Risk Stratification: Who Should Receive Chemotherapy?
Elderly patients enrolled in studies make up a highly select fit subset that is not necessarily representative of the larger elderly population for whom treatment decisions are being made in the community. The challenge lies in the application of clinical trial evidence to individual elderly patients, taking into account important considerations including physical frailty, other comorbid illness, risk of complications from treatment, and degree of support available to a given individual.
Of key importance is the presence of comorbid conditions that can impact upon a patient’s physiologic reserve to withstand systemic treatments and can act as a competing cause of mortality.[33] Older patients are more likely to be coping with other major physical illnesses at the time of cancer diagnosis, and the presence of comorbid conditions may be associated with more advanced stage at diagnosis.[34] Although intuitively related, comorbidity burden and functional status assessments were found to provide independent information when administered as part of a battery of diagnostic instruments to elderly cancer patients.[35] The ideal prognostic index will thus factor in comorbidity information and functional status, and would be able to predict mortality risk as well as the impact of cancer treatment.
Screening Tools
In recent years, numerous publications have addressed the applicability and impact of a comprehensive geriatric assessment (CGA) for elderly cancer patients.[36,37] The key domains of any screening tool covered in the CGA include evaluation of an older individual’s functional status, comorbid medical conditions, cognition, nutritional status, psychological state, and a medication review. The multidisciplinary CGA is followed by development of a coordinated intervention plan to optimize the health and autonomy of the individual, and should also aid in the appropriate cancer treatment selection. The CGA can be used to optimize functional status and improve quality of life in cancer patients, but its impact on survival is less clear.[37] Such assessment is resource-intensive and may be necessary only for frail elderly patients with significant physical illnesses.
Shorter instruments that can effectively select patients for more comprehensive assessment exist and are being explored as screening options.[38,39] A core component of any instrument will be a functional evaluation including assessment of activities of daily living (ADL) and instrumental ADL, which can provide important predictive information regarding morbidity and mortality.[40]
A recent life-table analysis of older individuals with stage III colon cancer revealed a life expectancy of approximately 5 years for a 67-year-old patient with three or more chronic comorbid illnesses. This compares to 3 years for the corresponding 81 year old (Table 1).[41] With four-fifths of disease recurrences occurring within the first 3 years after definitive treatment,[42] all but the oldest of elderly patients with multiple comorbid illnesses may be considered as potentially benefitting from adjuvant chemotherapy following surgery. Overall survival in the metastatic setting ranges from 6 months without therapy to beyond 24 months with optimal treatment,[43] providing a strong rationale for consideration of adjuvant treatment and discussion with most patients.
