Gerontology & Geriatrics

Abstract

Despite the widespread belief that cancer in older adults follows a slower or more “benign” course, evidence demonstrates that aging-related biological changes often promote tumorigenesis and complicate progression. Elderly patients frequently present with advanced-stage malignancies, multimorbidity, and decreased physiological reserve, all of which influence therapeutic decision-making and outcomes.

Recent advances in targeted therapies, monoclonal antibodies, immune checkpoint inhibitors, and cancer vaccines have expanded options for geriatric populations. However, efficacy and tolerability must be balanced against age-specific toxicities and frailties. This review examines epidemiology, pathophysiology, tumor evolution, clinical outcomes, and the impact of novel biotherapies in oncogeriatric care, proposing future strategies for personalized, multidisciplinary managemen.^2–6

Key words: oncogeriatric care, older adults, Aging and Cancer, mitochondrial dysfunction, tumor control, geriatric cohorts, chemotherapy

Definition of “geronte” and pathophysiology of aging and cancer

A “geronte” is conventionally defined as an individual aged 65 years or older; however, chronological age does not always align with biological age. Biological aging reflects cumulative molecular and cellular damage, manifesting as genomic instability, telomere attrition, epigenetic alterations, and mitochondrial dysfunction.

Cellular senescence acts as a double-edged sword: while it halts proliferation of damaged cells, the senescence-associated secretory phenotype (SASP) releases proinflammatory cytokines, growth factors, and proteases that can foster a pro-tumorigenic microenvironment. Chronic low-grade inflammation—“inflammaging”—enhances DNA damage, angiogenesis, and immune suppression, increasing cancer risk.

Immunosenescence, characterized by thymic involution, diminished naïve T-cell output, and altered innate immune function, reduces tumor surveillance and may impair immunotherapy responses in the elderly. Hormonal shifts, metabolic dysregulation, and reduced DNA repair capacity further promote oncogenesis and influence treatment toxicity.

Predominance of cancer in the elderly and common tumor types

Older adults account for ≈ 60 % of new cancer diagnoses and nearly 70 % of cancer-related deaths worldwide. Incidence rates rise steeply after age 65, with variations by tumor type, sex, and región (Table 1).

Tumor type	Proportion of cases (%)	Key clinical notes
Prostate	25	Often indolent; high prevalence of low-risk lesions
Breast	20	Hormone receptor–positive subtypes dominate
Colorectal	15	Frequently diagnosed at advanced stages
Lung	12	High mortality; smoking-related in most patients
NH Lymphoma	8	Aggressive subtypes more common in elderly

Table 1 Major tumors in elderly patients with prevalence and clinical remarks

Evolution of tumors in older adults

Contrary to the benign-evolution myth, tumors in geriatric patients can exhibit aggressive biology. Delayed diagnosis—due to atypical symptom presentation, under-screening, or ageism—often leads to advanced-stage disease at presentation.

Certain subtypes, such as triple-negative breast cancer and small-cell lung cancer, may progress rapidly and show poor differentiation in older adults. Comorbidities can mask early tumor symptoms or contraindicate standard therapies, complicating management.

Reduced physiological reserve and frailty limit tolerance to cytotoxic regimens, often necessitating dose reductions or delays that adversely affect tumor control.

Impact of novel biological therapies

Tyrosine kinase inhibitors (TKIs)

Imatinib in chronic myeloid leukemia shows survival benefits with manageable toxicity in patients ≥ 65 years.
Osimertinib in EGFR-mutant NSCLC prolongs PFS but demands monitoring for cardiopulmonary AEs.

Monoclonal antibodies

Trastuzumab improves outcomes in HER2+ breast cancer; cardiotoxicity risk rises with age and heart disease.
Rituximab in DLBCL boosts response rates but increases infection and infusion reactions in geriatric cohorts.

Immune checkpoint inhibitors

PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, atezolizumab) yield durable responses in melanoma, lung, and urothelial cancers.^7–15
Immune-related AEs occur at similar rates across ages but may have larger impact in frail patients.

Cancer vaccines

Sipuleucel-T extends survival in metastatic prostate cancer with minimal severe toxicity.

Experimental melanoma and HPV-targeted vaccines show promise; efficacy in immunosenescent hosts under study (Table 2).

Therapy Class	Representative Agent	Efficacy Endpoint	Age-Specific Toxicities
TKIs	Imatinib; Osimertinib	OS; PFS	Cardiotoxicity; interstitial lung disease
Monoclonal antibodies	Trastuzumab; Rituximab	RR; DFS	Cardiomyopathy; infusion reactions
Checkpoint inhibitors	Nivolumab; Atezolizumab	Durable responses; OS	Immune-related AEs
Therapeutic vaccines	Sipuleucel-T	OS	Cytokine release; injection site pain

Table 2 Efficacy and geriatric-specific toxicities of major biotherapies

Outcomes: cure, survival, stability, and treatment failure

Curative: Early-stage breast/prostate cancer treated surgically with adjuvant therapy achieves high cure rates in fit elders.
Increased survival: TKIs and ICIs in advanced lung/melanoma can double median OS vs. chemotherapy.
Stable disease: Indolent lymphomas may follow watchful waiting, preserving quality of life.
Chronic Management: Metastatic colorectal cancer managed with maintenance biologics can become a chronic disease model.
Treatment failure: AML in frail elders with adverse cytogenetics often requires palliative focus due to low response rates.

Approved and ongoing protocols

Approved regimens

Atezolizumab + chemotherapy in frontline NSCLC.
Daratumumab monotherapy for frail elderly multiple myeloma patients.
Trastuzumab deruxtecan in HER2-low breast cancer, including older subgroups.

Ongoing trials

IMpower010: adjuvant atezolizumab in resected NSCLC, with geriatric subanalysis.
GAP70+: geriatric assessment–guided chemotherapy for DLBCL in patients ≥ 70 years.
EORTC Elderly Cancer Trials: pan-European studies of immunotherapy/targeted agents in older adults (Table 3).

Trial/regimen	Indication	Population focus	Key endpoint
Atezolizumab + Chemo	Stage IV NSCLC	All ages; geriatric sub	OS; PFS
Daratumumab	Multiple myeloma in frail elders	≥ 75 years	ORR; safety
Trastuzumab deruxtecan	HER2-low breast cancer	Older adults included	ORR; durability
IMpower010	Adjuvant NSCLC	Geriatric subanalysis	DFS
GAP70+	DLBCL in patients ≥ 70 years	Geriatric assessment	Treatment tolerance

Table 3 Selected geriatric-focused oncology protocols

Future perspectives

Personalized geriatric oncology: integrate genomics with frailty indices and CGA.
AI-driven decision support to predict toxicity and outcomes in elders.
Immune rejuvenation: combine senolytics (e.g., IL-7) with immunotherapies.
Age-adapted therapeutic vaccines with senolytic adjuvants.
Trial design reforms: mandate elder inclusion and geriatric endpoints.^16–30

Conclusion

Cancer in the elderly is neither inherently benign nor uniformly aggressive. It reflects a complex interplay of aging biology, comorbidity, and tumor heterogeneity. Optimizing outcomes requires an interdisciplinary approach blending oncologic innovation with geriatric principles, personalized risk–benefit assessment, and shared decision-making. Future research must prioritize inclusion of older adults in clinical trials and develop aging-adapted therapeutic strategies.