BACKGROUND:Metformin is a widely used anti-diabetic drug. Several studies have suggested that metformin has anticancer activity in some malignancies, including prostate cancer. Metformin might also mitigate the adverse metabolic effects of androgen-deprivation therapy (ADT). We hypothesised that metformin might improve survival in patients with metastatic hormone-sensitive prostate cancer and reduce metabolic complications associated with ADT. METHODS:The STAMPEDE multi-arm, multi-stage, randomised phase 3 trial recruited patients with high-risk locally advanced or metastatic adenocarcinoma of the prostate staged by conventional imaging with isotope bone and CT scanning. This publication reports findings for the most recent STAMPEDE research question, testing the addition of metformin to standard of care for non-diabetic (glycated haemoglobin [HbA1c] <48 mmol/mol [equivalent to <6·5%]) patients with metastatic disease with adequate renal function (glomerular filtration rate ≥45 ml/min/1·73 m2) and WHO performance status 0-2. This trial recruited from 112 hospitals in the UK and Switzerland to the STAMPEDE protocol. Patients were randomly allocated (1:1) to standard of care or standard of care plus metformin 850 mg twice daily. Random assignment was by telephone using minimisation with a random element of 20% (developed and maintained by the MRC Clinical Trials Unit at UCL), stratified for randomising hospital, age (<70 years vs ≥70 years), WHO performance status (0 vs 1 or 2), type of ADT, regular long-term use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs; yes vs no), pelvic nodal status (positive vs negative), planned radiotherapy (yes vs no), and planned docetaxel or androgen receptor pathway inhibitor (ARPI) use (docetaxel vs abiraterone, enzalutamide, or apalutamide vs none). Standard of care comprised ADT with or without radiotherapy and with or without docetaxel or ARPI. The primary outcome measure was overall survival, defined as the time to death from any cause, assessed in the intention-to-treat population. Safety was assessed in patients who started treatment. The trial is registered with ClinicalTrials.gov, NCT00268476 and ISRCTN, ISRCTN78818544. FINDINGS:Between Sep 5, 2016, and Mar 31, 2023, 1874 patients with metastatic disease were randomly allocated to standard of care (n=938) or standard of care plus metformin (n=936). The median patient age was 69 years (IQR 63-73) and the median PSA was 84 ng/mL (24-352). 1758 (94%) of 1874 patients were newly diagnosed with metastatic disease and 116 (6%) were diagnosed with metachronous relapsing disease. 1543 (82%) of 1874 patients received ADT plus docetaxel and 52 (3%) received abiraterone, enzalutamide, or apalutamide. The median time to most recent case report form follow-up was 60 months (IQR 49-72). 473 deaths were reported in the standard of care group; median survival was 61·8 months (IQR 29·7 to not reached). There were 453 deaths in the metformin group; median survival was 67·4 months (32·5 to not reached; HR 0·91, 95% CI 0·80-1·03; p=0·15). Grade 3 or worse adverse events were reported in 487 (52%) of 938 patients in the standard of care group and 523 (57%) of 921 patients in the standard of care plus metformin group. 61 (7%) patients in the standard of care group and 84 (9%) patients in the standard of care plus metformin group reported at least one grade 3 or worse gastrointestinal adverse event; all other body systems showed no difference in grade 3 adverse events. There were six drug-related deaths in the standard of care group and one in the standard of care plus metformin group. INTERPRETATION:We did not find significant evidence of an overall survival benefit of adding metformin to standard of care in the overall population of patients with metastatic hormone-sensitive prostate cancer. The side-effect profile of metformin was as expected and consisted mainly of diarrhoea. Adverse metabolic side-effects of ADT were significantly reduced in the metformin group compared with the standard of care group. FUNDING:Cancer Research UK, Prostate Cancer UK, and UK Research and Innovation Medical Research Council.

