With advances in early detection and cancer treatments, numbers of cancer survivors are rising [
Studies among cancer survivors have shown that the consequences of cancer treatment are numerous and depend on the type of cancer and treatment characteristics [
Therefore, we aim to examine from a generic GP perspective the occurrence of pre-existing (prevalent) and subsequent (incident) chronic diseases among cancer patients aged over 60, in comparison with non-cancer patients of the same age, sex, and practice in a large retrospective primary care-based cohort study.
This study was carried out within the context of the Registration Network Family Practices (RegistratieNet Huisartspraktijken, RNH) [
All relevant health problems—current as well as past—are recorded on a problem list. A health problem is defined as “anything that has required, does or may require health care management and has affected or could significantly affect a persons’ physical or emotional well-being.” Health problems are coded using the International Classification of Primary Care (ICPC), following the criteria of the International Classification of Health Problems in Primary Care (ICHPPC-2-defined) for diagnoses [
The design of this study is a retrospective cohort, including all patients who were members of the RNH database between 1 January 1998 and 31 December 2010, and aged 60 years and over. Patients with a previous cancer history (diagnosed before January 1998) were excluded. Neoplasms of the skin were excluded as well, as due to the ICPC coding we were unable to distinguish between benign and malign neoplasma of the skin. Each cancer patient, diagnosed between January 1998 and December 2010 (
Only ICPC codes that correspond to severe or chronic diseases were selected and categorized as previously described by Knottnerus et al. [
Pre-existing chronic diseases were defined as all diagnoses established before the cancer diagnosis or reference date. Subsequent chronic diseases were defined as all diagnoses established after the cancer diagnosis or reference date. All diagnoses that were established within a 3-month period before removal from the RNH database were excluded, as these might reflect the palliative phase, in which the disease pattern might be different. Pre-existing chronic diseases were assessed by calculating the lifetime prevalence (per 1000 persons) cross-sectionally at the time of the cancer diagnosis or the reference date and were compared between cancer patients and their matched non-cancer patients using logistic regression analyses, adjusted for age and sex. Prevalence and odds ratios were calculated for all cancer patients together, and for breast, prostate, and colorectal cancer patients separately. The occurrence of subsequent chronic diseases was longitudinally assessed by calculating the incidence per 1000 person-years at risk, excluding patients with a previous diagnosis of the disease. Hazard ratios and their 95% confidence intervals (95% CIs) were calculated using multivariate Cox regression analyses, adjusted for age, sex, and presence of cardiovascular diseases, respiratory diseases, or diabetes at baseline (please see Table 1 in the Supplementary Material on the journal website for the precise cardiovascular and respiratory diseases which were included). Incidence and hazard ratios were computed for all cancer patients in comparison with their age, sex, and practice-matched controls and for all breast, prostate, and colorectal cancer patients separately, in comparison with their respective matched controls. The proportional hazards assumption was tested using Schoenfeld residuals. For venous thrombosis (K93+K94), limited mental function (P28), lipid disorders (T93), and other endocrine/metabolic/nutritional diseases (T99), proportional hazards assumption was violated. This was resolved by splitting the survival time.
Analyses were processed with the STATA statistical software package (StataCorp. 2009. Stata: Release 11. Statistical Software. College Station, TX: StataCorp LP). Throughout all analyses, a two-sided
In the thirteen-year study period (1998–2010), there were 3,835 patients with a first diagnosis of cancer who were 60 years or older at the time of their cancer diagnosis (see Table
Characteristics of older cancer patients and non-cancer patients at time of cancer diagnosis or reference date.
Cancer patients | Non-cancer patients | |||
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( |
( |
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Mean | (SD) | Mean | (SD) | |
Age (years) | ||||
Men | 71.95 | (7.35) | 70.87 | (7.13) |
Women | 73.22 | (8.42) | 72.90 | (8.27) |
Survival time (years)1 | ||||
Men | 2.92 | (3.06) | 3.87 | (3.15) |
Women | 3.32 | (3.39) | 4.17 | (3.27) |
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(%) |
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(%) | |
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Sex | ||||
Men | 2163 | (56) | 6179 | (52) |
Women | 1672 | (44) | 5794 | (48) |
Number of chronic diseases at baseline2 | ||||
0 | 846 | (22) | 2617 | (22) |
1 | 908 | (24) | 2916 | (24) |
2 | 752 | (20) | 2288 | (19) |
3 | 534 | (14) | 1682 | (14) |
≥4 | 795 | (21) | 2470 | (21) |
Five most common tumour sites | ||||
Colon/rectum | 675 | (18) | ||
Prostate | 573 | (15) | ||
Bronchus/lung | 550 | (14) | ||
Breast | 493 | (13) | ||
Bladder | 218 | (7) |
1Survival time: time from date of diagnosis or reference date until death or end of follow-up.
2Number of chronic diseases excluding cancer.
