1 Comprehensive Cancer Center South, Eindhoven; 2 Department of Internal Medicine, Oosterschelde Hospital, Goes; 3 Department of Internal Medicine, Maxima Medical Center, Veldhoven; 4 Department of Surgery, Maxima Medical Center, Eindhoven; 5 Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands
* Correspondence to: Mr V. E. P. P. Lemmens, IKZ, PO Box 231, 5600 AE Eindhoven, the Netherlands. Tel: +31-40-297-1616; Fax: +31-40-297-1610; Email: research{at}ikz.nl
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Abstract |
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Patients and methods:: All resected patients aged 6579 with stage III colon carcinoma, diagnosed between 1995 and 2001 in the Comprehensive Cancer Centre South registry area in the Netherlands were included (n=577). We examined determinants of receipt of adjuvant chemotherapy and their relation to survival.
Results:: The proportion of elderly patients receiving adjuvant chemotherapy increased from 19% in 1995 to 50% in 2001, but a large inter-hospital variation remained. In a multivariable analysis, females [odds ratio (OR) 0.5, P=0.006], patients with comorbidity [OR 0.5, P=0.005], and patients with a low socioeconomic status [OR 0.5, P=0.02] received less adjuvant therapy. Between 1995 and 2001 survival of elderly patients improved (hazard ratio 0.8, P=0.04).
Conclusion:: Although an increasing proportion of elderly patients with colon cancer are treated with adjuvant chemotherapy, many elderly patients still do not receive this treatment. As expected, receipt of adjuvant treatment decreased in the presence of comorbidity, but the clinical rationale for undertreatment of women and patients with low socioeconomic status is not clear.
Key words: adjuvant chemotherapy, cancer registry, colon cancer, elderly, survival
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Introduction |
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Since the mid 1990s, administration of adjuvant chemotherapy has been recommended in Dutch treatment guidelines [10]. In order to evaluate adherence to these guidelines for elderly patients with stage III colon cancer in the south of the Netherlands, we determined the proportion of patients receiving adjuvant chemotherapy. We assessed factors associated with receipt of chemotherapy, and to what extent these factors were related to survival.
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Patients and methods |
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Colon tumours were defined as C18.0C18.7 according to ICD-O-3. All patients aged 65 years or older diagnosed in the period 19952001 who had been operated on for stage III colon adenocarcinoma were selected from the database of the Eindhoven Cancer Registry (n=772). Only one patient older than 80 years received adjuvant chemotherapy. Therefore, we restricted our analyses to patients aged 6579 (n=577).
Trained registrars recorded the following patient characteristics: age at time of diagnosis, gender and serious comorbidity, the latter according to a slightly modified version of the Charlson classification (Table 1) [12]. Socioeconomic status (SES) of the patient was defined at neighbourhood level (based on postal code of residence area, 17 households on average) combining mean household income (in 1998) and mean value of the house/apartment (in 2000), derived from individual fiscal data made available at an aggregated level. Postal codes were assigned to three SES categories: low (1st3rd decile), intermediate (4th7th decile) and high (8th10th decile). Postal codes of institutions, such as nursing homes, were assigned to a separate category and were excluded from the logistic regression and survival analysis (33 patients). These excluded patients had a median age of 76.5 years, compared to a median age of 72 years for the total study population.
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Adjuvant chemotherapy (yes versus no; information on type and dose was not available), year of diagnosis (periods 19951998 and 19992001) and hospital of surgery were also recorded.
Vital status of all patients on 1 January 2004 was assessed through the Central Bureau for Genealogy, the institution where all deceased persons in The Netherlands are registered. Patients who had moved abroad (estimation: 0.2%) were possibly wrongly considered as being alive. At the end of follow-up (January 2004) 219 patients (38%) were still alive.
Analyses
Differences in adjuvant treatment between subgroups were tested by means of a 2 test (gender and tumour grade) or a CochranArmitage trend test (number of comorbid conditions, SES, stage group and year of diagnosis).
The independent influence of the patient and tumour characteristics on administration of adjuvant chemotherapy was evaluated by means of a logistic regression analysis (LOGISTIC procedure). A log rank test was used to compare 5-year survival proportions (LIFETEST procedure). Multivariable proportional hazards regression analysis (PHREG procedure) was used to discriminate independent risk factors for death. Since the numbers of patients treated with adjuvant chemotherapy were very low in some hospitals, we did not incorporate hospital of treatment in the logistic regression or survival analysis.
For all analyses the SAS/STAT® statistical software (SAS system 8.2, SAS Institute, Cary, NC) was used.