A potential role may be played by receptor-type protein tyrosine phosphatase kappa (PTPRK) in angiogenesis due to its critical function in coordinating intracellular signal transduction from various receptors reliant on tyrosine phosphorylation. In the present study, we investigated the involvement of PTPRK in the cellular functions of vascular endothelial cells (HECV) and its role in angiogenesis using in vitro assays and a PTPRK knockdown vascular endothelial cell model. PTPRK knockdown in HECV cells (HECVPTPRKkd) resulted in a decrease of cell proliferation and cell-matrix adhesion; however, increased cell spreading and motility were seen. Reduced focal adhesion kinase (FAK) and paxillin protein levels were seen in the PTPRK knockdown cells which may contribute to the inhibitory effect on adhesion. HECVPTPRKkd cells were more responsive to the treatment of fibroblast growth factor (FGF) in their migration compared with the untreated control and cells treated with VEGF. Moreover, elevated c-Src and Akt1 were seen in the PTPRK knockdown cells. The FGF-promoted cell migration was remarkably suppressed by an addition of PLCγ inhibitor compared with other small inhibitors. Knockdown of PTPRK suppressed the ability of HECV cells to form tubules and also impaired the tubule formation that was induced by FGF and conditioned medium of cancer cells. Taken together, it suggests that PTPRK plays dual roles in coordinating angiogenesis. It plays a positive role in cell proliferation, adhesion and tubule formation, but suppresses cell migration, in particular, the FGF-promoted migration. PTPRK bears potential to be targeted for the prevention of tumour associated angiogenesis.

Importance The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear. Objective To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening. Design, Setting, and Participants This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021. Intervention Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation). Main Outcomes and Measures The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis. Results Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P = .03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] <= 6: 2.2% vs 1.6%; P < .001) and localized (T1/T2: 3.6% vs 3.1%; P < .001) disease but not intermediate (GS of 7), high-grade (GS >= 8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P = .11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small.

BackgroundLong-term patient-reported outcomes are needed to inform treatment decisions for localized prostate cancer.MethodsPatient-reported outcomes of 1643 randomly assigned participants in the ProtecT (Prostate Testing for Cancer and Treatment) trial were evaluated to assess the functional and quality-of-life impacts of prostatectomy, radiotherapy with neoadjuvant androgen deprivation, and active monitoring. This article focuses on the outcomes of the randomly assigned participants from 7 to 12 years using mixed effects linear and logistic models.ResultsResponse rates exceeded 80% for most measures. Among the randomized groups over 7 to 12 years, generic quality-of-life scores were similar. Among those in the prostatectomy group, urinary leakage requiring pads occurred in 18 to 24% of patients over 7 to 12 years, compared with 9 to 11% in the active monitoring group and 3 to 8% in the radiotherapy group. In the prostatectomy group, 18% reported erections sufficient for intercourse at 7 years, compared with 30% in the active monitoring and 27% in the radiotherapy groups; all converged to low levels of potency by year 12. Nocturia (voiding at least twice per night) occurred in 34% in the prostatectomy group compared with 48% in the radiotherapy group and 47% in the active monitoring group at 12 years. Fecal leakage affected 12% in the radiotherapy group compared with 6% in the other groups by year 12. The active monitoring group experienced gradual age-related declines in sexual and urinary function, avoiding radical treatment effects unless they changed management.ConclusionsProtecT provides robust evidence about continued impacts of treatments in the long term. These data allow patients newly diagnosed with localized prostate cancer and their clinicians to assess the trade-offs between treatment harms and benefits and enable better informed and prudent treatment decisions. (Funded by the UK National Institute for Health and Care Research Health Technology Assessment Programme projects 96/20/06 and 96/20/99; ISRCTN number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.)

Supplementary Tables 1-4, Figures 1-2 from A Novel Tumor Antigen Derived from Enhanced Degradation of Bax Protein in Human Cancers

