Background: In recognition of the value and impact of holistic and patient-centred care, clinicians, patients, and healthcare organisations have advocated for practical changes to help integrate existing services. Technology is needed to enable the scale and speed of data organisation and sharing and communication needed to integrate clinical services and sites. Implementing complex or technology-supported interventions is difficult, and has high failure rates, as it requires changes to a number of embedded and interrelated processes, roles, and policies. Implementation Science (IS), which draws from a multidisciplinary base and has established theories, models, and frameworks (TMF) is increasingly used to improve research translation and efficiency. While there has been a widely reported rapid increase in the number of new TMF, including frameworks specific to either complex or technology-supported interventions, there is no single framework specific to the implementation of complex and technology-supported interventions (which are increasingly used). This paper describes the structured way that Realist Research, the Consolidated Framework for Implementation Science (CFIR), and the Non-Adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework were combined, applied, and tested to plan, implement, and evaluate a complex technology-supported intervention to integrate existing services. Aim: The FIT in Integrated Care study aimed, as part of a multi-site Randomised Controlled Trial, to build on existing IS to co-design, test, and evaluate a structured, practical, and comprehensive way to plan, implement, and evaluate the implementation of a complex technology-supported intervention that integrates existing services. Methods: The FIT in Integrated Care was co-designed in three stages. The first stage defined the function that the new framework needed to fulfil and identified suitable IS theory and practice to inform its structure and content. The second stage involved developing the new framework (structure, content) and applying it to the GERONTE* intervention. Realist research, the CFIR, and the NASSS framework were chosen and combined because of their relevance (to IS and to complex and technology-supported interventions), evidence base, combined comprehensiveness, and compatibility. The new fr↔amework was refined based on end-user feedback. The third stage, which is ongoing, involves the broader and longer-term testing, evaluation, and reporting on the framework’s functionality and user-friendliness in implementing a complex technology-supported intervention to integrate existing care services. Results: The FIT in Integrated Care study resulted in the combination and application of existing IS theory and practice, into an evidenced-based, structured, practical, user-friendly multi-stakeholder framework to plan, implement, and evaluate the implementation of a complex technology-supported intervention that integrates existing services. This new framework focuses research and analysis on the ‘context, mechanism of action, and outcomes’ to enable understanding of ‘how, in what context and for who’ the intervention works (so as to support wider adoption and/ or adaptation). Conclusion: Combining Realist research, the CFIR, and NASSS framework provides an evidence-based, robust, user-friendly way to plan, implement, and evaluate a complex technology-supported intervention that integrates existing healthcare services.

BACKGROUND:Co-design methods, which create innovation tailored to the end-user needs and setting, are increasingly used to improve research uptake and impact. Peer review and methodologists have emphasised the need for early, meaningful, and continuous involvement of stakeholders, and the transparent and detailed reporting of co-design methods. The implementation of both complex interventions (such as an integrated care pathway), and technology, into healthcare is difficult and has high failure rates. Designing, implementing, and adapting interventions to ensure they work in the local context requires in-depth understanding of multiple end-users' needs, processes, and contexts. Achieving this requires early, meaningful, and continuous engagement between multiple end-users. This study aimed to contribute to co-design research by reporting the: 1) process used to develop and test Participatory Rapid Appraisal and Focus Groups methods to co-design integrated care. 2) details of how the method was applied in the GERONTE project. 3) core steps involved in this co-design method (to facilitate use and/ or adaptation of the method). AIM:The study aimed to develop, test, and evaluate a co-design method that: I. enabled early, continuous, and meaningful engagement of multiple end-users in different locations and across different design iterations. II. enabled timely feedback and checking between the end-users and design team. III. optimised end-users participation by being flexible in the time, duration, and method of data collection and feedback. MATERIALS AND METHODS:The Participatory Rapid Appraisal and Focus Group to co-design integrated care method was developed in four stages. The first stage involved defining the project's co-design needs and reviewing the co-design literature to identify how to meet these. GERONTE aimed to co-design, evaluate, and prepare for EU-wide deployment, an integrated technology-supported care pathway for older adults with cancer and other morbidities. Focus Groups and Participatory Rapid Appraisal, in combination, were chosen as an empirically-based and practical approach. Focus Groups (FG) provided a participatory-based way to collect data in order to identify and agree multiple stakeholders' needs and collective priorities. Participatory Rapid Appraisal (PRA) provided a timely way; to gain participant feedback on the data collected; and, to ensure accuracy in the data sent to the pathway and technology design teams. The second stage involved applying the method in the GERONTE Project (using meetings between the project team, technologists, and older adults to develop a co-design protocol for the project). The third stage involved the use, refinement, evaluation, and reporting of the co-design method. The fourth stage, evaluation of the method, is ongoing. RESULTS AND DISCUSSION:This study resulted in the development of a structured approach to using Participatory Rapid Appraisal and Focus Groups in combination to co-design technology-supported integrated care. This method is proposed as an evidenced-based, practical, user-friendly way to co-design (or adapt an existing design) an integrated technology-supported care pathway. This co-design method involves three cycles of design. Each cycle involves multidisciplinary FG to collect semi-structured data followed by rapid analysis and feedback of the FG data to the participants to design or refine the intervention.

PURPOSE OF REVIEW:Managing multimorbidity in older adults with cancer is a central, complex challenge in modern oncology. Historically, this population was underrepresented in clinical trials, leaving clinicians without practical guidance. This review synthesizes recent evidence that moves beyond simply documenting frailty to deploying targeted, evidence-based interventions to improve supportive and palliative care. RECENT FINDINGS:The literature supports a practical 2-step approach to assessment, using screening tools like the Geriatric-8 to trigger a full Comprehensive Geriatric Assessment (CGA) with management, which is proven to reduce treatment toxicity. Goal-aligned deprescribing has emerged as an active clinical skill to manage polypharmacy. In decision-making, the focus has shifted from guideline-concordant to goal-concordant care. Finally, a needs-based paradigm for integrating palliative care is replacing older, prognosis-based models, distinguishing between generalist skills for all clinicians and specialist consultation for complex cases. SUMMARY:Recent evidence provides clinicians with practical approaches. By using validated screening, CGA-led interventions, systematic deprescribing, and needs-based palliative care, clinical teams can reduce treatment toxicity, lessen medication burden, and align complex cancer care with the personal priorities and quality-of-life goals of older patients.