The prevalence of pre-existing chronic diseases was high; 78% of all cancer patients had at least one disease additional to the malignancy at time of cancer diagnosis (see Table
The most common pre-existing chronic diseases were the same for cancer patients and non-cancer patients. These were diabetes, lipid disorders, ischemic heart disease, myocardial infarction, and COPD. COPD was significantly more prevalent among cancer patients compared to non-cancer patients (OR 1.21, 95% CI 1.06–1.37). Furthermore, dementia (OR 0.48, 95% CI 0.36–0.64) and personality disorder (OR 0.53, 95% CI 0.33–0.84) were significantly less prevalent in cancer patients compared to non-cancer patients (see Table
Pre-existing chronic diseases in men and women.
Cancer patients | Non-cancer patients |
|
OR2 | (95% CI) | |||
---|---|---|---|---|---|---|---|
|
Prev1 |
|
Prev1 | ||||
Ten most common pre-existing diseases in cancer patients | |||||||
Diabetes mellitus | 586 | 152.80 | 1864 | 155.68 | 0.48 | 0.96 | (0.87–1.07) |
Lipid disorders | 508 | 132.46 | 1559 | 130.21 | 0.60 | 1.03 | (0.92–1.15) |
Ischemic heart disease with angina | 459 | 119.69 | 1326 | 110.75 | 0.73 | 1.02 | (0.91–1.14) |
Myocardial infarction | 405 | 105.61 | 1162 | 97.05 | 0.86 | 1.01 | (0.90–1.14) |
Ischemic heart disease without angina | 393 | 102.48 | 1151 | 96.13 | 0.98 | 1.00 | (0.88–1.13) |
Chronic obstructive pulmonary disease | 382 | 99.61 | 944 | 78.84 |
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Osteoarthrosis knee | 312 | 81.36 | 1054 | 88.03 | 0.17 | 0.91 | (0.80–1.04) |
Benign prostatic hypertrophy | 297 | 77.44 | 740 | 61.81 | 0.33 | 1.08 | (0.93–1.25) |
Back syndrome without radiating pain | 281 | 73.27 | 888 | 74.17 | 0.70 | 0.97 | (0.85–1.12) |
Osteoarthrosis hip | 272 | 70.93 | 885 | 73.92 | 0.47 | 0.95 | (0.82–1.09) |
Significant differences between cancer and non-cancer patients3 | |||||||
Dementia | 60 | 15.65 | 344 | 28.73 |
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Personality disorder | 21 | 5.48 | 127 | 10.61 |
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1Prev: lifetime prevalence per 1000 persons.
2OR: odds ratio adjusted for sex and age.
3Please see Table 2 in the Supplementary Material on the journal website for all other diseases.
When stratified by cancer type (data not shown), we found no differences within breast cancer patients (
Just as for pre-existing chronic diseases, risk of subsequent chronic diseases was similar among cancer survivors and non-cancer patients. The most common incident diseases in cancer patients were diabetes, venous thrombosis, osteoporosis, COPD, and heart failure. In non-cancer patients these were diabetes, benign prostatic hypertrophy, stroke, dementia, and COPD. In cancer survivors, the incidence of subsequent venous thrombosis was significantly higher compared to non-cancer patients during the first two years of survival (HR 4.20, 95% CI 2.74–6.44). Thereafter, this difference was no longer statistically significant (see Table
Subsequent chronic diseases in men and women.
Cancer survivors | Non-cancer patients |
|
HR2 | (95% CI) | ||||
---|---|---|---|---|---|---|---|---|
|
Inc1 |
|
Inc1 | |||||
Ten most common subsequent diseases in cancer patients | ||||||||
Diabetes mellitus† | 133 | 13.46 | 589 | 14.79 | 0.31 | 0.91 | 0.75 | 1.09 |
Venous thrombosis | ||||||||
Baseline—2 years | 45 | 9.27 | 40 | 2.11 |
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2 years—end of follow-up† | 20 | 3.10 | 58 | 2.11 | 0.15 | 1.45 | 0.87 | 2.41 |
Osteoporosis | 99 | 8.93 | 354 | 7.90 | 0.15 | 1.18 | 0.94 | 1.47 |
Chronic obstructive pulmonary disease | 95 | 8.81 | 378 | 8.56 | 0.97 | 1.00 | 0.80 | 1.25 |
Heart failure |
94 | 8.31 | 380 | 8.28 | 0.80 | 0.97 | 0.77 | 1.22 |
Stroke/cerebrovascular accident | 92 | 8.27 | 435 | 9.81 | 0.08 | 0.82 | 0.65 | 1.03 |
Dementia |
83 | 7.16 | 417 | 8.93 | 0.07 | 0.81 | 0.64 | 1.02 |
Ischemic heart disease without angina |
71 | 6.76 | 308 | 7.17 | 0.50 | 0.92 | 0.71 | 1.19 |
Ischemic heart disease with angina | 65 | 6.29 | 294 | 7.03 | 0.36 | 0.88 | 0.67 | 1.15 |
Osteoarthrosis hip | 66 | 6.05 | 268 | 6.11 | 0.95 | 1.01 | 0.77 | 1.32 |
Significant differences between cancer and non-cancer patients3 | ||||||||
Hypertension with organ damage | 41 | 3.67 | 250 | 5.55 |
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Lipid disorders | ||||||||
Baseline—2 years | 16 | 3.66 | 129 | 7.62 |
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2 years—end of follow-up | 31 | 5.27 | 171 | 7.08 | 0.16 | 0.76 | 0.52 | 1.11 |
Benign prostatic hypertrophy | 27 | 5.05 | 223 | 10.87 |
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1Inc: incidence per 1000 person years at risk.
