Cancer trials still leave older adults at the margins
Older adults aged 65 years and older make up the majority of people diagnosed with cancer, yet they remain underrepresented across the research pathway. The result is familiar to every oncology service: treatment decisions are often built on evidence generated from younger, fitter populations, even though age-related biology, competing comorbidity, polypharmacy, frailty, and different goals of care can alter both benefit and harm at the bedside.
This manifesto argues that underrepresentation is no longer an acceptable structural feature of cancer research. It calls on funders, regulators, researchers, and journals to make systematic inclusion of older adults the norm across studies spanning prevention, diagnosis, treatment, survivorship, and end-of-life care.
The central message is blunt. Cancer evidence cannot be considered complete when the group most likely to develop the disease is still treated as an afterthought in trial design.
Why exclusion distorts oncology evidence
The age gap in cancer research is not merely a recruitment inconvenience. It shapes the clinical meaning of nearly every endpoint used in oncology studies. Older adults are more likely to have multimorbidity, reduced physiologic reserve, functional vulnerability, and higher background rates of non-cancer mortality, all of which can influence whether a therapy improves survival, preserves independence, or simply adds toxicity without extending meaningful life.
When older adults are filtered out through restrictive eligibility criteria, the trial population becomes increasingly unlike the real-world population seen in clinic. The consequence is a mismatch between the efficacy signal measured in a study and the therapeutic decision made at the bedside. A regimen that appears tolerable in a selected younger cohort may produce a different toxicity profile, a different discontinuation rate, or a different net value when applied to a patient in their late seventies or eighties.
Evidence gaps also affect prevention research. Modifiable risk factors do not lose relevance with age, and older adults still stand to benefit from preventive strategies, risk reduction, and earlier detection when those approaches are appropriate to their life expectancy and baseline health. Excluding them from these studies leaves public health planning and clinical counseling with an incomplete map of risk and benefit.
Endpoints must reflect geriatric oncology realities
A trial framework centered only on tumor response or overall survival can miss the outcomes that matter most to older adults. Function, independence, cognition, symptom burden, treatment burden, and the ability to remain at home often carry as much weight as radiographic response. In older patients, a few months of disease control may mean very little if it comes with falls, delirium, prolonged hospitalization, or irreversible loss of mobility.
The authors point toward pragmatic strategies for older-adult trial design and endpoints, aligning with the broader direction of geriatric oncology methodology. In practice, this means testing research questions in ways that capture vulnerability rather than excluding it, and measuring outcomes that connect directly to daily life. A narrow focus on tumor-centric metrics can overstate the value of treatment in a population where maintaining autonomy may be the most important therapeutic goal.
One sentence captures the clinical problem: survival alone is not enough when treatment costs a patient their independence.
Enrollment barriers start long before consent
Older-adult underrepresentation does not arise from a single failure point. It begins with protocol design, continues through site-level screening, and is reinforced by assumptions from clinicians, patients, and investigators. Previous work cited in the manifesto has documented barriers to participation in older women with breast cancer and decision-making patterns in breast cancer trial enrollment, while later reviews have summarized persistent obstacles and proposed interventions.
Those barriers are familiar in oncology clinics. Some trials use exclusion criteria that remove patients on the basis of age-linked conditions rather than trial-relevant risk. Others require frequent visits or complex procedures that are poorly matched to functional limitations, transportation challenges, or caregiving responsibilities. Even when older adults meet criteria, they may be less likely to be offered participation because clinicians anticipate lower tolerance or lower willingness, sometimes without direct evidence from the individual patient in front of them.
The result is self-reinforcing. When older adults are rarely enrolled, investigators lack data to guide age-specific selection, and the next protocol is written with the same blind spots.
Prevention to end of life demands a continuous evidence chain
The manifesto does not limit its argument to drug trials or late-phase oncology studies. It spans the full cancer continuum, from prevention to end-of-life care. That framing matters because older adults interact with oncology services at every stage: they undergo screening decisions, diagnostic workups, surgery, systemic therapy, supportive care, palliative interventions, and transitions to hospice or comfort-focused treatment.
Each step requires data that are relevant to age. Preventive studies need to establish whether interventions remain worthwhile in older populations with different baseline risks and life expectancy. Diagnostic research should account for presentation patterns and workup delays. Treatment studies must evaluate dosing, toxicity, function, and patient priorities. End-of-life care research has to address symptom control, communication, and the trade-offs between disease-directed therapy and comfort.
A research agenda that stops at tumor shrinkage leaves the most vulnerable phase of care unanswered. Older adults are not a special subgroup on the margins of oncology. They are the core population.
A research culture shift, not a token recruitment fix
The call here is broader than adding older participants to existing studies as an afterthought. It requires a change in how oncology research is funded, regulated, reviewed, and published. Sponsors and funders need to support trial designs that are intentionally inclusive. Regulators need to accept endpoints and eligibility structures that reflect geriatric complexity. Journals need to treat older-adult representation as a core quality issue rather than a descriptive footnote.
There is also a practical scientific reason for this shift. Age is not a nuisance variable to be controlled away; it is a biologically and clinically meaningful determinant of treatment effect, toxicity, recovery, and patient-defined benefit. If cancer research is meant to inform real practice, then the evidence base has to resemble real practice.
The manifesto closes the gap between demographic reality and research design with unusual directness. Cancer incidence rises with age, yet the oldest patients remain the least visible in the literature that guides their care. Until that changes, oncology will keep extrapolating from an evidence base that does not fully belong to the people it is meant to serve.