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Changes in health-related quality of life in older women after diagnosis with gynecologic cancer
YGYNO-977736; No. of pages: 7; 4C: Gynecologic Oncology xxx (xxxx) xxx
Contents lists available at ScienceDirect
Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
Changes in health-related quality of life in older women after diagnosis with gynecologic cancer Amy K. Klapheke a,b,⁎, Theresa H.M. Keegan b,c, Rachel Ruskin d, Rosemary D. Cress a,b a
Public Health Institute, Cancer Registry of Greater California, Sacramento, CA, United States of America Department of Public Health Sciences, University of California Davis, Davis, CA, United States of America Division of Hematology and Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, CA, United States of America d Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California Davis Comprehensive Cancer Center, Sacramento, CA, United States of America b c
H I G H L I G H T S • • • • •
Older women experience significant declines in physical and mental health after diagnosis with gynecologic cancer. Deficits in physical and mental well-being were significantly worse in women with cancer than in cancer-free women. The most notable changes were in role limitations due to emotional problems, general health, and physical functioning. Impairment was greatest in women with advanced disease and women within one year of diagnosis. Interventions are needed to better support and prepare older women for changes in health after cancer diagnosis.
a r t i c l e
i n f o
Article history: Received 27 August 2019 Received in revised form 21 November 2019 Accepted 24 November 2019 Available online xxxx Keywords: Gynecologic cancer Quality of life Depression Older adults Cancer survivor
a b s t r a c t Purpose. The impact of gynecologic cancer on health-related quality of life (HRQOL) is not fully understood. To our knowledge, this is the first longitudinal study to measure HRQOL changes from before to after gynecologic cancer diagnosis in older women. Methods. Data were obtained from the Surveillance, Epidemiology, and End Results – Medicare Health Outcomes Survey database. Women aged 65 and older who were diagnosed with cervical, ovarian, or uterine cancer between baseline and follow-up surveys (n = 248; mean time from diagnosis = 12.54 ± 7.11 months) were propensity-matched to cancer-free controls (n = 1240). Logistic regression was used to assess risk of functional impairments and depressive symptoms at follow-up. Changes in HRQOL, as measured by the Medical Outcomes Study Short Form-36 and Veterans RAND 12-Item Survey, were estimated with mixed effects linear models. Results. Women who were within 12 months of diagnosis and women diagnosed with regional/distant disease had significantly greater odds than controls of impairment at follow-up. HRQOL declines were greatest in those with advanced disease, with the most notable changes from baseline to follow-up observed for role limitations due to emotional problems (−8.60 vs. −3.42 in controls), general health (−7.76 vs 0.10), and physical functioning (−7.70 vs. −1.67). There were significant decreases in physical functioning and role limitations due to emotional problems for all cancer patients regardless of time since diagnosis. Conclusions. Gynecologic cancer has significant impacts on physical and mental aspects of HRQOL in older women. Interventions are needed to reduce pain, provide support, and prepare patients for changes in functioning and health. © 2018 Elsevier Inc. All rights reserved.
1. Introduction Gynecologic tumors are among the most common cancers diagnoses in older women. Incidence and mortality rates of cervical, ovarian, and uterine cancers are highest in women aged 65 and over [1], and of the ⁎ Corresponding author at: Public Health Institute, Cancer Registry of Greater California, 1750 Howe Ave, Ste 550, Sacramento, CA 95825, United States of America. E-mail address: [email protected] (A.K. Klapheke).
approximately 1.2 million American survivors of one of these cancers [1], over half are currently over the age of 65 [2]. While advances in early detection and treatment have led to improved survival [3,4], older women with these cancers experience physical and mental problems that may seriously impact their health-related quality of life (HRQOL), including diagnosis-related distress and anxiety, adverse side effects of treatment, and age-related chronic conditions [2,5]. Though there is increasing interest in studying HRQOL in cancer patients, existing research with respect to gynecologic cancers is limited,
https://doi.org/10.1016/j.ygyno.2019.11.033 0090-8258/© 2018 Elsevier Inc. All rights reserved.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Changes in health-related quality of life in older women after diagnosis with gynecologic cancer, Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2019.11.033
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A.K. Klapheke et al. / Gynecologic Oncology xxx (xxxx) xxx
especially in older women. Relatively few studies focus specifically on these cancers, and much of HRQOL research is limited to clinical trials, in which older women are underrepresented [6,7]. Studies often include a wide age range of patients, which can mask important differences in health and functioning between older and younger women. Further, many studies lack cancer-free controls, which limits the ability to assess the specific impact of cancer in older persons who are likely to have other chronic conditions. One of the greatest limitations is an absence of HRQOL data before a woman's cancer diagnosis, which makes it difficult to understand the changes in HRQOL associated with cancer [8,9]. As such, much remains to be understood about the trajectory of HRQOL in older women with gynecologic cancer. While many studies have evaluated the impact of cancer treatment on HRQOL [10–15], to our knowledge, no other study has measured how HRQOL changes from before to after diagnosis with cervical, ovarian, or uterine cancer. Therefore, this longitudinal study aimed 1) to assess the likelihood of developing functional impairments in older women after gynecologic cancer diagnosis and 2) to estimate the pre- to post-diagnosis changes in HRQOL in these women compared to cancer-free controls. A better understanding of these issues would help providers prepare patients for adjustment difficulties and link them with appropriate supportive services after cancer diagnosis. 2. Methods 2.1. Data source and study population This study analyzed data from the Surveillance, Epidemiology, and End-Results – Medicare Health Outcomes Survey (SEER-MHOS) linked database. Extensive details of the SEER-MHOS linkage have been published elsewhere [16]. Briefly, SEER-MHOS links cancer data from the SEER program of population-based registries with MHOS data of Medicare Advantage (MA) enrollees. SEER-MHOS provides a valuable tool for studying the HRQOL of adults aged 65 and older in the SEER regions of Connecticut, Hawaii, Iowa, New Mexico, Utah, Kentucky, Louisiana, New Jersey, California, Detroit, Atlanta, Seattle-Puget Sound, and greater Georgia. The MHOS was designed to collect valid and clinically meaningful data on health outcomes of MA beneficiaries and has been used by the Centers for Medicare and Medicaid Services to monitor the quality of care given by Medicare managed care plans since 1998. Each year, a baseline MHOS is administered to a cohort of 1000 to 1200 randomly selected MA beneficiaries from each managed care plan, and they are then asked to take a follow-up survey 2 years later if they remain in the same plan. The present study utilizes 15 cohorts of MHOS data covering survey years 1998–2014 and SEER cases diagnosed through the end of 2013. The Public Health Institute institutional review board granted this research exemption from review. We identified women diagnosed with a first primary invasive ovarian, uterine, or cervical cancer between a baseline and two-year followup MHOS. Women diagnosed with other primary cancers before either survey were excluded. Next, we selected cancer-free controls who completed a baseline and two-year follow-up MHOS, resided in a SEER region, and participated in the same managed care plans as cases. For controls who completed baseline and follow-up surveys in multiple cohorts, the first set of surveys was used. All women, regardless of cancer status, must have been at least 65 years old at the time of the baseline survey. 2.2. Measures At baseline and follow-up, HRQOL was measured using the Medical Outcomes Study Short Form-36 (SF-36) and the Veterans RAND 12-Item Health Survey (VR-12) for survey years 1998–2005 and 2006–2014, respectively. The two instruments have been linked using a published algorithm [17]. The items on the questionnaires
