Corrigendum to "RPN (Radius, Position of tumour, iNvasion of renal sinus) Classification and Nephrometry Scoring System: An Internationally Developed Clinical Classification To Describe the Surgical Difficulty for Renal Masses for Which Robotic Partial Nephrectomy Is Planned" [Eur. Urol. Open Sci. 54 (2023) 33-42].

[This corrects the article DOI: 10.1016/j.euros.2023.05.007.].

Reporting of costs and economic impacts in randomized trials of de-implementation interventions for low-value care: a systematic scoping review.

BACKGROUND: De-implementation of low-value care can increase health care sustainability. We evaluated the reporting of direct costs of de-implementation and subsequent change (increase or decrease) in health care costs in randomized trials of de-implementation research. METHODS: We searched MEDLINE and Scopus databases without any language restrictions up to May 2021. We conducted study screening and data extraction independently and in duplicate. We extracted information related to study characteristics, types and characteristics of interventions, de-implementation costs, and impacts on health care costs. We assessed risk of bias using a modified Cochrane risk-of-bias tool. RESULTS: We screened 10,733 articles, with 227 studies meeting the inclusion criteria, of which 50 included information on direct cost of de-implementation or impact of de-implementation on health care costs. Studies were mostly conducted in North America (36%) or Europe (32%) and in the primary care context (70%). The most common practice of interest was reduction in the use of antibiotics or other medications (74%). Most studies used education strategies (meetings, materials) (64%). Studies used either a single strategy (52%) or were multifaceted (48%). Of the 227 eligible studies, 18 (8%) reported on direct costs of the used de-implementation strategy; of which, 13 reported total costs, and 12 reported per unit costs (7 reported both). The costs of de-implementation strategies varied considerably. Of the 227 eligible studies, 43 (19%) reported on impact of de-implementation on health care costs. Health care costs decreased in 27 studies (63%), increased in 2 (5%), and were unchanged in 14 (33%). CONCLUSION: De-implementation randomized controlled trials typically did not report direct costs of the de-implementation strategies (92%) or the impacts of de-implementation on health care costs (81%). Lack of cost information may limit the value of de-implementation trials to decision-makers. TRIAL REGISTRATION: OSF (Open Science Framework): https://osf.io/ueq32 .

Adjuvant therapy for renal cell carcinoma: 2023 Canadian Kidney Cancer Forum consensus statement.

INTRODUCTION: Several recent randomized trials evaluated the impact of adjuvant immune checkpoint inhibitor (ICI)-based therapy on post-surgical outcomes in renal cell carcinoma (RCC), with disparate results. The objective of this consensus statement is to provide data-driven guidance regarding the use of ICIs after complete resection of clear-cell RCC in a Canadian context. METHODS: An expert panel of genitourinary medical oncologists, urologic oncologists, and radiation oncologists with expertise in RCC management was convened in a dedicated session during the 2022 Canadian Kidney Cancer Forum in Toronto, Canada. Topic statements on the management of patients after surgery for RCC, including counselling, risk stratification, indications for medical oncology referral, appropriate followup, eligibility and management for adjuvant ICIs, as well as treatment options for patients with recurrence who received adjuvant immunotherapy, were discussed. Participants were asked to vote if they agreed or disagreed with each statement. Consensus was achieved if greater than 75% of participants agreed with the topic statement. RESULTS: A total of 22 RCC experts voted on 14 statements. Consensus was achieved on all topic statements. The panel felt patients with clear-cell RCC at increased risk of recurrence after surgery, as per the Keynote-564 group definitions, should be counselled about recurrence risk by a urologist, should be informed about the potential role of adjuvant ICI systemic therapy, and be offered referral to discuss risks and benefits with a medical oncologist. The panel felt that one year of pembrolizumab is currently the only regimen that should be considered if adjuvant therapy is selected. Panelists emphasized current opinions are based on disease-free survival given the available results. Significant uncertainty regarding the benefit and harms of adjuvant therapy remains, primarily due to a lack of consistent benefit observed across similar trials of adjuvant ICI-based therapies and immature overall survival (OS) data. CONCLUSIONS: This consensus document provides guidance from Canadian RCC experts regarding the potential role of ICI-based adjuvant systemic therapy after surgery. This rapidly evolving field requires frequent evidence-based re-evaluation.

Theranostic 64Cu-DOTHA2-PSMA allows low toxicity radioligand therapy in mice prostate cancer model.

