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A Report From the American Cancer Society's Studies of Cancer Survivors
Article first published online: 14 APR 2011
Copyright © 2011 American Cancer Society
Volume 117, Issue 12, pages 2779–2790, 15 June 2011
How to Cite
Shi, Q., Smith, T. G., Michonski, J. D., Stein, K. D., Kaw, C. and Cleeland, C. S. (2011), Symptom burden in cancer survivors 1 year after diagnosis. Cancer, 117: 2779–2790. doi: 10.1002/cncr.26146
Presented as a poster at the Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, June 4-8, 2010.
The authors acknowledge Jeanie F. Woodruff, ELS, of the Department of Symptom Research at The University of Texas MD Anderson Cancer for editorial assistance and Dr. Xianglin Du of The University of Texas School of Public Health for review and comment on the article.
The American Cancer Society acknowledges the cooperation and efforts of the cancer registries and public health departments from the states of Alabama, Connecticut, Iowa, Idaho, Minnesota, New Jersey, Ohio, Pennsylvania, Rhode Island, South Carolina, and Wyoming. We also thank the staff of the hundreds of hospitals, including Stamford Hospital, who reported cases to the participating cancer registries. Last, we are grateful to the thousands of cancer survivors, their physicians, and their loved ones who contributed to the collection of these data.
Qiuling Shi had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
- Issue published online: 7 JUN 2011
- Article first published online: 14 APR 2011
- Manuscript Accepted: 25 FEB 2011
- Manuscript Revised: 14 FEB 2011
- Manuscript Received: 23 DEC 2010
- cancer survivorship;
- symptom burden;
- late effects;
- risk factors;
- quality of life;
- cluster analysis
Few studies have examined risk for severe symptoms during early cancer survivorship. By using baseline data from the American Cancer Society's Study of Cancer Survivors-I, the authors examined cancer survivors with high symptom burden, identified risk factors associated with high symptom burden, and evaluated the impact of high symptom burden on health-related quality of life (HRQoL) 1 year postdiagnosis.
Participants were enrolled from 11 state cancer registries approximately 1 year after diagnosis and were surveyed by telephone or mail. The outcomes measures used were the Modified Rotterdam Symptom Checklist and the Profile of Mood States-37 (to assess symptom burden) and the Satisfaction with Life Domains Scale-Cancer (to assess HRQoL).
Of 4903 survivors, 4512 (92%) reported symptoms related to their cancer and/or its treatment. Two-step clustering yielded 2 subgroups, 1 with low symptom burden (n = 3113) and 1 with high symptom burden (n = 1399). Variables that were associated with high symptom burden included lung cancer (odds ratio [OR], 2.27), metastatic cancer (OR, 2.05), the number of comorbid conditions (OR, 1.76), remaining on active chemotherapy (OR, 1.93), younger age (OR, 2.31), lacking insurance/being underinsured (OR, 1.57), having lower income (OR, 1.61), being unemployed (OR, 1.27), and being less educated (OR, 1.29). Depression, fatigue, and pain had the greatest impact on HRQoL in survivors with high symptom burden, who also had lower HRQoL (P < .0001).
More than 1 in 4 cancer survivors had high symptom burden 1 year postdiagnosis, even after treatment termination. These results indicate a need for continued symptom monitoring and management in early post-treatment survivorship, especially for the underserved. Cancer 2011;. © 2011 American Cancer Society.
A cancer survivor is any individual who has received a diagnosis of cancer; survivorship begins at diagnosis and continues through the balance of the patient's life.1 Because of advances in cancer detection and treatment, the number of individuals living years after their cancer diagnosis has increased steadily. The 5-year survival rate for all US cancer patients diagnosed between 1996 and 2004 has increased to 66%, and there are more than 11 million cancer survivors in the United States.2
The benefit of a longer life is offset for many survivors, however, by multiple, persistent symptoms, including fatigue, distress, pain, and cognitive impairment. Some survivors remain on anticancer treatment and, thus, continue to experience treatment-related symptoms. Others who have completed treatment will experience residual symptoms of both the disease and the treatment, compounded by lack of the close medical monitoring that accompanies active therapy. In either case, symptoms cause a significant burden that diminishes survivors' quality of life.3-6
The 12 months after diagnosis may be especially stressful for patients,7 and risk for symptom burden induced by cancer and its treatment remains high during this period. Individual variations in the presence and severity of physical and psychological morbidities are common as patients move into the post-treatment period.8 The severity of symptoms is critical, because higher levels of symptom burden disproportionately impair function and quality of life.9, 10
Therefore, it is important to identify specific groups of cancer survivors who are at greater risk for severe symptoms. Historically, however, in most symptom research, the determination of variables associated with high symptom burden has been limited by several factors, including lack of statistical power because of small sample size11; lack of the assessment of symptom severity, an understanding of which would allow identification of the most symptomatic survivors12; confounding because of variability in the length of time as a survivor13; and a tendency to consider symptoms individually, regardless of the co-occurrence of multiple symptoms.14
To address these limitations, we conducted an analysis of population-based data from the American Cancer Society's Study of Cancer Survivors-I (SCS-I). All patients had received their cancer diagnosis approximately 1 year before enrollment. Our objective was to identify a subgroup with higher symptom burden in the early stages of cancer survivorship and to document possible factors that could contribute to having more severe symptoms in early survivorship. We also investigated the pattern of multiple symptoms in this high-symptom group and identified symptoms that had the greatest impact on survivors' ratings of health-related quality of life (HRQoL).
