure. Genomic pathways of interest included TP53, ATM, RB1, BRCA1/2, SPOP, and WNT (APC, CTNNB1, RNF43). Genomic associations with MOP/POF were compared using χ 2 tests. Exploratory analyses revealed that the COSMIC mutational signature and differential gene expression were also correlated with MOP/POF. Overall survival (OS) was calculated via the Kaplan-Meier method from the time of first failure., Key Findings and Clinical Implications: We included 267 patients in our analysis; the majority had either one (47%) or two (30%) metastatic lesions at oligometastasis. The 3-yr OS rate was significantly associated with MOP (71% for polyprogression vs 91% for oligoprogression; p = 0.005). TP53 mutation was associated with a significantly lower LTC rate (27.6% vs 42.3%; p = 0.04) and RB1 mutation was associated with a high rate of polyprogression (50% vs 19.9%; p = 0.022). Regarding POF, bone failure was significantly more common with tumors harboring TP53 mutations (44.8% vs25.9%; p = 0.005) and less common with SPOP mutations (7.1% vs 31.4%; p = 0.007). Visceral failure was more common with tumors harboring either WNT pathway mutations (17.2% vs 6.8%, p = 0.05) or SPOP mutations (17.9% vs 6.3%; p = 0.04). Finally, visceral and bone failures were associated with distinct gene-expression profiles., Conclusions and Clinical Implications: Tumor genomics provides novel insight into MOP and POF following treatment for metachronous omCSPC. Patients with TP53 and RB1 mutations have a higher likelihood of progression, and TP53, SPOP, and WNT pathway mutations may have a role in metastatic organotropism., Patient Summary: We evaluated cancer progression after a first treatment for metastatic prostate cancer with up to five metastases. We found that mutations in certain genes were associated with the location and extent of further metastasis in these patients., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objective: Innovations have improved outcomes in advanced prostate cancer (PC). Nonetheless, we continue to lack high-level evidence on a variety of topics that greatly impact daily practice. The 2024 Advanced Prostate Cancer Consensus Conference (APCCC) surveyed experts on key questions in clinical management in order to supplement evidence-based guidelines. Here we present voting results for questions from APCCC 2024., Methods: Before the conference, a panel of 120 international PC experts used a modified Delphi process to develop 183 multiple-choice consensus questions on eight different topics. Before the conference, these questions were administered via a web-based survey to the voting panel members ("panellists")., Key Findings and Limitations: Consensus was a priori defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. The voting results show varying degrees of consensus, as discussed in this article and detailed in the Supplementary material. These findings do not include a formal literature review or meta-analysis., Conclusions and Clinical Implications: The voting results can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers in prioritising areas for future research. Diagnostic and treatment decisions should always be individualised on the basis of patient and cancer characteristics, and should incorporate current and emerging clinical evidence, guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2024 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Muscle invasive bladder cancer (MIBC) treatment combines systemic therapy and radical cystectomy (RC) or local (chemo-)radiotherapy. Response to systemic therapy is an important outcome predictor but is difficult to assess pre-operatively., Methods: We analyzed multiparametric MRI (mpMRI) in consecutive MIBC patients receiving cisplatin-based neo-adjuvant chemotherapy at our institution. Two readers, blinded for pathological outcome, independently scored mpMRI before and after 2 and 4 cycles using both a qualitative 3-step method and nacVI-RADS. We analyzed accuracy of mpMRI scores to predict pathologic complete response (pCR) and inter-observer agreement., Results: We analyzed 46 patients receiving NAC, 6 patients did not undergo RC after NAC and were excluded. Eleven out of 40 (28%) patients showed a pCR. mpMRI could be assessed in over 90% of patients. Radiologic complete response (rCR) using both methods was significantly associated with pCR, with an overall specificity of 96% and sensitivity of 36% and a high inter-observer agreement. rCR as assessed by the 3-step score was significantly associated with disease free survival (DFS) benefit., Conclusion: The use of nacVI-RADS can predict pCR after NAC with high specificity but low sensitivity and a high inter-observer agreement. A 3-step score adds value in determining local residual disease, rCR assessed by this method could correlate with DFS benefit. mpMRI scores should be prospectively assessed in future trials of multimodal management of MIBC and can be a predictive asset in routine clinical management., (© 2024. The Author(s).)

Background: Treatment recommendations for patients with limited nodal recurrences are lacking, and different locoregional treatment approaches are currently being used., Objective: The aim of this trial is to compare metastasis-directed therapy (MDT) with or without elective nodal pelvic radiotherapy (ENRT)., Design, Setting, and Participants: PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM) is an international, phase 2, open-label, randomized, superiority trial (ClinicalTrials.gov identifier: NCT03569241). Patients diagnosed with positron emission tomography-detected pelvic nodal oligorecurrence (five or fewer nodes) following radical local treatment for prostate cancer were randomized in a 1:1 ratio between arm A (MDT and 6 mo of androgen deprivation therapy [ADT]) and arm B (ENRT [25 × 1.8 Gy] with MDT and 6 mo of ADT)., Outcome Measurements and Statistical Analysis: We report the secondary endpoint acute toxicity, defined as worst grade ≥2 Common Terminology Criteria for Adverse Events v4.0 gastrointestinal (GI) or genitourinary (GU) toxicity within 3 mo of treatment. The chi-square test was used to compare toxicity between treatment arms. We also compare the quality of life (QoL) using the European Organisation for Research and Treatment of Cancer QLQ C30 and PR25 questionnaires., Results and Limitations: Between June 2018 and April 2021, 196 patients were assigned randomly to MDT or ENRT. Ninety-seven of 99 patients allocated to MDT and 93 of 97 allocated to ENRT received per-protocol treatment. Worst acute GI toxicity proportions were as follows: grade ≥2 events in three (3%) in the MDT group versus four (4%) in the ENRT group (p = 0.11). Worst acute GU toxicity proportions were as follows: grade ≥2 events in eight (8%) in the MDT group versus 12 (13%) in the ENRT group (p = 0.95). We observed no significant difference between the study groups in the proportion of patients with a clinically significant QoL reduction from baseline for any subdomain score area., Conclusions: No clinically meaningful differences were observed in worst grade ≥2 acute GI or GU toxicity or in QoL subdomains between MDT and ENRT., Patient Summary: We found no evidence of differential acute bowel or urinary side effects using metastasis-directed therapy and elective nodal radiotherapy for the treatment of patients with a pelvic lymph node recurrence., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Moderate hypofractionated radiotherapy (HFRT) is a standard treatment for prostate cancer patients. We compared 2 moderate HFRT regimens, with a biologically equivalent dose of 80 Gy in 2 Gy fractions, with a modest simultaneous integrated boost to the dominant intraprostatic lesion., Material and Methods: This is a multicenter, non-inferiority, randomized phase 3 trial with acute toxicity as the primary endpoint, comparing: 56 Gy in 4 weeks (16x3.5 Gy, 4 days/week, Arm A) with 67 Gy in 5 weeks (25x2.68 Gy, 5 days/week, Arm B). The H0 hypothesis is that both regimens are equivalent in terms of acute grade ≥ 2 gastro-intestinal toxicity, defined as a difference in acute grade ≥ 2 gastro-intestinal toxicity of ≤ 10 %. Here we report on acute and late toxicity., Results: We included 170 patients in Arm A and 172 patients in Arm B. The median follow-up time for all patients was 42 months. Acute grade ≥ 2 gastrointestinal toxicity was reported by 24 % of patients in both groups. Acute grade 2 and 3 urinary toxicity was observed in 52 % and 9 % of patients in Arm A and 53 % and 7 % in Arm B. Late grade 2 and grade ≥ 3 gastrointestinal toxicity occurred in 19 % and 4 % of patients in Arm A compared with 15 % and 4 % in Arm B. Late grade 2 and grade ≥ 3 urinary toxicity was observed in 37 % and 10 % of patients in Arm A and 36 % and 6 % in Arm B., Conclusion: This analysis confirms that both HFRT regimens are safe and equivalent in terms of acute grade ≥ 2 gastrointestinal toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To develop an approach to the diagnosis and treatment of prostate cancer using one platform for fusion biopsy, followed by focal gland ablation utilizing permanent prostate brachytherapy with and without a rectal spacer., Material and Methods: Prostate phantoms containing multiparametric magnetic resonance imaging (mpMRI) regions of interest (ROI) underwent fusion biopsy, followed by image co-registration of positive sites to a treatment planning brachytherapy program. A partial hemi-ablation and both posterior lobes using a Mick applicator and linked stranded seeds were simulated. Dummy sources were modeled as iodine-125 ( 125 I) with a prescribed dose of at least 210 Gy to gross tumor (GTV) and clinical target volume (CTV), as defined by mpMRI visible ROI and surrounding negative biopsy sites. Computer tomograms (CT) were performed post-implant prior to and after rectal spacer insertion. Different prostate and rectal constraints were compared with and without the spacer., Results: The intra-operative focal volumes of CTV ranged from 6.2 to 14.9 cc (mean, 11.3 cc), and the ratio of focal volume/whole prostate volume ranged between 0.19 and 0.42 (mean, 0.31). The intra- and post-operative mean focal D 90 of GTV, CTV, and for the entire prostate gland was 265 Gy and 235 Gy, 214 Gy and 213 Gy, and 66.1 Gy and 57 Gy, respectively. On average, 13 mm separation was achieved between the prostate and the rectum (range, 12-14 mm) on post-operative CT. The mean doses in Gy to 2 cc of the rectum (D 2cc ) without spacer vs. with spacer were 39.8 Gy vs. 32.6 Gy, respectively., Conclusions: Doses above 200 Gy and the implantation of seeds in clinically significant region for focal therapy in phantoms are feasible. All rectal dosimetric parameters improved for the spacer implants, as compared with the non-spacer implants. Further validation of this concept is warranted in clinical trials., (Copyright © 2024 Termedia.)