correspond to eight health domains and are summarized by physical component summary (PCS) and mental component summary (MCS) scores. Both summary scores are derived from a weighted combination of all eight scales, with PCS scores reflecting higher weights for general health, physical functioning, role limitations due to physical problems, and bodily pain subscales. MCS scores have higher weights for mental health, social functioning, role limitations due to emotional problems, and vitality. Scores were normalized to the U.S. general population on a scale of 0 to 100 (mean ± SD score 50 ± 100), with higher scores reflecting better HRQOL. A difference of two points or greater was considered a minimally important difference (MID) for each score, which has been deemed clinically meaningful [18–20]. Functional limitations at both baseline and follow-up were measured using an activity of daily living (ADL) index [21], which asked: “Because of a health or physical problem, do you have any difficulty doing the following activities without special equipment or help from another person? (I am unable to do this activity/Yes, I have difficulty/ No, I do not have difficulty)” Six activities were assessed: bathing, dressing, eating, getting in/out of chairs, walking, and using the toilet. A binary variable (yes/no) was created for each ADL to indicate whether the respondent had difficulty performing the activity. The number of limitations was summed to create an ADL index score, with higher scores indicating more disability. Screening positively for depression at the time of each survey was defined using an algorithm by Rost et al. [22] and was based on responses to questions from the Diagnostic Interview Schedule in the MHOS. There were two methods to determine positive depression screen. The first method requires an affirmative response to the question, “In the past year, have you had 2 weeks or more during which you felt sad, blue, or depressed; or when you lost interest or pleasure in things that you usually cared about or enjoyed? (yes/no).” The second screening method includes an affirmative response to both of the following questions: (1) “In the past year, have you felt depressed or sad much of the time? (yes/no)” and (2) “Have you ever had 2 years or more in your life when you felt depressed or sad most days, even if you felt okay sometimes? (yes/no),” as well as responding at least “some of the time” to the question, “How much of the time during the past 4 weeks have you felt downhearted and blue? (none of the time/ some of the time/most of the time/all of the time).” Participants who fit either of the two criteria were classified as having depressive symptoms. These depression-related questions were asked on the baseline surveys for all study subjects (survey years 1998–2012), but they were not included in the follow-up surveys for MHOS cohorts 14 and 15 (survey years 2013–2014). Because of this, the development of depressive symptoms at follow-up was only assessed for women in cohorts 1–13 (80.17% of study population). All other analyses included all 15 cohorts. We assessed the presence (yes/no) of several self-reported comorbid conditions at both baseline and follow-up. The chronic conditions indicated on the baseline survey were defined as preexisting, while those newly reported at follow-up were classified as newly diagnosed. These health problems included: hypertension, cardiovascular disease, stroke, lung disease, gastrointestinal disorders, arthritis, sciatica, and diabetes. Other key variables included age at baseline, race/ethnicity, educational attainment, marital status at baseline, change in marital status (divorced, separated, or widowed) between baseline and follow-up, household income, smoking status at baseline, SEER geographic region, survey administration at both baseline and follow-up, and survey completer at both baseline and follow-up. For women with cancer, stage at diagnosis was based on SEER historical staging. To approximate treatment effects, cancer patients were stratified by time between cancer diagnosis and follow-up survey (≤ 12 months, N12 months). These time periods were chosen to reflect active and early post-treatment effects and post-treatment effects, respectively.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Changes in health-related quality of life in older women after diagnosis with gynecologic cancer, Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2019.11.033
A.K. Klapheke et al. / Gynecologic Oncology xxx (xxxx) xxx
2.3. Statistical analysis Using propensity scores and a greedy matching algorithm [23], five cancer-free controls were matched to cancer cases on propensity score to balance the distribution of and minimize potential bias related to baseline characteristics (age, race/ethnicity, education level, marital status, household income, smoking status, SEER region, survey administration and proxy response, pre-existing comorbid conditions, and MHOS cohort). The characteristics of study participants were summarized by cancer status and compared using chi-square and t-tests for categorical and continuous variables, respectively. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for functional impairments and depressive symptoms at the time of follow-up in women with cancer compared to controls. Models were adjusted for presence of the outcome at baseline and all variables in Table 1 except time between surveys and the cancer-related variables. Stratified analyses by stage at diagnosis and by time since diagnosis were both conducted, with cancer-free controls as the referent group. Scores for each HRQOL domain at both baseline and follow-up were estimated using mixed effects linear models. Models accounted for clustering due to health care plan membership and case-control matching using random effects. Fixed effects included cancer status, time (baseline or follow-up), the interaction of cancer and time, comorbid conditions, the interactions of comorbid conditions with time, age at baseline, race/ethnicity, education level, marital status at baseline, change in marital status, household income, smoking status, SEER region, and survey administration and completer at baseline and followup. The fixed effects were used to estimate and test the differences in scores between women with and without cancer and changes in scores between baseline and follow-up. All analysis was performed using SAS version 9.4 (Cary, NC). 3. Results 3.1. Study population characteristics A total of 248 women with cancer (11, 64, and 173 with cervical, ovarian, and uterine cancer, respectively) and 1240 controls were identified for analysis. The characteristics of study participants are displayed in Table 1. After propensity score matching, the only statistically significant baseline difference between women with and without cancer was a higher percentage of controls completing the first survey by mail than cases (88.87% vs. 83.47%). In addition, more controls were diagnosed with gastrointestinal disorders between baseline and follow-up; cases and controls were otherwise similar with respect to preexisting and newly diagnosed comorbidities. Among cases, the mean (± SD) time between cancer diagnosis and follow-up survey was 12.54 (± 7.11) months; 134 took a survey within one year of diagnosis, and the other 114 cases took a survey 13–27 months after diagnosis. The mean (± SD) number of months between baseline and follow-up surveys was 24.50 (± 1.25) and 24.58 (± 1.30) months for cancer cases and controls, respectively, with times ranging between 21 and 28 months. About half (52.20%) of cancer patients were diagnosed with localized disease and 44.35% were diagnosed at the regional/distant stage. 3.2. Development of functional impairments and depressive symptoms At baseline, women with and without cancer did not significantly differ with respect to the number of ADL impairments, though cancer patients appeared to have fewer functional limitations (mean ± SD, 0.63 ± 1.08 in cancer patients vs. 0.78 ± 1.43 in controls; p = .0616). At follow-up, however, women with cancer had significantly greater odds of impairment. Tables 2.1 and 2.2 present the adjusted ORs for functional impairments and depressive symptoms for cancer patients relative to controls. Women who were diagnosed with localized disease
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Table 1 Characteristics of the study population (N = 1488).
