Management of Cancer in the Elderly

Medicine is the crossroad between social and clinical sciences. The evolving social landscape indicates the goals of clinical research; the achievements of clinical research, in turn, influence social evolution. For example, improved medical and hygienic conditions have decreased mortality, resulting in the aging of the population, which has led to an explosion of chronic diseases including cancer.[1,2] The development of geriatric oncology represents one of the earliest and most consistent medical responses to the aging of the population, perhaps because cancer is largely a disease of aging.[1,3]

From Bedside to Bench: The History of Geriatric Oncology

In retrospect, one may wonder why a special interest in cancer and aging had emerged only in the past 2 decades, given that the average life expectancy of the population had been progressively increasing since World War II. Two factors likely delayed the development of geriatric oncology: The first is the absence of effective treatment or prevention of most advanced cancers, irrespective of a person's age, until 30 years ago. The second involves the difficulty of defining the boundaries of adulthood and aging, and the reluctance of clinical scientists to engage in the exploration of these unknown territories.

Undoubtedly, the foundation of geriatric oncology was laid at a National Institute of Aging conference held in 1981. Convened by Drs. Rosemary Yancik and Jerome W Yates, the conference addressed the topic of cancer and aging, serving a twofold purpose: It highlighted the extent of the problem and it provided a common forum for geriatricians, gerontologists, and oncologists. This encounter catalyzed the clinical developments that justified the existence of geriatric oncology—the application of geriatric principles to the assessment of older cancer patients. For the first time, clinical scientists studying cancer treatment were able to formulate specific questions about cancer and aging: Is the patient going to live long enough to die of and suffer from cancer? Can the patient tolerate the complications of cancer treatment? In the principles of geriatric assessments, clinicians were provided the means to address these questions.

After the conference, several reviews of the literature indicated that older individuals were underrepresented in clinical trials, which led to the elimination of upper age limits as discriminatory in studies sponsored by the National Cancer Institute (NCI). At the same time, numerous clinical trials focusing on older individuals were conducted, especially in large cell lymphoma. These trials established that older individuals may benefit from chemotherapy to the same extent as younger individuals (as long as the chemotherapy is administered in an adequate dose intensity) and that older individuals were more vulnerable to the complications of cytotoxic chemotherapy, especially myelotoxicity, mucositis, and cardiotoxicity.[4-10] It also became clear that the prognosis for some neoplasms—including acute myelogenous leukemia (AML),[11] lymphoma,[12] breast cancer,[13] and ovarian cancer[1,3]—changes with aging, and the mechanisms of these changes were in part clarified.

Ensuing Conferences, Task Forces, and Initiatives

The need to organize the wealth of emerging information led to a number of international conferences with the combined sponsorship of the H. Lee Moffitt Cancer Center and Research Institute of Tampa, the Florida Exchange Center of Gerontology in Tampa, and the Istituto Nazionale Tumori of Genova, Italy. The attendees of these conferences became the original nucleus of the International Society of Geriatric Oncology (SIOG), founded in 2000 in New York and led by first president Dr. Paul Calabresi, a pioneer of medical oncology and one of the founders of the American Society of Clinical Oncology (ASCO). At almost the same time, a number of US clinicians and clinical scientists congregated as the Geriatric Oncology Consortium (GOC), the first cooperative group fully dedicated to the study of older cancer patients.[14]

Perhaps two initiatives have been the most consequential in promoting geriatric oncology: a retreat in Puerto Rico organized by the Hartford Foundation in 1997, which led to the financing of 10 training programs in geriatrics and oncology, and a combined conference of the NCI and National Institute on Aging (NIA) in 2002, attended by all the directors of the NCI-designated comprehensive cancer centers in the country, which led to the funding of eight multidisciplinary research programs in geriatric oncology and finally provided a legitimacy to this new discipline.

During the same period, the major cancer and geriatric organizations (American Association of Cancer Research, ASCO, American Geriatric Society) established task forces, special interest groups, and educational tracks in geriatric oncology, and the major cooperative oncology groups instituted subcommittees on cancer and aging.

One should not forget to mention simultaneous international initiatives. The European Organization for Research and Treatment of Cancer (EORTC) established a committee on cancer and aging; two cooperative groups in Italy (GROG and SIGERO) and one in France (Gerico) focused their activity on the study of older individuals, and most major European countries now have a representative group of geriatric oncologists.

Key Accomplishments

The notable achievements of these activities include the following:

• Determination of age as a risk factor for carcinogenesis.
• Determination of biologic differences in some malignancies occurring both in younger and older patients.
• Fine-tuning of life expectancy and treatment tolerance estimates based on function and comorbidity. Appreciation of the social issues (caregiver, transportation, nutritional, and emotional support) involved in the treatment of older persons with cancer.
• Feasibility and value of cancer prevention and early detection in older individuals.
• Feasibility of clinical trials accommodating the diversity of the older population.

The past 2 decades have established beyond doubt that age is a risk factor for cancer and that there are age-specific issues related to the prevention and management of cancer. These findings provide the basis for accommodating recent advances in both the biology of aging and the management of cancer, exemplified by the discovery that inflammatory cytokines represent biologic markers of aging,[15] the use of simple clinical tests such as those involved in the Cardiovascular Health Study (CHS),[16] the production of antidotes to chemotherapy-related toxicity, and most of all, the development of targeted antineoplastic therapy.

Managing Cancer in Older Patients

In the United States, 60% of all cancers and 80% of all cancer-related deaths affect the 12% of individuals aged 65 and older.[17] By the year 2030, 70% of all malignancies and 85% of all cancer-related deaths are expected to occur in this population. In the near future, older persons will likely represent the prototype of cancer patient. The remainder of this article will explore the differences between managing cancer in older and younger individuals and will provide a framework of reference for medical decisions in older people with cancer. We’ll address the following questions:

• Why does cancer become more common with aging?
• Are tumors different in older and younger patients?
• Who is the older patient?
• Is chemotherapy effective in older individuals? Why Does Cancer Become More Common With Aging?

The association between cancer and aging may be accounted for by three non-mutually exclusive explanations.

First, carcinogenesis is a time-consuming process whose final product cancer is more likely to become apparent late in life.

Second, aging cells show a number of molecular changes that mimic late-stage carcinogenesis and prime the cell to the action of late-stage carcinogens.[3,18] In other words, older individuals are more prone than younger individuals to develop cancer when exposed to the same dose of carcinogens.

Third, environmental bodily changes associated with aging may favor the development and the growth of cancer. These include immune senescence[19] and proliferative senescence.[20] Immune senescence may favor the growth of highly immunogenic tumors.[21] The loss of self-replicating ability by the stromal cells is associated with the production of tumor growth factors and metalloproteinase, which disrupt the tumor stroma and favor metastases.

The clinical implications of these findings include the possibility of targeting the molecular changes of aging as a form of cancer chemoprevention.