Background: This study aims to explore the priorities and counselling needs of patients with muscle-invasive bladder cancer faced with a decision between radical cystectomy and trimodality therapy., Methods: We performed a qualitative study according to the phenomenological approach. Sixteen muscle-invasive bladder cancer survivors who underwent radical cystectomy or trimodality therapy completed a semi-structured interview between May 2022 and February 2023. Patients were recruited via Ghent University Hospital and a patient organisation. Data were analysed with inductive thematic analysis by a multi-disciplinary team using an iterative approach and investigators' triangulation., Results: Four main priorities determining the treatment decision were identified. (1) curing the disease; (2) health-related quality of life (physical, mental and social); (3) confidence in the treatment, which was mainly based on trust in the clinician; and (4) personal attributes. Trust in the clinician can be achieved by fulfilling the patient's information needs (accurate, complete, clear, impartial, personalised, realistic, and transparent information), ensuring accessibility of the clinician, and creating a clear and personalised treatment plan, involving patients to the extend they desire. Many patients considered a patient decision aid as a valuable asset in this process., Conclusion: Priorities vary between patients with muscle-invasive bladder cancer. Identifying individual priorities and offering personalised information about them is crucial for ensuring trust in the clinician and confidence in the treatment. Use of a patient decision aid can be beneficial in this process., (© 2024. The Author(s).)

Objective: To evaluate the impact of metastases-directed stereotactic body radiotherapy (SBRT) on health-related quality of life (HRQoL) in men with oligometastatic prostate cancer (PCa) using real-world data from the OligoCare cohort., Materials and Methods: OligoCare is a pragmatic, observational cohort designed to assess the impact of metastases-directed SBRT on patients with oligometastatic disease (OMD). We report an interim analyses of the secondary endpoint HRQoL, assessed using the EORTC QLQ-C30, within six months of metastases-directed SBRT for oligometastatic disease in men with PCa among the first 1600 registered patients. HRQoL data collection was optional within the OligoCare cohort. To compare HRQoL between baseline and first follow-up assessment, a Wilcoxon signed-rank test was used. A multiple linear regression model was used to explore the HRQoL associations with predefined factors., Results: Out of the 1600 registered patients, 658 were treated for oligometastatic PCa, of which 233 had baseline QoL data and 132 patients had both baseline and follow-up HRQoL data. At baseline, most patients had a WHO performance status of 0 or 1 (87 %), were de-novo oligometastatic (79 %), had one metastasis (90 %), and had a good overall global health status (mean 80.81, SD16.11, IQR 75-92). 51 % received hormonal therapy as concomitant systemic treatment. Patients with comorbidities as assessed by the Charlson Comorbidity index had a worse global health status at baseline (-4.88, 95 % CI:-9.35, -0.42). No clinically meaningful significant difference in global health status was observed at first assessment following SBRT (median 3.0 months) compared with baseline (mean difference 2.27, 95 % CI:-1.54, 6.08). Upon evaluating the proportions, meaningful clinically important differences (a 10-point or more difference) was observed in, 17 % and 11 % of the patients reporting deterioration and improvement of global health status, respectively., Conclusion: Metastases-directed stereotactic body radiotherapy had no negative impact on global HRQoL within the first six months after treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. -Matthias Guckenberger and Piet Ost are PIs of the ESTRO-EORTC 1811-E2-RADIatE OligoCare trial.-Matthias Guckenberger is president-elect of ESTRO.-Mieke Van Hemelrijck is board member of the EORTC.-Piet Ost reports a relationship with Janssen, Advanced Accelerator Applications, Curium, Bayer and MSD that includes: consulting or advisory. Piet Ost reports a relationship with Bayer and Varian that includes: funding grants, (© 2023 The Author(s).)

Background: Despite the encouraging results of the SCORAD trial, single fraction radiotherapy (SFRT) remains underused for patients with complicated bone metastases with rates as low as 18-39%. We aimed to evaluate the incidence and treatment patterns of these metastases in patients being referred to a tertiary centre for palliative radiotherapy., Materials and Methods: We performed a retrospective review of all bone metastases treated at our centre from January 2013 until December 2017. Lesions were classified as uncomplicated or complicated. Complicated was defined as associated with (impending) fracture, existing spinal cord or cauda equina compression. Our protocol suggests using SFRT for all patients with complicated bone metastases, except for those with symptomatic neuraxial compression and a life expectancy of ≥28 weeks., Results: Overall, 37 % of all bone metastases were classified as complicated. Most often as a result of an (impending) fracture (56 %) or spinal cord compression (44 %). In 93 % of cases, complicated lesions were located in the spine, most commonly originating from prostate, breast and lung cancer (60 %). Median survival of patients with complicated bone metastases was 4 months. The use of SFRT for complicated bone metastases increased from 51 % to 85 % over the study period, reaching 100 % for patients with the poorest prognosis., Conclusions: Approximately 37 % of bone metastases are classified as complicated with the majority related to (impending) fracture. Patients with complicated bone metastases have a median survival of 4 months and were mostly treated with SFRT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

In metastatic castration-sensitive prostate cancer (mCSPC), disease volume plays an integral role in guiding treatment recommendations, including selection of docetaxel therapy, metastasis-directed therapy, and radiation to the prostate. Although there are multiple definitions of disease volume, they have commonly been studied in the context of metastases detected via conventional imaging (CIM). One such numeric definition of disease volume, termed oligometastasis, is heavily dependent on the sensitivity of the imaging modality. We performed an international multi-institutional retrospective review of men with metachronous oligometastatic CSPC (omCSPC), detected via either advanced molecular imaging alone (AMIM) or CIM. Patients were compared with respect to clinical and genomic features using the Mann-Whitney U test, Pearson's χ 2 test, and Kaplan-Meier overall survival (OS) analyses with a log-rank test. A total of 295 patients were included for analysis. Patients with CIM-omCSPC had significantly higher Gleason grade group (p = 0.032), higher prostate-specific antigen at omCSPC diagnosis (8.0 vs 1.7 ng/ml; p < 0.001), more frequent pathogenic TP53 mutations (28% vs 17%; p = 0.030), and worse 10-yr OS (85% vs 100%; p < 0.001). This is the first report of clinical and biological differences between AMIM-detected and CIM-detected omCSPC. Our findings are particularly important for ongoing and planned clinical trials in omCSPC. PATIENT SUMMARY: Metastatic prostate cancer with just a few metastases only detected via newer scanning methods (called molecular imaging) is associated with fewer high-risk DNA mutations and better survival in comparison to metastatic cancer detected via conventional scan methods., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Prostate cancer patients treated with radiotherapy are susceptible to acute gastrointestinal (GI) toxicity due to substantial overlap of the intestines with the radiation volume. Due to their intimate relationship with GI toxicity, faecal microbiome and metabolome dynamics during radiotherapy were investigated., Material & Methods: This prospective study included 50 prostate cancer patients treated with prostate (bed) only radiotherapy (PBRT) (n = 28) or whole pelvis radiotherapy (WPRT) (n = 22) (NCT04638049). Longitudinal sampling was performed prior to radiotherapy, after 10 fractions, near the end of radiotherapy and at follow-up. Patient symptoms were dichotomized into a single toxicity score. Microbiome and metabolome fingerprints were analyzed by 16S rRNA gene sequencing and ultra-high-performance liquid chromatography hybrid high-resolution mass spectrometry, respectively., Results: The individual α-diversity did not significantly change over time. Microbiota composition (β-diversity) changed significantly over treatment (PERMANOVA p-value = 0.03), but there was no significant difference in stability when comparing PBRT versus WPRT. Levels of various metabolites were significantly altered during radiotherapy. Baseline α-diversity was not associated with any toxicity outcome. Based on the metabolic fingerprint, no natural clustering according to toxicity profile could be achieved., Conclusions: Radiation dose and treatment volume demonstrated limited effects on microbiome and metabolome fingerprints. In addition, no distinctive signature for toxicity status could be established. There is an ongoing need for toxicity risk stratification tools for diagnostic and therapeutic purposes, but the current evidence implies that the translation of metabolic and microbial biomarkers into routine clinical practice remains challenging., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NS reports speaker fees from Janssen-Cilag., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity across 4 cancer types (prostate, head and neck, breast, and lung)., Methods: A genome-wide association study meta-analysis was performed using 19 cohorts totaling 12 042 patients. Acute standardized total average toxicity (STATacute) was modelled using a generalized linear regression model for additive effect of genetic variants, adjusted for demographic and clinical covariates (rSTATacute). Linkage disequilibrium score regression estimated shared single-nucleotide variation (SNV-formerly SNP)-based heritability of rSTATacute in all patients and for each cancer type., Results: Shared SNV-based heritability of STATacute among all cancer types was estimated at 10% (SE = 0.02) and was higher for prostate (17%, SE = 0.07), head and neck (27%, SE = 0.09), and breast (16%, SE = 0.09) cancers. We identified 130 suggestive associated SNVs with rSTATacute (5.0 × 10‒8 < P < 1.0 × 10‒5) across 25 genomic regions. rs142667902 showed the strongest association (effect allele A; effect size ‒0.17; P = 1.7 × 10‒7), which is located near DPPA4, encoding a protein involved in pluripotency in stem cells, which are essential for repair of radiation-induced tissue injury. Gene-set enrichment analysis identified 'RNA splicing via endonucleolytic cleavage and ligation' (P = 5.1 × 10‒6, P = .079 corrected) as the top gene set associated with rSTATacute among all patients. In silico gene expression analysis showed that the genes associated with rSTATacute were statistically significantly up-regulated in skin (not sun exposed P = .004 corrected; sun exposed P = .026 corrected)., Conclusions: There is shared SNV-based heritability for acute radiation-induced toxicity across and within individual cancer sites. Future meta-genome-wide association studies among large radiation therapy patient cohorts are worthwhile to identify the common causal variants for acute radiotoxicity across cancer types., (© The Author(s) 2023. Published by Oxford University Press.)