Age at baseline survey, Mean (SD) Race/Ethnicity White Asian or Pacific Islander Black or African American Hispanic Other Education Level Less than high school High school graduate Some college or 2-year degree College graduate or more Unknown Marital status at baseline Married Divorced/separated Widowed Never married Marital status change Household income b$20,000 $20,000–$39,999 ≥$40,000 Unknown Smoking status at baseline Every day or some days Not at all Unknown Region West Midwest/Northeast South Survey administration by mail Baseline Follow-up Self-completed survey
No cancer
(N = 248)
(N = 1240)
N (%)
N (%)
74.10 (5.83) 192 (77.42) 23 (9.27) 18 (7.26) 13 (5.24)
74.92 (6.57) 0.0691 1.0000 959 (77.34) 116 (9.35) 90 (7.26) 65 (5.24)
a
a
53 (21.37) 84 (33.87) 70 (28.23) 40 (16.13)
312 (25.16) 453 (36.53) 275 (22.18) 188 (15.16) 12 (0.97)
0.2180
a
1.0000 101 (40.73) 39 (15.73) 85 (34.27) 23 (9.27) a
505 (40.73) 196 (15.81) 425 (34.27) 114 (9.19) 52 (4.19)
85 (34.27) 65 (26.21) 44 (17.74) 54 (21.77)
436 (35.16) 309 (24.92) 220 (17.74) 275 (22.18)
a
207 (83.47) 31 (12.50)
81 (6.53) 964 (77.74) 195 (15.73)
150 (60.48) 55 (22.18) 43 (17.34)
715 (57.66) 302 (24.35) 223 (17.98)
0.1960 0.9778
0.1114
0.6908
207 (83.47) 219 (88.31)
Baseline
220 (88.71)
Follow-up
210 (84.68)
Preexisting conditions Hypertension Cardiovascular disease Stroke Lung disease Gastrointestinal disorders Arthritis Sciatic Diabetes Newly diagnosed conditions Hypertension Cardiovascular disease Stroke Lung disease Gastrointestinal disorders Arthritis Sciatica Diabetes ADL score at baseline, mean (SD) Depressive symptoms at baseline Months between surveys, mean (SD) Months between diagnosis and follow-up, mean (SD) Cancer site Cervix Ovary Uterus Stage at diagnosis
P-Valueb
Gynecological cancer
1102 (88.87) 1113 (89.76) 1082 (87.26) 1040 (83.87)
0.0170⁎ 0.4957 0.1078 0.9357
140 (56.45) 58 (23.39) 14 (5.65) 20 (8.06) 11 (4.44) 117 (47.18) 47 (18.95) 41 (16.53)
723 (58.31) 328 (26.45) 75 (6.05) 98 (7.90) 78 (6.29) 667 (53.79) 274 (22.10) 207 (16.69)
0.3238 0.4418 0.8237 0.9316 0.4156 0.0743 0.2459 0.6032
23 (9.27) 19 (7.66)
0.63 (1.08) 41 (16.53) 24.50 (1.25)
92 (7.42) 79 (6.37) 29 (2.34) 58 (4.68) 28 (2.26) 115 (9.27) 113 (9.11) 41 (3.31) 0.78 (1.43) 226 (18.23) 24.58 (1.30)
0.1042 0.3991 0.4659 0.1337 0.0184⁎ 0.0662 0.8126 0.4408 0.0616 0.8031 0.3700
12.54 (7.11)
–
11 (4.44) 64 (25.81) 173 (69.76)
– – –
a a a
35 (14.11) 21 (8.47) a
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Changes in health-related quality of life in older women after diagnosis with gynecologic cancer, Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2019.11.033
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A.K. Klapheke et al. / Gynecologic Oncology xxx (xxxx) xxx
Table 1 (continued) Gynecological cancer
Localized Regional/Distant Unstaged/Unknown
No cancer
(N = 248)
(N = 1240)
N (%)
N (%)
129 (52.02) 110 (44.35)
– – –
a
P-Value
b
Statistically significant at pb0.05. a
In compliance with Surveillance, Epidemiology, and End Results-Medicare guidelines, cell counts b11 are not
The adjusted mean changes in HRQOL scores stratified by time since diagnosis are displayed in Fig. 2. Women who were within 12 months of diagnosis experienced statistically significant declines in vitality (−4.54), social functioning (−4.51), physical functioning (−4.47), and general health (−3.78). The decrements in physical functioning and role limitations due to emotional problems appeared to persist in women who were N12 months post-diagnosis (−5.83 and −4.77, respectively). 4. Discussion
shown. b Two-tailed P-values were generated from chi-square tests for categorical variables and t-tests for continuous variables.
had similar odds of impairment as cancer-free women, but those diagnosed at regional/distant stages were significantly more likely to have difficulty performing ADLs (Table 2.1). Women who were within a year of their cancer diagnosis had significantly greater odds of having difficulty bathing, eating, and walking at follow-up than cancer-free women (Table 2.2). Though there were similar percentages of women with and without cancer having depressive symptoms at baseline (16.53% in cancer patients, 18.23% in controls, p = .8031), cancer patients had nearly twice the odds of developing depressive symptoms at follow-up (OR = 1.95, 95% CI: 1.03, 3.68, p = .0391). Similar odds were seen after stratifying women by time since diagnosis.
3.3. Changes in HRQOL between baseline and follow-up Except for role limitations due to physical problems, there were no significant differences in adjusted baseline HRQOL scores between women with and without cancer (Supplementary Table 1). While both cases and controls experienced declines in HRQOL between surveys, women with cancer had significantly lower HRQOL scores at follow-up for all physical domains as well as social functioning and vitality. The greatest differences in follow-up scores between cases and controls were for physical component summary (−4.75), role limitations due to physical problems (−4.18), general health (−4.05), and vitality (−3.94). Fig. 1 depicts the changes in HRQOL scores stratified by stage at diagnosis. Decreases in HRQOL were most striking in women diagnosed with regional/distant disease; all declines observed in this group exceeded the MID threshold. With respect to physical scales, the greatest decrements were observed for general health (−7.76 vs 0.10 in controls) and physical functioning (−7.70 vs. −1.67). For mental health domains, the worst declines were seen in role limitations due to emotional problems (−8.60 vs. −3.42) and social functioning (−6.79 vs. −0.46).
In this longitudinal study, we determined that within the first 2 years after gynecologic cancer diagnosis, older women experienced significant declines in functioning and decrements in physical and mental domains of HRQOL relative to cancer-free women. Though women without cancer also presented with deficits in HRQOL, decreases in scores were greater in cancer patients, some by two to four times the amount considered clinically meaningful. This finding suggests that although older age contributes to worsening HRQOL, gynecologic cancer can increase the likelihood and exacerbate the extent of impairment. We found that changes in roles and physical functioning were strongly affected by cancer, with cancer patients significantly more likely to have declines in physical health and difficulty performing ADLs than noncancer controls. Physical impairments were most notable among women with advanced disease and those who were within 1 year-post diagnosis, suggesting that active or aggressive cancer treatment could account for many of these changes in health and functioning. In addition to their cancer-specific symptoms, women undergoing treatment for gynecologic cancer have been found to experience debilitating and distressing side effects, including pain, fatigue, nausea, vomiting, incontinence, bowel dysfunction, neuropathy, and lymphedema [5,8,24,25]. The significant declines in HRQOL observed in our study may be largely attributable to the treatment of cancer, rather than the disease itself. While HRQOL suffers during treatment, studies suggest that health and functioning can vary considerably throughout the course of cancer and may even improve post-treatment. A prospective study of 98 gynecologic cancer patients of varying ages found that women had decrements in functioning and well-being at their initial clinic visit before surgery, but that quality of life and mood improved in the first year following treatment [16]. Similarly, a Canadian study of 460 middle-aged gynecologic cancer patients found that HRQOL was significantly lower in women undergoing surgery as well as preoperatively, but that HRQOL returned to normal 6 months post-operation [26]. Findings from these other studies may not hold true for older gynecologic cancer patients, however, as they may take longer to recover from treatment and be less likely to return to pre-diagnosis health levels than younger women [27]. Indeed, we found that older women who were more than 1 year-post cancer diagnosis still experienced greater declines in
Table 2.1 Adjusteda odds of functional impairments and depressive symptoms at follow-up in women with gynecologic cancer relative to cancer-free controls, stratified by stage at diagnosis. Health problem
Difficulty bathing Difficulty dressing Difficulty eating Difficulty getting in/Out of chairs Difficulty walking Difficulty using the toilet Depressive symptoms
All patients
Localized disease
Regional/Distant disease
OR (95% CI)
P-Value
OR (95% CI)
P-Value
OR (95% CI)
P-Value
1.61 (0.83, 3.12) 1.63 (0.79, 3.35) 4.85 (1.94, 12.13) 1.47 (0.87, 2.48) 2.02 (1.20, 3.41) 2.26 (0.97, 5.30) 1.95 (1.03, 3.68)
0.1603 0.1855 0.0007⁎ 0.1516 0.0084⁎
0.99 (0.38, 2.58) 0.95 (0.33, 2.72) 0.51 (0.07, 3.56) 1.12 (0.55, 2.25) 1.68 (0.87, 3.28) 1.07 (0.30, 3.84) 2.01 (0.88, 4.63)
0.9890 0.9221 0.4942 0.7580 0.1251 0.9154 0.0991
2.40 (1.00, 5.78) 3.25 (1.30, 8.13) 19.71 (6.17, 63.02) 2.06 (0.99, 4.25) 2.61 (1.23, 5.55) 4.46 (1.50, 13.24) 2.09 (0.87, 5.02)
0.0506 0.0116⁎ b0.0001⁎ 0.0520 0.0127⁎ 0.0071⁎
0.0605 0.0391⁎
0.1001