MATERIALS AND METHODS
The SCS-I study was designed to identify longitudinal patterns of change in cancer survivors' HRQoL over an 11-year period. Cancer survivors representing diverse diagnoses, geographic regions, and demographic groups were recruited randomly from the cancer registries of 11 states. All survivors were at least aged 18 years, were diagnosed with 1 of the 10 most highly incident cancers (non-Hodgkin lymphoma; skin melanoma; or prostate, female breast, lung, colorectal, urinary bladder, kidney, ovarian, or uterine cancer), and were approximately 1 year postdiagnosis at the time of recruitment and initial assessment. Sampling and investigation details for the SCS-I study have been described.15 Overall approval for the SCS-I was obtained from the Institutional Review Board (IRB) of Emory University. Additional IRB and/or regulatory approvals were obtained for each state registry.15 To ensure the reliability of our analyses, we selected only those survivors whose missing-response rate on the study's baseline symptom assessment was <20%.
Medical, demographic, and socioeconomic data in the SCS-I database were obtained from the state cancer registries or through a self-report survey. Patient-reported HRQoL and symptom severity were collected by mailed questionnaires. The Modified Rotterdam Checklist (RSCL-M) was used to assess physical symptoms: Patients indicated the extent to which they had been bothered by each of 30 symptoms during the past week (not at all, a little, quite a bit, or very much).16 The short-form Profile of Mood States (POMS-37) was used to assess psychological symptoms: Patients indicated for 37 adjectives from 6 subscales (tension, depression, confusion, fatigue, anger, and vigor) the extent to which they had been feeling that way during the past 2 weeks (not at all, a little, moderately, quite a bit, or extremely).17 The Satisfaction with Life Domains Scale-Cancer (SLDS-C) was used to assess HRQoL: Patients indicated their current satisfaction with 17 life domains relevant to HRQoL by choosing 1 of 7 faces, ranging from a “terrible” face with a deep, down-turned frown to a “delighted” face with a large smile.18
Because the current study focused on symptomatic cancer survivors, respondents who reported “not at all” for all RSCL-M and POMS-37 items were removed from analysis. For missed symptom items, mean imputation was used for both scales according to the instrument's manual. Symptom scores were transformed linearly to a 0 to 100 metric to facilitate interpretation, with higher scores indicating more severe symptoms. Because of their inverse scoring, 6 symptoms on the POMS-37 vigor subscale were reverse scored for a consistent interpretation with other symptoms.
To identify survivors with high symptom burden, we applied a 2-step cluster analysis to divide cancer survivors into groups with distinct levels of symptom severity (high vs low). With the 67 symptoms from the RSCL-M and POMS-37 as variables, the clustering solution was obtained using log-likelihood estimation, and the optimal number of groups was defined as that with the lowest Bayesian Information Criterion. To confirm that 2-step clustering effectively differentiated survivors according to symptom burden, we used the Student t test and the Cohen d effect size to compare the severity of individual symptoms between the high-symptom and low-symptom groups. The magnitude of effect size was based on the value of d, with 0.2 considered a small effect size, 0.5 considered a medium effect size, and 0.8 considered a large effect size.19 We expected the 2-step clustering to generate subgroups of survivors with distinct levels of symptoms with at least a medium effect size. We used the total score on the SLDS-C to represent HRQoL, with lower scores indicating poorer HRQoL; t tests were used to compare SLDS-C scores among groups with different symptom levels.
To estimate the associations between demographic and clinical variables and symptoms, we conducted logistic modeling with group membership as the dependent variable. Independent variables were all demographic, socioeconomic, and disease characteristics, including age, sex, race, education level, annual household income, marital status, current health insurance status, current employment status, cancer stage, number of comorbid conditions, cancer type, and type of therapy (surgery, chemotherapy, and/or radiotherapy). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the effect of each risk factor. Only survivors who had complete data for all variables were included for this analysis.
To explore the pattern of physical symptoms in the high-symptom group, we conducted exploratory factor analysis of the RSCL-M items using principal axis factoring as the extraction method. A factor loading ≥0.30 was deemed significant.20 Factor-based component scores were computed by averaging items loading principally on a particular factor. We used regression analyses to compare RSCL-M factor scores and POMS-37 subscale scores between survivors who were actively receiving chemotherapy or radiotherapy and survivors who already had completed therapy.