Background: In contrast to other cancers, the concept of oligometastatic disease (OMD) has not been investigated in bladder cancer (BC)., Objective: To develop an acceptable definition, classification, and staging recommendations for oligometastatic BC (OMBC) spanning the issues of patient selection and the roles of systemic therapy and ablative local therapy., Design, Setting, and Participants: A European consensus group of 29 experts, led by the European Association of Urology (EAU), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Medical Oncology (ESMO), and including members from all other relevant European societies, was established., Outcome Measurements and Statistical Analysis: A modified Delphi method was used. A systematic review was used to build consensus questions. Consensus statements were extracted from two consecutive surveys. The statements were formulated during two consensus meetings. Agreement levels were measured to determine if consensus was achieved (≥75% agreement)., Results and Limitations: The first survey included 14 questions and the second survey had 12. Owing to a considerable lack of evidence, which was the major limitation, definition was limited in the context of de novo OMBC, which was further classified as synchronous OMD, oligorecurrence, and oligoprogression. A maximum of three metastatic sites, all resectable or amenable to stereotactic therapy, was proposed as the definition of OMBC. Pelvic lymph nodes represented the only "organ" not included in the definition of OMBC. For staging, no consensus on the role of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography was reached. A favourable response to systemic treatment was proposed as the criterion for selection of patients for metastasis-directed therapy., Conclusions: A consensus statement on the definition and staging of OMBC has been formulated. This statement will help to standardise inclusion criteria in future trials, potentiate research on aspects of OMBC for which consensus was not achieved, and hopefully will lead to the development of guidelines on optimal management of OMBC., Patient Summary: As an intermediate state between localised cancer and disease with extensive metastasis, oligometastatic bladder cancer (OMBC) might benefit from a combination of systemic treatment and local therapy. We report the first consensus statements on OMBC drawn up by an international expert group. These statements can provide a basis for standardisation of future research, which will lead to high-quality evidence in the field., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

Background: The European Society for Radiotherapy & Oncology (ESTRO) Advisory Committee for Radiation Oncology Practice (ACROP) panel on prostate bed delineation reflected on macroscopic local recurrences in patients referred for postoperative radiotherapy (PORT), a challenging situation without standardized approach, and decided to propose a consensus recommendation on target volume selection and definition., Methods: An ESTRO ACROP contouring consensus panel consisting of 12 radiation oncologists and one radiologist, all with subspecialty expertise in prostate cancer, was established. Participants were asked to delineate the prostate bed clinical target volumes (CTVs) in two separate clinically relevant scenarios: a local recurrence at the seminal vesicle bed and one apically at the level of the anastomosis. Both recurrences were prostate-specific membrane antigen (PSMA)-avid and had an anatomical correlate on magnetic resonance imaging (MRI). Participants also answered case-specific questionnaires addressing detailed recommendations on target delineation. Discussions via electronic mails and videoconferences for final editing and consensus were performed., Results: Contouring of the two cases confirmed considerable variation among the panelists. Finally, however, a consensus recommendation could be agreed upon. Firstly, it was proposed to always delineate the entire prostate bed as clinical target volume and not the local recurrence alone. The panel judged the risk of further microscopic disease outside of the visible recurrence too high to safely exclude the rest of the prostate bed from the CTV. A focused, "stereotactic" approach should be reserved for re-irradiation after previous PORT. Secondly, the option of a focal boost on the recurrence was discussed., Conclusion: Radiation oncologists are increasingly confronted with macroscopic local recurrences visible on imaging in patients referred for postoperative radiotherapy. It was recommended to always delineate and irradiate the entire prostate bed, and not the local recurrence alone, whatever the exact location of that recurrence. Secondly, specific dose-escalation on the macroscopic recurrence should only be considered if an anatomic correlate is visible. Such a focal boost is probably feasible, provided that OAR constraints are prioritized. Possible dose is also dependent on the location of the recurrence. Its potential benefit should urgently be investigated in prospective clinical trials., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose: Investigating the use of the EORTC bladder cancer (BC) modules by evaluating: (a) study contexts/designs; (b) languages/countries in which the modules were administered; (c) their acceptance by patients/investigators; and (d) their psychometric properties., Methods: A systematic review was performed with studies from 1998 until 20/10/2021 in five databases. Articles/conference abstracts using the EORTC-QLQBLM30 (muscle invasive BC) and the EORTC-QLQNMIBC24 (previously referred to as QLQ-BLS24; non-muscle invasive BC) were included. Two authors independently screened titles/abstracts/full-texts and performed data extraction., Results: A total of 76 eligible studies were identified. Most studies included the BLM30 (n = 53), were in a urological surgery context (n = 41) and were cross-sectional (n = 35) or prospective (n = 30) in design. The BC modules were administered in 14 languages across 19 countries. Missing data were low-moderate for all non-sex related questions (< 1% to 15%). Sex-related questions had higher rates of missing data (ranging from 6.9% to 84%). Most investigators did not use all scales of the questionnaires. One validation study for the original BLS24 led to the development of the NMIBC24, which adopted a new scale structure for which good structural validity was confirmed (n = 3). Good reliability and validity was shown for the NMIBC24 module, except for malaise and bloating/flatulence scales. Psychometric evidence for BLM30 is lacking., Conclusion: These results provide insight into how the EORTC BC quality of life modules could be further improved. Current work is ongoing to update the modules and to determine if the two modules can be combined into a single questionnaire that works well in both the NMIBC and MIBC settings., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Pronounced underuse of radiotherapy (RT) in muscle-invasive bladder cancer (MIBC) is reported. This study aims to assess the awareness about the role of RT in different MIBC settings and see whether this has increased since 2017., Materials and Methods: We reviewed the bladder cancer guidelines of the EAU, ESMO, NCCN, NICE, and AUA/ASCO/ASTRO/SUO, focusing on the role of RT in MIBC. In 2017, we evaluated the use of RT in MIBC in Belgium. This raised awareness about the indications of RT in different MIBC settings. Here, we present a retrospective pattern of care analysis of the RT use for MIBC patients at our center from January 2012 until December 2021. Frequency of RT use, patient, disease and treatment characteristics were compared between two 5-year periods (2012-2016 and 2017-2021)., Results: Review of the guidelines suggested that RT can be used as a treatment option in most MIBC settings. However, differences between guideline recommendations existed and high-level evidence was often lacking. Overall, 221 unique MIBC patients received RT at our center. RT use for MIBC was 39% higher in the second 5-year period (Between the same periods, the number of new MIBC registrations increased with 26%). The most pronounced increase, ie, 529%, was observed in the primary setting and was in parallel with patient preference becoming the main indication for RT. Participation in clinical trials seems to have had an important impact on the frequency of RT use in the adjuvant and metastatic setting., Conclusion: We provide a critical overview of the RT indications in MIBC as recommended by the international guidelines. Increased awareness about RT as a treatment option in MIBC seems to have an impact on the treatment choice in clinical practice, as was observed in our tertiary center., Competing Interests: The authors report no competing interests in this work., (© 2023 Verghote et al.)