Statistically significant at pb0.05. The referent group for all comparisons is cancer-free controls. a Logistic regression models were adjusted for baseline measure of the outcome, age at baseline survey, race/ethnicity, education level, marital status at baseline, change in marital status between baseline and follow-up, household income, smoking status at baseline, SEER region, survey completer and administration mode at baseline and follow-up, pre-existing comorbid conditions (hypertension, cardiovascular disease, stroke, lung disease, gastrointestinal disorders, arthritis, sciatica, diabetes), and comorbid conditions diagnosed between baseline and follow-up.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Changes in health-related quality of life in older women after diagnosis with gynecologic cancer, Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2019.11.033
A.K. Klapheke et al. / Gynecologic Oncology xxx (xxxx) xxx
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Table 2.2 Adjusteda odds of functional impairments and depressive symptoms at follow-up in women with gynecologic cancer relative to cancer-free controls, stratified by time since diagnosis. Health problem
≤12 Months since diagnosis
All patients
Difficulty bathing Difficulty dressing Difficulty eating Difficulty getting in/Out of chairs Difficulty walking Difficulty using the toilet Depressive symptoms
N12 Months since diagnosis
OR (95% CI)
P-Value
OR (95% CI)
P-Value
OR (95% CI)
P-Value
1.61 (0.83, 3.12) 1.63 (0.79, 3.35) 4.85 (1.94, 12.13) 1.47 (0.87, 2.48) 2.02 (1.20, 3.41) 2.26 (0.97, 5.30) 1.95 (1.03, 3.68)
0.1603 0.1855 0.0007⁎ 0.1516 0.0084⁎
2.23 (1.00, 4.98) 1.60 (0.62, 4.10) 7.45 (2.73, 20.29) 1.49 (0.75, 2.94) 3.04 (1.56, 5.92) 2.05 (0.72, 5.84) 1.63 (0.69, 3.84)
0.0496⁎ 0.3323 b0.0001⁎ 0.2563 0.0011⁎
0.97 (0.34, 2.78) 1.66 (0.63, 4.41) 1.83 (0.36, 9.23) 1.45 (0.70, 2.98) 1.23 (0.57, 2.63) 2.60 (0.80, 8.48) 2.35 (1.01, 5.49)
0.9585 0.3064 0.4656 0.3174 0.5966 0.1132 0.0477⁎
0.0605 0.0391⁎
0.1802 0.2617
Statistically significant at pb0.05. The referent group for all comparisons is cancer-free controls. a Logistic regression models were adjusted for baseline measure of the outcome, age at baseline survey, race/ethnicity, education level, marital status at baseline, change in marital status between baseline and follow-up, household income, smoking status at baseline, SEER region, survey completer and administration mode at baseline and follow-up, pre-existing comorbid conditions (hypertension, cardiovascular disease, stroke, lung disease, gastrointestinal disorders, arthritis, sciatica, diabetes), and comorbid conditions diagnosed between baseline and follow-up.
physical and mental health scores than cancer-free women. Decreases in HRQOL were similar among cancer patients regardless of time since diagnosis, indicating that these issues may persist, at least in the first 2 years after diagnosis. These findings stress the need for health care providers to monitor their patients' physical and mental functioning throughout the course of diagnosis, treatment, and recovery. In addition, future studies should build upon the present analysis and estimate HRQOL at various time points after diagnosis to get a more comprehensive understanding of the HRQOL trajectory in older women. We observed that older women with cancer, particularly those with advanced disease, experienced significant declines in mental wellbeing, and that cancer patients had about twice the odds of developing depressive symptoms. Prior studies indicate that rates of depression [28,29] and anxiety [12] are high among women with gynecologic cancer soon after diagnosis as well as during and after treatment. In addition, depressive symptoms have been found to be strongly associated with comorbid conditions in older gynecologic cancer patients, which can further exacerbate declines in HRQOL [30]. We also noted significant deficits to social functioning and role limitations due to emotional problems. Women with gynecologic cancer often experience altered relationships with loved ones as well as social stigma, isolation, body image issues, and sexual dysfunction after cancer treatment [31,32]. Additionally, functional impairments affect a woman's independence and self-esteem, which may strain relationships and worsen emotional health [33,34]. One prospective study of 248 Austrian women with gynecologic cancer found that emotional functioning scores were low after cancer diagnosis and before treatment [15], which may reflect psychological stress associated with a serious diagnosis as well as the uncertainty of treatment. Our findings provide some empirical insight
into the extent to which such psychological issues affect older women during the first 2 years post-diagnosis. Given that rates of referral to specialized psychosocial oncology care decline with older age [35], and that many gynecologic cancer patients are unlikely to receive treatment for depression or supportive counseling [28], our findings underscore the crucial need for timely supportive services for older women with cancer. There were several notable limitations of this study. Though we had sufficient power to detect HRQOL changes in the combined gynecologic cancer group, the smaller sample size limited our ability to assess the three cancer sites separately and to adequately adjust for diseasespecific variables, including histology, tumor grade, and treatment regimen. Similarly, we combined regional and distant diagnoses into one category, which provides sufficient statistical power but limits the ability to differentiate HRQOL by stage. Additionally, information on chemotherapy and adjuvant therapies are not available in SEER, and surgery and radiation data are limited [36,37]. We could not determine the timing of the survey in relation to treatment or account for duration or sequence of treatments. However, analyzing HRQOL by stage at diagnosis and time since diagnosis provides broad insight into the possible effects that treatment or disease-related symptoms may have in gynecologic cancer patients. The comorbidities assessed in this study are based on self-report, and the relative severity of each was not known. This study focuses on older women, and results may not be generalizable to younger populations. While follow-up response rates for the MHOS range from approximately 70 to 85% [16], the exclusion of patients without a follow-up survey may have skewed our study population to include healthier women. Finally, this study population includes MA enrollees from SEER regions only, as data on Medicare
4.00 2.00
Score Change
0.00 -2.00 -4.00
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Fig. 1. Adjusted+ mean changes in health-related quality of life scores between baseline and follow-up by stage at diagnosis in gynecologic cancer patients and controls.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Changes in health-related quality of life in older women after diagnosis with gynecologic cancer, Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2019.11.033
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Fig. 2. Adjusted+ mean changes in physical health-related quality of life scores between baseline and follow-up by time since diagnosis in gynecologic cancer patients and controls.
fee-for-service beneficiaries was not available. While one study found that health status is similar between MA and fee-for-service beneficiaries [38], others suggest that managed care enrollees are healthier than the general Medicare population [39]. Thus, our findings may underestimate the deficits in HRQOL in the population of older women with cancer. Despite these limitations, this study adds important contributions to existing literature. This longitudinal analysis is among the first to assess changes in HRQOL from before to after gynecologic cancer diagnosis in older women. The comparison to cancer-free controls minimizes the confounding effects of aging and age-related conditions, which enhances our understanding of the specific impacts of cancer on older women's physical and mental well-being and their daily functioning. Though it is already known that cancer has negative effects on physical and mental health, this study quantified these impacts, which may be used as reference points in future research [40]. Additionally, our findings point to some of the specific aspects of daily life and functioning that are impacted by cancer, which may help providers better identify and prioritize their patients' needs. These findings may also be the basis of future studies seeking to further understand how diseaserelated symptoms, treatment, and care affect physical and mental health, and they may support clinical interventions designed to address negative impacts on HRQOL. Finally, this study demonstrates the potential utility of measuring HRQOL and other patient-reported outcomes in clinical practice, which may help providers routinely monitor changes in physical and mental well-being, inform treatment decisions, and determine appropriate supportive care. In summary, these findings provide insight into the changes in functional status and quality of life associated with gynecologic cancer. We determined that older women with gynecologic cancer were more likely to experience functional limitations and depressive symptoms and to have significantly greater decrements in HRQOL than cancerfree women. These findings highlight the need for interventions to reduce pain, provide support, and prepare older women for changes in functioning and health after diagnosis with gynecologic cancer. Supplementary data to this article can be found online at https://doi. org/10.1016/j.ygyno.2019.11.033. Funding None. Declaration of competing interest The authors have no conflicts of interest to disclose.
