Aging and cancer

DEFINITION: The most significant risk factor associated with developing cancer is age, with 60 percent of all cancers occurring in people who are sixty-five and over. Mortality rates are also highest in this age group; older individuals typically have additional chronic medical conditions that enhance the risk for simultaneously occurring psychiatric morbidity. These complex and potentiating trends have created clinical challenges that threaten to overwhelm the health care system. Based on projections by the National Institute on Aging, 1 in 5 Americans will be over the age of sixty-five by 2050. Researchers and physicians are working to understand the influence of age on cancer detection, diagnosis, and treatment, with the goal of modifying infrastructure, practices, and the educational preparation for future healthcare providers.

Biology of aging and cancer: Based on population trends, research to illuminate the biology of aging and mechanisms that enhance cancer susceptibility is increasing. A more precise understanding of the age-related increase in cancer incidence is needed to develop primary cancer prevention strategies. This line of research has been designated as a priority by the National Cancer Institute. At present, three major hypotheses explain the association between cancer and age:

Hypothesis 1 holds that the link between aging and cancer is simply related to the duration of carcinogenesis. In other words, the high prevalence of cancer in older individuals simply reflects more prolonged exposure to carcinogens.

Hypothesis 2 proposes that age-related, progressive changes within the human organism may provide an increasingly favorable environment for the induction of new cancers and the growth of preexisting but latent cells. These mechanisms may be related to proliferative senescence, whereby aging cells lose their ability to undergo apoptosis (a form of cell death that leads to the sequential elimination of cells without releasing harmful substances into the body). When apoptosis does not work right, cells that should be eliminated become immortal, stimulating cancer-related mutations at the cellular level.

Hypothesis 3 combines aspects of the first two hypotheses and proposes that an accumulation of dysfunctional senescent cells characterizes the aging, cancer-prone human phenotype. These cells proliferate via synergistic, simultaneous physiologic processes that foster progressive accumulation of cancer-prone mutations, silencing of genes that previously functioned to prevent cancer-predisposing mutations from developing in response to carcinogens (failure of epigenetic gene silencing), and telomere dysfunction. (Telomeres are specialized structures at chromosome ends that regulate their replication and stability.) These changes are particularly relevant to the production of malignancies because they occur within the context of an aging microenvironment of surrounding tissues.

Cancer, aging, and psychiatric comorbidity: As cancer incidence rises due to increased longevity, those diagnosed often have one or more additional chronic medical conditions. Paradoxically, new treatment discoveries have extended survival for multiple medical illnesses but often within the context of troubling side effects and consequences that in turn have led to documented increases of psychiatric comorbidity, or the presence of two or more illnesses, typically mental illnesses. The incidence of psychiatric morbidity, or mental illness, is further enhanced as the burden of cancer care progressively shifts from the health care system to family caregivers. Family caregivers are often aging spouses with medical problems of their own or adult children with their own families, jobs, and responsibilities. When the role of providing complex cancer care for a loved one is added to their already stressful lives, risk for mental health issues is significantly enhanced.

The preceding trends are occurring within a system in which mental health services are only now being recognized as impactful and legitimate. Stigmas, limited knowledge regarding the nature and intensity of psychiatric symptoms associated with clinical need, and inconsistent or inadequate reimbursement mechanisms inhibit necessary care. The span and scope of research, professional education, and clinical services will need to improve as the population continues to age. Psychiatric symptoms are typically treated only when they emerge as disease states within an expensive, fragmented, specialty-oriented system. Reimbursement for psychiatric treatment can also be difficult to obtain, and paying out of pocket can be challenging for many. Limited solutions to these consequential problems potentiate untold human suffering, negative clinical outcomes, and high resource utilization.

Cancer screening in aging patients: Considerable uncertainty regarding the use of cancer screening procedures in the aging population is illustrated by the range of age cutoffs recommended by various guideline panels. It has been suggested that a comprehensive framework rather than specific age parameters should inform individual screening decisions in older cancer patients to address inconsistencies. Screening decisions should encompass estimates of life expectancy, risk of cancer death, documented screening outcomes, and a risk-benefit screening ratio. For example, harm may result from screening practices that detect and treat cancers that never would have become clinically significant. Because many cancer screening decisions in older adults cannot be answered solely by quantitative estimates of benefits and harms, consideration of predicted outcomes within the context of an individual’s values and preferences is an important aspect of informed screening decisions. Statistics from the American Cancer Society, the Centers for Disease Control and Prevention, and the National Cancer Institute reveal considerable underutilization of screening practices in the United States for certain types of cancer, such as colorectal and breast cancers. Having health insurance, a regular doctor, and a point of usual care all are associated with higher cancer screening rates and better preventive health care overall. When these supports are absent, cancer screening rates drop considerably.

Age-related differences in cancer treatment: Cancer treatments may produce different therapeutic and adverse responses based on patient age. For example, chemotherapy resistance and toxicity have been shown to vary by age, being more common and severe in older patients. Treatment toxicities may develop in old versus young recipients because of increased vulnerability of target organs and delayed renal excretion of treatment agents and metabolites. These problems should be managed with treatment modifications determined by kidney function and other relevant parameters of individual health status and treatment response. Aging cancer patients often do not receive adequate information to assist with or inform them of a definitive treatment plan. Understanding why these deficiencies exist is vital to reducing disparities in cancer mortality between young and old. Studies suggest that treatment uncertainty could be better addressed if elderly cancer patients were offered a choice from a group of definitive therapies. Treatment discussions should also address common concerns related to the costs and functional consequences of each treatment in relation to expected benefits. Current understanding of age-related differences in pharmacokinetics, drug interactions, adverse events, and treatment adherence is mostly limited, though studies have shown that adverse drug reactions (ADR) are more common in older patients and result in more frequent hospitalizations than in younger patients. Knowing this, a holistic, multidimensional treatment plan is necessary for older patients.