Introduction: To describe the changes in systemic treatments (ST) of synchronous metastatic hormone-sensitive prostate cancer (mHSPC) patients in a "real-world" setting and to explore reasons why contemporary standard of care (SOC) was not administrated to the patient., Patients and Methods: Since 2014, we prospectively register mHSPCpatients. Patients were grouped in 4 time periods: group 1 (Time period 1, January 2014-July 2015), group 2 after introduction of docetaxel (Time period 2, August 2015-July 2017), group 3 after introduction of abiraterone acetate (Time period 3, August 2017-February 2018) and group 4 after introduction of apalutamide (Time period 4, March 2018-October 2021). For every time period, we evaluated the initiated additional ST. In case patients received treatment that differed from contemporary SOC according to guidelines, reasons for this difference were explored., Results: In total, 243 patients were included. A progressive decline in ADT monotherapy from 85% to 29% over time was observed. The proportion of patients receiving additional STs increased from 34% to 59%. Forty percent of patients were not treated according to contemporary SOC, but this percentage varied strongly per time period (10%, 67%, 53%, and 32% from time period 1 to time period 4 respectively). Reasons for these variations were heterogenous and varied across the 4 time periods. Patients being unfit for treatment and treating physicians failing to consider additional STs were the most prevalent reasons. The proportion of patients unfit for additional ST decreased from 18% to 4% over time., Conclusion: Use of ADT monotherapy declined gradually after the introduction of additional systemic treatments. The proportion of patients unfit for additional ST declined as more treatments became available. Although compliance to SOC increased over time, these real-world data show that adherence to clinical practice guidelines remains suboptimal. Efforts should be made by clinicians to increase the adherence to practice guidelines., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: A clinical pathway in daily practice improved implementation of evidence-based strategies for the management of androgen deprivation-induced side effects in men with prostate cancer. This study aimed to explore patients' expectations and reasons to start with the clinical pathway; explore patients' experiences and attitudes toward the pathway; and identify key pathway ingredients and examine patients' attitudes about a possible transition toward the home environment after a hospital-based pathway participation., Data Sources: Focus group interviews were conducted through purposeful sampling, consisting of former and current participants of the clinical pathway at Ghent University Hospital. Data was audiotaped and transcribed verbatim, coded in NVivo12, and thematically and inductively analyzed through constant comparisons., Conclusion: Men with prostate cancer have positive experiences toward the use of a holistic multidisciplinary approach (ie, clinical pathway) to combat androgen deprivation therapy-induced side effects in practice. Patients identified several key ingredients of the pathway, such as peer support, physiotherapist involvement, and availability of a multidisciplinary team. Patients were, however, reluctant to continue the exercise component at home because of negative attitudes toward a public gym, practical issues, absence of known facilitators, and other priorities., Implications for Nursing Practice: Referral by a health care provider remains an important motivator for pathway participation. Peer support, physiotherapist involvement, and availability of a multidisciplinary team are crucial components of the clinical pathway and should be taken into account when developing and implementing similar pathways to increase program uptake in daily practice., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose/objective: Radiotherapy to the prostate bed is a potentially curative salvage option after radical prostatectomy. Although prostate bed contouring guidelines are available in the literature, important variabilities exist. The objective of this work is to provide a contemporary consensus guideline for prostate bed delineation for postoperative radiotherapy., Methods: An ESTRO-ACROP contouring consensus panel consisting of 11 radiation oncologists and one radiologist, all with known subspecialty expertise in prostate cancer, was established. Participants were asked to delineate the prostate bed clinical target volumes (CTVs) in 3 separate clinically relevant scenarios: adjuvant radiation, salvage radiation with PSA progression, and salvage radiation with persistently elevated PSA. These cases focused on the presence of positive surgical margin, extracapsular extension, and seminal vesicles involvement. None of the cases had radiographic evidence of local recurrence on imaging. A single computed tomography (CT) dataset was shared via FALCON platform and contours were performed using EduCaseTM software. Contours were analyzed qualitatively using heatmaps which provided a visual assessment of controversial regions and quantitatively analyzed using Sorensen-Dice similarity coefficients. Participants also answered case-specific questionnaires addressing detailed recommendations on target delineation. Discussions via electronic mails and videoconferences for final editing and consensus were performed., Results: The mean CTV for the adjuvant case was 76 cc (SD = 26.6), salvage radiation with PSA progression was 51.80 cc (SD = 22.7), and salvage radiation with persistently elevated PSA 57.63 cc (SD = 25.2). Compared to the median, the mean Sorensen-Dice similarity coefficient for the adjuvant case was 0.60 (SD 0.10), salvage radiation with PSA progression was 0.58 (SD = 0.12), and salvage radiation with persistently elevated PSA 0.60 (SD = 0.11). A heatmap for each clinical scenario was generated. The group agreed to proceed with a uniform recommendation for all cases, independent of the radiotherapy timing. Several controversial areas of the prostate bed CTV were identified based on both heatmaps and questionnaires. This formed the basis for discussions via videoconferences where the panel achieved consensus on the prostate bed CTV to be used as a novel guideline for postoperative prostate cancer radiotherapy., Conclusion: Variability was observed in a group formed by experienced genitourinary radiation oncologists and a radiologist. A single contemporary ESTRO-ACROP consensus guideline was developed to address areas of dissonance and improve consistency in prostate bed delineation, independent of the indication.There is important variability in existing contouring guidelines for postoperative prostate bed (PB) radiotherapy (RT) after radical prostatectomy. This work aimed at providing a contemporary consensus guideline for PB delineation. An ESTRO ACROP consensus panel including radiation oncologists and a radiologist, all with known subspecialty expertise in prostate cancer, delineated the PB CTV in 3 scenarios: adjuvant RT, salvage RT with PSA progression, and salvage RT with persistently elevated PSA. None of the cases had evidence of local recurrence. Contours were analysed qualitatively using heatmaps for visual assessment of controversial regions and quantitatively using Sorensen-Dice coefficient. Case-specific questionnaires were also discussed via e-mails and videoconferences for consensus. Several controversial areas of the PB CTV were identified based on both heatmaps and questionnaires. This formed the basis for discussions via videoconferences. Finally, a contemporary ESTRO-ACROP consensus guideline was developed to address areas of dissonance and improve consistency in PB delineation, independent of the indication., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence., Objective: To present the voting results of the APCCC 2022., Design, Setting, and Participants: The experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions., Outcome Measurements and Statistical Analysis: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions., Results and Limitations: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer., Conclusions: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials., Patient Summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer., Twitter Summary: Report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer., Take-Home Message: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration-resistant prostate cancer is summarised here., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Aurelis Omlin: Advisory role (compensated, institutional): Astra Zeneca, Astellas, Bayer, Janssen, Molecular Partners, MSD, Pfizer, Roche, Sanofi Aventis. Research support (institutional): TEVA, Janssen. Travel support: Astellas, Bayer, Janssen, Sanofi Aventis. Speakers Bureau (compensated, institutional): Bayer, Astellas, Janssen. Fizazi Karim: Participation to advisory boards or talks for: Amgen, Astellas, Astrazeneca, Bayer, Clovis, Janssen, MSD, Novartis, Pfizer, Sanofi. Honoraria are provided to Gustave Roussy, my institution. Participation to advisory boards with personal honorarium for: CureVac, Orion. Bossi Alberto: Honoraria: Astellas, Ipsen, Janssen, Myovant. Consulting or advisory role: Astellas, Ipsen, Janssen, Myovant. Speakers’ bureau: Astellas, Ipsen, Elketa. Research funding: Astellas, Ipsen, Myovant. Travel, accommodations, expenses: Janssen. Tombal Bertrand: Advisor for Astellas, Amgen, Bayer, Curium, Ferring, Myovant, Janssens, MSD, Novartis (AAA), Pfizer, Sanofi. Gillessen Silke: SG received personal honoraria for participation in advisory boards for Sanofi, Orion, Roche, Amgen, MSD; other honoraria from RSI (Televisione Svizzera