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Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Changes in health-related quality of life in older women after diagnosis with gynecologic cancer, Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2019.11.033
Contents lists available at ScienceDirect
Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
Changes in health-related quality of life in older women after diagnosis with gynecologic cancer Amy K. Klapheke a,b,⁎, Theresa H.M. Keegan b,c, Rachel Ruskin d, Rosemary D. Cress a,b a
Public Health Institute, Cancer Registry of Greater California, Sacramento, CA, United States of America Department of Public Health Sciences, University of California Davis, Davis, CA, United States of America Division of Hematology and Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, CA, United States of America d Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California Davis Comprehensive Cancer Center, Sacramento, CA, United States of America b c
H I G H L I G H T S • • • • •
Older women experience significant declines in physical and mental health after diagnosis with gynecologic cancer. Deficits in physical and mental well-being were significantly worse in women with cancer than in cancer-free women. The most notable changes were in role limitations due to emotional problems, general health, and physical functioning. Impairment was greatest in women with advanced disease and women within one year of diagnosis. Interventions are needed to better support and prepare older women for changes in health after cancer diagnosis.
a r t i c l e
i n f o
Article history: Received 27 August 2019 Received in revised form 21 November 2019 Accepted 24 November 2019 Available online xxxx Keywords: Gynecologic cancer Quality of life Depression Older adults Cancer survivor
a b s t r a c t Purpose. The impact of gynecologic cancer on health-related quality of life (HRQOL) is not fully understood. To our knowledge, this is the first longitudinal study to measure HRQOL changes from before to after gynecologic cancer diagnosis in older women. Methods. Data were obtained from the Surveillance, Epidemiology, and End Results – Medicare Health Outcomes Survey database. Women aged 65 and older who were diagnosed with cervical, ovarian, or uterine cancer between baseline and follow-up surveys (n = 248; mean time from diagnosis = 12.54 ± 7.11 months) were propensity-matched to cancer-free controls (n = 1240). Logistic regression was used to assess risk of functional impairments and depressive symptoms at follow-up. Changes in HRQOL, as measured by the Medical Outcomes Study Short Form-36 and Veterans RAND 12-Item Survey, were estimated with mixed effects linear models. Results. Women who were within 12 months of diagnosis and women diagnosed with regional/distant disease had significantly greater odds than controls of impairment at follow-up. HRQOL declines were greatest in those with advanced disease, with the most notable changes from baseline to follow-up observed for role limitations due to emotional problems (−8.60 vs. −3.42 in controls), general health (−7.76 vs 0.10), and physical functioning (−7.70 vs. −1.67). There were significant decreases in physical functioning and role limitations due to emotional problems for all cancer patients regardless of time since diagnosis. Conclusions. Gynecologic cancer has significant impacts on physical and mental aspects of HRQOL in older women. Interventions are needed to reduce pain, provide support, and prepare patients for changes in functioning and health. © 2018 Elsevier Inc. All rights reserved.
1. Introduction Gynecologic tumors are among the most common cancers diagnoses in older women. Incidence and mortality rates of cervical, ovarian, and uterine cancers are highest in women aged 65 and over [1], and of the ⁎ Corresponding author at: Public Health Institute, Cancer Registry of Greater California, 1750 Howe Ave, Ste 550, Sacramento, CA 95825, United States of America. E-mail address: [email protected] (A.K. Klapheke).
approximately 1.2 million American survivors of one of these cancers [1], over half are currently over the age of 65 [2]. While advances in early detection and treatment have led to improved survival [3,4], older women with these cancers experience physical and mental problems that may seriously impact their health-related quality of life (HRQOL), including diagnosis-related distress and anxiety, adverse side effects of treatment, and age-related chronic conditions [2,5]. Though there is increasing interest in studying HRQOL in cancer patients, existing research with respect to gynecologic cancers is limited,
https://doi.org/10.1016/j.ygyno.2019.11.033 0090-8258/© 2018 Elsevier Inc. All rights reserved.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Changes in health-related quality of life in older women after diagnosis with gynecologic cancer, Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2019.11.033
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especially in older women. Relatively few studies focus specifically on these cancers, and much of HRQOL research is limited to clinical trials, in which older women are underrepresented [6,7]. Studies often include a wide age range of patients, which can mask important differences in health and functioning between older and younger women. Further, many studies lack cancer-free controls, which limits the ability to assess the specific impact of cancer in older persons who are likely to have other chronic conditions. One of the greatest limitations is an absence of HRQOL data before a woman's cancer diagnosis, which makes it difficult to understand the changes in HRQOL associated with cancer [8,9]. As such, much remains to be understood about the trajectory of HRQOL in older women with gynecologic cancer. While many studies have evaluated the impact of cancer treatment on HRQOL [10–15], to our knowledge, no other study has measured how HRQOL changes from before to after diagnosis with cervical, ovarian, or uterine cancer. Therefore, this longitudinal study aimed 1) to assess the likelihood of developing functional impairments in older women after gynecologic cancer diagnosis and 2) to estimate the pre- to post-diagnosis changes in HRQOL in these women compared to cancer-free controls. A better understanding of these issues would help providers prepare patients for adjustment difficulties and link them with appropriate supportive services after cancer diagnosis. 2. Methods 2.1. Data source and study population This study analyzed data from the Surveillance, Epidemiology, and End-Results – Medicare Health Outcomes Survey (SEER-MHOS) linked database. Extensive details of the SEER-MHOS linkage have been published elsewhere [16]. Briefly, SEER-MHOS links cancer data from the SEER program of population-based registries with MHOS data of Medicare Advantage (MA) enrollees. SEER-MHOS provides a valuable tool for studying the HRQOL of adults aged 65 and older in the SEER regions of Connecticut, Hawaii, Iowa, New Mexico, Utah, Kentucky, Louisiana, New Jersey, California, Detroit, Atlanta, Seattle-Puget Sound, and greater Georgia. The MHOS was designed to collect valid and clinically meaningful data on health outcomes of MA beneficiaries and has been used by the Centers for Medicare and Medicaid Services to monitor the quality of care given by Medicare managed care plans since 1998. Each year, a baseline MHOS is administered to a cohort of 1000 to 1200 randomly selected MA beneficiaries from each managed care plan, and they are then asked to take a follow-up survey 2 years later if they remain in the same plan. The present study utilizes 15 cohorts of MHOS data covering survey years 1998–2014 and SEER cases diagnosed through the end of 2013. The Public Health Institute institutional review board granted this research exemption from review. We identified women diagnosed with a first primary invasive ovarian, uterine, or cervical cancer between a baseline and two-year followup MHOS. Women diagnosed with other primary cancers before either survey were excluded. Next, we selected cancer-free controls who completed a baseline and two-year follow-up MHOS, resided in a SEER region, and participated in the same managed care plans as cases. For controls who completed baseline and follow-up surveys in multiple cohorts, the first set of surveys was used. All women, regardless of cancer status, must have been at least 65 years old at the time of the baseline survey. 2.2. Measures At baseline and follow-up, HRQOL was measured using the Medical Outcomes Study Short Form-36 (SF-36) and the Veterans RAND 12-Item Health Survey (VR-12) for survey years 1998–2005 and 2006–2014, respectively. The two instruments have been linked using a published algorithm [17]. The items on the questionnaires
correspond to eight health domains and are summarized by physical component summary (PCS) and mental component summary (MCS) scores. Both summary scores are derived from a weighted combination of all eight scales, with PCS scores reflecting higher weights for general health, physical functioning, role limitations due to physical problems, and bodily pain subscales. MCS scores have higher weights for mental health, social functioning, role limitations due to emotional problems, and vitality. Scores were normalized to the U.S. general population on a scale of 0 to 100 (mean ± SD score 50 ± 100), with higher scores reflecting better HRQOL. A difference of two points or greater was considered a minimally important difference (MID) for each score, which has been deemed clinically meaningful [18–20]. Functional limitations at both baseline and follow-up were measured using an activity of daily living (ADL) index [21], which asked: “Because of a health or physical problem, do you have any difficulty doing the following activities without special equipment or help from another person? (I am unable to do this activity/Yes, I have difficulty/ No, I do not have difficulty)” Six activities were assessed: bathing, dressing, eating, getting in/out of chairs, walking, and using the toilet. A binary variable (yes/no) was created for each ADL to indicate whether the respondent had difficulty performing the activity. The number of limitations was summed to create an ADL index score, with higher scores indicating more disability. Screening positively for depression at the time of each survey was defined using an algorithm