The Hippocratic principle of not harming the patient has remained up to this day an undisputed dogma in medicine. It reminds the physician of the possible detrimental, if not lethal, outcome of the treatment he prescribes and implicitly enforces good medical practice, although the true impact will unlikely be known. Oncology is one subspecialty of Medicine where this dilemma-ie, the pros and cons of treatment-is continuously put to the test, as the physician must decide on treatment for an often life-threatening illness while taking into account individual factors such as the patient’s will, performance status, available standard treatment options, and possible experimental approaches.
The Hippocratic principle of not harming the patient has remained up to this day an undisputed dogma in medicine. It reminds the physician of the possible detrimental, if not lethal, outcome of the treatment he prescribes and implicitly enforces good medical practice, although the true impact will unlikely be known. Oncology is one subspecialty of Medicine where this dilemma-ie, the pros and cons of treatment-is continuously put to the test, as the physician must decide on treatment for an often life-threatening illness while taking into account individual factors such as the patient’s will, performance status, available standard treatment options, and possible experimental approaches.
Moreover, physician-related factors such as experience, communication skills, spiritual convictions, and intuition undoubtedly play a role in this decision-making process, and by their very nature are virtually impossible to measure. This decision-making process is further contextualized in the current public debate on “the war on cancer,” which raises the stakes for both patients and caregivers as well as their oncologists. Finally, several studies have described the existence of other patient-related factors-such as ethnic background, affluence, education, and age-that can have an impact on treatment approach and outcome.[1,2]
Oncologic care for the elderly patient is particularly important as our population ages. The tenor of many studies analyzing treatment in the elderly reveal an overall diminished use of chemotherapy,[3] despite a significant benefit for those who do receive therapy with equal[4] or at least manageable toxicity.[5] These data suggest that elderly patients may be a vulnerable population, from which valuable and sometimes lifesaving therapy is withheld.
In fact, the decision-making process is much more complicated. For example, while it would be alarming if a 40-year-old patient belonging to an ethnic minority with stage II colon cancer and insufficiently sampled lymph nodes did not receive adjuvant chemotherapy, it might be appropriate for an 85-year-old patient with stage III colon cancer to not receive adjuvant fluorouracil (5-FU) and leucovorin, for a variety of patient-specific reasons. Such reasons could include undocumented functional limitations, particular psychosocial factors, or merely respect for the patient’s will.
A recent French report of a cross-sectional study of 105 elderly cancer patients asked the provocative question of whether “a geriatric oncology consultation modified the cancer treatment plan for elderly patients?”[6] Of the 105 enrolled patients, 51 were believed to be eligible for chemotherapy based on an initial medical oncology evaluation. Following subsequent geriatric oncology assessment, treatment was modified in six cases and suspended in 7 cases. Thus, although the focus has been on undertreatment of the elderly, these data suggest that physicians may be just as guilty of overtreating some elderly patients.
Extrapolation of data from the limited elderly population enrolled in clinical trials may also be problematic. For example, an elderly patient who presents for treatment at a major cancer center and is willing to participate in a clinical trial likely is in a different patient category than a comparable elderly patient who elected not to pursue formal oncologic evaluation at a center of excellence despite its availability and proximity.
Furthermore, given the increased toxicity but apparently equal treatment-related mortality in elderly cancer patients, it would be of interest to evaluate the impact of oncologic treatment on nononcologic chronic medical care. This is illustrated by a recent retrospective study that showed a significant association between diabetes mellitus-a typical disease in elderly patients-and increased tumor recurrence in colorectal cancer, underscoring the potential importance of adequate management of nononcologic disease states and calling for further prospective study.[7]
Finally, the significance of age is likely to be different when discussing curative vs metastatic disease. In a study focusing on cancer care practices in late-stage cancer patients, a North American group prospectively studied aspects of care, communication, pain management, and acute care utilization in two patient groups of about 150 patients, one middle-aged (40–60 years) and one older (60–80 years).[8] As expected, comorbidities were more prevalent in the older group, but there was no statistically significant difference in daily activities, social support, spiritual well-being, or referral to the emergency room. Interestingly, anxiety and depression were less prevalent in older patients. Surprisingly, although physicians overestimated the desired aggressiveness of treatment approaches, they correctly recognized the wish for a less aggressive approach in the older group.
