J Cancer Surviv (2016) 10:514–523 DOI 10.1007/s11764-015-0496-1
Lost workdays in uterine cervical cancer survivors compared to the general population: impact of treatment and relapse Åsa H. Everhov 1,6 & Sara Ekberg 2 & Angelica Lindén Hirschberg 3 & Karin Bergmark 4 & Angelique Flöter Rådestad 3 & Ingrid Glimelius 2,5 & Karin E. Smedby 2
Received: 15 May 2015 / Accepted: 2 November 2015 / Published online: 12 November 2015 # Springer Science+Business Media New York 2015
Electronic supplementary material The online version of this article (doi:10.1007/s11764-015-0496-1) contains supplementary material, which is available to authorized users.
Results Cervical cancer patients had more lost workdays annually than comparators up to 8 years following diagnosis. Relapse-free patients had more lost workdays than comparators up to 4 years. Risk of disability pension during follow-up was increased among the relapse-free patients treated with hysterectomy (HR 1.8 [95 % confidence interval (CI) 1.1– 2.8]), hysterectomy plus chemotherapy and/or radiotherapy (HR 2.5 [95 % CI 1.2–5.4]), or chemotherapy and/or radiotherapy alone (HR 3.0 [95 % CI 1.3–6.8]), compared with the population. Women treated with fertility-sparing surgery did not have more lost workdays than the population beyond the first year and were not at increased risk of disability pension. Conclusion We observed a long-standing increased risk of lost workdays among cervical cancer patients, overall, as well as among relapse-free patients. Implications for Cancer Survivors Extensive but not limited treatment was associated with increased risk of lost workdays, possibly reflecting an association between treatment side effects and work ability.
* Åsa H. Everhov
[email protected]
Keywords Uterine cervical cancer . Sick leave . Disability pension . Hysterectomy . Chemotherapy . Radiotherapy
Abstract Purpose The aim of the present study was to examine the risk of lost workdays due to sick leave and disability pension by treatment modality and relapse in a population-based cohort of cervical cancer survivors versus matched comparators. Methods We identified 1971 cervical cancer patients aged ≤60 years (median 42) at diagnosis in Sweden 2003–2009 and 9254 population comparators. Information on sociodemographic and clinical characteristics, sick leave, and disability pension was retrieved from nationwide prospective registers. Differences in the annual mean number of lost workdays were calculated by linear regression, and hazard ratios (HRs) of disability pension were calculated by Cox regression analysis, with follow-up through September 2013.
1
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
2
Unit of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
3
Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
4
Department of Oncology, Sahlgrenska Academy, Gothenburg, Sweden
5
Department of Immunology, Genetics and Pathology, Unit of Oncology, Uppsala University, Uppsala, Sweden
6
Department of Surgery, South Hospital, SE 118 61, Stockholm, Sweden
Introduction Uterine cervical cancer affects women at a young age; about half of women are diagnosed before 50 years of age. The prognosis is excellent for early-stage disease, with a reported 5-year survival rate of 98 %, but poor for metastatic disease (5-year survival of 9 %) [1]. Treatment may include surgery, radiotherapy, and chemotherapy, often in combination. Studies of long-term survivors of cervical cancer have reported physical and psychological sequelae that may persist up to 15 years after
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diagnosis, particularly in those who have received radiotherapy [2, 3]. Patient-reported distressful symptoms after treatment include impaired anorectal function, urinary symptoms, lymphedema, anxiety, and depression [4, 5], all of which may affect work ability. Studies of cancer patients in general have reported returnto-work rates of 24–94 % [6, 7], with higher proportions returning to work with increasing time since cancer diagnosis. Individual and work-related factors, as well as treatment, are thought to influence work loss in cancer survivors [6–11]. Because treatments vary by cancer type and because of the relatively young age distribution and good prognosis of cervical cancer, the results for other cancer patients may not be generalizable to cervical cancer survivors. Few previous studies have investigated to what extent increased work loss among cancer patients can be attributed to cancer progression or relapse and if increased risks persist among relapse-free patients [12]. In the absence of relapse, sick leave and/or disability pension may be seen as proxies for severe side effects of the cancer treatment, which potentially could be prevented or alleviated. Assessment of work loss in Sweden is facilitated by nationwide registers that provide high-quality data on sickness compensation, sociodemographic variables, and health-care use. The Swedish social insurance is tax funded and provides compensation to all residents, including to those who are unemployed. Sick leave and disability pension can be part-time or full-time and are granted in case of reduced work ability caused by disease or injury. The aim of the present study was to examine work loss among working-age women (18–60 years) diagnosed and treated for cervical cancer compared with a matched cohort from the general population and to assess work loss among all patients as well as among relapse-free patients compared with the population.