by Rost et al. [22] and was based on responses to questions from the Diagnostic Interview Schedule in the MHOS. There were two methods to determine positive depression screen. The first method requires an affirmative response to the question, “In the past year, have you had 2 weeks or more during which you felt sad, blue, or depressed; or when you lost interest or pleasure in things that you usually cared about or enjoyed? (yes/no).” The second screening method includes an affirmative response to both of the following questions: (1) “In the past year, have you felt depressed or sad much of the time? (yes/no)” and (2) “Have you ever had 2 years or more in your life when you felt depressed or sad most days, even if you felt okay sometimes? (yes/no),” as well as responding at least “some of the time” to the question, “How much of the time during the past 4 weeks have you felt downhearted and blue? (none of the time/ some of the time/most of the time/all of the time).” Participants who fit either of the two criteria were classified as having depressive symptoms. These depression-related questions were asked on the baseline surveys for all study subjects (survey years 1998–2012), but they were not included in the follow-up surveys for MHOS cohorts 14 and 15 (survey years 2013–2014). Because of this, the development of depressive symptoms at follow-up was only assessed for women in cohorts 1–13 (80.17% of study population). All other analyses included all 15 cohorts. We assessed the presence (yes/no) of several self-reported comorbid conditions at both baseline and follow-up. The chronic conditions indicated on the baseline survey were defined as preexisting, while those newly reported at follow-up were classified as newly diagnosed. These health problems included: hypertension, cardiovascular disease, stroke, lung disease, gastrointestinal disorders, arthritis, sciatica, and diabetes. Other key variables included age at baseline, race/ethnicity, educational attainment, marital status at baseline, change in marital status (divorced, separated, or widowed) between baseline and follow-up, household income, smoking status at baseline, SEER geographic region, survey administration at both baseline and follow-up, and survey completer at both baseline and follow-up. For women with cancer, stage at diagnosis was based on SEER historical staging. To approximate treatment effects, cancer patients were stratified by time between cancer diagnosis and follow-up survey (≤ 12 months, N12 months). These time periods were chosen to reflect active and early post-treatment effects and post-treatment effects, respectively.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Changes in health-related quality of life in older women after diagnosis with gynecologic cancer, Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2019.11.033
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2.3. Statistical analysis Using propensity scores and a greedy matching algorithm [23], five cancer-free controls were matched to cancer cases on propensity score to balance the distribution of and minimize potential bias related to baseline characteristics (age, race/ethnicity, education level, marital status, household income, smoking status, SEER region, survey administration and proxy response, pre-existing comorbid conditions, and MHOS cohort). The characteristics of study participants were summarized by cancer status and compared using chi-square and t-tests for categorical and continuous variables, respectively. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for functional impairments and depressive symptoms at the time of follow-up in women with cancer compared to controls. Models were adjusted for presence of the outcome at baseline and all variables in Table 1 except time between surveys and the cancer-related variables. Stratified analyses by stage at diagnosis and by time since diagnosis were both conducted, with cancer-free controls as the referent group. Scores for each HRQOL domain at both baseline and follow-up were estimated using mixed effects linear models. Models accounted for clustering due to health care plan membership and case-control matching using random effects. Fixed effects included cancer status, time (baseline or follow-up), the interaction of cancer and time, comorbid conditions, the interactions of comorbid conditions with time, age at baseline, race/ethnicity, education level, marital status at baseline, change in marital status, household income, smoking status, SEER region, and survey administration and completer at baseline and followup. The fixed effects were used to estimate and test the differences in scores between women with and without cancer and changes in scores between baseline and follow-up. All analysis was performed using SAS version 9.4 (Cary, NC). 3. Results 3.1. Study population characteristics A total of 248 women with cancer (11, 64, and 173 with cervical, ovarian, and uterine cancer, respectively) and 1240 controls were identified for analysis. The characteristics of study participants are displayed in Table 1. After propensity score matching, the only statistically significant baseline difference between women with and without cancer was a higher percentage of controls completing the first survey by mail than cases (88.87% vs. 83.47%). In addition, more controls were diagnosed with gastrointestinal disorders between baseline and follow-up; cases and controls were otherwise similar with respect to preexisting and newly diagnosed comorbidities. Among cases, the mean (± SD) time between cancer diagnosis and follow-up survey was 12.54 (± 7.11) months; 134 took a survey within one year of diagnosis, and the other 114 cases took a survey 13–27 months after diagnosis. The mean (± SD) number of months between baseline and follow-up surveys was 24.50 (± 1.25) and 24.58 (± 1.30) months for cancer cases and controls, respectively, with times ranging between 21 and 28 months. About half (52.20%) of cancer patients were diagnosed with localized disease and 44.35% were diagnosed at the regional/distant stage. 3.2. Development of functional impairments and depressive symptoms At baseline, women with and without cancer did not significantly differ with respect to the number of ADL impairments, though cancer patients appeared to have fewer functional limitations (mean ± SD, 0.63 ± 1.08 in cancer patients vs. 0.78 ± 1.43 in controls; p = .0616). At follow-up, however, women with cancer had significantly greater odds of impairment. Tables 2.1 and 2.2 present the adjusted ORs for functional impairments and depressive symptoms for cancer patients relative to controls. Women who were diagnosed with localized disease
3
Table 1 Characteristics of the study population (N = 1488).
Age at baseline survey, Mean (SD) Race/Ethnicity White Asian or Pacific Islander Black or African American Hispanic Other Education Level Less than high school High school graduate Some college or 2-year degree College graduate or more Unknown Marital status at baseline Married Divorced/separated Widowed Never married Marital status change Household income b$20,000 $20,000–$39,999 ≥$40,000 Unknown Smoking status at baseline Every day or some days Not at all Unknown Region West Midwest/Northeast South Survey administration by mail Baseline Follow-up Self-completed survey
No cancer
(N = 248)
(N = 1240)
N (%)
N (%)
74.10 (5.83) 192 (77.42) 23 (9.27) 18 (7.26) 13 (5.24)
74.92 (6.57) 0.0691 1.0000 959 (77.34) 116 (9.35) 90 (7.26) 65 (5.24)
a
a
53 (21.37) 84 (33.87) 70 (28.23) 40 (16.13)
312 (25.16) 453 (36.53) 275 (22.18) 188 (15.16) 12 (0.97)
0.2180
a
1.0000 101 (40.73) 39 (15.73) 85 (34.27) 23 (9.27) a
505 (40.73) 196 (15.81) 425 (34.27) 114 (9.19) 52 (4.19)
85 (34.27) 65 (26.21) 44 (17.74) 54 (21.77)
436 (35.16) 309 (24.92) 220 (17.74) 275 (22.18)
a
207 (83.47) 31 (12.50)
81 (6.53) 964 (77.74) 195 (15.73)
150 (60.48) 55 (22.18) 43 (17.34)
715 (57.66) 302 (24.35) 223 (17.98)
0.1960 0.9778
0.1114
0.6908
207 (83.47) 219 (88.31)
Baseline
220 (88.71)
Follow-up
210 (84.68)
Preexisting conditions Hypertension Cardiovascular disease Stroke Lung disease Gastrointestinal disorders Arthritis Sciatic Diabetes Newly diagnosed conditions Hypertension Cardiovascular disease Stroke Lung disease Gastrointestinal disorders Arthritis Sciatica Diabetes ADL score at baseline, mean (SD) Depressive symptoms at baseline Months between surveys, mean (SD) Months between diagnosis and follow-up, mean (SD) Cancer site Cervix Ovary Uterus Stage at diagnosis
P-Valueb
Gynecological cancer
1102 (88.87) 1113 (89.76) 1082 (87.26) 1040 (83.87)
0.0170⁎ 0.4957 0.1078 0.9357
140 (56.45) 58 (23.39) 14 (5.65) 20 (8.06) 11 (4.44) 117 (47.18) 47 (18.95) 41 (16.53)
723 (58.31) 328 (26.45) 75 (6.05) 98 (7.90) 78 (6.29) 667 (53.79) 274 (22.10) 207 (16.69)
0.3238 0.4418 0.8237 0.9316 0.4156 0.0743 0.2459 0.6032
23 (9.27) 19 (7.66)
0.63 (1.08) 41 (16.53) 24.50 (1.25)
92 (7.42) 79 (6.37) 29 (2.34) 58 (4.68) 28 (2.26) 115 (9.27) 113 (9.11) 41 (3.31) 0.78 (1.43) 226 (18.23) 24.58 (1.30)
0.1042 0.3991 0.4659 0.1337 0.0184⁎ 0.0662 0.8126 0.4408 0.0616 0.8031 0.3700
12.54 (7.11)
–
11 (4.44) 64 (25.81) 173 (69.76)
– – –
a a a
35 (14.11) 21 (8.47) a
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Changes in health-related quality of life in older women after diagnosis with gynecologic cancer, Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2019.11.033
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A.K. Klapheke et al. / Gynecologic Oncology xxx (xxxx) xxx
Table 1 (continued) Gynecological cancer
Localized Regional/Distant Unstaged/Unknown
No cancer
(N = 248)
(N = 1240)
N (%)
N (%)
129 (52.02) 110 (44.35)
– – –
a
P-Value
b
Statistically significant at pb0.05. a
In compliance with Surveillance, Epidemiology, and End Results-Medicare guidelines, cell counts b11 are not
The adjusted mean changes in HRQOL scores stratified by time since diagnosis are displayed in Fig. 2. Women who were within 12 months of diagnosis experienced statistically significant declines in vitality (−4.54), social functioning (−4.51), physical functioning (−4.47), and general health (−3.78). The decrements in physical functioning and role limitations due to emotional problems appeared to persist in women who were N12 months post-diagnosis (−5.83 and −4.77, respectively). 4. Discussion
shown. b Two-tailed P-values were generated from chi-square tests for categorical variables and t-tests for continuous variables.