Italiana); invited speaker for ESMO, Swiss group for Clinical Cancer Research (SAKK), Swiss Academy of Multidisciplinary oncology (SAMO), Orikata academy research group, China Anti-Cancer Association Genitourinary Oncology Committee (CACA-GU); Speaker’s bureau for Janssen Cilag; travel grant from ProteoMEdiX; institutional honoraria for advisory boards for Bayer, Janssen Cilag, Roche, AAA International including Indipendent Data Monitoring Committee and IDMC and Steering Committee member for Amgen, Menarini Silicon Biosystems, Astellas Pharma, Tolero Pharmaceutcials, MSD, Pfizer, Telixpharma, BMS and Orion; patent royalties and other intellectual property for a research method for biomarker WO2009138392. Ian Davis: Research Funding: Company: Astellas Pharma, Recipient: Your Institution; Company: Pfizer, Recipient: Your Institution; Company: Roche/Genentech, Recipient: Your Institution; Company: MSD Oncology, Recipient: Your Institution; Company: AstraZeneca, Recipient: Your Institution; Company: Janssen Oncology, Recipient: Your Institution; Company: Eisai, Recipient: Your Institution; Company: Bayer, Recipient: Your Institution; Company: Amgen, Recipient: Your Institution; Company: Bristol-Myers Squibb, Recipient: Your Institution; Company: Movember Foundation, Recipient: Your Institution; Company: Exelixis, Recipient: Your Institution; Company: Ipsen, Recipient: Your Institution; Company: Medivation, Recipient: Your Institution; Company: Seagen, Recipient: Your Institution. Patents, Royalties, Other Intellectual Property: Please describe: International Patent Application No: PCT /US2004/032147 (NY-ESO-1) through Ludwig Institute for Cancer Research; Recipient: You. Christopher Sweeney: Receipt of grants/research supports: Astellas, Bayer, Janssen, Pfizer, Sanofi, Dendreon; Receipt of honoraria or consultation fees: Astellas, Bayer, Janssen, Pfizer, Sanofi, Lilly, Genentech. Eric J. Small: Receipt of honoraria or consultation fees: Jannsen, Johnson & Johnson; Participation in a company sponsored speaker’s bureau: Jannsen, Fortis, Teon, Ulgragenyx, Fortis, Harpoon Johann de Bono: Receipt of grants/research supports: Professor De Bono is an employee of The Institute of Cancer Research, which has received funding or other support for his research work from Astellas, Astra Zeneca, Bayer, Cellcentric, Daiichi, Genentech Roche, Genmab, GlaxoSmithKline, Harpoon, Janssen, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Sanofi Aventis, Sierra Oncology, Taiho, Vertex Pharmaceuticals, and which has a commercial interest in abiraterone, PARP inhibition in DNA repair defective cancers and PI3K/AKT pathway inhibitors (no personal income); Receipt of honoraria or consultation fees: Professor De Bono has served on advisory boards and received fees from Amgen, Astellas, Astra Zeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi, Eisai, Genentech Roche, Genmab, GlaxoSmithKline, Harpoon, Janssen, Menarini Silicon. Biosystems, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals; Participation in a company sponsored speaker’s bureau: AstraZeneca, MSD. Matthew Smith: Receipt of grants/research supports: Clinical trial funding to my institution from: Amgen, Bayer, ESSA, Janssen, ORIC, Pfizer; Receipt of honoraria or consultation fees: Amgen, Astellas, Astrazeneca, Bayer, Janssen, ORIC, Pfizer. Neal Shore: Receipt of honoraria or consultation fees: Abbvie, Amgen, Astellas, Astrazeneca, Bayer, BMS, Boston Scientific, Clovis Oncology, Cold Genesys, Dendreon, Exact Imaging, Exact Sciences, FerGene, Foundation Medicine, Genesis Care, Invitae, Janssen, MDxhealth, Merck, Myvovant, Myriad, Nymox, Pacific Edge, Pfizer, Phosphorous, Propella, Sanofi, Genzyme, Sesen Bio, Tolmar, Urogen; Partecipation in a company sponsored speaker's bureau: Astellas, Astrazeneca, Bayer, Clovis Oncology, Foundation Medicina, Janssen, Merck, Pfizer, Guardant Health. Nicholas James: Receipt of grants/research supports: • Funding for STAMPEDE trial – Coordinating PI – financial interest, Institutional. Name of commercial company: Astellas. • Funding for RADIO trial bladder cancer – Coordinating. PI – financial interest, Institutional. Name of commercial company: AstraZeneca. • Funding for STAMPEDE trial – Coordinating PI – No. financial interest, Institutional. Name of commercial company: Janssen; Receipt of honoraria or consultation fees: • Advisory Board – Advice around PARP inhibitors, Personal,<€5000. Name of commercial company: AstraZeneca dvisory Board – Prostate cancer therapies, Personal,<€5000. Name of commercial company: Clovis. Expert Testimony – Assisted with submissions. regarding licensing for abiraterone, Institutional>€100,001. Name of commercial company: Janssen. Advisory Board – Prostate cancer therapies, Personal, €5001–€10,000. Name of commercial company: Janssen. Advisory Board – Bladder cancer therapy, Personal,<€5000. Name of commercial company: Merck. Advisory Board – Prostate cancer therapies, Personal,<€5000. Name of commercial company: Novartis Expert Testimony – Providing STAMPEDE trial data to facilitate licence extensions internationally for docetaxel, Institutional,>€100,001. Name of commercial company: Sanofi. Advisory Board - Docetaxel, Personal,<€5000. Name of commercial company: Sanofi. Participation in a company sponsored speaker’s bureau: Bayer, Novartis. Nicolas MOTTET: Receipt of grants/research supports: Astellas, Sanofi Pasteur, Pierre Fabre; Receipt of honoraria or consultation fees: Astellas, Jansen, BMS, Bayer, IPSEN, Ferring, Sanofi, Steba, Astra Zeneca, Carrik, Arquer. diagnostics, GE, Takeda. Thomas ZILLI. AFFILIATION: Geneva University Hospital, Geneva, Switzerland. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: Varian Medical Systems International AG; Debiopharm. Receipt of honoraria or consultation fees: Janssen, Astellas, Debiopharm, Ferring, Varian Medical Systems International AG. Participation in a company sponsored speaker’s bureau: Janssen, Astellas, Debiopharm. Stock shareholder: Spouse/partner: Other support (please specify): Signature: Date: Geneva 07.02.2022. Christopher Logothetis. AFFILIATION: MD Anderson Cancer Center. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: Janssen, ORIC Pharmaceuticals, Novartis, Aragon Pharmaceuticals. Receipt of honoraria or consultation fees: Merck, Sharp & Dohme, Bayer, Amgen. Participation in a company sponsored speakers bureau: None. Stock shareholder: None. Spouse/partner: None. Other support (please specify): None. Signature: Date: February 7, 2022. William Oh. AFFILIATION: Chief Medical Officer at Sema4 and Clinical Professor of Medicine, Div. of Hematology/Medical Oncology at Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: Receipt of honoraria or consultation fees: GSK, Janssen, Merck, Pfizer. Participation in a company sponsored speakers bureau: Stock shareholder: Spouse/partner: Other support (please specify): Signature: Date: February 7, 2022. Himisha Beltran. AFFILIATION: Dana Farber Cancer Institute. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: Janssen, AbbVie/Stemcentrx, Eli Lilly, Millennium Pharmaceuticals, Bristol Myers Squibb. Receipt of honoraria or consultation fees: Janssen, Astellas, Astra Zeneca, Merck, Pfizer, Foundation Medicine, Blue Earth Diagnostics, Amgen, Oncorus, LOXO. Participation in a company sponsored speaker’s bureau: NONE. Stock shareholder: NONE. Spouse/partner: NONE. Other support (please specify): Signature: Date: Feb 7, 2022. Pirkko-Liisa Kellokumpu-Lehtinen. AFFILIATION: Tampere University and Tampere University Hospital, Tampere, Finland. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: Only directly to my hospital; Lilly, Merck and Finnish Cancer Society. Receipt of honoraria or consultation fees: BMS, Merck. Participation in a company sponsored speaker’s bureau: NONE. Stock shareholder: NONE. Spouse/partner: NONE. Other support (please specify):reimbursement of expenses to attend conference; Sanofi. Signature: Date: Feb 7, 2022. Prof. Mark A. Rubin, MD. AFFILIATION: University of Bern, Department for BioMedical Research (DBMR). Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: Janssen, Roche, Novartis. Receipt of honoraria or consultation fees: NeoGenomics Labs. Participation in a company sponsored speaker’s bureau: Stock shareholder: Spouse/partner: Other support (please specify): Signature: Date: Feb 8, 2022. Prof. Dr. Thomas Steuber. AFFILIATION: Martini-Klinik, Prostate Cancer Center, University Hospital Hamburg-Eppendorf. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: NONE. Receipt of honoraria or consultation fees: Astellas, Amgen, Bayer, Janssen, ProteoMedix, Sanofi, Merck, Astra Zeneca. Participation in a company sponsored speaker’s bureau: Stock shareholder: Spouse/partner: Other support (please specify): Signature: Date: Feb 8, 2022. Prof. Rob Bristow. AFFILIATION: University of Manchester. I have no potential conflict of interest to report. IGNACIO DURAN. AFFILIATION: HOSPITAL UNIVERSITARIO MARQUES DE VALDECILLA. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: Roche and Astra-Zeneca. Receipt of honoraria or consultation fees: Bristol Myers Squibb, MSD, Ipsen, Roche- Genentech, Janssen, Astellas Pharma, EUSA Pharma, Bayer, Novartis. Participation in a company sponsored speaker’s bureau: Stock shareholder: Spouse/partner: Other support (please specify): Signature: Date: February 8th 2022. FERNANDO MALUF. AFFILIATION: ONCOLOGIST. I have no potential conflict of interest to report. Signature: Date: February 8th 2022. Hiroyoshi Suzuki. AFFILIATION: Department of Urology, Toho University Sakura Medical Center. