Commentary (Balducci): Ovarian Cancer in Elderly Women

With the population aging, cancer in older persons is becoming an increasingly common problem.[1] The benefit of antineoplastic treatment may be diminished and the risk enhanced by aging, due to a progressive reduction in life expectancy and in the functional reserve of multiple organ systems.[ 2] To establish the most suitable course of action in individual cases, the practitioner needs to be able to address the following questions: Is the cancer going to compromise the survival or the quality of life of the patient? Is the patient able to tolerate the potential risk of cancer treatment? These questions are particularly compelling when treatment may effect a cure or a substantial prolongation of survival. Lambrou and Bristow review the management of ovarian cancer-a disease that is responsive to multiple forms of chemotherapy and to aggressive surgical debulking.

Physiologic vs Chronologic Age

The authors essentially examine the patterns of care in younger vs older women and the risk of treatment complications. Based on a number of recent reviews, they report that:

• Older women and especially women over age 80 are less likely to receive adequate surgical management[ 3,4] or multimodality treatment for ovarian cancer.[5]

• According to an extensive Italian review of chemotherapy for ovarian cancer in individuals over age 70, the risk of grade 3/4 myelotoxicity was high (40%), but only a small percentage of patients (6.5%) required discontinuation of treatment.[6]

• Women over age 70 are underrepresented in clinical trials of ovarian cancer treatment.[5]

Clearly, these data suggest that older individuals may be denied the full extent of modern treatment for ovarian cancer, because age is widely thought to be associated with a poorer outcome and an unacceptable rate of treatment-related complications. Thus, it is difficult to argue with the authors' conclusion that age itself should not be a barrier to appropriate treatment or to inclusion into clinical trials, and that treatment plans should be based on the physiologic rather than chronologic age of the patient. These well-founded recommendations need to be complemented by two additional considerations.

Biologic Interaction

First, the authors conclude that the poorer prognosis of older ovarian cancer patients is due to inadequate treatment or late diagnosis. Although inadequate treatment certainly may contribute to a poorer prognosis, one should not dismiss the possibility that age by itself, through poorly defined mechanisms, may contribute to a more aggressive or less responsive disease. In fact, a recent review of the Gynecologic Oncology Group experience suggests that this may be the case,[7] and this finding is hardly new. In a number of malignancies, including acute myelogenous leukemia, non- Hodgkin's lymphoma, and breast cancer, the patient's age appears to be an independent prognostic factor.[8]

This possibility has both theoretical and practical implications. The biology of the tumor may be influenced by two factors: the intrinsic biology of the tumor cell and the ability of the tumor host to support neoplastic growth. The identification of age-related factors that may alter the tumor biology may signify the discovery of new therapeutic targets. For example, the poorer prognosis of acute myelogenous leukemia patients aged 60 and older appears to be related to the increased prevalence of multidrug resistance, which may be pharmacologically modulated.

Practical Assessment

Second, the authors fall short of recommending a practical approach to the assessment of older persons. The comprehensive geriatric assessment described in their Table 2 is time-consuming and impractical for use in the whole geriatric population. Furthermore, it is not clear how this assessment may lead to an estimate of life expectancy and treatment tolerance.

Numerous screening instruments are available to help the physician decide which older individuals need a full geriatric assessment. These include simple questionnaires, such as the one recommended by the National Comprehensive Cancer Network guidelines,[9] the Vulnerable Elders Survey (VES-13), and evaluations of physical function such as the Get Up and Go test.[8]

Functional status, assessed as the ability to perform activities of daily living and instrumental activities of daily living, is an independent prognostic factor for the risk of chemotherapy- induced myelotoxicity.[8] A simple estimate of life expectancy may be obtained with the comprehensive geriatric assessment.[10] Some laboratory tests, including serum concentrations of interleukin-6 and D-dimer, may predict the risk of functional dependence and mortality.[11]

Conclusions

Lambrou and Bristow make an important contribution to the study of ovarian cancer in older women by highlighting the fact that these women may be undertreated and unnecessarily excluded from clinical trials. Their review would be complemented by a more thorough discussion of the biologic interaction of cancer and age and a practical approach to the assessment of older patients.

Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

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