BACKGROUND AND PURPOSE:There is no consensus concerning the appropriate use of androgen deprivation therapy (ADT) during primary and postoperative external-beam radiotherapy (EBRT) in the management of prostate cancer (PCa). Thus, the European Society for Radiotherapy and Oncology (ESTRO) Advisory Committee for Radiation Oncology Practice (ACROP) guidelines seeks to present current recommendations for the clinical use of ADT in the various indications of EBRT. MATERIAL AND METHODS:A literature search was conducted in MEDLINE PubMed that evaluated EBRT and ADT in prostate cancer. The search focused on randomized, Phase II and III trials published in English from January 2000 to May 2022. In case topics were addressed in the absence of Phase II or III trials, recommendations were labelled accordingly based on the limited body of evidence. Localized PCa was classified according to D'Amico et al. classification in low-, intermediate and high risk PCa. The ACROP clinical committee identified 13 European experts who discussed and analyzed the body of evidence concerning the use of ADT with EBRT for prostate cancer. RESULTS:Key issues were identified and are discussed: It was concluded that no additional ADT is recommended for low-risk prostate cancer patients, whereas for intermediate- and high-risk patients four to six months and two to three years of ADT are recommended. Likewise, patients with locally advanced prostate cancer are recommended to receive ADT for two to three years and when ≥ 2 high-risk factors (cT3-4, ISUP grade ≥ 4 or PSA ≥ 40 ng/ml) or cN1 is present ADT for three years plus additional Abiraterone for two years is recommended. For postoperative patients no ADT is recommended for adjuvant EBRT in pN0 patients whereas for pN1 patients adjuvant EBRT with long-term ADT is performed for at least 24 to 36 months. In the setting of salvage EBRT ADT is performed in biochemically persistent PCa patients with no evidence of metastatic disease. Long-term ADT (24 months) is recommended in pN0 patients with high risk of further progression (PSA ≥ 0.7 ng/ml and ISUP grade group ≥ 4) and a life expectancy of over ten years, whereas short-term ADT (6 months) is recommended in pN0 patients with lower risk profile (PSA < 0.7 ng/ml and ISUP grade group 4). Patients considered for ultra-hypofractionated EBRT as well as patients with image based local recurrence within the prostatic fossa or lymph node recurrence should participate in appropriate clinical trials evaluating the role of additional ADT. CONCLUSION:These ESTRO-ACROP recommendations are evidence-based and relevant to the use of ADT in combination with EBRT in PCa for the most common clinical settings.

Microscope images of Hsp70 in irradiated tumour cells.

PDF file - 59K, PD-1 expression in CD4 and CD8 subsets derived from CLL patients and normal age-matched controls.

Over the last 12 years, the Wales Cancer Biobank (WCB) has consented to more than 2000 patients with colorectal cancer (CRC). From these patients, clinical data has been collected and patients have been followed through their cancer journey. Clinical data from these patients have been analyzed to identify any correlation between disease grade and outcome. In a small cohort, consisting of 407 patients, WCB has performed genetic analysis on patient primary tumor samples, identifying and characterizing mutations in the KRAS, NRAS, BRAF, PIK3CA and TP53 genes. The majority of patients with CRC who were consented to WCB were male with a mean age of 69 years and received surgery as the primary treatment for their disease. Pathology and disease-free survival data confirmed worse prognoses associated with more advanced disease. Heterogeneity within the primary tumor was explored in a subgroup of patients. Analysis of the KRAS and TP53 genes confirmed that more than 40% of CRC patients who were tested, harbored a genetic mutation within these genes in their primary tumor. Due to the limited sample size tested, most mutations did not show significant differences in disease-free survival, however, mutation of the BRAF gene did show a decrease in the disease specific survival, in keeping with the published data. Analysis of the patients diagnosed with CRC within the Biobank has provided us with valuable information on the status of CRC disease and treatment within the Welsh population. Over 12 years of consenting, we have witnessed significant changes in the information that researchers are interested in when sourcing samples for translational research. The development of new drugs that are tailored to the genetics of a cancer is emerging and at WCB we are focusing our collections on samples and data that meet the needs of this ever-evolving field.

BACKGROUND Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy. METHODS At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes). RESULTS Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P = 0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis. CONCLUSIONS After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.).

Supplementary Figure 1 from Human Tumor-Derived Exosomes Selectively Impair Lymphocyte Responses to Interleukin-2

Supplementary Figure Legend from Cancer Exosomes Trigger Fibroblast to Myofibroblast Differentiation

Background Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. Methods We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0-2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m(2) intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). Findings Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86-107) in the abiraterone trial and 72 months (61-74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76.6 months (95% CI 67.8-86.9) in the abiraterone group versus 45.7 months (41.6-52.0) in the standard of care group (hazard ratio [HR] 0.62 [95% CI 0.53-0.73]; p<0.0001). In the abiraterone and enzalutamide trial, median overall survival was 73.1 months (61.9-81.3) in the abiraterone and enzalutamide group versus 51.8 months (45.3-59.0) in the standard of care group (HR 0.65 [0.55-0.77]; p<0.0001). We found no difference in the treatment effect between these two trials (interaction HR 1.05 [0.83-1.32]; p interaction=0.71) or between-trial heterogeneity (I-2 p=0.70). In the first 5 years of treatment, grade 3-5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial). Interpretation Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting longterm androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd.