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: Takeda, AsahiKasei, Taiho, Ono, Chugai, Sanofi, Daiichi-Sankyo, Nihon, Nippon Shinyaku. Receipt of honoraria or consultation fees: Bayer, Janssen, AstraZeneca, Astellas, Chuga-Roche, MSD. Participation in a company sponsored speaker’s bureau:Takeda, Bayer, Janssen, AstraZeneca, Astellas, Sanofi. Stock shareholder: Spouse/partner: Other support (please specify): Signature: Date: February 8th 2022. Danny M. Rabah. AFFILIATION: King Saud University and king Faisal specialist hospital and research centre. I have no potential conflict of interest to report. Signature: Date: February 8th 2022. LEVENT TÜRKERİ. AFFILIATION: ACIBADEM M.A. AYDINLAR UNIVERSITY, ISTANBUL, TURKEY. I have no potential conflict of interest to report. Signature: Date: February 8th 2022. Mark Frydenberg. AFFILIATION: ACIBADEM M.A. AYDINLAR UNIVERSITY, ISTANBUL, TURKEY. I have no potential conflict of interest to report. Signature: Date: February 8th 2022. Anders Bjartell. AFFILIATION: Dept. Of Urology, Skane University Hospital Malmö, Sweden. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: Ferring, Bayer, Astellas. Receipt of honoraria or consultation fees: Astellas, AstraZeneca, Bayer, Janssen, Merck, Recordati, Sandoz. Participation in a company sponsored speaker’s bureau:Astellas, Bayer, IPSEN, Janssen, Recordati, Sandoz. Stock shareholder: LIDDS Pharma, Glactone Pharma, WntResearch. Spouse/partner: NONE. Other support (please specify): Signature: Date: February 9th 2022. Dingwei Ye. AFFILIATION: Fudan University Shanghai Cancer Center. I have no potential conflict of interest to report. Signature: Date: February 9th 2022. Ros Eeles. AFFILIATION: ………………………………………. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: GU-ASCO, The Royal Marsden NHS Foundation Trust, University of Chicago, ESMO, AstraZeneca UK Limited. Receipt of honoraria or consultation fees: Honorarium as speaker. Participation in a company sponsored speaker’s bureau: Stock shareholder: Spouse/partner: Other support (please specify): January 2016. Signature: Date: February 15th 2022. Inge van Oort. AFFILIATION: Urology, Radboudumc, Nijmegen, The Netherlands. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: Astellas, Bayer, Janssen. Receipt of honoraria or consultation fees: Astellas, Bayer, MSD-Astra Zeneca, Janssen. Participation in a company sponsored speaker’s bureau: Bayer, Astellas. Stock shareholder: Spouse/partner: Other support (please specify): Signature: Date: February 22nd 2022. Ravindran Kanesvaran. AFFILIATION: Urology, Radboudumc, Nijmegen, The Netherlands. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: Sanofi, Eisai. Receipt of honoraria or consultation fees: MSD, BMS, AstraZeneca, Amgen, Astellas, Johnson&Johnson, Novartis, Merck, Pfizer. Participation in a company sponsored speaker’s bureau:MSD, BMS, AstraZeneca, Amgen, Astellas, Johnson&Johnson, Novartis, Merck, Pfizer. Stock shareholder: Spouse/partner: Other support (please specify): Signature: Date: February 22nd 2022. Signature: Date: February 9th 2022. Nicola Fossati. AFFILIATION: Urology, Ente Ospedaliero Cantonale (EOC), Lugano, CH. I have no potential conflict of interest to report. Signature: Date: February 1st March 2022. Hiroji Uemura. AFFILIATION: Department of Urology and Renal Transplantation, Yokohama City University Medical Center. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: none. Receipt of honoraria or consultation fees: Bayer, Janssen, Sanofi, Takeda, Astellas, AstraZeneca, Amgen, Dai-ichi Sankyo, Pfizer, MSD, Chugai. Participation in a company sponsored speaker’s bureau:none. Stock shareholder: none. Spouse/partner: none. Other support (please specify): none. Signature: Date: March 7th 2022. Lisa Horvath. AFFILIATION: Chris O′Brien Lifehouse. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: Astellas. Receipt of honoraria or consultation fees: Astellas, Janssen, Bayer, Imagion Biosystems. Participation in a company sponsored speaker’s bureau:Astellas, Janssen, Bayer. Stock shareholder: Imagion Biosystems. Spouse/partner: Connected Medicine Solutions (Employee, stocks). Other support (please specify): none. Signature: Date: March 9th 2022. Robert Reiter. AFFILIATION: UCLA Urology. X I have no potential conflict of interest to report. Signature: Date: March 11th 2022. Daniel Castellano. AFFILIATION: MEDICAL ONCOLOGIST HEAD GU UNIT HOSPITAL UNIVERSITARIO 12 DE OCTUBRE. MADRID-UNIVERSIDAD COMPLUTENSE. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports: JANSSEN. Receipt of honoraria or consultation fees:ASTELLAS, ROCHE, MERCK, PFIZER, NOVARTIS, MSD, BMS, IPSEN, GILEAD, JANSSEN, BAYER. Participation in a company sponsored speaker’s bureau:none. Stock shareholder: none. Spouse/partner: none. Other support (please specify): none. Signature: 28th March 2022. Sandy Srinivas. AFFILIATION: Stanford University, CA. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:. Receipt of honoraria or consultation fees:BAYER, JANSSEN, MERCK, NOVARTIS. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 31ST March 2022. Matthew Sydes. AFFILIATION: MRC Clinical Trials Unit at UCL. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:ASTELLAS, CLOVIS ONCOLOGY, JANSSEN, NOVARTIS, PFIZER, SANOFI AVENTIS. Receipt of honoraria or consultation fees:ELI LILLY, JANSSEN. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 3Oth March 2022. Ekeke, Onyanunam Ngozi. AFFILIATION: DEPARTMENT OF SURGERY, UNIVERSITY OF PORT HARCOURT TEACHING HOSPITAL, PORT HARCOUT, NIGERIA. X I have no potential conflict of interest to report. Signature: Date: March 30 h 2022. Susan Halabi, PhD. AFFILIATION: Duke University. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:ASCO TAPUR, Astellas. Receipt of honoraria or consultation fees:Sanofi, Aveo Oncology. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 3Oth March 2022. Cora N. Sternberg, MD, FACP. AFFILIATION: Eeill Cornell Medicine, New York Presbyterian. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:. Receipt of honoraria or consultation fees:Astellas Pharma, Astrazeneca, Bayer, Genzyme, Gilead, Incyte, Medscape, Janssen, Bristol Myers Squibb, Merck, Msd, Pfizer, Roche, Impact Pharma, Sanofi-Genzyme, Urotoday, Cco Clinical, Nci. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 3Oth March 2022. Hirotsugu Uemura. AFFILIATION:. Kindai University Faculty of Medicine. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:AstraZeneca, Janssen, Takeda, Astellas, Sanofi, Taiho, Ono pharm, Kissei. Receipt of honoraria or consultation fees:Bayer, Sanofi, Janssen, MSD, Ono, BMS, Pfizer. Participation in a company sponsored speaker’s bureau:Bayer, Sanofi, Janssen, MSD, Ono, BMS, Pfizer. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 31st March 2022. Orazio Caffo. AFFILIATION: Santa Chiara Hospital – Trento (Italy). Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:none. Receipt of honoraria or consultation fees:AAA, Astella, Bayer, Janssen, MSD, Pfizer. Participation in a company sponsored speaker’s bureau:Astellas, Bayer, Janssen, Ipsen, MSD. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 31st March 2022. Valérie Fonteyne. AFFILIATION:Ghent University Hospital. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:Ipsen. Receipt of honoraria or consultation fees:Ipsen, Astellas, Janssen. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 31st March 2022. Muhammad Bulbul. AFFILIATION: American University of Beirut. X I have no potential conflict of interest to report. Signature: Date: March 31st 2022. Claire Vale. AFFILIATION: MRC Clinical Trials Unit at UCL. X I have no potential conflict of interest to report. Signature: Date: March 31st 2022. MRABTI Hind. AFFILIATION: Institut National d′oncologie, Mohamed V University. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:. Receipt of honoraria or consultation fees:Astellas, Sanofi, Janssen, AstraZeneca, Ipsen, MSD, Pfizer, Amgen. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 31st March 2022. Deborah Mukherji. AFFILIATION: American University of Beirut. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:Astellas. Receipt of honoraria or consultation fees:Astellas, Janssen, MSD, Ipsen, BMS. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 31st March 2022. Sloan Kettering Cancer Center. AIQ Pharma. Epic Sciences. Janssen. Menarini Silicon Biosystems. ThermoFisher. Howard I. Scher, MD, FASCO. AFFILIATION: Memorial Sloan Kettering Cancer Center. Howard I. Scher, MD, FASCO - Disclosure Form. March 31, 2022. Honoraria. Sidney Kimmel Cancer Center, Jefferson Health. Elsevier, LTD. Arsenal Capital. Consultancy/Advisory Board. Ambry Genetics Corporation, Konica Minolta,Inc. Amgen. Bayer. Janssen Research & Development, LLC. Pfizer Inc. Sun Pharmaceuticals Industries, Inc. WCG Oncology. Research Funding to Memorial Sloan Kettering Cancer Center. AIQ Pharma. Epic Sciences. Janssen. Menarini Silicon Biosystems. ThermoFisher. Evan Y. Yu, M.D. AFFILIATION: Fred Hutchinson Cancer Center and University of Washington. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:Bayer, Blue Earth, Daiichi-Sankyo, Dendreon, Lantheus, Merck, Seagen. Receipt of honoraria or consultation fees:Abbvie, Advanced Accelerator Applications, Bayer, Clovis, Exelixis, Janssen, Merck, Sanofi. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 31st March 2022. Gedske Daugaard. AFFILIATION: Rigshospitalet, Copenhagen. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:. Receipt of honoraria or consultation fees:Bayer, Sanofi, Astellas, MSD, Bristol Myers. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 30th March 2022. Celestia S. Higano, MD, FACP. AFFILIATION: University of Columbia. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:None last 24 months. Receipt of honoraria or consultation fees:AstraZeneca, Astellas, Genentech, Merck Sharp & Dohme, Myovant, Tolmar, Vaccitech, Verity. Participation in a company sponsored speaker’s bureau:none. Stock shareholder: CTI Biopharma. Spouse/partner: none. Other support (please specify): Expert testimony, Ferring. Signature: 31st March 2022. Dr. Vedang Murthy. AFFILIATION: Radiotion Oncology. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:Varian Medical Systems. Receipt of honoraria or consultation fees:. Participation in a company sponsored speaker’s bureau: Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 1st April 2022. Gero Kramer. AFFILIATION: Department of Urology, Medical University of Vienna. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:None. Receipt of honoraria or consultation fees:Astellas, AstraZeneca, Bayer, BMS, Ipsen, Janssen, MSD, Novartis, Sanofi Genzyme, Takeda, Ferring. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 31st March 2022. Niven Mehra. AFFILIATION: Radboudumc. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:Astellas, Astrazeneca, BMS. Receipt of honoraria or consultation fees:Astellas, Astrazeneca, Bayer, Janssen. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 1st April 2022. Juan Pablo Sade. AFFILIATION: Instituto Alexnder Fleming, Buenos Aires, Argentina. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:Janssen, Astellas, AtraZeneca, MSD, BMS. Receipt of honoraria or consultation fees:Janssen, Bayer, Pfizer, Astellas. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 3rd April 2022. Dr Maria De Santis. AFFILIATION: Charité Universitätsmedizin Berlin, Department of Urology. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:. Receipt of honoraria or consultation fees:AAA, Amgen, Astellas, AstraZeneca, Basilea, Bayer, Bioclin, BMS, EISAI, Ferring, Immunomedics, Ipsen, Janssen, MSD, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, SeaGen. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 1st April 2022. Iwona Skoneczna. AFFILIATION: Maria Sklodowska-Curie National Research Institute of Oncology, Szpital Grochowski, Warsaw, Poland. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:Astellas, Bayer, BMS, Janssen, Roche. Receipt of honoraria or consultation fees:Astellas, Bayer, Janssen. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 1st April 2022. Laurence Klotz. AFFILIATION: University of Toronto. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:miR Scientific, Exact Imaging. Receipt of honoraria or consultation fees:miR Scientific, Antev. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 30th March 2022. Yüksel Ürün. AFFILIATION: Ankara University School of Medicine. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:. Receipt of honoraria or consultation fees:Astellas, AtraZeneca, BMS, Janssen Oncology, MSD, Pfizer, Roche. Participation in a company sponsored speaker’s bureau:Astellas, Amgen, AtraZeneca, BMS, Janssen Oncology, Pfizer, Roche. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 01st April 2022. Howard R. Soule. AFFILIATION: Prostate Cancer Foundation. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:. Receipt of honoraria or consultation fees:Compugen. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 4th April 2022. Simon Chowdhury. AFFILIATION:. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:Janssen Oncology, Beigene, Clovis Oncology, Pfizer,. Receipt of honoraria or consultation fees:. Participation in a company sponsored speaker’s bureau:Janssen Oncology, AstraZeneca, Bayer, Pfizer, Sandoz. Stock shareholder:. Spouse/partner:. Other support (please specify): Janssen Oncology (Advisory board). Novartis (advisory board, consultancy). Bayer (Advisory board). Astellas (advisory board, consultancy). Athenex (advisory board). Beigene (advisory board). Clovis Oncology (Advisory board). Telix (advisory board, consultancy). Curve.Life (founder and stock). Huma (consulting fees and Stock). Remedy Bio: consulting fees, Stock. Signature: 4th April 2022. Daniel Heinrich. AFFILIATION: Innlandet Hospital, Department of Oncology and Radiotherapy, Gjøvik, Norway. X I have no potential conflict of interest to report. Signature: Date: 28th February 2022. Raya Leibowitz. AFFILIATION: Shamir Medical Center, Zerifin, Be’er Yaakov, Israel. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:none. Receipt of honoraria or consultation fees:MSD, BMS, Isotopia, Bayer, AstraZeneca, Astellas, Janssen, Pfizer. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Signature: 05th April 2022. Raja Khauli. AFFILIATION: American University of Beirut Medical Ctr Clinical. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:none. Receipt of honoraria or consultation fees:. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify): honoraria: Astellas, Janssen, Algorithm SAL. Signature: 06th April 2022. Axel Merseburger. AFFILIATION: Campus Lübeck, University Hospital Schleswig-Holstein. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:none. Receipt of honoraria or consultation fees:. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify):. Lectures/Speaker/Honoraria:. Astra Zeneca, Bristol-Myers Squibb, Eisai, Ferring, Ipsen, MSD, Merck Serono, Janssen, Takeda, TEVA, Astellas, Novartis, Pfizer, Recordati and Roche. Consultant:. AstraZeneca, Astellas, Bristol-Myers Squibb, Ferring, Ipsen, Janssen, EUSAPharm, MSD, Merck Serono, Novartis, Takeda, Teva, Pfizer, Recordati and Roche. Research and clinical trials:. AstraZeneca, Astellas, Bristol-Myers Squibb, Ipsen, Janssen, EUSAPharm, MSD, Merck Serono, Novartis, Takeda, Teva, Pfizer und Roche. Signature: 06th April 2022. Carmel Pezaro. AFFILIATION: Sheffield Teaching Hospitals NHS Foundation Trust. Type of affiliation / financial interest Name of commercial company. Receipt of grants/research supports:none. Receipt of honoraria or consultation fees:Advanced Accelerator Applications, Astellas, AstraZeneca, Bayer, Janssen. Participation in a company sponsored speaker’s bureau:. Stock shareholder:. Spouse/partner:. Other support (please specify): Bayer, Ipsen (travel support). Signature: 06th April 2022. All remaining authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: WNT signaling is a cellular pathway that has been implicated in the development and progression of prostate cancer. Oligometastatic castration-sensitive prostate cancer (omCSPC) represents a unique state of disease in which metastasis-directed therapy (MDT) has demonstrated improvement in progression-free survival. Herein, we investigate the clinical implications of genomic alterations in the WNT signaling cascade in men with omCSPC., Methods and Materials: We performed an international multi-institutional retrospective study of 277 men with metachronous omCSPC who underwent targeted DNA sequencing of their primary/metastatic tumor. Patients were classified by presence or absence of pathogenic WNT pathway mutations (in the genes APC, RNF43, and CTNNB1). Pearson χ 2 and Mann-Whitney U tests were used to determine differences in clinical factors between genomic strata. Kaplan-Meier survival curves were generated for radiographic progression-free survival and overall survival, stratified according to WNT pathway mutation status., Results: A pathogenic WNT pathway mutation was detected in 11.2% of patients. Patients with WNT pathway mutations were more likely to have visceral metastases (22.6% vs 2.8%; P < .01) and less likely to have regional lymph node metastases (29.0% vs 50.4%; P = .02). At time of oligometastasis, these patients were treated with MDT alone (33.9%), MDT + limited course of systemic therapy (20.6%), systemic therapy alone (22.4%), or observation (defined as no treatment for ≥6 months after metastatic diagnosis). Multivariable cox regression demonstrated WNT pathway mutations associated with significantly worse overall survival (hazard ratio, 3.87; 95% confidence interval, 1.25-12.00)., Conclusions: Somatic WNT pathway alterations are present in approximately 11% of patients with omCSPC and are associated with an increased likelihood of visceral metastases. Although these patients have a worse natural history, they may benefit from MDT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) has been shown to lead to better outcomes regarding early continence compared to standard anterior RARP (SA-RARP). The goal of this study was to assess the feasibility and safety of implementing RS-RARP in a tertiary center with experience in SA-RARP., Methods: From February 2020, all newly diagnosed non-metastatic prostate cancer patients for whom RARP was indicated were evaluated for RS-RARP. Data from the first 100 RS-RARP patients were prospectively collected and compared with data from the last 100 SA-RARP patients. Patients were evaluated for Clavien Dindo grade ≥3a complications, urinary continence after 2 and 6 weeks, 3, 6 and 12 months, erectile function, positive surgical margins (PSMs) and biochemical recurrence (BCR)., Results: There was no significant difference in postoperative complications at Clavien-Dindo grade ≥3a (SA-RARP: 6, RS-RARP: 4; p = 0.292). At all time points, significantly higher proportions of RS-RARP patients were continent ( p < 0.001). No significant differences in postoperative potency were observed (52% vs. 59%, respectively, p = 0.608). PSMs were more frequent in the RS-RARP group (43% vs. 29%, p = 0.034), especially in locally advanced tumors (pT3: 64.6% vs. 43.8%, p = 0.041-pT2: 23.5% vs. 15.4%, p = 0.329). The one-year BCR-free survival was 82.6% vs. 81.6% in the SA-RARP and RS-RARP groups, respectively ( p = 0.567). The median follow-up was 22 [18-27] vs. 24.5 [17-35] months in the RS-RARP and SA-RARP groups, respectively ( p = 0.008)., Conclusions: The transition from SA-RARP to RS-RARP can be safely performed by surgeons proficient in SA-RARP. Continence results after RS-RARP were significantly better at any time point. A higher proportion of PSMs was observed, although it did not result in a worse BCR-free survival.