To evaluate the impact of cancer-related symptoms on HRQoL in the high-symptom group, we used a linear regression model of the factor-based composite scores from the RSCL-M and 4 subscale scores from the POMS-37 (depression, tension, anger, and confusion). The POMS-37 fatigue and vigor subscales were excluded to avoid redundancy with the RSCL-M variables (which also measured fatigue). The most distressing symptoms were selected on the basis of the standardized regression coefficient, a parameter used to identify the independent variable that has a greater unique effect on the criterion (SLDS-C total score). The larger the standardized coefficient value, the greater the effect.21
We used SPSS version 16.0 statistical software (SPSS, Inc., Chicago, Ill) to perform the 2-step cluster analysis and SAS version 9.2 statistical software (SAS Institute, Cary, NC) to perform all other analyses. All statistical tests were 2-sided, and P values < .05 were considered statistically significant.
The SCS-I database contained 5277 cancer survivors whose self-reported cancer site was consistent with information in the cancer registry. From these, we identified 4903 survivors (93%) whose missing-response rate on the study's baseline symptom assessment was <20%. Demographic and clinical characteristics are listed in Table 1. Of the 4903 survivors who had adequate symptom data, 391 (8%) were nonsymptomatic (ie, reported “not at all” for all RSCL-M and POMS-37 items) and were excluded from further analyses, resulting in a sample of 4512 survivors with some level of symptom burden.
|No. of Survivors (%)|
|Characteristic||Symptomatic Survivors, n=4512||Asymptomatic Survivors, n=391||P|
|Women||2633 (58.4)||188 (48.1)||<.0001|
|Men||1879 (41.6)||203 (51.9)|
|<55||2200 (48.8)||192 (49.1)||.896|
|≥55||2312 (51.2)||199 (50.9)|
|Non-Hispanic white||3957 (87.7)||349 (89.3)|
|Black||310 (6.9)||17 (4.3)|
|Hispanic||153 (3.4)||13 (3.3)|
|Other||92 (2.0)||12 (3.1)|
|Yes||3302 (73.6)||305 (78.0)||.064|
|No||1183 (26.4)||86 (22.0)|
|≥College||2676 (60.2)||263 (68.1)||.007|
|Other||1766 (39.8)||128 (32.9)|
|Annual household income|
|<$5000||56 (1.3)||1 (0.3)||.149|
|$5000-$9999||170 (3.9)||5 (1.3)|
|$10,000-$19,999||437 (9.9)||17 (1.3)|
|$20,000-$39,999||1001 (22.9)||79 (20.2)|
|$40,000-$74,999||1251 (28.6)||118 (30.2)|
|≥$75,000||1005 (23.0)||120 (30.7)|
|Yes||2342 (51.9)||233 (59.6)||.004|
|No||2170 (48.1)||158 (40.4)|
|Employer paid||2427 (54.7)||244 (66.8)||.004|
|A plan that you or someone else buys on your own||250 (5.6)||22 (5.6)|
|Military, CHAMPUS, TriCare, Veterans Administration||51 (1.2)||1 (0.3)|
|Medicare||1117 (25.2)||92 (23.5)|
|Medicaid or medical assistance||122 (2.8)||4 (1.0)|
|Other source||80 (1.8)||2 (0.5)|
|None||97 (2.2)||2 (0.5)|
|Breast||1098 (24.3)||81 (20.7)||<.0001|
|Prostate||822 (18.2)||81 (20.7)|
|Colorectal||676 (15.0)||63 (16.1)|
|Bladder||179 (4.0)||16 (4.1)|
|Uterine||222 (4.9)||20 (5.1)|
|Melanoma||210 (4.6)||61 (15.6)|
|Non-Hodgkin lymphoma||287 (6.4)||21 (5.4)|
|Kidney||269 (6.0)||27 (6.9)|
|Lung||463 (10.3)||7 (1.8)|
|Ovarian||286 (6.3)||14 (3.6)|
|In situ||100 (2.2)||10 (2.6)||<.0001|
|Localized||2616 (58.0)||275 (70.3)|
|Regional||1245 (27.6)||81 (20.7)|
|Distant||551 (12.2)||25 (6.4)|
|None||1977 (43.8)||226 (57.8)||<.0001|
|1||1251 (27.7)||116 (29.7)|
|≥2||1284 (28.5)||49 (12.5)|
|Previous surgery||3684 (83.9)||333 (85.2)||.083|
|Completed||1594 (36.8)||107 (27.4)||.231|
|Active||512 (11.8)||43 (11.0)|
|Completed||1520 (35.3)||104 (26.6)||.253|
|Active||393 (9.1)||34 (8.7)|
Survivors With High Symptom Burden
Two-step clustering generated 2 groups: a low-symptom group (n = 3113; 69%) and a high-symptom group with significantly higher mean symptom severity (n = 1399; 31%). Except for weight gain and problems controlling urine, effect sizes (Cohen d) of differences between the high-symptom and low-symptom groups for all symptoms were ≥0.5, indicating a medium-to-large magnitude of effect (Table 2). We compared HRQoL in the high-symptom and low-symptom groups using the SLDS-C total score as an index of overall HRQoL. The high-symptom group reported significantly lower mean SLDS-C scores than the low-symptom group (73.72 [95%CI, 72.74-74.70] vs 98.24 [95%CI, 97.79-98.69], respectively; P < .0001).