Introduction: We have previously shown that copper-64 (64Cu)-DOTHA2-PSMA can be used for positron emission tomography (PET) imaging of prostate cancer. Owing to the long-lasting, high tumoral uptake of 64Cu-DOTHA2-PSMA, the objective of the current study was to evaluate the therapeutic potential of 64Cu-DOTHA2-PSMA in vivo. Methods: LNCaP tumor-bearing NOD-Rag1nullIL2rgnull (NRG) mice were treated with an intraveinous single-dose of 64Cu-DOTHA2-PSMA at maximal tolerated injected activity, natCu-DOTHA2-PSMA at equimolar amount (control) or lutetium-177 (177Lu)-PSMA-617 at 120 MBq to assess their impact on survival. Weight, well-being and tumor size were followed until mice reached 62 days post-injection or ethical limits. Toxicity was assessed through weight, red blood cells (RBCs) counts, pathology and dosimetry calculations. Results: Survival was longer with 64Cu-DOTHA2-PSMA than with natCu-DOTHA2-PSMA (p < 0.001). Likewise, survival was also longer when compared to 177Lu-PSMA-617, although it did not reach statistical significance (p = 0.09). RBCs counts remained within normal range for the 64Cu-DOTHA2-PSMA group. 64Cu-DOTHA2-PSMA treated mice showed non-pathological fibrosis and no other signs of radiation injury. Human extrapolation of dosimetry yielded an effective dose of 3.14 × 10-2 mSv/MBq, with highest organs doses to gastrointestinal tract and liver. Discussion: Collectively, our data showed that 64Cu-DOTHA2-PSMA-directed radioligand therapy was effective for the treatment of LNCaP tumor-bearing NRG mice with acceptable toxicity and dosimetry. The main potential challenge is the hepatic and gastrointestinal irradiation.

UroBOT: A national survey of Canadian urology residents and fellows on robot-assisted surgery.

INTRODUCTION: Robot-assisted surgery (RAS) has a positive impact on the quality of care given to patients. Its increasing adoption in Canadian urology practice also influences the surgical training of residents and fellows. Currently, the lack of clear objectives makes RAS education challenging. The main objective of our study was to highlight how urology trainees perceive the importance of RAS and the standardization of its training. METHODS: In 2021, we conducted a survey of all the residents and fellows enrolled in a Canadian urology program. The questions assessed their opinion on the importance of RAS and on their robotic surgery training. RESULTS: The response rate was 29%. The majority of participants (67%) wished they would have a better exposure to RAS during their surgical training. Only 7% of respondents reported that their program had clear criteria to help them progress through the steps of RAS, and most trainees (81%) felt their residency program should provide them with a formal RAS training program. Seventy-six percent of respondents believed that RAS would become a core skill required by the Royal College in the future, although 32% feared it would hinder their ability to learn other important techniques, such as open surgery. CONCLUSIONS: Our study revealed that although most respondents are interested in RAS, their training lacks standardization. Moreover, the potential integration of RAS as a core skill of the Royal College faces some important challenges, mostly due to the perceived lack of time to learn a new surgical technique.

Evolution of Bosniak IIF Renal Cysts and Impact of the 2019 Bosniak Classification.

PURPOSE: The follow-up of Bosniak IIF renal cysts is associated with significant costs, radiation, and anxiety. Recent studies have suggested a risk of malignancy and upgrading lower than previously reported. We aimed to determine their clinical outcomes and to evaluate the impact of the 2019 Bosniak classification on the diagnosis of such lesions. MATERIALS AND METHODS: We identified all radiology reports with the diagnosis of a Bosniak IIF cyst at our institution between January 2000 and December 2018. Imaging was reviewed to confirm the diagnosis and determine progression based on the 2005 Bosniak classification. Radiological and clinical characteristics were established, and the 2019 Bosniak criteria were retrospectively applied. RESULTS: Out of 252 cysts reviewed, 55 (22%) were reclassified as Bosniak II upon revision using the 2005 Bosniak classification. A total of 181 Bosniak IIF cysts were included for final analysis. The median imaging follow-up was 50 months. Four (2.2%) cysts progressed to Bosniak III or IV. Five (2.8%) patients underwent surgical interventions, with only 1 malignant pathology being reported. No malignant progression was observed after 36 months. When applied to our cohort, the 2019 Bosniak classification would have led to a 76% decrease in Bosniak IIF diagnoses, with no increase in Bosniak III or IV diagnoses, and identical classification of the confirmed malignant pathology. CONCLUSIONS: Upgrading and malignancy rates among Bosniak IIF cysts was markedly lower than traditionally reported. No patient had a significant progression beyond 36 months. More than 20% of Bosniak IIF cysts were initially overdiagnosed. The 2019 Bosniak classification may help to reduce the overdiagnosis of Bosniak IIF lesions requiring follow-up.