Background: In recognition of the value and impact of holistic and patient-centred care, clinicians, patients, and healthcare organisations have advocated for practical changes to help integrate existing services. Technology is needed to enable the scale and speed of data organisation and sharing and communication needed to integrate clinical services and sites. Implementing complex or technology-supported interventions is difficult, and has high failure rates, as it requires changes to a number of embedded and interrelated processes, roles, and policies. Implementation Science (IS), which draws from a multidisciplinary base and has established theories, models, and frameworks (TMF) is increasingly used to improve research translation and efficiency. While there has been a widely reported rapid increase in the number of new TMF, including frameworks specific to either complex or technology-supported interventions, there is no single framework specific to the implementation of complex and technology-supported interventions (which are increasingly used). This paper describes the structured way that Realist Research, the Consolidated Framework for Implementation Science (CFIR), and the Non-Adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework were combined, applied, and tested to plan, implement, and evaluate a complex technology-supported intervention to integrate existing services. Aim: The FIT in Integrated Care study aimed, as part of a multi-site Randomised Controlled Trial, to build on existing IS to co-design, test, and evaluate a structured, practical, and comprehensive way to plan, implement, and evaluate the implementation of a complex technology-supported intervention that integrates existing services. Methods: The FIT in Integrated Care was co-designed in three stages. The first stage defined the function that the new framework needed to fulfil and identified suitable IS theory and practice to inform its structure and content. The second stage involved developing the new framework (structure, content) and applying it to the GERONTE* intervention. Realist research, the CFIR, and the NASSS framework were chosen and combined because of their relevance (to IS and to complex and technology-supported interventions), evidence base, combined comprehensiveness, and compatibility. The new fr↔amework was refined based on end-user feedback. The third stage, which is ongoing, involves the broader and longer-term testing, evaluation, and reporting on the framework’s functionality and user-friendliness in implementing a complex technology-supported intervention to integrate existing care services. Results: The FIT in Integrated Care study resulted in the combination and application of existing IS theory and practice, into an evidenced-based, structured, practical, user-friendly multi-stakeholder framework to plan, implement, and evaluate the implementation of a complex technology-supported intervention that integrates existing services. This new framework focuses research and analysis on the ‘context, mechanism of action, and outcomes’ to enable understanding of ‘how, in what context and for who’ the intervention works (so as to support wider adoption and/ or adaptation). Conclusion: Combining Realist research, the CFIR, and NASSS framework provides an evidence-based, robust, user-friendly way to plan, implement, and evaluate a complex technology-supported intervention that integrates existing healthcare services.

Radiation therapy (RT) is a cornerstone of cancer management, required in approximately half of all cancer cases, and is particularly relevant for older adults, who constitute the majority of oncology patients. Despite its localized nature and generally favorable toxicity profile, RT remains underutilized in this population, often due to age-related biases, comorbidities, or the limited integration of geriatric assessment into treatment planning. This review examines the evolving role of RT as an age-inclusive modality, highlighting innovations such as intensity-modulated and stereotactic techniques that enable more conformal, less toxic, and increasingly personalized regimens for older adults. Special attention is given to the challenges of frailty, cognitive impairment, and movement disorders, which may complicate treatment delivery and necessitate tailored adaptations. The role of comprehensive geriatric assessment and frailty screening tools is critically appraised, with emphasis on their predictive value in identifying treatment-limiting vulnerabilities and supporting shared decision-making. The review underscores the need to shift from age-based to function-based treatment paradigms, advocating for greater inclusion of older adults in clinical trials and for a multidisciplinary approach that aligns oncologic goals with patient priorities. When appropriately tailored, RT provides a safe, effective, and goal-concordant treatment option for older adults, and its optimized integration into geriatric oncology care is essential to meet the needs of an aging global population.

Cancer disproportionately affects older adults, who account for the majority of diagnoses and deaths globally. However, research and clinical care often fail to adequately address their unique needs. This collection of studies in Age and Ageing highlights challenges and opportunities in geriatric oncology. The rising incidence of cancer in the older population, driven by demographic shifts and socioeconomic factors, underscores the need for targeted prevention and control strategies. Despite this, older adults remain underrepresented in clinical trials, with barriers including social isolation, healthcare professionals' biases and a lack of dedicated studies. Frailty assessment is gaining ground as a key tool in geriatric oncology. Studies on frailty scores such as the Hospital Frailty Risk Score, and comprehensive geriatric assessment (CGA), show their ability to predict outcomes and guide interventions. CGA-based care has been shown to reduce treatment toxicity without compromising survival, yet its integration into routine practice remains limited. Treatment challenges are common, particularly with novel therapies like immune checkpoint inhibitors, which carry age-specific risks of adverse events. Tailored services are essential to address the diverse needs of older cancer patients. Research highlights the importance of improving communication around cancer screening for older adults and developing specialised care pathways for vulnerable populations, such as those with dementia. Continuity of care remains a significant challenge, requiring better coordination across healthcare providers. These findings emphasise the urgent need for age-attuned research, frailty-informed care models and tailored interventions to improve outcomes for older adults with cancer.

OBJECTIVE:To describe the distribution of disease stages, receipt of major surgery, 1-year net survival (NS) and 1-year conditional NS in relation to age and frailty in adults aged ≥50 diagnosed with colon cancer in England. METHODS:We obtained data on adults aged 50-99 diagnosed with colon cancer between 2014 and 2019, followed up through December 2021, from the national population-based COloRECTal cancer Repository. Frailty was assessed using the Secondary Care Administrative Records Frailty (SCARF) index categorised into fit, mild, moderate and severe frailty. Data on major resection were obtained through linkage with Hospital Episode Statistics dataset. Major resection rates were calculated in adults with stage I-III cancer. Descriptive statistics were used as appropriate. One-year NS from cancer diagnosis and 1-year conditional NS were estimated using the Pohar-Perme estimator. RESULTS:Out of 130 360 individuals (48% females-50% over 75), 48.9% were fit, ranging from 69% in the 50-64 age group to 31% in the 85-99 age group. Over 80% of adults with stage I-III cancer underwent a major resection. This percentage was 58% amongst fit adults aged over 85. One-year NS decreased as age increased across all frailty levels. Differences in NS between the 50-64 age group and the 85-99 age group were reduced in adults who survived beyond 1 year from diagnosis except for severely frail adults. CONCLUSION:This population-based study shows that a non-negligible proportion of older adults diagnosed with colon cancer and deemed 'fit' through the SCARF did not receive surgery that may impact their survival.