|Mean (95% CI)|
|Symptom||High Symptom Burden, n=1399||Low Symptom Burden, n=3113||Effect Size, Cohen d|
|Tiredness||62.55 (61.12-63.98)||27.46 (26.72-28.20)||1.51|
|Lack of energy||61.06 (59.60-62.53)||24.47 (23.71-25.23)||1.54|
|Difficulty sleeping||49.74 (48.03-51.46)||20.52 (19.68-21.36)||1.08|
|Decreased sexual interest||47.31 (45.29-49.33)||26.77 (25.67-27.87)||0.61|
|Low back pain||42.13 (40.34-43.92)||17.97 (17.15-18.79)||0.89|
|Sore muscles||42.05 (40.39-43.70)||16.55 (15.81-17.29)||1.03|
|Pain other than low back pain||41.60 (39.85-43.35)||15.28 (14.52-16.04)||1.02|
|Shortness of breath||32.00 (30.37-33.63)||10.28 (9.61-10.95)||0.92|
|Tingling hands or feet||30.90 (29.17-32.63)||12.21 (11.45-12.97)||0.72|
|Weight gain||29.63 (27.82-31.44)||17.09 (16.25-17.93)||0.45|
|Heartburn/belching||27.31 (25.74-28.89)||11.36 (10.69-12.03)||0.70|
|Dry mouth||27.31 (25.72-28.90)||9.38 (8.73-10.03)||0.79|
|Problems controlling your urine||26.05 (24.42-27.68)||13.85 (13.11-14.59)||0.49|
|Headaches||25.55 (24.05-27.04)||7.34 (6.79-7.89)||0.89|
|Constipation||23.65 (22.06-25.25)||9.21 (8.56-9.86)||0.63|
|Coughing||23.45 (21.95-24.95)||8.59 (7.96-9.22)||0.68|
|Abdominal aches||22.01 (20.56-23.47)||5.95 (5.46-6.44)||0.83|
|Lack of appetite||19.46 (17.99-20.93)||3.83 (3.42-4.24)||0.85|
|Dizziness||19.11 (17.83-20.39)||4.24 (3.83-4.65)||0.89|
|Loss of hair||18.87 (17.20-20.54)||5.57 (4.96-6.18)||0.58|
|Swelling of arms or legs||18.31 (16.85-19.76)||5.60 (5.09-6.11)||0.65|
|Skin irritation||18.19 (16.78-19.60)||6.46 (5.91-7.01)||0.59|
|Diarrhea||18.00 (16.59-19.41)||5.93 (5.42-6.44)||0.62|
|Problems controlling your bowels||17.52 (16.06-18.98)||5.52 (5.01-6.03)||0.61|
|Burning/sore eyes||16.69 (15.44-17.93)||4.75 (4.30-5.20)||0.70|
|Nausea||15.32 (14.03-16.61)||1.99 (1.70-2.28)||0.86|
|Shivering||13.56 (12.37-14.76)||2.28 (1.97-2.59)||0.77|
|Weight loss||11.62 (10.40-12.84)||2.98 (2.61-3.35)||0.55|
|Sore mouth/pain when swallowing||9.77 (8.70-10.83)||1.52 (1.25-1.79)||0.64|
|Vomiting||7.36 (6.33-8.39)||0.57 (0.41-0.73)||0.59|
|Vigorousa||82.93 (81.77-84.09)||58.41 (57.43-59.39)||0.93|
|Full of pepa||81.91 (80.72-83.10)||51.86 (50.94-52.78)||1.19|
|Energetica||76.05 (74.88-77.22)||47.65 (46.79-48.51)||1.19|
|Livelya||70.27 (69.07-71.47)||43.24 (42.42-44.06)||1.16|
|Activea||64.58 (63.31-65.85)||38.46 (37.64-39.28)||1.11|
|Fatigued||62.51 (61.17-63.85)||27.20 (26.49-27.91)||1.62|
|Worn-out||62.20 (60.84-63.57)||25.95 (25.24-26.66)||1.64|
|Cheerfula||60.79 (59.62-61.97)||35.12 (34.36-35.88)||1.17|
|Exhausted||57.29 (55.82-58.77)||20.75 (20.06-21.44)||1.61|
|Bushed||52.45 (50.95-53.94)||19.27 (18.60-19.94)||1.48|
|Weary||48.55 (47.15-49.96)||16.71 (16.08-17.34)||1.51|
|Uncertain about things||44.98 (43.55-46.40)||16.66 (16.03-17.29)||1.34|