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Results |
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Discussion |
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The lower probability of receiving adjuvant treatment for elderly patients with colon cancer had already been shown previously [68
, 14
17
]. The reason why these patients are less likely to receive adjuvant treatment is multifactorial. In addition to the presence of concomitant diseases, more patient refusal among the elderly, the absence of supportive caregivers, a decrease in the patients' general condition and cognitive abilities and especially frailty could result in lower chemotherapy rates [9
, 18
20
]. Most of the available studies present evidence of tolerance and efficacy of chemotherapy among both selected and unselected elderly colon cancer patients [6
, 7
, 9
, 21
], thus counteracting the persisting ageism in colon cancer care. However, there are probably still uncertainties about the riskbenefit ratio of aggressive treatment, as is suggested by the observed inter-hospital variation.
The reported higher intolerance among females for 5-FU-based chemotherapy due to a lower level of dihydropyrimidine dehydrogenase, together with a higher refusal rate among elderly women, may partly be responsible for the finding that they were less likely to receive adjuvant treatment than men [8, 22
, 23
]. However, higher intolerance among females may have been overcome in most cases by alternative 5-FU doses or schedules, and the magnitude of the observed effect in our study seems too large to be explained by a higher refusal rate among elderly women.
In view of the good access to health care facilities and the Dutch health insurance system with a coverage of 99% [24
], our finding that patients with a low SES are two times less likely to be treated with adjuvant chemotherapy than patients with a high SES is remarkable. SES has previously been reported to influence adjuvant treatment of colorectal cancer patients [8
, 9
], although the impact was much smaller than that observed in the present study. A possible explanation of the effect of SES on adjuvant treatment may be that patients with a higher SES have a more active behaviour, in terms of seeking more aggressive treatment or making and keeping appointments with specialists. SES could be associated with education as well, which might influence acceptance rates. Patients with a higher SES also have a more positive self-rated health [25
, 26
], which in turn may affect treatment decision-making [27
]. The institutionalised patients who were excluded from the analyses received adjuvant chemotherapy as often as the included patients with the same age and gender. As we do not expect that the average SES of nursing home residents differs significantly from the average SES of other patients, we consider the possible impact of excluding the 33 institutionalised patients to be relatively small.
Patients presenting with comorbidity received adjuvant chemotherapy less often, in agreement with previous retrospective studies [8, 9
, 16
, 17
]. Few prospective studies have reported the effect of comorbidity on the safety and efficacy of chemotherapy and, as a result, few guidelines exist for patients with specific comorbid conditions.
We do not have a clear explanation for our finding that patients with stage IIIB disease (T34, N1) received adjuvant chemotherapy more often than patients with stage IIIC disease (any T, N2); perhaps these elderly patients with stage IIIC disease were considered to have a less favourable riskbenefit ratio regarding adjuvant treatment.
As reported in several other population-based studies, adjuvant chemotherapy had a marked independent prognostic impact [17, 21
]. Due to the population-based nature of our data, we do not know the extent to which this positive prognostic impact was caused by selection of the fitter patients for adjuvant chemotherapy, or by other factors associated with treatment allocation besides those controlled for in our analysis (e.g. performance status). Very likely, frail elderly less often receive adjuvant chemotherapy. The worse prognosis of these frail patients has probably biased the prognostic impact of adjuvant chemotherapy in the current study. This is supported by the fact that the survival difference between treated and non-treated patients was larger than found in randomised clinical trials [6
].
A possible explanation for the improved survival between 19951998 and 19992001 may be more accurate staging due to a more thorough search for positive lymph nodes by the pathologist, promoted by the presence of effective adjuvant treatment for lymph node-positive cancers [28]. Moreover, staging may also have been improved by a better identification of distant metastases.
Our finding that patients aged 70 or older had a better prognosis than patients aged 6569 years is odd, but in line with the results of a large single-hospital study where patients with stage III colon cancer aged 65 years or older had an overall 5-year survival of 74%, compared to 54% for patients younger than 65 years [29]. A possible explanation for this finding might be a selection of the more robust individuals living long enough to develop colon cancer, or a potential decrease in aggressiveness of the tumour with rising age.
Data extraction from the patient's medical record is regarded as the most complete source of information on the patient's past and current health status [30]. Yet, performance status could not be included in our study, since this is not mentioned in the medical records routinely. Performance score and comorbidity are both predictive factors of treatment and survival for cancer patients, independent of each other [31
, 32
]. However, performance status is often amenable to the malignant disease and its treatment, in contrast to comorbidity.
Although the proportion of elderly patients with colon cancer receiving adjuvant chemotherapy is increasing, many elderly patients still do not receive or accept this treatment. Development of age-based guidelines and increased awareness among both physicians and patients through education is important to prevent undertreatment of (subgroups of) elderly patients who are eligible for chemotherapy. With decision making becoming more individualised with the rise of age, the use of a comprehensive geriatric assessment may be helpful in choosing the most adequate treatment for these patients.
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Acknowledgements |
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Received for publication November 2, 2004. Revision received December 29, 2004. Accepted for publication December 30, 2004.
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