INTRODUCTION:In cancer care, symptom monitoring during treatment results in improved clinical outcomes such as improved quality of life, longer survival, and fewer hospital admissions. However, as the majority of patients with cancer are older and have multimorbidity, they may benefit from monitoring of additional symptoms. The aim of this study was to identify a core set of symptoms to monitor in older patients with multimorbidity treated for cancer, including symptoms caused by treatment side effects, destabilization of comorbidities, and functional decline.MATERIALS AND METHODS:During a scoping literature search, 17 quality of life questionnaires were used to select 53 possible symptoms to monitor. An expert panel of cancer and geriatrics specialists was asked to participate in multiple online surveys to indicate whether these symptoms were not relevant to monitor, only relevant to monitor in a specific patient group, or relevant to monitor in all patients. In a subsequent round the list was reduced and the panel indicated how frequently these symptoms should be monitored during cancer treatment and after cancer treatment completion. Finally, a digital consensus meeting was organised to decide when symptoms had to trigger a recommendation to the patient to get in touch with their medical team.RESULTS:In total, 30 healthcare professionals participated in the online surveys. After two rounds, a dataset of 19 symptoms related to cancer, cancer treatment, functional decline, and destabilization of comorbidities was agreed upon for monitoring. Five symptoms were selected for daily monitoring during treatment, seven for weekly, and seven for monthly. After treatment completion, the panel agreed upon less frequent reporting. Additionally, nine symptoms to be monitored only in patients with specific cancer types or treatment types were chosen, such as "cough up blood" in lung cancer.DISCUSSION:This study is the first to identify a core set of symptoms to monitor in older patients with multimorbidity treated for cancer. Future research is needed to investigate whether the monitoring of these symptoms is feasible and improves clinical outcomes in older patients with multimorbidity treated for cancer.

To evaluate the feasibility of a conversation coaching intervention for people with dementia and their communication partners. Participant feedback indicates that conversation coaching intervention is feasible with people with dementia. Communication function and well-being were either maintained or improved. Conversation coaching intervention is collaborative and enhances the retained communication abilities of people living with dementia. Conversation abilities of people with dementia are impacted by cognitive-communication deficits. Communication interventions can improve quality of life by increasing positive interactions and well-being. This study evaluates the feasibility of a conversation coaching intervention for people with dementia and their communication partners. A mixed-method design was used. Thirty-four people were recruited over 12 months; 17 people with dementia and 17 communication partners. Participants with dementia were aged between 62 and 79 years (8 females, 9 males) and the communication partners were aged 33–77 years (5 males, 12 females). This conversation coaching intervention involved two assessment sessions (pre and post intervention) and 6 weekly sessions, alternating between individual and group-based sessions. These were facilitated by two experienced speech and language therapists with a three-month follow-up period. Participants were assessed initially and three months following intervention using Profiling Communication Ability in Dementia (P-CAD), Goal Attainment Scaling, and Capability Index for Older people (ICECAP-O). Twenty-eight participants completed the conversation coaching intervention. P-CAD scores for people with dementia were maintained at three months for 71

PURPOSE:A substantial proportion of patients with cancer are older and experience multimorbidity. As the population is ageing, the management of older patients with multimorbidity including cancer will represent a significant challenge to current clinical practice. METHODS:This study aimed to (1) identify which chronic health conditions may cause change in oncologic decision-making and care in older patients and (2) provide guidance on how to incorporate these in decision-making and care provision of older patients with cancer. Based on a scoping literature review, an initial list of prevalent morbidities was developed. A subsequent survey among healthcare providers involved in the care for older patients with cancer assessed which chronic health conditions were relevant and why. RESULTS:A list of 53 chronic health conditions was developed, of which 34 were considered likely or very likely to influence decision-making or care according to the 39 healthcare professionals who responded. These conditions were further categorized into five patient profiles. From these conditions, five patient profiles were developed, namely, (1) a somatic profile consisting of cardiovascular, metabolic, and pulmonary disease, (2) a functional profile, including conditions that cause disability, dependency or a high caregiver burden, (3) a psychosocial profile, including cognitive impairment, (4) a nutritional profile also including digestive system diseases, and finally, (5) a concurrent cancer profile. All profiles were considered likely to impact decision-making with differences between treatment modalities. The impact on the care trajectory was generally considered less significant, except for patients with care dependency and psychosocial health problems. CONCLUSIONS:Chronic health conditions have various ways of influencing oncologic decision-making and the care trajectory in older adults with cancer. Understanding why specific chronic health conditions may impact the oncologic care trajectory can aid clinicians in the management of older patients with multimorbidity, including cancer.

Introduction: Current hospital-based care pathways are generally single-disease centred. As a result, coexisting morbidities are often suboptimally evaluated and managed, a deficiency becoming increasingly apparent among older patients who exhibit heterogeneity in health status, functional abilities, frailty, and other geriatric impairments. To address this issue, our study aims to assess a newly developed patient-centred care pathway for older patients with multimorbidity and cancer. The new care pathway was based on currently available evidence and co-designed by end-users including health care professionals, patients, and informal caregivers. Within this care pathway, all healthcare professionals involved in the care of older patients with multimorbidity and cancer will form a Health Professional Consortium (HPC). The role of the HPC will be to centralise oncologic and non-oncologic treatment recommendations in accordance with the patient's priorities. Moreover, an Advanced Practice Nurse will act as case-manager by being the primary point of contact for the patient, thus improving coordination between specialists, and by organising and leading the consortium. Patient monitoring and the HPC collaboration will be facilitated by digital communication tools designed specifically for this purpose, with the added benefit of being customisable for each patient. Materials and Methods: The GERONTE study is a prospective international, multicentric study consisting of two stepped -wedge trials performed at 16 clinical sites across three European countries. Each trial will include 720 patients aged 70 years and over with a new or progressive cancer (breast, lung, colorectal, prostate) and at least one moderate or severe multimorbidity. The patients in the intervention group will receive the new care pathway whereas patients in the control group will receive usual oncologic care. Discussion: GERONTE will evaluate whether this kind of holistic, patient -oriented healthcare management can improve quality of life (primary outcome) and other valuable endpoints in older patients with multimorbidity and cancer. An ancillary study will assess in depth the socio-economic impact of the intervention and deliver concrete implementation guidelines for the GERONTE intervention care pathway. Trial registration: FRONE: NCT05720910 TWOBE: NCT05423808

Introduction: As the population is ageing, the number of older patients with multimorbidity including cancer continues to increase. To improve care for these patients, the European Union-funded project "Streamlined Geriatric and Oncological evaluation based on IC Technology" (GERONTE) was initiated to develop a new, patientcentred, holistic care pathway. The aim of this paper is to analyse what challenges are encountered in everyday clinical practice according to patients, their informal caregivers, and healthcare professionals as a starting point for the development of the care pathway.Materials and Methods: An expert panel of cancer and geriatrics specialists participated in an online survey to answer what challenges they experience in caring for older patients with multimorbidity including cancer and what treatment outcomes could be improved. Furthermore, in-depth interviews with older patients and their informal caregivers were organised to assess what challenges they experience.Results: Healthcare professionals (n = 36) most frequently mentioned the challenge of choosing the best treatment in light of the lack of evidence in this population and how to handle interactions between the (cancer) treatment and multimorbidities. Twelve patients and caregivers participated, and they most frequently mentioned challenges related to treatment outcomes, such as how to deal with symptoms of disease or treatment and how to maintain quality of life. From the challenges, five main themes emerged that should be taken into account when developing a new care pathway for older patients with multimorbidity including cancer. Two themes focus on decision making aspects such as personalized treatment recommendations and inclusion of nononcologic information, two focus on patient support and monitoring to maintain quality of life and functioning, and one overarching theme addresses care coordination to prevent fragmentation of care.Discussion: In conclusion, the management of older patients with multimorbidity including cancer is complex and although progress has been made on improving aspects of their care, challenges remain and patients are at risk of receiving inappropriate, unnecessary, and potentially harmful treatment. A patient-centred care pathway that integrates solutions to the five main themes and that moves away from a single-disease centred approach is needed.