Methods
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The Longitudinal Integrated Database for Health Insurance and Labour Market Studies [17] contains data on socioeconomic factors and labor force participation (unemployment) for all Swedish citizens by calendar year since 1994. The Micro Data for Analysis of the Social Insurance Database contains nationwide administrative data on lost workdays [12]. The exact dates of sick leave are registered for episodes >14 days/year. New episodes occurring within 5 days of a previous sick leave are registered from the first day. Disability pension is recorded from the first day. The Total Population Register [18] records dates of emigration and death of all residents in Sweden and is continuously updated. Exposure/treatment Treatment of cervical cancer is based on the International Federation of Gynecology and Obstetrics (FIGO) staging system, which classifies the tumor according to its size and extension into and beyond the pelvis. Treatment guidelines in Sweden varied slightly by region during the study period, but generally, patients diagnosed at early stages were treated with radical hysterectomy and pelvic lymphadenectomy or, in selected cases, with simple hysterectomy or fertility-sparing trachelectomy or cervical resection (conization) alone. Postoperative radiotherapy with concomitant chemotherapy (chemoradiation) was used in case of adverse prognostic factors, such as lymph node metastases or poor resection margins. Locally advanced-stage disease was treated with primary chemoradiation, and metastatic disease was treated with chemotherapy. All women aged 18–60 years at diagnosis of first incident cervical cancer, from 1 January 2003 to 31 December 2009, were identified in the Swedish Cancer Register, with no exclusion criteria. We used codes from the National Patient Register from 6 months before the date of diagnosis up to 1 year after to classify the primary cancer treatment of each individual (Supplementary Table S1). The women were divided into four groups based on the cancer treatment received, as follows:
Sources of data The Swedish Cancer Register [13], founded in 1958, contains information on date of diagnosis, tumor site, and histology according to the International Classification of Diseases (ICD), with an estimated population coverage of >96 % [14]. The Swedish National Patient Register [15] contains information on dates of hospital care (nationwide from 1987) and specialized outpatient visits (from 2001) with ICD codes for diagnoses and surgical procedure codes according to the Swedish version of the Classification of Surgical Procedures (NOMESKO), with a population coverage exceeding 99 % [16].
1. Fertility-sparing surgery: cervical resection or trachelectomy, no chemotherapy/radiotherapy 2. Hysterectomy, no chemotherapy/radiotherapy 3. Any surgery plus chemotherapy/radiotherapy 4. Chemotherapy and/or radiotherapy alone, no surgery The occurrence of relapse or metastatic disease was determined from the patient register either through the existence of an ICD code for metastasis at any time point or through the combination of coding for radiotherapy and/or chemotherapy plus cervical cancer >1 year after primary diagnosis (without diagnosis of another primary cancer).