Palliative cancer care for aging patients: Despite ambitious research, treatment, and educational initiatives, the quality of palliative care provided to the elderly has historically been and remains inadequate. Research consistently demonstrates unnecessary suffering among elderly patients with advanced cancer. Their suffering is related to myriad issues, including uncontrolled physical symptoms, depression, and unaddressed existential concerns. Wide gaps in palliative care services targeted to elderly patients with cancer occur across a range of settings, including hospice, where the approach to palliative care has been largely insufficient.

Some studies report lower levels of psychological distress in elderly versus young cancer patients, which has been erroneously interpreted to mean that elders are better equipped to manage existential concerns because they are at a stage in life when death is expected. However, this data may more accurately reflect age-related differences in lack of exposure to prevention, screening, and treatment practices, the resultant cancer course, and symptom profiles. Results, therefore, indicate the need for ongoing research and education to unraveling the complex relationship between aging and cancer. Knowledge development and dissemination must be met with clinical initiatives as population, demographic, and clinical trends continue to outpace the availability of resources for elderly individuals with cancer.

Despite generally despairing research, some important understandings and practical adjustments have been made to aid the aging population in terms of medical care in general. For example, a study published in 2022 provided physicians with a comprehensive list of the difficulties of aging in the twenty-first century as well as possible treatment implementations. Research is ongoing, and care must be individualized due to comorbidity potential. Still, recognition of the challenges of aging, particularly when it comes to facing cancer and other terminal illnesses, demonstrates meaningful progress toward better care.

Bibliography

Behl, Christian. Cell Aging: Molecular Mechanism and Implications for Disease. Berlin: Springer, 2014. Print.

Bellizzi, Keith M., and Margot Gosney. Cancer and Aging Handbook: Research and Practice. Hoboken: Wiley, 2012. Print.

Campisi, Judith. "Aging, Cellular Senescence, and Cancer." Annual Review of Physiology 75 (2013): 685–705. Print.

Extermann, Martine. Cancer and Aging: From Bench to Clinics. New York: Basel, 2013. Print.

Hassett, M. J., et al. “Frequency and Cost of Chemotherapy-Related Serious Adverse Effects in a Population Sample of Women with Breast Cancer.” Journal of the National Cancer Institute 98.16 (2006): 1108–17.

Jung, S. Y., et al. "Comorbidity as a Mediator of Survival Disparity Between Younger and Older Women Diagnosed With Metastatic Breast Cancer." Hypertension 59 (2012): 205–11. Print.

Kumar, H., P. Soares, L. Balducci, and B. Djulbegovic. “Treatment Tolerance and Efficacy in Geriatric Oncology: A Systematic Review of Phase III Randomized Trials Conducted by Five National Cancer Institute-Sponsored Cooperative Groups.” Journal of Clinical Oncology 25.10 (2007): 1272–76.

Leitzmann, Michael F., and Sabine Rohrmann. "Risk Factors for the Onset of Prostatic Cancer: Age, Location, and Behavioral Correlates." Clin Epidemiol 4 (2012): 1–11. Print.

Lichtman, S. M., et al. “International Society of Geriatric Oncology Chemotherapy Taskforce: Evaluation of Chemotherapy in Older Patients an Analysis of the Medical Literature.” Journal of Clinical Oncology 25.14 (2007): 1832–43.

Montégut, L., et al. "Aging and Cancer." Molecular Cancer 23, Article 106 (2024). doi.org/10.1186/s12943-024-02020-z.

Muss, H. B. “Older Age: Not a Barrier to Cancer Treatment.” New England Journal of Medicine 345 (2001): 28–29.

Reynolds, Charles F., et al. “Mental Health Care for Older Adults: Recent Advances and New Directions in Clinical Practice and Research.” World Psychiatry: Official Journal of the World Psychiatric Association (WPA) 21.3 (2022): 336-363. doi:10.1002/wps.20996.

Talarico, Lilia, Gang Chen, and Richard Pazdur. “Enrollment of Elderly Patients in Clinical Trials for Cancer Drug Registration: A Seven-Year Experience by the U.S. Food and Drug Administration.” Journal of Clinical Oncology 22.22 (2004): 4626–31.

Trimble, E. L., and M. C. Christian. “Cancer Treatment and the Older Patient.” Clinical Cancer Research 12.7 (2006): 1956–7.

Yancik, R., et al. “Perspectives on Comorbidity and Cancer in Older Patients: Approaches to Expand the Knowledge Base.” Journal of Clinical Oncology 19 (2006): 1147–51.

Zazzara, Maria Beatrice, et al. “Adverse Drug Reactions in Older Adults: A Narrative Review of the Literature.” European Geriatric Medicine 12.3 (2021): 463-473. doi:10.1007/s41999-021-00481-9.