|Tense||44.47 (43.05-45.88)||17.41 (16.80-18.02)||1.30|
|Sad||43.91 (42.50-45.32)||12.27 (11.76-12.78)||1.64|
|Unhappy||43.49 (42.20-44.79)||14.96 (14.39-15.53)||1.48|
|Restless||43.05 (41.71-44.38)||15.75 (15.16-16.34)||1.36|
|Discouraged||41.47 (40.04-42.91)||8.87 (8.40-9.34)||1.72|
|Blue||40.97 (39.57-42.37)||9.99 (9.50-10.48)||1.65|
|Nervous||40.64 (39.17-42.11)||12.29 (11.74-12.84)||1.40|
|Forgetful||40.03 (38.62-41.45)||20.29 (19.62-20.96)||0.91|
|Anxious||39.89 (38.47-41.31)||15.41 (14.76-16.06)||1.15|
|On edge||39.66 (38.29-41.04)||11.26 (10.73-11.79)||1.49|
|Annoyed||37.97 (36.63-39.30)||13.04 (12.51-13.57)||1.32|
|Grouchy||35.86 (34.51-37.21)||13.02 (12.49-13.55)||1.20|
|Unable to concentrate||35.70 (34.37-37.03)||11.49 (10.88-12.10)||1.20|
|Uneasy||33.92 (32.61-35.23)||8.29 (7.84-8.74)||1.45|
|Angry||33.89 (32.49-35.28)||10.87 (10.36-11.38)||1.19|
|Peeved||30.96 (29.60-32.32)||9.09 (8.60-9.58)||1.19|
|Miserable||30.79 (29.34-32.24)||3.07 (2.76-3.38)||1.62|
|Confused||28.98 (27.58-30.38)||6.21 (5.74-6.68)||1.23|
|Helpless||28.81 (27.33-30.29)||3.73 (3.38-4.08)||1.40|
|Hopeless||26.32 (24.85-27.78)||2.24 (1.97-2.51)||1.42|
|Resentful||26.15 (24.74-27.57)||4.91 (4.50-5.32)||1.19|
|Worthless||23.72 (22.20-25.24)||1.91 (1.64-2.18)||1.26|
|Bewildered||23.33 (22.05-24.60)||3.34 (3.01-3.67)||1.27|
|Bitter||23.33 (21.87-24.79)||2.65 (2.36-2.94)||1.21|
|Furious||18.92 (17.55-20.29)||2.06 (1.81-2.31)||1.07|
Variables Associated With Symptom Burden
Multivariate logistic regression modeling revealed that survivors aged <55 years (OR, 2.31; 95% CI, 1.91-2.80), had an annual household income <$40,000 (OR, 1.61; 95% CI, 1.34-1.94), were currently unemployed (OR, 1.27; 95% CI, 1.05-1.53), had no more than a high school education (OR, 1.29; 95% CI, 1.09-1.53), or were uninsured/underinsured (ie, on Medicaid or medical assistance; OR, 1.57; 95% CI, 1.10-2.24) were more likely to experience severe symptoms (Table 3). Clinical characteristics for severe symptoms included having lung cancer (OR, 2.27; 95% CI, 1.76-2.94), having distant metastases (OR, 2.05; 95% CI, 1.60-2.62), or actively receiving chemotherapy (OR, 1.93; 95% CI, 1.47-2.54). Furthermore, the likelihood of severe symptoms increased as the number of comorbidities increased (OR, 1.76; 95% CI, 1.59-1.95). Because survivors with lung cancer were more likely to report severe symptoms, we repeated the logistic regression analyses separately in survivors with lung cancer and those with other cancers. Survivors with other cancers were similar to the entire sample in the associations between symptom burden and multiple variables. In lung cancer survivors, younger age, low income, unemployment, minimal health insurance, more comorbidities, and metastasis remained significantly associated with high symptom burden (data not shown).