had similar odds of impairment as cancer-free women, but those diagnosed at regional/distant stages were significantly more likely to have difficulty performing ADLs (Table 2.1). Women who were within a year of their cancer diagnosis had significantly greater odds of having difficulty bathing, eating, and walking at follow-up than cancer-free women (Table 2.2). Though there were similar percentages of women with and without cancer having depressive symptoms at baseline (16.53% in cancer patients, 18.23% in controls, p = .8031), cancer patients had nearly twice the odds of developing depressive symptoms at follow-up (OR = 1.95, 95% CI: 1.03, 3.68, p = .0391). Similar odds were seen after stratifying women by time since diagnosis.
3.3. Changes in HRQOL between baseline and follow-up Except for role limitations due to physical problems, there were no significant differences in adjusted baseline HRQOL scores between women with and without cancer (Supplementary Table 1). While both cases and controls experienced declines in HRQOL between surveys, women with cancer had significantly lower HRQOL scores at follow-up for all physical domains as well as social functioning and vitality. The greatest differences in follow-up scores between cases and controls were for physical component summary (−4.75), role limitations due to physical problems (−4.18), general health (−4.05), and vitality (−3.94). Fig. 1 depicts the changes in HRQOL scores stratified by stage at diagnosis. Decreases in HRQOL were most striking in women diagnosed with regional/distant disease; all declines observed in this group exceeded the MID threshold. With respect to physical scales, the greatest decrements were observed for general health (−7.76 vs 0.10 in controls) and physical functioning (−7.70 vs. −1.67). For mental health domains, the worst declines were seen in role limitations due to emotional problems (−8.60 vs. −3.42) and social functioning (−6.79 vs. −0.46).
In this longitudinal study, we determined that within the first 2 years after gynecologic cancer diagnosis, older women experienced significant declines in functioning and decrements in physical and mental domains of HRQOL relative to cancer-free women. Though women without cancer also presented with deficits in HRQOL, decreases in scores were greater in cancer patients, some by two to four times the amount considered clinically meaningful. This finding suggests that although older age contributes to worsening HRQOL, gynecologic cancer can increase the likelihood and exacerbate the extent of impairment. We found that changes in roles and physical functioning were strongly affected by cancer, with cancer patients significantly more likely to have declines in physical health and difficulty performing ADLs than noncancer controls. Physical impairments were most notable among women with advanced disease and those who were within 1 year-post diagnosis, suggesting that active or aggressive cancer treatment could account for many of these changes in health and functioning. In addition to their cancer-specific symptoms, women undergoing treatment for gynecologic cancer have been found to experience debilitating and distressing side effects, including pain, fatigue, nausea, vomiting, incontinence, bowel dysfunction, neuropathy, and lymphedema [5,8,24,25]. The significant declines in HRQOL observed in our study may be largely attributable to the treatment of cancer, rather than the disease itself. While HRQOL suffers during treatment, studies suggest that health and functioning can vary considerably throughout the course of cancer and may even improve post-treatment. A prospective study of 98 gynecologic cancer patients of varying ages found that women had decrements in functioning and well-being at their initial clinic visit before surgery, but that quality of life and mood improved in the first year following treatment [16]. Similarly, a Canadian study of 460 middle-aged gynecologic cancer patients found that HRQOL was significantly lower in women undergoing surgery as well as preoperatively, but that HRQOL returned to normal 6 months post-operation [26]. Findings from these other studies may not hold true for older gynecologic cancer patients, however, as they may take longer to recover from treatment and be less likely to return to pre-diagnosis health levels than younger women [27]. Indeed, we found that older women who were more than 1 year-post cancer diagnosis still experienced greater declines in
Table 2.1 Adjusteda odds of functional impairments and depressive symptoms at follow-up in women with gynecologic cancer relative to cancer-free controls, stratified by stage at diagnosis. Health problem
Difficulty bathing Difficulty dressing Difficulty eating Difficulty getting in/Out of chairs Difficulty walking Difficulty using the toilet Depressive symptoms
All patients
Localized disease
Regional/Distant disease
OR (95% CI)
P-Value
OR (95% CI)
P-Value
OR (95% CI)
P-Value
1.61 (0.83, 3.12) 1.63 (0.79, 3.35) 4.85 (1.94, 12.13) 1.47 (0.87, 2.48) 2.02 (1.20, 3.41) 2.26 (0.97, 5.30) 1.95 (1.03, 3.68)
0.1603 0.1855 0.0007⁎ 0.1516 0.0084⁎
0.99 (0.38, 2.58) 0.95 (0.33, 2.72) 0.51 (0.07, 3.56) 1.12 (0.55, 2.25) 1.68 (0.87, 3.28) 1.07 (0.30, 3.84) 2.01 (0.88, 4.63)
0.9890 0.9221 0.4942 0.7580 0.1251 0.9154 0.0991
2.40 (1.00, 5.78) 3.25 (1.30, 8.13) 19.71 (6.17, 63.02) 2.06 (0.99, 4.25) 2.61 (1.23, 5.55) 4.46 (1.50, 13.24) 2.09 (0.87, 5.02)
0.0506 0.0116⁎ b0.0001⁎ 0.0520 0.0127⁎ 0.0071⁎
0.0605 0.0391⁎
0.1001
Statistically significant at pb0.05. The referent group for all comparisons is cancer-free controls. a Logistic regression models were adjusted for baseline measure of the outcome, age at baseline survey, race/ethnicity, education level, marital status at baseline, change in marital status between baseline and follow-up, household income, smoking status at baseline, SEER region, survey completer and administration mode at baseline and follow-up, pre-existing comorbid conditions (hypertension, cardiovascular disease, stroke, lung disease, gastrointestinal disorders, arthritis, sciatica, diabetes), and comorbid conditions diagnosed between baseline and follow-up.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Changes in health-related quality of life in older women after diagnosis with gynecologic cancer, Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2019.11.033
A.K. Klapheke et al. / Gynecologic Oncology xxx (xxxx) xxx
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Table 2.2 Adjusteda odds of functional impairments and depressive symptoms at follow-up in women with gynecologic cancer relative to cancer-free controls, stratified by time since diagnosis. Health problem
≤12 Months since diagnosis
All patients
Difficulty bathing Difficulty dressing Difficulty eating Difficulty getting in/Out of chairs Difficulty walking Difficulty using the toilet Depressive symptoms
N12 Months since diagnosis
OR (95% CI)
P-Value
OR (95% CI)
P-Value
OR (95% CI)
P-Value
1.61 (0.83, 3.12) 1.63 (0.79, 3.35) 4.85 (1.94, 12.13) 1.47 (0.87, 2.48) 2.02 (1.20, 3.41) 2.26 (0.97, 5.30) 1.95 (1.03, 3.68)
0.1603 0.1855 0.0007⁎ 0.1516 0.0084⁎
2.23 (1.00, 4.98) 1.60 (0.62, 4.10) 7.45 (2.73, 20.29) 1.49 (0.75, 2.94) 3.04 (1.56, 5.92) 2.05 (0.72, 5.84) 1.63 (0.69, 3.84)
0.0496⁎ 0.3323 b0.0001⁎ 0.2563 0.0011⁎
0.97 (0.34, 2.78) 1.66 (0.63, 4.41) 1.83 (0.36, 9.23) 1.45 (0.70, 2.98) 1.23 (0.57, 2.63) 2.60 (0.80, 8.48) 2.35 (1.01, 5.49)
0.9585 0.3064 0.4656 0.3174 0.5966 0.1132 0.0477⁎
0.0605 0.0391⁎
0.1802 0.2617
Statistically significant at pb0.05. The referent group for all comparisons is cancer-free controls. a Logistic regression models were adjusted for baseline measure of the outcome, age at baseline survey, race/ethnicity, education level, marital status at baseline, change in marital status between baseline and follow-up, household income, smoking status at baseline, SEER region, survey completer and administration mode at baseline and follow-up, pre-existing comorbid conditions (hypertension, cardiovascular disease, stroke, lung disease, gastrointestinal disorders, arthritis, sciatica, diabetes), and comorbid conditions diagnosed between baseline and follow-up.