Background: The optimal treatment for patients with pathological node-positive (pN1) prostate cancer (PCa) is unclear., Objective: To evaluate whether whole-pelvis radiotherapy (WPRT) improves clinical relapse-free survival (cRFS) in comparison to prostate-only radiotherapy (PORT) in pN1 PCa., Design, Setting, and Participants: PROPER was a phase 3 trial randomizing patients to WPRT or PORT. All patients had pN1cM0 PCa with fewer than five lymph nodes involved., Intervention: All patients underwent pelvic lymph node dissection followed by radical prostatectomy/primary radiotherapy + 2 yr of androgen deprivation therapy (ADT). Patients were randomized to PORT (arm A) or WPRT (arm B)., Outcome Measurements and Statistical Analysis: The primary outcome was cRFS. The secondary endpoints were overall survival (OS), biochemical relapse-free survival (bRFS), and toxicity. The study was stopped because of poor accrual in June 2021 after the inclusion of 69 patients. We report on OS, bRFS, cRFS, and acute and late toxicity., Results and Limitations: The median follow-up was 30 mo in arm A (n = 33) and 36 mo in arm B (n = 31). The 3-yr OS rate was 92% ± 5% in arm A and 93% ± 5% in arm B (p = 0.61). None of the patients died of PCa. The 3-yr bRFS was 79% ± 9% in arm A and 92% ± 5% in arm B (p = 0.08). The 3-yr cRFS rate was 88% ± 6% in arm A and 92% ± 5% in arm B (p = 0.31). No pelvic recurrence was observed in arm B. Acute grade 2 gastrointestinal toxicity was higher with WPRT (15% in arm A vs 45% in arm B; p = 0.03). Limitations are the early closure because of poor accrual and the limited follow-up., Conclusions: The results of our trial are hypothesis-generating but add evidence supporting the recommendation to offer WPRT to patients with pN1 PCa. However, WPRT is associated with more acute gastrointestinal toxicity., Patient Summary: We looked at the impact of radiotherapy to the whole pelvis (WPRT) for patients with prostate cancer that had spread to the lymph nodes. Although the trial was closed early because of poor enrolment, we found that WPRT improves survival free from relapse, and no recurrences were observed in the pelvis. WPRT is associated with more acute side effects on the gastrointestinal system in comparison to radiotherapy to just the prostate., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management., Objective: To present consensus voting results for select questions from APCCC 2022., Design, Setting, and Participants: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members ("panellists") who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1-3., Outcome Measurements and Statistical Analysis: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement., Results and Limitations: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis., Conclusions: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials., Patient Summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: The aim is to evaluate the incidental dose to the lymphatic regions in prostate-only radiotherapy (PORT) and to compare hematological outcome between PORT and whole pelvic radiotherapy (WPRT) in node-positive prostate cancer (pN1 PCa), in the era of modern radiotherapy techniques. Methods: We performed a prospective phase 3 trial in which a total of 64 pN1 PCa patients were randomized between PORT (ARM A) and WPRT (ARM B) delivered with volumetric-modulated arc therapy (VMAT). The lymph node (LN) regions were delineated separately and differences between groups were calculated using Welch t -tests. Hematological toxicity was scored according to common terminology criteria for adverse events (CTCAE) version 4.03. To evaluate differences in the evolution of red blood cell (RBC), white blood cell (WBC), and platelet count over time between PORT and WPRT, 3 linear mixed models with a random intercept for the patient was fit with model terms randomization group, study time point, and the interaction between both categorical predictors. Results: Except for dose to the obturator region, the incidental dose to the surrounding LN areas was low in ARM A. None of the patients developed severe hematological toxicity. The change in RBC from time point pre-external beam radiotherapy (EBRT) to month 3 and for WBC from time point pre-EBRT to months 3 and 12 was significantly different with ARM B showing a larger decrease. Conclusion: The incidental dose to the lymphatic areas becomes neglectable when PORT is delivered with VMAT. Hematological toxicity is very low after WPRT with VMAT and when bone marrow constraints are used for planning, although WPRT causes a decrease in RBC and WBC count over time.

Introduction: Previous studies showed that healthcare professionals and patients had only moderate to low agreement on their assessment of treatment-related symptoms. We aimed to determine the levels of agreement in a large cohort of prostate cancer patients., Methods: Analyses were made of data from 1,756 prostate cancer patients treated with external beam radiotherapy (RT) and/or brachytherapy in Europe and the USA and recruited into the prospective multicentre observational REQUITE study. Eleven pelvic symptoms at the end of RT were compared after translating patient-reported outcomes (PROs) into CTCAE-based healthcare professional ratings. Gwet's AC2 agreement coefficient and 95% confidence intervals were calculated for each symptom. To compare severity of grading between patients and healthcare professionals, percent agreement and deviations for each symptom were graphically depicted. Stratified and sensitivity analyses were conducted to identify potential influencing factors and to assess heterogeneity and robustness of results., Results: The agreement for the 11 pelvic symptoms varied from very good (AC2 > 0.8: haematuria, rectal bleeding, management of sphincter control) to poor agreement (AC2 ≤ 0.2: proctitis and urinary urgency). Fatigue had a negative impact on the agreement. Patients tended to grade symptoms more severely than healthcare professionals. Information on sexual dysfunction was missing more frequently in healthcare professional assessment than PROs., Conclusion: Agreement was better for observable than subjective symptoms, with patients usually grading symptoms more severely than healthcare professionals. Our findings emphasize that PROs should complement symptom assessment by healthcare professionals and be taken into consideration for clinical decision-making to incorporate the patient perspective., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of Interest D. Azria: none related to the current manuscript. Outside the current manuscript: involved in the creation of the start-up NovaGray in 2015. D. De Ruysscher: none related to the current manuscript. Outside the current manuscript: advisory board of Astra Zeneca, Bristol-Myers-Squibb, Roche/Genentech, Merck/Pfizer, Celgene, Noxxon, Mologen and has received investigator initiated grants from Bristol-Myers-Squibb, Boehringer Ingelheim and Astra-Zeneca. E. Sperk: none related to the current manuscript. Outside the current manuscript: Lecture honoraria Zeiss Meditec Ag, travel support Zeiss Meditec AG., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)