|No. Patients (%)|
|Variable||High-Symptom Group, n=1054a||Low-Symptom Group, n=2338a||OR [95% CI]||P|
|≥55||433 (27.7)||1132 (72.3)||1.00|
|<55||621 (34.0)||1206 (66.0)||2.31 [1.91-2.80]||<.0001|
|Men||410 (29.3)||989 (70.7)||1.00|
|Women||644 (32.3)||1349 (67.7)||1.05 [0.88-1.25]||.592|
|Non-Hispanic white||904 (30.0)||2106 (70.0)||1.00|
|Other||150 (39.3)||232 (60.7)||1.07 [0.84-1.36]||.597|
|Yes||730 (28.9)||1794 (71.1)||1.00|
|No||324 (37.3)||544 (62.7)||1.18 [0.98-1.42]||.090|
|≥College||595 (27.4)||1576 (72.6)||1.00|
|≤High school||459 (37.6)||762 (62.4)||1.29 [1.09-1.53]||.003|
|Annual household income|
|≥$40,000||525 (25.3)||1548 (74.7)||1.00|
|<$40,000||529 (40.1)||790 (59.9)||1.61 [1.34-1.94]||<.0001|
|Yes||542 (27.6)||1419 (72.4)||1.00|
|No||512 (35.8)||919 (64.2)||1.27 [1.05-1.53]||.012|
|Yes||954 (29.7)||2263 (70.3)||1.00|
|None/Medicaid||100 (57.1)||75 (54.3)||1.57 [1.10-2.24]||.012|
|No||865 (29.0)||2113 (71.0)||1.00|
|Yes||189 (45.7)||225 (54.3)||2.05 [1.60-2.62]||<.0001|
|No. of comorbidities||1.76 [1.59-1.95]||<.0001|
|None||369 (24.0)||1168 (76.0)||1.00|
|1||283 (29.1)||688 (70.9)||1.52 [1.26-1.83]||<.0001|
|≥2||402 (45.5)||482 (54.5)||3.22 [2.65-3.91]||<.0001|
|No||900 (29.3)||2175 (70.7)||1.00|
|Yes||154 (48.6)||163 (51.4)||2.27 [1.76-2.94]||<.0001|
|No||183 (35.7)||330 (64.3)||1.00|
|Yes||871 (30.3)||2008 (69.7)||0.96 [0.76-1.21]||.748|
|No therapy||471 (27.1)||1268 (72.9)||1.00|
|Therapy completed||417 (33.2)||840 (66.8)||1.23 [1.02-1.49]||.031|
|Active therapy||166 (41.9)||230 (58.1)||1.93 [1.47-2.54]||<.0001|
|Active therapy vs therapy completed||1.45 [1.11-1.90]||<.0001|
|No therapy||593 (31.0)||1318 (69.0)||1.00|
|Therapy completed||367 (30.5)||837 (69.5)||1.02 [0.85-1.21]||.863|
|Active therapy||94 (33.9)||183 (66.1)||0.82 [0.85-1.21]||.211|
|Active therapy vs therapy completed||0.83 [0.60-1.15]||.627|
Symptom Profiles in the High-Symptom Group
Exploratory factor analysis of the RSCL-M in the high-symptom group revealed 7 factors (Table 4): pain, treatment-related symptoms, fatigue, nausea, bowel/bladder control problems, weight change, and lung symptoms, which accounted for 7%, 6%, 5%, 4%, 4%, and 3%, respectively, of the total variance among the RSCL-M items. The pain factor comprised 5 items that loaded principally upon it: pain (other than low back), sore muscles, low back pain, difficulty sleeping, and headaches. The treatment-related symptoms factor included dry mouth, burning/sore eyes, loss of hair, sore mouth/pain when swallowing, tingling in hands/feet, skin irritation, swelling of arms/legs, and dizziness. The fatigue factor was composed of tiredness and lack of energy. The nausea factor included nausea and vomiting. The control-problems factor included problems controlling bowels, diarrhea, and abdominal aches. The weight-change factor was composed of weight loss, lack of appetite, and weight gain, which exhibited a negative loading. The lung-symptoms factor included coughing and shortness of breath. Five items did not belong to any factor, because their factor loadings were <0.30: These included decreased sexual interest, shivering, constipation, heartburn/belching, and problems controlling urine.
|Pain (other than low back pain)||0.691|
|Low back pain||0.591|
|Decreased sexual interest||0.158|
|Loss of hair||0.393|
|Sore mouth/pain when swallowing||0.392|
|Tingling hands or feet||0.372|
|Swelling of arms or legs||0.365|
|Lack of energy||0.818|
|Problems controlling your bowels||0.799|
|Problems controlling your urine||0.291|
|Lack of appetite||0.606|
|Shortness of breath||0.453|
To derive a component score for each RSCL-M factor or POMS-37 subscale in the high-symptom group, we averaged the ratings for all items that were loaded on a particular factor or subscale. The 3 highest RSCL-M symptom factor scores were for fatigue, pain, and lung symptoms, whereas the top-scoring POMS-37 subscales were vigor, fatigue, and tension (Table 5).
