Critical Reviews in Oncology/Hematology 58 (2006) 60–67
Impact of comorbidity on treatment and prognosis of prostate cancer patients: A population-based study S. Houterman a,∗ , M.L.G. Janssen-Heijnen a , A.J.M. Hendrikx b , H.A. van den Berg c , J.W.W. Coebergh a,d a
Eindhoven Cancer Registry, Comprehensive Cancer Centre South, P.O. Box 231, 5600 AE Eindhoven, The Netherlands b Department of Urology, Catharina Hospital, Eindhoven, The Netherlands c Department of Radiotherapy, Catharina Hospital, Eindhoven, The Netherlands d Department of Public Health, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands Accepted 9 August 2005
Contents 1. 2. 3.
4.
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Prevalence of comorbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.1. Treatment and age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.2. Treatment and comorbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Survival . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.1. Survival and age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.2. Survival and comorbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.3. Multivariable analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Comorbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. Survival . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Biography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
61 61 62 62 62 62 63 63 63 63 63 63 63 65 66 66 66 66 66 67
Abstract This study investigates the independent influence of serious comorbidity and age on treatment and survival of prostate cancer patients diagnosed between 1995 and 2002 in the southern part of the Netherlands. Eight percent of patients < 60 years had two or more concomitant diseases versus 27% of those aged 80 years or older. The number of patients undergoing radical prostatectomy or curative radiotherapy decreased significantly with increasing age. The proportion of patients aged 60–69 years undergoing prostatectomy decreased significantly from 32% of patients without comorbidity to 17% of patients with two or more comorbid conditions and from 8% to 3%, respectively, of those aged 70–79 years. The risk of dying was significantly higher for patients with two or more comorbid conditions compared to patients without comorbidity. Serious comorbidity led to less aggressive treatment and negatively affected the prognosis of prostate cancer patients aged 60–79 years. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Comorbidity; Treatment; Prognosis; Prostate cancer ∗
Corresponding author. Tel.: +31 40 2971616; fax: +31 40 2971610. E-mail address:
[email protected] (S. Houterman).
1040-8428/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.critrevonc.2005.08.003
S. Houterman et al. / Critical Reviews in Oncology/Hematology 58 (2006) 60–67
1. Introduction Since 1997 prostate cancer has been the most common tumour among males in the Netherlands [1]. Due to the introduction of PSA testing in the early 1990s, prostate cancer is increasingly being detected at an earlier stage. More patients have become eligible for radical prostatectomy, curative radiotherapy and lately also brachytherapy [2,3]. Due to aging of the population, the number of patients with a comorbid condition will increase, which may influence treatment decisions [4–6]. However, in a population-based study carried out in the southern part of the Netherlands between 1993 and 1996, treatment decisions were determined largely by the patient’s age and the experience of the urologist instead of the patient’s comorbid conditions [7]. Little data is available on treatment of older patients and patients with comorbidity because they are often excluded from clinical trials. A previous study carried out in the registration area of the Eindhoven Cancer Registry showed that comorbidity negatively influenced 3-year survival of patients younger than 75 years [8]. In this population-based study we investigated the influence of comorbidity on treatment and 5-year survival of prostate cancer patients. In addition to the previous studies carried out in our registration area [7,8], we now also include patients aged 75 years or older, more recent incidence years (1995–2002) with better registration of comorbidity and a longer follow-up.
2. Methods The Eindhoven Cancer Registry (ECR) collects data on all patients with newly diagnosed cancer in the Dutch province of North Brabant and in the northern part of the adjacent province of Limburg. The registry now serves a population of 2.3 million inhabitants. The area offers good access to specialised medical care in 10 general hospitals and two large radiotherapy institutes. Information on diagnosis, staging and treatment was extracted from the medical records by trained registrars. Since 1993 serious comorbidity with an impact on prognosis has also been recorded for all patients according to a slightly modified version of the index developed by Charlson et al. [9]. Only comorbid conditions with potential negative prognostic effect were included (Table 1). The data was extracted from previous admissions, letters from and to other specialists, medical history, and preoperative screening. Comorbidity was defined as diseases that were present at the time of cancer diagnosis. All prostate cancer patients newly diagnosed between 1995 and 2002 (N = 6340) were included in this study. Clinical stage was recorded according to the TNM classification in use [10]. Since pathological stage is only available after radical prostatectomy and treatment decisions are based on clinical stage, only the latter was used (except for lymph node involvement and distant metastasis which was based also on pathological stage, because this can still influence
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Table 1 Classification of co-morbidity, according to an adapted list of Charlson et al. [9] Heart diseases (myocardial infarction, heart failure, angina pectoris) Peripheral vascular diseases (intermittent claudication, abdominal aneurysm, peripheral arterial disease) Cerebrovascular diseases (cerebrovascular accident, hemiplegia) Other malignancies (except basal cell skin carcinoma) Chronic obstructive pulmonary diseases (COPD) Hypertension Diabetes mellitus Other: Dementia Tuberculosis and other chronic infections Connective tissue diseases (Besnier Boeck’s disease (sarcoidosis), systemic lupus erythematosis (SLE), Wegener’s granulomatosis) Rheumatoid arthritis (only severe) Kidney diseases (chronic glomerulonephritis, chronic pyelonephritis) Bowel diseases (Crohn’s disease, colitis ulcerosa) Liver diseases (cirrhosis, hepatitis)
treatment decisions). The clinical tumour classification was simplified as T1, T2, T3, T4 or as ‘unknown’ (Tx) if insufficient information was available for accurate staging. In case of lymph node involvement (N1) or distant metastases (M1), stage was defined as metastasized. Histological grading was recorded according to the TNM classification of malignant tumours [10]. Patients with undifferentiated tumours (