Randomized controlled trials in de-implementation research: a systematic scoping review.

BACKGROUND: Healthcare costs are rising, and a substantial proportion of medical care is of little value. De-implementation of low-value practices is important for improving overall health outcomes and reducing costs. We aimed to identify and synthesize randomized controlled trials (RCTs) on de-implementation interventions and to provide guidance to improve future research. METHODS: MEDLINE and Scopus up to May 24, 2021, for individual and cluster RCTs comparing de-implementation interventions to usual care, another intervention, or placebo. We applied independent duplicate assessment of eligibility, study characteristics, outcomes, intervention categories, implementation theories, and risk of bias. RESULTS: Of the 227 eligible trials, 145 (64%) were cluster randomized trials (median 24 clusters; median follow-up time 305 days), and 82 (36%) were individually randomized trials (median follow-up time 274 days). Of the trials, 118 (52%) were published after 2010, 149 (66%) were conducted in a primary care setting, 163 (72%) aimed to reduce the use of drug treatment, 194 (85%) measured the total volume of care, and 64 (28%) low-value care use as outcomes. Of the trials, 48 (21%) described a theoretical basis for the intervention, and 40 (18%) had the study tailored by context-specific factors. Of the de-implementation interventions, 193 (85%) were targeted at physicians, 115 (51%) tested educational sessions, and 152 (67%) multicomponent interventions. Missing data led to high risk of bias in 137 (60%) trials, followed by baseline imbalances in 99 (44%), and deficiencies in allocation concealment in 56 (25%). CONCLUSIONS: De-implementation trials were mainly conducted in primary care and typically aimed to reduce low-value drug treatments. Limitations of current de-implementation research may have led to unreliable effect estimates and decreased clinical applicability of studied de-implementation strategies. We identified potential research gaps, including de-implementation in secondary and tertiary care settings, and interventions targeted at other than physicians. Future trials could be improved by favoring simpler intervention designs, better control of potential confounders, larger number of clusters in cluster trials, considering context-specific factors when planning the intervention (tailoring), and using a theoretical basis in intervention design. REGISTRATION: OSF Open Science Framework hk4b2.

64Cu-DOTHA2-PSMA, a Novel PSMA PET Radiotracer for Prostate Cancer with a Long Imaging Time Window.

Prostate cancer imaging and late-stage management can be improved with prostate-specific membrane antigen (PSMA)-targeting radiotracers. We developed a PSMA positron emission tomography (PET) radiotracer, DOTHA2-PSMA radiolabeled with 64Cu (T1/2: 12.7 h), to leverage its large imaging time window. This preclinical study aimed to evaluate the biological and imaging properties of 64Cu-DOTHA2-PSMA. Its stability was assessed in plasma ex vivo and in mice. Cellular behavior was studied for up to 48 h in LNCaP cells. Biodistribution studies were performed in balb/c mice for up to 48 h. Dynamic (1 h) and static (4 h and 24 h) PET imaging was completed in LNCaP tumor-bearing mice. 64Cu-DOTHA2-PSMA was stable ex vivo in plasma and reached cellular internalization up to 34.1 ± 4.9% injected activity (IA)/106 cells at 48 h post-injection (p.i.). Biodistribution results showed significantly lower uptake in kidneys than 68Ga-PSMA-617, our reference PET tracer (p < 0.001), but higher liver uptake at 2 h p.i. (p < 0.001). PET images showed 64Cu-DOTHA2-PSMA's highest tumoral uptake at 4 h p.i., with a significant difference between blocked and non-blocked groups from the time of injection to 24 h p.i. The high stability and tumor uptake with a long tumor imaging time window of 64Cu-DOTHA2-PSMA potentially contribute to the prostate cancer theranostic approach and its local recurrence detection.

Patients' perceptions on active surveillance for the treatment of small renal masses.