|Measure||Total, n=1399||Completed, n=523||Active, n=212||Completed, n=460||Active, n=137|
|Fatigue||61.81 ± 26.40||64.96 ± 26.18||66.12 ± 25.88||63.97 ± 23.35||64.36 ± 28.16|
|Pain||40.21 ± 21.86||41.60 ± 22.30||39.15 ± 21.36||39.17 ± 21.23||43.06 ± 23.00|
|Lung symptoms||27.73 ± 25.12||27.08 ± 25.25||30.90 ± 26.72||27.68 ± 25.94||32.97 ± 25.04|
|Weight change||20.24 ± 16.20||21.64 ± 15.96||22.48 ± 18.00||21.31 ± 16.73||23.56 ± 17.91|
|Treatment-related symptoms||19.89 ± 14.80||22.67 ± 15.41||21.33 ± 15.67||20.41 ± 14.45||24.33 ± 17.45|
|Bowel/bladder control problems||19.18 ± 20.95||19.22 ± 21.13||23.72 ± 23.09||18.47 ± 21.40||24.17 ± 23.49|
|Nausea||11.34 ± 20.12||11.81 ± 20.02||17.22 ± 26.33a||11.02 ± 19.57||14.12 ± 22.96|
|Vigor||72.76 ± 16.34||72.17 ± 17.04||74.90 ± 15.67||72.28 ± 16.57||71.20 ± 17.84|
|Fatigue||56.60 ± 22.21||57.73 ± 23.05||58.74 ± 20.78||56.76 ± 21.78||57.25 ± 23.33|
|Tension||40.27 ± 20.26||38.95 ± 19.96||38.40 ± 21.24||37.80 ± 19.42||41.13 ± 21.60|
|Depression||34.94 ± 20.93||33.47 ± 21.27||34.33 ± 20.78||32.86 ± 20.22||33.93 ± 21.27|
|Confusion||34.60 ± 18.60||35.50 ± 19.27||33.36 ± 18.88||32.92 ± 18.15||34.76 ± 19.14|
|Anger||29.58 ± 20.57||28.61 ± 20.64||26.84 ± 20.19||27.39 ± 19.64||29.04 ± 21.77|
Because actively receiving chemotherapy contributed to membership in the high-symptom group, we examined whether completion of chemotherapy or radiotherapy affected symptom severity in the high-symptom group, which included 523 survivors (37%) who had completed chemotherapy, 212 survivors (15%) who still were receiving chemotherapy, 460 survivors (33%) who had completed radiotherapy, and 137 survivors (10%) who still were receiving radiotherapy. No significant differences in symptom severity between survivors who were actively receiving chemotherapy and survivors who had completed chemotherapy were observed for any symptom other than nausea (which was higher in the active treatment group; P = .005). No significant differences in any symptoms were observed between survivors who had completed radiation and those who still were receiving treatment (Table 5).
Impact of Symptoms on HRQoL
We estimated the effects of symptoms on HRQoL in the high-symptom group using a linear regression model with the total score of SLDS-C as the dependent variable. The POMS-37 depression subscale, the RSCL-M fatigue factor, and the RSCL-M pain factor had the strongest standardized coefficients (−0.41, −0.22, and −0.09, respectively), suggesting that, among all 67 symptom items, depression, fatigue, and pain affected a survivor's HRQoL most (Table 6).
|Variable||Estimate||Standard Error||t||P||Standardized Estimate|
|Bowel/bladder control problems||−0.025||0.015||−1.67||.095||−0.021|
In this analysis of 1-year cancer survivors drawn from nationwide, population-based survey data, more than 1 in 4 survivors were categorized into a high-symptom group using 2-step cluster analysis. Survivors in this high-symptom group had significantly higher mean symptom severity on 2 assessment measures (RSCL-M and POMS-37) and had lower HRQoL ratings compared with survivors in the low-symptom group. Characteristics associated with the high-symptom group included age <55 years, low socioeconomic status (no better than a high-school education, annual household income <$40,000, no health insurance [or Medicaid/medical assistance], and being unemployed), lung and/or metastatic cancer, comorbid conditions, and current chemotherapy. To control the effect of cancer site, we stratified the entire sample by lung cancer versus other cancers and produced similar results, suggesting that risk factors for high symptom burden are common in all cancer survivors. In survivors with high symptom burden, exploratory factor analysis of RSCL-M symptom items revealed 7 factors, of which fatigue and pain contained the items with the highest severity scores. For the high-symptom group, symptom severity was similar whether or not therapy had been completed. Fatigue, pain, and depression most negatively affected survivors' ratings of HRQoL.
Previous studies of symptom burden in cancer survivors have compared the mean symptom burden of the entire cancer survivor population with the healthy population. In the current study, we identified a subgroup of survivors with high symptom burden, which should enable us to identify survivors who may require additional symptom monitoring and management after termination of therapy. The transition from active cancer therapy to follow-up has been identified as a period of disrupted adjustment during survivorship.7 Residual symptoms from cancer and cancer treatment often are not monitored as closely during follow-up as during active cancer therapy, which may contribute significantly to this disrupted adjustment. Cancer survivors in our study were approximately 1 year postdiagnosis, and >80% had completed anticancer treatment. Similar levels of major symptoms (eg, fatigue, pain, and depression) were reported in survivors who completed their therapy and those who still were in active therapy, suggesting that symptom burden in the early period of survivorship may persist whether or not cancer treatment has been completed.