2HR: hazard ratio adjusted for sex, age, cardiovascular diseases, respiratory diseases, and diabetes.
3Please see Table 3 in the Supplementary Material on the journal website for all other diseases.
†Adjusted for age as time-varying coefficient.
When stratified by cancer type (data not shown), we found no differences for breast cancer patients compared to their respective controls. In prostate cancer patients, the incidence of venous thrombosis (HR 7.10, 95% CI 2.25–22.40) was significantly higher compared to non-cancer patients, and the incidence of benign prostatic hypertrophy was significantly lower (HR 0.17, 95% CI 0.06–0.48). In colorectal cancer patients, the incidence of venous thrombosis (HR 2.43, 95% CI 1.22–4.81) was significantly higher compared to non-cancer patients.
The number of chronic diseases additional to cancer proved to be high and is probably associated with high age in the first place. Both prevalence at diagnosis and incidence, however, tend to be largely similar in older cancer and non-cancer patients. The latter is consistent with recent other studies [
At time of cancer diagnosis, 78% of all cancer patients had at least one disease additional to the malignancy. This highlights the enormous burden of comorbidity in older cancer patients. However, from the perspective of a GP, it is also important that cancer and non-cancer patients were similar with respect to prevalence of chronic diseases. Still, there were some exceptions. In cancer patients, the prevalence of COPD was significantly higher compared to non-cancer patients. When stratified by cancer type, this difference remained significant, only within the group of lung cancer patients (OR 2.88, 95% CI 2.20–3.78) (data not shown). This is in line with previous reports [
We found a significant lower prevalence of dementia in cancer patients compared to non-cancer patients. This has been previously reported and is also known as inverse cancer comorbidity [
After cancer diagnosis we showed similar to pre-existing diseases that the most common new diseases in cancer survivors were also the most common ones in non-cancer survivors. In line, a recent and similar study by Khan et al. showed that long-term cancer survivors are a population at risk but that the absolute increase in disease burden is small [
For venous thrombosis we showed a significantly increased hazard ratio during the first two years of survival. This is in line with previous studies on consequences of cancer treatment [
Although it is not the scope of this study, we were unable to confirm a higher incidence of osteoporosis (due to hormone replacement therapy), hypothyroidism (due to radiotherapy), and heart failure (due to radiotherapy and chemotherapy) in specific groups of cancer survivors compared to non-cancer survivors [
Besides the increased risk for venous thrombosis, we found a lower incidence of hypertension with organ damage and lipid disorders (only during the first two years after cancer diagnosis) in cancer patients compared to non-cancer patients. In the first period after diagnosis, a decrease in food intake due to side effects of treatment and emotional factors, and later increased surveillance, and attention for healthy lifestyle might explain this lower incidence. A recent study showed, however, no obvious difference in lifestyle factors among short- and long-term cancer survivors compared to controls [
An important strength of this study was that the comprehensive registration of diseases was based on GPs’ daily practice and that this data was analysed in a retrospective cohort design.
A shortcoming of this study was that information on cancer treatment and smoking status was incomplete. Therefore we were unable to analyse the risk of comorbidity according to treatment type and to consider smoking as a confounder. This is an important drawback because late effects in cancer survivors are treatment specific [
Another limitation was that some associations may have occurred by chance (Type I error) due to multiple comparisons. The chance of Type I errors can be diminished by applying a Bonferroni correction. However, this would dramatically increase the chance for Type II errors. According to Rothman it is not necessary to correct for multiple comparisons as the underlying premise of research is that nature follows regular laws that may be studied through observation [
Because of the similarities between older cancer and non-cancer patients and the GPs’ expertise in dealing with multimorbidity, we believe that GPs could play an important role in aftercare for cancer survivors. However, the participation of primary care in cancer care is still in its infancy. Hence, further research is needed. Future studies could focus on the coordination of aftercare between primary and secondary care, the development of guidelines for cancer patients with comorbidity, and the use of patient goals in the determination of care planning in patients with complex care needs.
The authors declared no conflict of interests.
This work was supported by the Working Group on “Primary Care for Cancer Patients during Follow-up” of the Signalling Committee Cancer of the Dutch Cancer Society. The authors would like to thank Dr. Carla Truyers for her statistical advice and all GPs from the Registration Network Family Practices for their ongoing work. This work was financially supported by and reported to the Dutch Cancer Society. The author had complete authority over the design, execution, analysis and interpretation of the study.