PDF file - 134K, Lymphocyte gating strategy forT cell subsets.

Globally, an estimated one in five people will develop cancer in their lifetime, and an estimated one in eight men and one in 11 women will die from the disease. 1 International Agency for Research on CancerLatest global cancer data: Cancer burden rises to 19.3 million new cases and 10.0 million cancer deaths in 2020. https://www.iarc.who.int/wp-content/uploads/2020/12/pr292_E.pdfDate: Dec 15, 2020 Date accessed: September 10, 2022 Google Scholar The snowballing incidence, mortality, and burden of cancer are especially pervasive in low-income and middle-income countries (LMICs) such as Nigeria, the largest country in the African continent with a population of 206 million people. In 2020, the estimated new cases and deaths from cancer in Nigeria were 124 815 cases and 78 899 deaths. These numbers are projected to increase by 85% in the next 15 years. 2 Oihoma J New plan will help improve cancer treatment and save lives in Nigeria. https://www.clintonhealthaccess.org/blog/new-plan-will-help-improve-cancer-treatment-save-lives-nigeria/Date: 2018 Date accessed: September 10, 2022 Google Scholar The most common types of cancer in Nigeria are breast, prostate, cervical, colorectal, and non-Hodgkin lymphoma.

PDF file - 95K, Prognostic significance of IGHV mutation status, CD38 expression and ZAP-70 expression and their relationship with CD4:CD8 ratio.

Context: The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed. Objective: To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent. Evidence acquisition: A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO Evidence synthesis: We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, Conclusions: Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment Patient summary: We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth & COPY; 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Aspirin as a possible treatment of cancer has been of increasing interest for over 50 years, but the balance of the risks and benefits remains a point of contention. We summarise the valid published evidence 'for' and 'against' the use of aspirin as a cancer treatment and we present what we believe are relevant ethical implications. Reasons for aspirin include the benefits of aspirin taken by patients with cancer upon relevant biological cancer mechanisms. These explain the observed reductions in metastatic cancer and vascular complications in cancer patients. Meta-analyses of 118 observational studies of mortality in cancer patients give evidence consistent with reductions of about 20% in mortality associated with aspirin use. Reasons against aspirin use include increased risk of a gastrointestinal bleed though there appears to be no valid evidence that aspirin is responsible for fatal gastrointestinal bleeding. Few trials have been reported and there are inconsistencies in the results. In conclusion, given the relative safety and the favourable effects of aspirin, its use in cancer seems justified, and ethical implications of this imply that cancer patients should be informed of the present evidence and encouraged to raise the topic with their healthcare team.

ContextHarmonisation of outcome reporting and definitions for clinical trials and routine patient records can enable health care systems to provide more efficient outcome-driven and patient-centred interventions. We report on the work of the PIONEER Consortium in this context for prostate cancer (PCa).ObjectiveTo update and integrate existing core outcome sets (COS) for PCa for the different stages of the disease, assess their applicability, and develop standardised definitions of prioritised outcomes.Evidence acquisitionWe followed a four-stage process involving: (1) systematic reviews; (2) qualitative interviews; (3) expert group meetings to agree standardised terminologies; and (4) recommendations for the most appropriate definitions of clinician-reported outcomes.Evidence synthesisFollowing four systematic reviews, a multinational interview study, and expert group consensus meetings, we defined the most clinically suitable definitions for (1) COS for localised and locally advanced PCa and (2) COS for metastatic and nonmetastatic castration-resistant PCa. No new outcomes were identified in our COS for localised and locally advanced PCa. For our COS for metastatic and nonmetastatic castration-resistant PCa, nine new core outcomes were identified.ConclusionsThese are the first COS for PCa for which the definitions of prioritised outcomes have been surveyed in a systematic, transparent, and replicable way. This is also the first time that outcome definitions across all prostate cancer COS have been agreed on by a multidisciplinary expert group and recommended for use in research and clinical practice. To limit heterogeneity across research, these COS should be recommended for future effectiveness trials, systematic reviews, guidelines and clinical practice of localised and metastatic PCa.Patient summaryPatient outcomes after treatment for prostate cancer (PCa) are difficult to compare because of variability. To allow better use of data from patients with PCa, the PIONEER Consortium has standardised and recommended outcomes (and their definitions) that should be collected as a minimum in all future studies.