BACKGROUND: Most patients diagnosed with a small renal mass (SRM) are treated with definitive treatments such as surgery or thermal ablation. Given that some SRMs are benign or have low metastatic potential, active surveillance seeks to reduce the overtreatment and the potential complications. Active surveillance is an alternative that is being increasingly considered. Active surveillance has already been shown to be effective, but there is a current knowledge gap regarding patients' perceptions of active surveillance and factors influencing their decision. OBJECTIVE: To describe patients' perceptions of active surveillance of SRMs and to identify factors influencing those perceptions. DESIGN, SETTING, AND PARTICIPANTS: This multicenter descriptive qualitative study recruited patients diagnosed with a renal mass from three institutions, using purposeful sampling. Data were collected using focus group discussions, which were recorded and transcribed. A mixed thematic analysis was performed. RESULTS: Six focus group discussions were conducted with a total of 24 participants. Participants perceived active surveillance as an option to avoid definitive treatments and their potential risks. Active surveillance was, however, perceived to be a temporary solution that would affect their chance of survival and their quality of life. Seven factors were documented as influencing patients' perceptions of active surveillance, the most important being their physician's recommendation. CONCLUSIONS: Perceptions of patients with SRMs toward active surveillance varies among individuals. The development of more patient-oriented information tools is needed to educate patients, to reduce physician influence on the decision-making process and to ensure that the patients' decision reflects their own values and preferences.

Building resilience in oncology teams: Protocol for a realist evaluation of multiple cases.

BACKGROUND: Teams caring for people living with cancer face many difficult clinical situations that are compounded by the pandemic and can have serious consequences on professional and personal life. This study aims to better understand how a multi-component intervention builds resilience in oncology teams. The intervention is based on a salutogenic approach, theories and empirical research on team resilience at work. This intervention research involves partnership between researchers and stakeholders in defining situations of adversity and solutions appropriate to context. METHODS: The principles of realist evaluation are used to develop context-mechanism-outcome configurations of a multi-component intervention developed by researchers and field partners concerned with the resilience of oncology teams. The multiple case study involves oncology teams in natural contexts in four healthcare establishments in Québec (Canada). Qualitative and quantitative methods are employed. Qualitative data from individual interviews, group interviews and observation are analyzed using thematic content analysis. Quantitative data are collected through validated questionnaires measuring team resilience at work and its effect on teaming processes and cost-effectiveness. Integration of these data enables the elucidation of associations between intervention, context, mechanism and outcome. DISCUSSION: The study will provide original data on contextual factors and mechanisms that promote team resilience in oncology settings. It suggests courses of action to better manage difficult situations that arise in a specialized care sector, minimize their negative effects and learn from them, during and after the waves of the pandemic. The mechanisms for problem resolution and arriving at realistic solutions to professional workforce and team effectiveness challenges can help improve practices in other settings.

Intravesical immunotherapy with a GM-CSF armed oncolytic vesicular stomatitis virus improves outcome in bladder cancer.

A significant proportion of non-muscle invasive bladder cancer cases will progress to muscle invasive disease. Transurethral resection followed by Bacillus Calmette Guerin immunotherapy can reduce this risk, while cystectomy prior to muscle invasion provides the best option for survival. Currently, there are no effective treatments for Bacillus Calmette Guerin refractory disease. A novel oncolytic vesicular stomatitis virus containing the human GM-CSF transgene (VSVd51-hGM-CSF) was rescued and tested as a potential bladder-sparing therapy for aggressive bladder cancer. The existing variant expressing mouse GM-CSF was also used. Measurement of gene expression and protein level alterations of canonical immunogenic cell death associated events on mouse and human bladder cancer cell lines and spheroids showed enhanced release of danger signals and immunogenic factors following infection with VSVd51-m/hGM-CSF. Intravesical instillation of VSVd51-mGM-CSF into MB49 bladder cancer bearing C57Bl/6 mice demonstrated enhanced activation of peripheral and bladder infiltrating effector immune cells, along with improved survival and reduced tumor volume. Importantly, virus-mediated anti-tumor immunity was recapitulated in bladder cancer patient-derived organoids. These results suggest that VSVd51-hGM-CSF is a promising viro/immunotherapy that could benefit bladder cancer patients.

Development and use of research vignettes to collect qualitative data from healthcare professionals: a scoping review.