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General population Comparators were randomly selected from the total population register and individually matched up to a ratio of 5 to 1 to the cervical cancer patients by age, region of residence, and highest attained education level before diagnosis/match date. The comparators were not allowed to have a history of cervical cancer at the time of diagnosis of the matched case and were censored in case of cervical cancer during follow-up. For 1718 patients (87 %), five comparators were available and 78 patients (4 %) were matched to four, 52 patients (3 %) were matched to three, 73 patients (4 %) were matched to two, and 50 patients (3 %) were matched to one comparator each. Outcome Sick leave compensation during the first year amounts to 80 % of an individual’s previous salary, with an upper limit of 7.5 times the Swedish national insurance base amount. During the second year, the compensation is 75 % of the previous salary up to a maximum of 550 days. The first day of sick leave is not compensated, and days 2–14 are paid by the employer. Disability pension can also be part-time or full-time and is granted if work capacity is permanently reduced by at least 25 %. Disability pension is compensated from day 1, and the compensation is based partially on a guaranteed amount (2.35 times the Swedish national insurance base amount in 2012) and partially on previous salary. Periods of sick leave can occur during the time not covered by disability pension. An individual can receive disability pension until 65 years of age, at which point it is replaced by retirement benefit. Retirement takes place between 61 and 67 years of age, usually at 65 years. The Swedish Social Insurance Agency bases its decisions on medical certificates provided by the treating physicians, and the agency also has its own physician advisors for consultation. For all study participants, the exact dates of sick leave and disability pension were retrieved from the social insurance database. The net number of lost workdays due to sick leave and/or disability pension per year of follow-up was calculated by multiplying the number of days with the proportion of compensation received, as previously described [19]. Thus, for instance, 4 days with 50 % compensation is equal to two lost workdays. Individuals with no episodes longer than 14 days of sick leave absence per year (and no disability pension) were assigned zero days, since episodes shorter than 14 days are not registered in the social insurance agency database. The occurrence of disability pension was also assessed separately during follow-up. Covariates From the Longitudinal Integrated Database for Health Insurance and Labour Market Studies, we retrieved data on
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education level and family situation at diagnosis/match year as well as unemployment 1–2 years before. Family situation was considered more informative than marital status in the Swedish setting, where many couples live together without being married, even though they may have children. From the social insurance database, we retrieved information on sick leave and disability pension 1–2 years before diagnosis. The year immediately before diagnosis was not chosen due to potential associations with early cancer symptoms. Follow-up Patients and comparators were followed from the date of diagnosis/match date up to age 65 years (retirement), migration, death, or the end of the study period (30 September 2013), whichever came first. Therefore, as is typical in cohort studies with a long enrollment period, participants diagnosed in the more recent years of the study period had a shorter follow-up than those included during the earlier years. In the analysis of relapse-free patients versus comparators, subjects were followed until 3 months before first relapse, retirement, migration, death, or the end of the study period. The 3-month lag period was used in this analysis to avoid sick leave and disability pension related to early symptoms of cancer relapse. Ethics The regional ethics board in Stockholm approved this study (Dnr 2007/1335-31/4, 2010/1624-32). Statistics Differences in the distribution of demographic characteristics between patients and comparators were tested with the χ2 test. The mean number of lost workdays per year during follow-up was assessed, and differences between patients and comparators were computed for each year separately by multivariable linear regression. Ninety-five percent confidence intervals (CIs) were estimated by nonparametric bootstrapping to avoid distributional assumptions. The linear regression models were adjusted for the matching variables: age (12 years) as well as family situation (single with children, single without children, couple with children, and couple without children), previous sick leave (yes/no), previous disability pension (yes/no), and previous unemployment (yes/ no). These covariates were chosen a priori based on previous knowledge of possible confounding factors. Relative risks of disability pension were calculated using the Cox regression model and presented as hazard ratios (HRs) with 95 % CI,
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with stratification of baseline hazards by the matching variables and adjustment for family situation, previous sick leave, and previous unemployment. Patients with disability pension before diagnosis were excluded from the analysis of risk of disability pension during follow-up. The proportional hazard assumption was tested with Schoenfeld residuals and was not violated. Associations of sociodemographic factors with risk of disability pension during follow-up among the cervical cancer patients only were examined with Cox regression using the same adjustment variables as listed above. Effect modification by previous sick leave and cervical cancer treatment of the occurrence of disability pension during follow-up was examined using an interaction term in the Cox regression model. All statistical tests were two-sided, and p
