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The emergence of the precision medicine paradigm in oncology has led to increasing interest in the integration of real-world data (RWD) into cancer clinical research. As sources of real-world evidence (RWE), such data could potentially help address the uncertainties that surround the adoption of novel anticancer therapies into the clinic following their investigation in clinical trials. At present, RWE-generating studies which investigate antitumour interventions seem to primarily focus on collecting and analysing observational RWD, typically forgoing the use of randomisation despite its methodological benefits. This is appropriate in situations where randomised controlled trials (RCTs) are not feasible and non-randomised RWD analyses can offer valuable insights. Nevertheless, depending on how they are designed, RCTs have the potential to produce strong and actionable RWE themselves. The choice of which methodology to employ for RWD studies should be guided by the nature of the research question they are intended to answer. Here, we attempt to define some of the questions that do not necessarily require the conduct of RCTs. Moreover, we outline the strategy of the European Organisation for Research and Treatment of Cancer (EORTC) to contribute to the generation of robust and high-quality RWE by prioritising the execution of pragmatic trials and studies set up according to the trials-within-cohorts approach. If treatment allocation cannot be left up to random chance due to practical or ethical concerns, the EORTC will consider undertaking observational RWD research based on the target trial principle. New EORTC-sponsored RCTs may also feature concurrent prospective cohorts composed of off-trial patients. • The role of real-world data (RWD) in cancer clinical research is increasing. • A false dichotomy exists between RWD studies and randomised controlled trials (RCTs). • There are different methodologies for RWD studies, including RCT designs. • The methodology to be employed should be determined by the research question. • We outline the RWD strategy of a large academic clinical cancer research organisation. [ABSTRACT FROM AUTHOR]

Background: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics., Objective: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data., Design, Setting, and Participants: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146)., Outcome Measurements and Statistical Analysis: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data., Results and Limitations: The most common comorbidities were hypertension (35-73%), obesity (9.2-54%), and type 2 diabetes (11-28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12-25%) and emergency department visits (10-14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent., Conclusions: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data., Patient Summary: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To describe the approach and outcomes from two cancer centres in Southern and Northern Europe during the first wave of coronavirus disease 2019 (COVID-19) of patients with head and neck cancer (HNC)., Methods: Data collection was performed on a retrospective cohort of patients surgically treated for primary HNC between March and May 2020, using data from two tertiary hospitals: the European Institute of Oncology (Milan) and Guy's & St Thomas' NHS Foundation Trust (London)., Results: We included 77 patients with HNC. More patients with COVID-19 were taking angiotensin-converting enzyme (ACE) inhibitors and had Clavien-Dindo Classification grade I compared to negative patients, respectively (60% vs 22% [ p = 0.058] and 40% vs 8% [ p = 0.025]). Multivariate logistic regression analyses confirmed our data ( p = 0.05 and 0.03, respectively). Sex and age were statistically significantly different ( p = 0.05 and <0.001 respectively), showing more male patients (75% vs 53.66%, respectively) and more elderly patients in Italy than in the United Kingdom (patients aged >63 years: 69.44% vs 29.27%)., Conclusions: This study presents a large cohort of patients with HNC with nasopharyngeal swab during the first peak of the COVID-19 pandemic in Europe. Patients with HNC with COVID-19 appeared more likely to develop postsurgical complications and to be taking ACE inhibitors. The preventive measures adopted guaranteed the continuation of therapeutic surgical intervention.

Introduction: As part of the PIONEER (Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe) Consortium, we will explore which diagnostic and prognostic factors (DPFs) are currently being researched to previously defined clinical and patient-reported outcomes for prostate cancer (PCa)., Methods and Analysis: This research project will follow the following four steps: (1) a broad systematic literature review of DPFs for all stages of PCa, covering evidence from 2014 onwards; (2) discussion of systematic review findings by a multidisciplinary expert panel; (3) risk of bias assessment and applicability with Prediction model Risk Of Bias Assessment Tool criteria, Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and the Quality In Prognosis Studies tool (QUIPS) and (4) additional quantitative assessments if required., Ethics and Dissemination: We aim to develop an online tool to present the DPFs identified in this research and make them available across all stakeholders. There are no ethical implications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent., Methods and Analysis: A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, ≤T2a, prostate-specific antigen (PSA) <15 ng/mL, PSA density ≤0.2 ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10 mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled., Ethics and Dissemination: Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals., Trial Registration Number: NCT02914873., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

One of the more recently investigated adverse long-term side effects of gonadotropin-releasing hormone (GnRH) agonists for prostate cancer (PCa) is cardiovascular disease (CVD). Studies suggest lower risk of CVD following GnRH antagonists (degarelix) than GnRH agonists. This protocol describes precise codes used to extract variables from five European databases for a study that compares risk of CVD following GnRH agonists and antagonists for PCa. PCa men on primary GnRH agonists or antagonists were identified from the UK THIN (The Health Improvement Network) database, National Health Service (NHS) Scotland, Belgian Cancer Registry (BCR), Dutch PHARMO Database Network and French National Database (SNIIRAM). Cohort entry was defined as date of treatment initiation. CVD event was defined as any first incident or fatal CVD after cohort entry. Readcodes in THIN and ICD codes in NHS Scotland, BCR, PHARMO and SNIIRAM were used to extract variables. Risk of Bias in Non-randomised studies of Interventions (ROBINS-I) tool was used to assess the potential risk of biases in this study. 51 572 men with a median follow-up time of 2 years started on GnRH agonists and 2 417 men with a median follow-up time of 1 year started on GnRH antagonists between 2010 and 2017 in the UK, Scotland, Belgium, the Netherlands and France. Data from five countries improved the study power and internal validity required to compare risk of CVD between GnRH agonists and antagonists, the latter being a fairly new drug with limited data in individual countries., (© 2019 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Françaisede Pharmacologie et de Thérapeutique.)

Background: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa)., Objective: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation., Design, Setting, and Participants: We compared data from 10296 men on AS from 21 centres across 12 countries., Outcome Measurements and Statistical Analysis: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation., Results and Limitations: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4-28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0-13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5-2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4-2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5yr, 4561 had follow-up for <5yr, and 149 were lost to follow-up. Cumulative incidence of progression was 27.5% (95% CI: 26.4-28.6%) at 5yr and 38.2% (95% CI: 36.7-39.9%) at 10yr. A limitation is that not all centres were included due to limited information on the reason for discontinuation and limited follow-up., Conclusions: Our descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression., Patient Summary: Our assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)