OBJECTIVES: To clarify the definition of vignette-based methodology in qualitative research and to identify key elements underpinning its development and utilisation in qualitative empirical studies involving healthcare professionals. DESIGN: Scoping review according to the Joanna Briggs Institute framework and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. DATA SOURCES: Electronic databases: Academic Search Complete, CINAHL Plus, MEDLINE, PsycINFO and SocINDEX (January 2000-December 2020). ELIGIBILITY CRITERIA: Empirical studies in English or French with a qualitative design including an explicit methodological description of the development and/or use of vignettes to collect qualitative data from healthcare professionals. Titles and abstracts were screened, and full text was reviewed by pairs of researchers according to inclusion/exclusion criteria. DATA EXTRACTION AND SYNTHESIS: Data extraction included study characteristics, definition, development and utilisation of a vignette, as well as strengths, limitations and recommendations from authors of the included articles. Systematic qualitative thematic analysis was performed, followed by data matrices to display the findings according to the scoping review questions. RESULTS: Ten articles were included. An explicit definition of vignettes was provided in only half the studies. Variations of the development process (steps, expert consultation and pretesting), data collection and analysis demonstrate opportunities for improvement in rigour and transparency of the whole research process. Most studies failed to address quality criteria of the wider qualitative design and to discuss study limitations. CONCLUSIONS: Vignette-based studies in qualitative research appear promising to deepen our understanding of sensitive and challenging situations lived by healthcare professionals. However, vignettes require conceptual clarification and robust methodological guidance so that researchers can systematically plan their study. Focusing on quality criteria of qualitative design can produce stronger evidence around measures that may help healthcare professionals reflect on and learn to cope with adversity.

Liproca Depot: A New Antiandrogen Treatment for Active Surveillance Patients.

BACKGROUND: There is increasing interest in nonmorbid treatments for low- and intermediate-risk prostate cancer with fewer side effects than surgery or radiotherapy. OBJECTIVE: To investigate the tolerability, safety, and antitumor effects of the intraprostatic NanoZolid depot formulation Liproca Depot (LIDDS AB, Uppsala, Sweden) with antiandrogen 2-hydroxyflutamide (2-HOF) in men with low- or intermediate-risk localized prostate cancer managed with active surveillance. DESIGN, SETTING, AND PARTICIPANTS: This clinical phase 2b trial, LPC-004, involved 61 patients. The 2-HOF-containing formulation Liproca Depot was injected transrectally into the prostate under ultrasound guidance. A single dose of 35% or 45% of the prostate volume (study part 1) and a fixed dose of 16 or 20 ml (study part 2) of the formulation were evaluated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: The primary endpoints were tolerability and the reduction in serum prostate-specific antigen (PSA) 5 mo after injection. Antitumor effects were evaluated with magnetic resonance imaging (MRI) and prostate biopsies. Quality of life was assessed using a validated questionnaire (International Prostate Symptom Score). RESULTS AND LIMITATIONS: All doses were safe and well tolerated, without hormonal side effects. In part 2 of the study, the PSA reduction was greatest for the group receiving 16 ml, with an average decrease of 14%, and 95% of patients had a PSA reduction. Some 78% of patients showed a prostate volume decrease compared to baseline. Prostate MRI and biopsies confirmed stable or reduced lesion size. However, post treatment biopsies were performed at the discretion of the investigator, and not routinely. Most patients were amenable to a second injection. CONCLUSIONS: PSA and prostate volume decreased in most patients. Indications of efficacy were shown by post-treatment MRI and biopsies demonstrating stabilization or regression in the majority of cases. PATIENT SUMMARY: Liproca Depot is a safe, minimally invasive treatment that offers the potential for cancer control in patients with intermediate-risk prostate cancer. Further clinical evaluation is warranted.

Interpreting and Appraising Noninferiority Trials: A Guide for Urologists and Clinicians.

Noninferiority trials are increasingly used in urology. Understanding the methodology and assessment of such trials can be challenging for clinicians. We provide an approach to interpreting the results, validity, and applicability of noninferiority studies in clinical practice.

Evaluation of Benefits and Harms of Surgical Treatments for Post-radical Prostatectomy Urinary Incontinence: A Systematic Review and Meta-analysis.