physical and mental health scores than cancer-free women. Decreases in HRQOL were similar among cancer patients regardless of time since diagnosis, indicating that these issues may persist, at least in the first 2 years after diagnosis. These findings stress the need for health care providers to monitor their patients' physical and mental functioning throughout the course of diagnosis, treatment, and recovery. In addition, future studies should build upon the present analysis and estimate HRQOL at various time points after diagnosis to get a more comprehensive understanding of the HRQOL trajectory in older women. We observed that older women with cancer, particularly those with advanced disease, experienced significant declines in mental wellbeing, and that cancer patients had about twice the odds of developing depressive symptoms. Prior studies indicate that rates of depression [28,29] and anxiety [12] are high among women with gynecologic cancer soon after diagnosis as well as during and after treatment. In addition, depressive symptoms have been found to be strongly associated with comorbid conditions in older gynecologic cancer patients, which can further exacerbate declines in HRQOL [30]. We also noted significant deficits to social functioning and role limitations due to emotional problems. Women with gynecologic cancer often experience altered relationships with loved ones as well as social stigma, isolation, body image issues, and sexual dysfunction after cancer treatment [31,32]. Additionally, functional impairments affect a woman's independence and self-esteem, which may strain relationships and worsen emotional health [33,34]. One prospective study of 248 Austrian women with gynecologic cancer found that emotional functioning scores were low after cancer diagnosis and before treatment [15], which may reflect psychological stress associated with a serious diagnosis as well as the uncertainty of treatment. Our findings provide some empirical insight
into the extent to which such psychological issues affect older women during the first 2 years post-diagnosis. Given that rates of referral to specialized psychosocial oncology care decline with older age [35], and that many gynecologic cancer patients are unlikely to receive treatment for depression or supportive counseling [28], our findings underscore the crucial need for timely supportive services for older women with cancer. There were several notable limitations of this study. Though we had sufficient power to detect HRQOL changes in the combined gynecologic cancer group, the smaller sample size limited our ability to assess the three cancer sites separately and to adequately adjust for diseasespecific variables, including histology, tumor grade, and treatment regimen. Similarly, we combined regional and distant diagnoses into one category, which provides sufficient statistical power but limits the ability to differentiate HRQOL by stage. Additionally, information on chemotherapy and adjuvant therapies are not available in SEER, and surgery and radiation data are limited [36,37]. We could not determine the timing of the survey in relation to treatment or account for duration or sequence of treatments. However, analyzing HRQOL by stage at diagnosis and time since diagnosis provides broad insight into the possible effects that treatment or disease-related symptoms may have in gynecologic cancer patients. The comorbidities assessed in this study are based on self-report, and the relative severity of each was not known. This study focuses on older women, and results may not be generalizable to younger populations. While follow-up response rates for the MHOS range from approximately 70 to 85% [16], the exclusion of patients without a follow-up survey may have skewed our study population to include healthier women. Finally, this study population includes MA enrollees from SEER regions only, as data on Medicare
4.00 2.00
Score Change
0.00 -2.00 -4.00
-6.00 -8.00 -10.00 -12.00 -14.00 Physical Component Summary
General Health
Physical Role Bodily Pain Mental Functioning Limitations Component due to Summary Physical Problems Controls
Localized
Mental Health
Social Role Functioning Limitations due to Emotional Problems
Vitality
Regional/Distant
Fig. 1. Adjusted+ mean changes in health-related quality of life scores between baseline and follow-up by stage at diagnosis in gynecologic cancer patients and controls.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Changes in health-related quality of life in older women after diagnosis with gynecologic cancer, Gynecologic Oncology, https://doi.org/10.1016/j.ygyno.2019.11.033
6
A.K. Klapheke et al. / Gynecologic Oncology xxx (xxxx) xxx 4.00 2.00
Score Change
0.00 -2.00 -4.00 -6.00 -8.00 -10.00 -12.00 -14.00 Physical Component Summary
General Health
Physical Role Bodily Pain Mental Functioning Limitations Component due to Summary Physical Problems
Controls
< 12 Months
Mental Health
Social Role Functioning Limitations due to Emotional Problems
Vitality
> 12 Months
Fig. 2. Adjusted+ mean changes in physical health-related quality of life scores between baseline and follow-up by time since diagnosis in gynecologic cancer patients and controls.
fee-for-service beneficiaries was not available. While one study found that health status is similar between MA and fee-for-service beneficiaries [38], others suggest that managed care enrollees are healthier than the general Medicare population [39]. Thus, our findings may underestimate the deficits in HRQOL in the population of older women with cancer. Despite these limitations, this study adds important contributions to existing literature. This longitudinal analysis is among the first to assess changes in HRQOL from before to after gynecologic cancer diagnosis in older women. The comparison to cancer-free controls minimizes the confounding effects of aging and age-related conditions, which enhances our understanding of the specific impacts of cancer on older women's physical and mental well-being and their daily functioning. Though it is already known that cancer has negative effects on physical and mental health, this study quantified these impacts, which may be used as reference points in future research [40]. Additionally, our findings point to some of the specific aspects of daily life and functioning that are impacted by cancer, which may help providers better identify and prioritize their patients' needs. These findings may also be the basis of future studies seeking to further understand how diseaserelated symptoms, treatment, and care affect physical and mental health, and they may support clinical interventions designed to address negative impacts on HRQOL. Finally, this study demonstrates the potential utility of measuring HRQOL and other patient-reported outcomes in clinical practice, which may help providers routinely monitor changes in physical and mental well-being, inform treatment decisions, and determine appropriate supportive care. In summary, these findings provide insight into the changes in functional status and quality of life associated with gynecologic cancer. We determined that older women with gynecologic cancer were more likely to experience functional limitations and depressive symptoms and to have significantly greater decrements in HRQOL than cancerfree women. These findings highlight the need for interventions to reduce pain, provide support, and prepare older women for changes in functioning and health after diagnosis with gynecologic cancer. Supplementary data to this article can be found online at https://doi. org/10.1016/j.ygyno.2019.11.033. Funding None. Declaration of competing interest The authors have no conflicts of interest to disclose.
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