Several of the socioeconomic variables we identified as associated with membership in the high-symptom group are used often to define “medically underserved” individuals, including 4 characteristics that represent low socioeconomic status: low annual income, low education level, unemployment, and minimal health insurance. It is generally accepted that socioeconomic status may affect the adequacy of symptom control and, thus, the level of symptom burden, with results from numerous studies indicating that symptom control may be comparatively poorer for medically underserved populations. For example, it has been reported that patients with low socioeconomic status were unable to access appropriate health care services for their disease22 or to communicate with clinicians who could aid in managing symptoms after treatment had ended.23 Socioeconomic disparity in cancer survivors has been associated with poor survival rates, more-rapid disease progression,24 poor HRQoL,25 and serious psychological distress.26 However, whether or not low income or unemployment caused high symptom burden could not be determined from the available data, because these variables were collected only once: 1 year after diagnosis. High symptom burden may contribute to change in a survivor's income or employment status—or vice versa. Studies tracking longitudinal changes in survivor income and employment over time would help to characterize the association between symptom burden and socioeconomic status. Finally, our sample tended to be well educated and well insured. Better representation from medically underserved populations might have resulted in a higher percentage of survivors with greater symptom burden. Nonetheless, even in our well educated and well insured sample, we identified a subset of cancer survivors with higher symptom burden.
The finding of greater risk for higher symptom burden in younger survivors is consistent with a report from the 2002 National Health Interview Survey,12 which evaluated the contribution of age to the presence of multiple symptoms in 1904 cancer survivors, and with a 2005 report from Baker et al, who observed that younger survivors were more likely than older survivors to report psychosocial problems as a result of their disease and treatment.27 Younger cancer survivors may have higher symptom burden because they are more likely to receive aggressive cancer therapies.28 In addition, younger patients may have higher expectations for resuming full vocational and family obligations, which may exacerbate symptoms.29
Fatigue, pain, and depression were identified in the National Institutes of Health (NIH) State-of-the-Science Statement on symptom management in cancer30 as the most common symptoms of which clinicians and researchers need to be aware. Not surprisingly, our analyses revealed that fatigue, pain, and depression had the greatest negative impact on HRQoL. These symptoms are highly correlated with poor HRQoL in patients with cancer,31, 32 affecting their daily activities and their ability to work and socialize; and it has been demonstrated that pain predicts disease recurrence and survival.33, 34 In addition, depressive symptoms usually occur with fatigue, pain, and sleep disturbance.35 The NIH report suggests that these symptoms frequently are undertreated in patients with cancer, although guidelines for their management have been published by the National Comprehensive Cancer Network36 and other groups. Our findings suggest that these critical symptoms should be monitored well beyond the end of curative treatment into the early stage of survivorship, when survivors often attempt to return to normal roles.
The current study had several potential limitations. For example, the physical and psychological aspects of symptom burden were measured by different instruments that had different response formats. In addition, our study attempted to provide an overview of symptom burden among US cancer survivors by collapsing heterogeneous cancer types into 1 broad category. Certain types of cancers, such as lung cancer, are associated with higher symptom burden, and symptom patterns may vary by diagnosis or anticancer treatment. Future studies need to describe how such variables as disease site and treatment contribute to survivor symptom burden. Like most studies of symptoms in cancer survivors, the cross-sectional nature of the data limited our ability to describe developmental trajectories of symptom burden. However, the longitudinal design of SCS-I provides cancer survivors the opportunity to contribute information about the persistence of symptoms throughout their survival.
Because our findings were derived from a population-based, nationwide survey, they have implications for the clinical care of cancer survivors. The finding that 25% of cancer survivors in the current study experienced high symptom burden highlights the need for routine post-treatment symptom assessment and management, especially in the first year after diagnosis. Symptom assessment and routine medical monitoring are likely to be infrequent after active therapy has ended, yet it is possible that some severe symptoms reported by our sample could have been addressed, which would have led to better functioning and less distress.7 In addition, the significantly higher burden experienced by uninsured and underinsured cancer survivors suggests another area of disparity in health care delivery that needs to be addressed at a policy level.
The American Cancer Society Studies of Cancer Survivors were funded as an intramural program of research conducted by the American Cancer Society's Behavioral Research Center. Research support for The University of Texas MD Anderson Cancer Center was provided by funds from the Hawn Foundation, Dallas, Texas (Dr. Shi), the National Cancer Institute (R01 CA026582; Drs. Shi and Cleeland), and MD Anderson's Department of Symptom Research (Mr. Michonski). The funding organizations played no role in study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
CONFLICT OF INTEREST DISCLOSURES
The authors made no disclosures.
- 1Office of Cancer Survivorship. About Cancer Survivorship Research: Survivorship Definitions. http://cancercontrol.cancer.gov/ocs/definitions.html. Accessed February 1, 2011.
- 2American Cancer Society. Cancer Facts and Figures 2009. http://www.cancer.org/acs/groups/content/@nho/documents/document/500809webpdf.pdf. Accessed December 2, 2010.
- 7From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, DC: The National Academies Press; 2006., .
- 20Factor analysis in the development and refinement of clinical assessment instruments. Psychological Assessment. 1995; 7: 286-299., .
- 21SAS System for Regression. 3rd ed. Cary, NC: SAS Institute, Inc.; 2000., .
- 30NIH State-of-the-Science Statement on symptom management in cancer: pain, depression, and fatigue. NIH Consens State Sci Statements. 2002; 19: 1-29.
- 36National Comprehensive Cancer Network. NCCN Guidelines for Supportive Care. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#supportive. Accessed December 2, 2010.