CONTEXT: No meta-analysis has comprehensively addressed both benefits and harms, or the certainty of evidence of the implantable continence devices used in men to treat postprostatectomy urinary incontinence (PPI). OBJECTIVE: To evaluate the benefits and harms of surgical treatments for patients suffering from PPI and assess the certainty of evidence. The primary benefit was cure (one or fewer pad per day), and the primary harm was reoperations defined by surgical procedures following implantation. EVIDENCE ACQUISITION: We perform a search of Medline, PubMed, Embase, Cochrane Library, and gray literature. We included observational studies addressing PPI surgical interventions if they involved cohorts of ≥50 participants. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach provided the framework for certainty of evidence assessment informed by value and preference judgments provided by patients, and an advocacy group member (Canadian Cancer Society). EVIDENCE SYNTHESIS: Of 85 observational studies involving 13 100 patients, three addressed bulking agents, 35 male synthetic slings, ten adjustable continence therapies (ACTs), and 37 artificial urinary sphincters (AUSs). Cure was 26.1% (95% confidence interval [CI]: 10.6-51.4, I2 = 92.8%, very-low-quality evidence) for bulking agents, 58.6% (95% CI: 51.3-65.5, I2 = 89.1%, low-quality evidence) for slings, 63.2% (95% CI: 57.6-68.5, I2 = 22.5%, very-low-quality evidence) for ACT, and 74.0% (95% CI:61.2-83.7, I2 = 92.1%, very-low-quality evidence) for AUS. Estimated rates of reoperation were 5.8% (95% CI: 1.9-11.6, I2 = 94.1%, moderate-quality evidence) for slings, 23.8% (95% CI: 5.9-61.0, I2 = 95.5%, low-quality evidence) for ACT, and 22.2% (95% CI: 15.2-31.3, I2 = 92.3%, high-quality evidence) for AUS. CONCLUSIONS: Available evidence regarding the benefits of surgical interventions for PPI remains mainly uncertain while suggesting important harms. These results should guide consent procedures for PPI surgery in the context of shared decision-making, with disclosure of the uncertainty of evidence. PATIENT SUMMARY: Despite being used worldwide, available evidence regarding the benefits of surgeries to treat postprostatectomy urinary incontinence remains mainly uncertain while suggesting important harms. This highlights the need for a more rigorous evaluation process for commercially available surgical devices.

The Triple-Tracer strategy against Metastatic PrOstate cancer (3TMPO) study protocol.

OBJECTIVE: To determine the prevalence of intra-patient inter-metastatic heterogeneity based on positron emission tomography (PET)/computed tomography (CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) and to determine the prevalence of neuroendocrine disease in these patients and their eligibility for radioligand therapies (RLTs). PATIENTS AND METHODS: This multicentre observational prospective clinical study will include 100 patients with mCRPC from five Canadian academic centres. Patients with radiological or biochemical progression and harbouring at least three metastases by conventional imaging will be accrued. Intra-patient inter-metastatic heterogeneity will be determined with triple-tracer imaging using fluorine-18 fluorodeoxyglucose (18 F-FDG), gallium-68-(68 Ga)-prostate-specific membrane antigen (PSMA)-617 and 68 Ga-DOTATATE, which are a glucose analogue, a PSMA receptor ligand and a somatostatin receptor ligand, respectively. The 68 Ga-PSMA-617 and 18 F-FDG PET/CT scans will be performed first. If at least one PSMA-negative/FDG-positive lesion is observed, an additional PET/CT scan with 68 Ga-DOTATATE will be performed. The tracer uptake of individual lesions will be assessed for each PET tracer and patients with lesions presenting discordant uptake profiles will be considered as having inter-metastatic heterogeneous disease and may be offered a biopsy. EXPECTED RESULTS: The proposed triple-tracer approach will allow whole-body mCRPC characterisation, investigating the inter-metastatic heterogeneity in order to better understand the phenotypic plasticity of prostate cancer, including the neuroendocrine transdifferentiation that occurs during mCRPC progression. Based on 68 Ga-PSMA-617 or 68 Ga-DOTATATE PET positivity, the potential eligibility of patients for PSMA and DOTATATE-based RLT will be assessed. Non-invasive whole-body determination of mCRPC heterogeneity and transdifferentiation is highly innovative and might establish the basis for new therapeutic strategies. Comparison of molecular imaging findings with biopsies will also link metastasis biology to radiomic features. CONCLUSION: This study will add novel, biologically relevant dimensions to molecular imaging: the non-invasive detection of inter-metastatic heterogeneity and transdifferentiation to neuroendocrine prostate cancer by using a multi-tracer PET/CT strategy to further personalise the care of patients with mCRPC.