Most cancers occur in older people and the burden in this age group is increasing. Over the past two decades the evidence on how best to treat this population has increased rapidly. However, implementation of new best practices has been slow and needs involvement of policymakers. This perspective paper explains why older people with cancer have different needs than the wider population. An overview is given of the recommended approach for older people with cancer and its benefits on clinical outcomes and cost-effectiveness. In older patients, the geriatric assessment (GA) is the gold standard to measure level of fitness and to determine treatment tolerability. The GA, with multiple domains of physical health, functional status, psychological health and socio-environmental factors, prevents initiation of inappropriate oncologic treatment and recommends geriatric interventions to optimize the patient's general health and thus resilience for receiving treatments. Multiple studies have proven its benefits such as reduced toxicity, better quality of life, better patient-centred communication and lower healthcare use. Although GA might require investment of time and resources, this is relatively small compared to the improved outcomes, possible cost-savings and compared to the large cost of oncologic treatments as a whole.

A list of questions patients with cancer and multimorbidity can use to be better prepared for their next consultation with their health care provider.

Older adults remain at higher risk for severe COVID-19 infection outcomes and, although the development of vaccines has changed the course of the disease, immunosenescence can result in lower vaccine immunogenicity [[1]Collier D.A. Ferreira I.A.T.M. Kotagiri P. et al.Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2.Nature. 2021; 596: 417-422Crossref PubMed Scopus (342) Google Scholar]. Older patients with solid tumours or haematologic malignancies receiving anti-cancer treatment are often immunocompromised and unable to provide an adequate immune response to COVID-19 vaccination [2Barriere J. Chamorey E. Adjtoutah Z. et al.Impaired immunogenicity of BNT162b2 anti-SARS-CoV-2 vaccine in patients treated for solid tumors.Ann Oncol. 2021; 32: 1053-1055Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 3Herishanu Y. Avivi I. 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Effect of cancer on clinical outcomes of patients with COVID-19: a meta-analysis of patient data.JCO Glob Oncol. 2020; 6: 799-808Crossref PubMed Scopus (128) Google Scholar]. Today, several drugs are available for the treatment of COVID-19 infection, with the best treatment option for each individual patient determined by their therapeutic indication, efficacy, availability, feasibility of administration, safety, and prevalence of infection variants. Older adults with cancer represent a vulnerable population. The impact of geriatric syndromes, comorbidities, immunosuppression, increased risk of side effects, and drug-drug interactions due to polypharmacy and/or oncological treatment, must be considered in the risk-benefit balance influencing the choice of COVID-19 treatments [[11]Elkrief A. Hennessy C. Kuderer N.M. et al.Geriatric risk factors for serious COVID-19 outcomes among older adults with cancer: a cohort study from the COVID-19 and cancer consortium.Lancet Healthy Longev. 2022; 3: e143-e152Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar]. The SIOG COVID-19 Working Group continues to advocate for the optimal management of older adults with cancer during the pandemic era. Therefore, we reviewed the data on currently available COVID-19 treatments mainly in outpatients setting and their potential use among older adults with cancer. The COVID-19 pandemic has triggered an unprecedented acceleration in drug development. Patients with mild to moderate COVID-19 infection, considered to be at higher risk for COVID-19 adverse outcomes, may benefit from different therapies. High-risk groups for SARS-CoV-2 complications and death are defined according to age, vaccination status, immune status, and the presence of risk factors for clinical progression [[12]COVID-19 Treatment Guidelines Panel Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health, 2023https://www.covid19treatmentguidelines.nih.gov/Google Scholar]. Age alone is a key risk factor, but comorbidities, often prevalent among older adults, may further increase the risk of COVID-19 disease progression and poor outcomes [[13]Battisti N.M.L. Mislang A.R. Cooper L. et al.Adapting care for older cancer patients during the COVID-19 pandemic: recommendations from the International Society of Geriatric Oncology (SIOG) COVID-19 working group.J Geriatric Oncol. 2020; 11: 1190-1198Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar]. Although older individuals may derive significant benefits from novel COVID-19 treatments, studies published to date mostly included very selected populations. Currently, therapeutic strategies for COVID-19 involve antiviral agents (often administered at early stages of the disease), steroids, and immunotherapeutic agents. For non-hospitalised adults affected by mild or moderate COVID-19 at high risk of disease progression, ritonavir-boosted nirmatrelvir or remdesivir are considered first-line treatment options [[12]COVID-19 Treatment Guidelines Panel Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health, 2023https://www.covid19treatmentguidelines.nih.gov/Google Scholar]. The protease inhibitor nirmatrelvir is combined with the strong cytochrome P450 (CYP) 3A4 inhibitor and pharmacokinetic boosting agent ritonavir. Coadministration of ritonavir is required to increase nirmatrelvir concentrations to the target therapeutic range [[14]Owen D.R. Allerton C.M.N. Anderson A.S. et al.An oral SARS-CoV-2 M(pro) inhibitor clinical candidate for the treatment of COVID-19.Science. 2021; 374: 1586-1593Crossref PubMed Scopus (672) Google Scholar]. The Evaluation of Protease Inhibition for COVID-19 in High-Risk patients (EPIC-HR) phase 2–3 trial [[15]Hammond J. Leister-Tebbe H. Gardner A. et al.Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19.N Engl J Med. 2022; 386: 1397-1408Crossref PubMed Scopus (703) Google Scholar] demonstrated the efficacy of oral nirmatrelvir associated to ritonavir within three days after the onset of symptoms. Authors reported an 89.1% relative risk reduction in COVID-19–related hospitalizations or deaths from any cause by day 28 compared to placebo among unvaccinated, non-hospitalised adults at high risk for progression to severe disease. In this study, 12% of the patients were aged ≥65 years and efficacy was supported by subgroup analyses (age, coexisting health conditions, etc). Fewer serious adverse events occurred in the population treated with nirmatrelvir plus ritonavir. Dysgeusia and diarrhoea are potentially dangerous events in older adults and occurred more frequently in ritonavir-boosted nirmatrelvir patients compared with placebo (6% versus 0.3% and 3% versus 2%, respectively). Ritonavir-boosted nirmatrelvir use involves a high risk of drug-drug interactions with concomitant medications that may increase the risk of toxicities. CYP3A4 inhibition occurs rapidly after initiating ritonavir, with maximum inhibition occurring within 48 h. After ritonavir is discontinued, 70% to 90% of CYP3A4 inhibition resolves within two to three days. The time to resolution of inhibition varies based on the patient's age and resolution may take longer in older adults [[12]COVID-19 Treatment Guidelines Panel Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health, 2023https://www.covid19treatmentguidelines.nih.gov/Google Scholar,[16]Katzenmaier S. Markert C. Riedel K.D. et al.Determining the time course of CYP3A inhibition by potent reversible and irreversible CYP3A inhibitors using a limited sampling strategy.Clin Pharmacol Ther. 2011; 90: 666-673Crossref PubMed Scopus (91) Google Scholar]. Ritonavir is also a well-known strong combined inhibitor of p-glycoprotein, therefore it can interact with oral anticoagulants and drug-drug interaction management is required. In this real-world series of 72 patients co-prescribed nirmatrelvir-ritonavir and an oral anticoagulant, recommended drug-drug interaction management strategies for apixaban, rivaroxaban, and warfarin seemed effective at minimizing adverse events [[17]Vazquez S.R. Wilson A.S. Witt D.M. Management of potential drug-drug interactions with nirmatrelvir-ritonavir and oral anticoagulants: a case series.J Thromb Thrombolysis. 2022; 54: 583-586Crossref PubMed Scopus (1) Google Scholar]. Also, a careful evaluation is required in older patients with cancer because of the risk of potential interactions with myelosuppressive agents and the risk of increasing concentrations of concomitant medications, including certain chemotherapeutic agents [[12]COVID-19 Treatment Guidelines Panel Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health, 2023https://www.covid19treatmentguidelines.nih.gov/Google Scholar]. Ritonavir-boosted nirmatrelvir should be used with caution in patients with pre-existing liver disease and is not recommended in the context of severe hepatic impairment. Dose reductions are also required in patients with moderate renal impairment. However, limited data are available for patients with advanced kidney disease. Regardless, older patients with cancer and renal failure are at high risk for COVID-19 morbidity and mortality and should not be excluded from treatment. Alternative antiviral options may be considered and a discussion between the physician and the patient about the potential risks and benefits of this drug is necessary prior to administering an adapted dose of nirmatrelvir/ritonavir [[18]Hiremath S. McGuinty M. Argyropoulos C. et al.Prescribing Nirmatrelvir/ritonavir for COVID-19 in advanced CKD.Clin J Am Soc Nephrol. 2022; 17: 1248-1249Google Scholar]. Intravenous remdesivir is approved for mild to moderate COVID-19 in patients at high risk of disease progression [[12]COVID-19 Treatment Guidelines Panel Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health, 2023https://www.covid19treatmentguidelines.nih.gov/Google Scholar,[19]Remdesivir Food and Drug Administration.https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214787Orig1s000lbl.pdfDate: 2020Google Scholar]. Benefits of combining dexamethasone and remdesivir have been reported in different studies, although data in older individuals are limited [ [20]Benfield T. Bodilsen J. Brieghel C. et al.Improved survival among hospitalized patients with coronavirus disease 2019 (COVID-19) treated with Remdesivir and dexamethasone. A Nationwide population-based cohort study.Clin Infect Dis. 2021; 73: 2031-2036Crossref PubMed Scopus (46) Google Scholar,[21]Wong C.K.H. Lau K.T.K. Au I.C.H. et al.Optimal timing of remdesivir initiation in hospitalized COVID-19 patients administered with dexamethasone.Clin Infect Dis. 2021; : ciab728Google Scholar]. The double blind, randomised, placebo-controlled, Adaptive COVID-19 Treatment Trial (ACTT) trial [[22]Beigel J.H. Tomashek K.M. Dodd L.E. et al.Remdesivir for the treatment of COVID-19—final report.N Engl J Med. 2020; 383: 1813-1826Crossref PubMed Scopus (4445) Google Scholar] evaluated remdesivir in unvaccinated, hospitalised adults with COVID-19. The study demonstrated a benefit on clinical recovery (7 versus 9; recovery rate ratio 1.45, 95% confidence interval [CI] 1.18–1.79) and mortality (hazard ratio [HR] for death 0.30, 95%CI 0.14–0.64) in patients requiring low-flow oxygen therapy. No significant benefit was shown in patients requiring high-flow oxygen (HFO) or non-invasive ventilation (NIV) (recovery rate ratio 1.09, 95%CI 0.76–1.57). Mean age was 58.9 years and 35% of patients were aged ≥65 years old. Half of the patients had more than two coexisting conditions, most commonly hypertension (50.2%), obesity (44.8%), and type 2 diabetes (30.3%). Only 8% (N = 80) had malignant neoplasms. The efficacy of remdesivir in hastening recovery did not vary according to prespecified age categories. Serious adverse events were similar between arms (25% versus 32%) [[22]Beigel J.H. Tomashek K.M. Dodd L.E. et al.Remdesivir for the treatment of COVID-19—final report.N Engl J Med. 2020; 383: 1813-1826Crossref PubMed Scopus (4445) Google Scholar]. A subsequent retrospective study compared survival outcomes in 34,230 patients treated with remdesivir within two days of hospitalisation versus patients who were not. In the remdesivir group, 8% of the patients were aged ≥85, 19% were 75–84, and 25% were 65–74 years old. About 8% had cancer and were immunosuppressed, 78% cardiovascular disease, 40% obesity, and 42% diabetes. Remdesivir initiation upon hospital admission was associated with improved survival [[23]Mozaffari E. Chandak A. Zhang Z. et al.Remdesivir treatment in hospitalized patients with COVID-19: a comparative analysis of in-hospital all-cause mortality in a large multicenter observational cohort.Clin Infect Dis. 2021; : ciab875Google Scholar]. Another prospective, observational study (median age 69 years) showed that among hospitalised patients affected by COVID-19 pneumonia who required oxygen supplementation, early (<5 days from symptom onset) remdesivir might reduce progression. Patients admitted within the first five days of symptom onset were older and had a higher prevalence of comorbidities and frailty [[24]Falcone M. Suardi L.R. Tiseo G. et al.Early use of remdesivir and risk of disease progression in hospitalized patients with mild to moderate COVID-19.Clin Ther. 2022; 44: 364-373Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. The phase 3, randomised, controlled, open-label DisCoVeRy trial [[25]Ader F. Bouscambert-Duchamp M. Hites M. et al.Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial.Lancet Infect Dis. 2022; 22: 209-221Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar], included unvaccinated, hospitalised patients with moderate or severe COVID-19. Although remdesivir delayed worsening of respiratory symptoms, the study showed no clinical and mortality benefit for treated patients. Median age was 64 years, 74% had one or more coexisting conditions and 8% had cancer. Remdesivir has also been tested in the ambulatory setting. The double-blind, placebo-controlled PINETREE study included non-hospitalised patients with COVID-19 at high risk for disease progression and demonstrated that three consecutive days of remdesivir resulted in a 87% relative reduction in the risk of hospitalisation or death (0.7% versus 5.3%; HR 0.13, 95%CI 0.03–0.59; p = 0.008). The study population of 562 patients included 30% aged ≥60 years, among whom 60% were affected by diabetes, 55% by obesity, and 45% by hypertension, with only 5.3% (N = 30) having a diagnosis of cancer [ [26]Gottlieb R.L. Vaca C.E. Paredes R. et al.Early remdesivir to prevent progression to severe COVID-19 in outpatients.N Engl J Med. 2022; 386: 305-315Crossref PubMed Scopus (517) Google Scholar]. Remdesivir may be associated with gastrointestinal toxicity, elevated transaminase levels, prolonged prothrombin time without change in the international normalized ratio, and hypersensitivity reactions [[19]Remdesivir Food and Drug Administration.https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214787Orig1s000lbl.pdfDate: 2020Google Scholar]. Remdesivir is available in two formulations (concentrated solution and lyophilized powder) containing sulfobutylether beta-cyclodextrin sodium (SBECD), which is eliminated by the kidneys and may result in toxicity in patients with renal impairment. Importantly, while some clinical trials excluded patients with an estimated glomerular filtration rate (eGFR) <50 mL/min, other studies involved an eGFR cutoff of <30 mL/min [[27]Pettit N.N. Pisano J. Nguyen C.T. et al.Remdesivir use in the setting of severe renal impairment: a theoretical concern or real risk?.Clin Infect Dis. 2021; 73: e3990-e3995Crossref PubMed Scopus (31) Google Scholar,[28]Ackley T.W. McManus D. Topal J.E. et al.A valid warning or clinical lore: an evaluation of safety outcomes of remdesivir in patients with impaired renal function from a multicenter matched cohort.Antimicrob Agents Chemother. 2021; 65 (e02290–20)Crossref Scopus (34) Google Scholar]. Nonetheless, remdesivir may be considered also for patients with an eGFR of <30 mL/min if the potential benefits outweigh the risks [[29]Adamsick M.L. Gandhi R.G. Bidell M.R. et al.Remdesivir in patients with acute or chronic kidney disease and COVID-19.J Am Soc Nephrol. 2020; 31: 1384-1386Crossref PubMed Scopus (115) Google Scholar]. A study by Kanai et al. [[30]Kanai O. Fujita K. Nanba K. et al.Safety of remdesivir for patients 80 years of age or older with coronavirus disease 2019 (COVID-19).Drugs Aging. 2021; 38: 1067-1074Crossref PubMed Scopus (6) Google Scholar] suggested that remdesivir's safety profile was comparable in hospitalised patients older or younger than 80 years, with no significant differences in the incidence of liver dysfunction, renal dysfunction, and asthenia between both groups. Systemic glucocorticoids are recommended for the treatment of patients with COVID-19 requiring supplemental oxygen [[12]COVID-19 Treatment Guidelines Panel Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health, 2023https://www.covid19treatmentguidelines.nih.gov/Google Scholar]. The multicentre, open-label, Randomised Evaluation of COVID-19 Therapy (RECOVERY) study [[31]Horby P. Lim W.S. Emberson J.R. et al.RECOVERY Collaborative GroupDexamethasone in hospitalized patients with Covid-19.N Engl J Med. 2021; 384: 693-704Crossref PubMed Scopus (6108) Google Scholar], showed that dexamethasone may reduce mortality in hospitalised patients with COVID-19 requiring supplemental oxygen, without significant survival differences between younger and older adults. Participants' mean age was 66 years and 56% of study population had one or more comorbidities (diabetes in 24%), without a report regarding the number of patients with cancer included. Gallay et al. [[32]Gallay L. Tran V.T. Perrodeau E. et al.Fourteen day survival among older adults with severe infection with severe acute respiratory syndrome coronavirus 2 treated with corticosteroid: a cohort study.Clin Microbiol Infect. 2021; 27: 1145-1150Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar] supported the use of corticosteroids in patients aged ≥80 years with severe COVID-19, with improved overall survival at day 14. In this study, corticosteroids were prescribed less often in patients with lower level of independence at baseline, as measured by the Group Iso Ressource score. Low autonomy was reported in 14% of the patients in the treatment group and 21% in the control group (Groupe Iso Ressource score 1/2). Among 131 patients receiving corticosteroids, 17% developed adverse events, including hyperglycaemia, heart failure, confusion, and infection. The COronavirus disease in Very elderly Intensive care Patients (COVIP) study [[33]Jung C. Wernly B. Fjølner J. et al.Steroid use in elderly critically ill COVID-19 patients.Eur Respir J. 2021; 58: 2100979Crossref PubMed Scopus (33) Google Scholar] included 3082 critically ill patients with COVID-19 aged ≥70 years. Univariate rates of 30-day mortality were higher in patients receiving corticosteroids (53% versus 42%; adjusted odds ratio [aOR] 1.16, 95%CI 1.28–2.02; p < 0.001) and this treatment remained associated with increased 30-day mortality after multivariable adjustment (aOR 1.60, 95%CI 1.26–2.04; p < 0.001). The benefit/risk ratio of systemic corticosteroid use in older adults remains unclear in the context of potential adverse events, such as delirium, hyperglycaemia, falls, immunosuppression, secondary infections, opportunistic fungal infections, reactivation of latent infections, gastrointestinal bleeding, and/or neuromuscular weakness. In addition, dexamethasone may reduce the efficacy of concomitant CYP3A4 substrates. These drug-related adverse effects may be more severe in older patients, especially in those with a cancer diagnosis who are also immunocompromised. Monoclonal Antibodies (mAbs) may reduce the risk of COVID-19 progression and death, particularly if ritonavir-boosted nirmatrelvir and remdesivir are not available or clinically appropriate, but few data are available in older adults [[12]COVID-19 Treatment Guidelines Panel Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health, 2023https://www.covid19treatmentguidelines.nih.gov/Google Scholar]. Bebtelovimab or tixagevimab plus cilgavimab are authorised for SARS-CoV-2 pre-exposure prophylaxis in individuals who may have an inadequate immune response to COVID-19 vaccination or are ineligible for vaccination and who have not been exposed to the infection. These could include older patients with cancer and/or haematological malignancies undergoing anticancer treatment. While the TACKLE study [[34]Montgomery H. Richard Hobbs F.D. Padilla F. et al.Efficacy and safety of intramuscular administration of tixagevimab-cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial.Lancet Respir Med. 2022; S2213-2600: 00180-00181Google Scholar] showed a statistically and clinically significant protection against progression to severe COVID-19 or death in unvaccinated