These results underscore the fact that the patient’s somatic eligibility does not necessarily make him psychologically eligible, and that the physician’s decision stands at the end of a complex decision process. Clearly, evaluation of these findings in different settings will be necessary to draw definite conclusions.
In his review, Ades addresses the use of adjuvant therapy for locally advanced colon cancer in the elderly.[9] After giving an overview of the literature noting the known treatment disparities, he discusses barriers to treating elderly patients. He then raises the key question, “Who should receive chemotherapy?” The sobering answer to this simple question is twofold: (1) We are not sure whether we can extrapolate from elderly patients who have enrolled on prospective clinical studies to elderly patients in the community setting-very likely not, and (2) There is no validated, simple assessment tool in this context that would be superior to history and physical exam.
In the ensuing discussion on treatment options, capecitabine (Xeloda) was suggested as a treatment choice for more frail elderly patients. In our experience, this option would not be our first treatment choice, given the potential liver toxicity and renal impairment prevalent in the elderly. More importantly, these patients are likely to be exposed to numerous medications, which may raise the issue of patient compliance. Finally, it is important to realize that our clinical decisions may be made more easily in the future, based on molecular markers of therapeutic benefit. For example, the role of microsatellite instability and 5-FU sensitivity[10] could have profound implications for the use of adjuvant therapy in colorectal cancer, particularly in the elderly population, where our apparent fear of doing harm is much more pointed.
In aging societies, the differences between medical oncology and geriatric oncology will be increasingly blurred. Geriatric oncology may indeed benefit from more subtle tools of measuring clinical performance and, in particular, clinical trials performed in the community setting. We would echo the underlying sentiment of Dr. Ades’ review, which states that we need increasing participation of elderly patients in clinical trials so that we may have more data applicable to the growing elderly population. In this way, we may rest assured in our promise made with the Hippocratic Oath: “I will come for the benefit of the sick, remaining free of all intentional injustice.”
Financial Disclosure:The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
1. Herndon JE 2nd, Kornblith AB, Holland JC, et al: Patient education level as a predictor of survival in lung cancer clinical trials. J Clin Oncol 26:4116-4123, 2008.
2. Griggs JJ, Culakova E, Sorbero ME, et al: Social and racial differences in selection of breast cancer adjuvant chemotherapy regimens. J Clin Oncol 25:2522-2527, 2007.
3. Hutchins LF, Unger JM, Crowley JJ, et al: Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 341:2061-2067, 1999.
4. Sargent DJ, Goldberg RM, Jacobson SD, et al: A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med 345:1091-1097, 2001.
5. Hurria A, Hurria A, Zuckerman E, et al: A prospective, longitudinal study of the functional status and quality of life of older patients with breast cancer receiving adjuvant chemotherapy. J Am Geriatr Soc 54:1119-1124, 2006.
6. Girre V, Falcou MC, Gisselbrecht M, et al: Does a geriatric oncology consultation modify the cancer treatment plan for elderly patients? J Gerontol A Biol Sci Med Sci 63:724-730, 2008.
7. Meyerhardt JA, Catalano PJ, Haller DG, et al: Impact of diabetes mellitus on outcomes in patients with colon cancer. J Clin Oncol 21:433-440, 2003.
8. Rose JH, O’Toole EE, Einstadter D, et al: Patient age, well-being, perspectives, and care practices in the early treatment phase for late-stage cancer. J Gerontol A Biol Sci Med Sci 63:960-968, 2008.
9. Ades S: Adjuvant chemotherapy for colon cancer in the elderly: Moving from evidence to practice. Oncology (Williston Park) 23:162-167, 2009.
10. Ribic CM, Sargent DJ, Moore MJ, et al: Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349:247-257, 2003.
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