individuals, only 13% (N = 116) were aged ≥65 years, limiting generalizability to older adults. Some mAbs are not effective against COVID-19 variants, so the prevalence of resistant variants should be considered in decision-making [[35]Hoffmann M. Krüger N. Schulz S. et al.The omicron variant is highly resistant against antibody-mediated neutralization: implications for control of the COVID-19 pandemic.Cell. 2022; 185: 447-456.e11Abstract Full Text Full Text PDF PubMed Scopus (469) Google Scholar]. The Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) phase 3 trial [[36]Dougan M. Nirula A. Azizad M. et al.The BLAZE-1 investigators. Bamlanivimab plus Etesevimab in mild or moderate Covid-19.N Engl J Med. 2021; 385: 1382-1392Crossref PubMed Scopus (393) Google Scholar] showed that among high-risk outpatients, bamlanivimab plus etesevimab was associated with a lower incidence of hospitalisation and death compared with placebo. The trial included 1035 patients with one or more risk factors for severe COVID-19 (age ≥ 65 years; body-mass index ≥35; and coexisting conditions), with 31% aged ≥65 years. Adverse events were similar between groups, and no patients discontinued treatment due to toxicity. In a retrospective study including 429 patients aged ≥65 years with mild to moderate SARS-CoV-2, treatment with bamlanivimab or casirivimab/imdevimab was associated with a lower risk of hospitalisation [[37]Sobolewski K.A. Smoke S. Brophy A. et al.Real-world evaluation of the impact of two anti-SARS-CoV-2 monoclonal antibody regimens on COVID-19 hospitalizations in older adults.Med Virol. 2022; 94: 2493-2499Crossref PubMed Scopus (1) Google Scholar]. Sotrovimab also reduced the incidence of all-cause hospitalisation and death among patients with mild to moderate COVID-19. In this series of 520 patients, 20% were aged ≥65 years [[38]Gupta A. Gonzalez-Rojas Y. Juarez E. et al.Effect of sotrovimab on hospitalization or death among high-risk patients with mild to moderate COVID-19: a randomized clinical trial.JAMA. 2022; 327: 1236-1246Crossref PubMed Scopus (121) Google Scholar]. Potential side effects include hypersensitivity, nausea, rash, dizziness, diarrhoea, and hypertension. As the Omicron variant has become dominant, the COVID-19 Treatment Guidelines Panel recommends against the use of bamlanivimab plus etesevimab, casirivimab plus imdevimab or sotrovimab for the treatment of COVID-19 disease [[12]COVID-19 Treatment Guidelines Panel Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health, 2023https://www.covid19treatmentguidelines.nih.gov/Google Scholar]. In December 2021, molnupiravir was authorized for the treatment of adults with mild to moderate COVID-19 infection at high risk of progression to severe disease, within five days of symptom onset and for whom alternative antiviral therapies are unaffordable or clinically inappropriate [[39]Food and Drug Administration Fact Sheet for Healthcare Providers: Emergency Use Authorization for Molnupiravir.2021Google Scholar]. Data from the phase 3 MOVe-OUT trial [[40]Bernal A. Gomes da Silva M. Musungaie D. el al. Molnupiravir for Oral treatment of Covid-19 in nonhospitalized patients.N Engl J Med. 2022; 386: 509-520Crossref PubMed Scopus (768) Google Scholar] showed that molnupiravir reduced the risk of hospitalisation or death in at-risk, unvaccinated adults with COVID-19. The analysis included 1433 participants, of whom 17% were aged ≥60 years. Among the participants, 74% had a body mass index ≥30 and 16% were affected by diabetes. Only 29 patients, representing 2% of the entire sample, had any active cancer. Serious adverse events (diarrhoea, nausea, and dizziness) were less frequent in the molnupiravir group. No drug-drug interactions were observed. Severely immunocompromised adults, such as patients affected by haematological malignancies receiving anticancer treatment, may have prolonged SARS-CoV-2 replication potentially leading to rapid viral evolution. In this setting, a single antiviral agent may be associated with the development of variants resistant to antivirals [[12]COVID-19 Treatment Guidelines Panel Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health, 2023https://www.covid19treatmentguidelines.nih.gov/Google Scholar]. However, the role of combined antiviral therapy in severely immunocompromised patients is still unclear and more research is warranted. The anti-interleukin (IL)-6 monoclonal antibody tocilizumab has been utilised for hospitalised patients with COVID-19 infection requiring supplemental oxygen or ventilatory support. The RECOVERY study [[41]RECOVERY Collaborative GroupTocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.Lancet. 2021; 397: 1637-1645Abstract Full Text Full Text PDF PubMed Scopus (1015) Google Scholar] randomised 4116 patients with progressive COVID-19 to tocilizumab versus standard care. Tocilizumab was associated with a lower 28-day mortality compared to standard care alone (Tocilizumab: 31%; standard care: 35%; rate ratio 0–85; 95%CI 0–76–0-94; p = 0–0028). The mean age was 64 years, including 11% of patients aged >80 years in the tocilizumab group and 12% in standard care. No differences in comorbidities were found between both groups. A Spanish single-centre retrospective observational study [[42]Duarte-Millan M.A. Mesa-Plaza N. Guerrero-Santillan M. et al.Prognostic factors and combined use of tocilizumab and corticosteroids in a Spanish cohort of elderly COVID-19 patients.J Med Virol. 2022; 94: 1540-1549Crossref PubMed Scopus (12) Google Scholar], documented a survival benefit in hospitalised patients aged >80 years with tocilizumab plus corticosteroids (HR 0.09, 95%CI: 0.01–0.74), with no benefits seen in patients receiving corticosteroids alone (HR 0.95, 95%CI 0.53–1.71). COVID-19 convalescent plasma (CCP) is authorised for use in immunocompromised patients. A randomised, double-blind, placebo-controlled trial of 160 non-hospitalised older patients showed that early administration of CCP to mildly ill older patients reduced disease progression. The study was conducted in 160 immunocompetent older adults affected by one or more comorbidities. Participants' mean age was 77 years, 45% were aged 65–74 years, and 55% were ≥ 75 years. No imbalances in baseline characteristics were found between CCP and placebo groups [[43]Libster R. Perez Marc G. Wappner D. et al.Early high-titer plasma therapy to prevent severe COVID-19 in older adults.N Engl J Med. 2021; 384: 610-618Crossref PubMed Scopus (575) Google Scholar]. Serious adverse reactions were infrequent and consistent with those of plasma infusions for other indications. Most clinical trials were completed before the appearance of circulating SARS-CoV-2 variants, so data regarding the use of CCP against variants are not available [[12]COVID-19 Treatment Guidelines Panel Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health, 2023https://www.covid19treatmentguidelines.nih.gov/Google Scholar]. Trials that evaluated colchicine in outpatients with COVID-19 failed to reach the efficacy endpoint of reducing hospitalizations and death [[44]Tardif J.C. Bouabdallaoui N. L’Allier P.L. et al.Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial.Lancet Respir Med. 2021; 9: 924-932Abstract Full Text Full Text PDF PubMed Scopus (177) Google Scholar], or the time of recovery from COVID-19 [[45]Dorward J. Yu L. Hayward G. et al.Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial.Br J Gen Pract. 2022; : e450-452Google Scholar]. In addition, more gastrointestinal adverse events were reported in patients receiving colchicine. Due to the lack of specific data, fluvoxamine should not be used as a preferred option for older adults with cancer. Regarding ivermectin, more data are needed to evaluate the use of this drug in the treatment of COVID-19 [[12]COVID-19 Treatment Guidelines Panel Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health, 2023https://www.covid19treatmentguidelines.nih.gov/Google Scholar]. Relative to the disease burden of COVID-19 among older adults, especially those with cancer, this population is underrepresented in most clinical trials of COVID-19 therapeutics, and evidence for making strong recommendations is lacking. In light of this limited evidence, the SIOG COVID-19 Working Group recommends following existing guidelines for other populations of older adults, and prioritizing treatments based on their availability, efficacy, and safety profile (Table 1). The following recommendations mainly concern outpatients.Table 1Recommendations of the SIOG COVID-19 working group on the use of COVID-19 drugs in older adults and in older patients with cancer.COVID-19 Therapeutics and RecommendationsSpecific Considerations in Older Adults with CancerRitonavir-boosted nirmatrelvir is recommended for the early treatment of non-hospitalised older adults with cancer affected by mild or moderate COVID-19 at high risk of disease progression who do not require supplemental oxygen, particularly dose who have not completed an approved vaccination schedule.•Monitoring of gastrointestinal side effects is required.•Pharmaceutical analysis of patient concomitant medications and potential drug-drug interactions, especially in polypharmacy, is requested before prescribing treatment. (https://www.covid19druginteractions.org/checker)•Particular attention is required in older adults with cancer because of the risk of interactions with immunosuppressants and of increasing concentrations of concomitant chemotherapeutic agents.•Adapted dosing is required in patients affected by moderate kidney disease. In severe disease category, evaluation of treatment risk/benefit is requested.•Particular attention is required in patients affected by liver diseases. Treatment is not recommended in severe hepatic impairment.•Treatment is available in oral form. An evaluation of cognitive function, social support, and ability to adhere to treatment is recommended before starting therapy in older adults with cancer.Remdesivir is recommended for the early treatment of non-hospitalised older adults with cancer with mild or moderate COVID-19 at high risk of disease progression who do not require supplemental oxygen or for whom minimal supplemental oxygen is required, particularly those who have not completed an approved vaccination schedule.Remdesivir might be co-prescribed with systemic corticosteroids for the treatment of hospitalised older adults with cancer and COVID-19 who require high-flow device supplemental oxygen or non-invasive ventilation.•Monitoring of gastrointestinal side effects is required.•Evaluation of liver function and prothrombin time tests is required before starting and during treatment.•Adapted dose is required in patients affected by moderate kidney disease. In severe disease category, evaluation of treatment risk/benefit is required.•The feasibility of administering parenteral medications in the outpatient setting must be considered. An evaluation of the patient's ability to obtain transportation and of social support is recommended.Treatment with corticosteroids is recommended for hospitalised older adults with cancer and COVID-19 who require supplemental oxygen, high-flow oxygen, non-invasive ventilation, or mechanical ventilation.•The use of corticosteroids in the older adults and in older patients with cancer may be associated with side effects such as delirium and falls. The risk/benefit decision must be evaluated for each individual patient, and evidence-based geriatric interventions should be implemented early.•Pharmaceutical analysis of patient's concomitant medications and potential drug-drug interactions, especially in polypharmacy, is required before prescribing treatment.•Close inpatient monitoring of potential side effects, especially in patients affected by geriatric syndromes, coexisting conditions, solid tumour and/or haematological malignancies, and polypharmacy.•Careful monitoring of secondary infections, opportunistic fungal infections, reactivation of latent infections, is necessary in older patients with cancer, particularly those who are receiving immunosuppressants.Monoclonal antibodies should not be the first option for the treatment of older adults with cancer and COVID-19, due to the lack of older-adult specific data and the low effectiveness against newer COVID-19 strains. Monoclonal antibodies could be utilized in cases where other more effective therapies are not available, particularly in those who have not completed an authorized vaccination schedule or who may not have an appropriate antibody response.Due to the lack of older adult specific data and the availability of other antiviral agents with improved results, monoclonal antibodies should not be a preferred option for older adults with cancer.Molnupiravir should not be the first option for the treatment of non-hospitalised older adults with cancer affected by mild or moderate COVID-19. This treatment could be considered in cases were alternative antiviral therapies are not accessible or clinically appropriate.Due to the lack of older adult specific data, the under-representation of patients with cancer in clinical trials, and the availability of other antiviral agents demonstrating better outcomes, molnupiravir should not be used as a preferred option for older adults with cancer.Tocilizumab should be considered in hospitalised older adults with cancer and COVID-19 who require supplemental oxygen, high-flow oxygen, non-invasive ventilation, or mechanical ventilation.Due to the lack of older adult specific data and the under-representation of patients with cancer in clinical trials, tocilizumab should not be the preferred treatment in older adults with cancer and should only be utilized in conjunction with other treatments.Although COVID-19 convalescent plasma is authorized for patients with COVID-19 affected by immunocompromising conditions or receiving immunosuppressive treatment, data regarding its effectiveness is scarce.Available data on effectiveness do not allow to make a recommendation regarding the use of convalescent plasma in older adults with cancer. 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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.