Abstract
Purpose
This study aimed to examine the symptom burden reported by survivors treated in survivorship clinics by describing the severity of symptoms and symptom interference with life activities, comparing symptom severity by sex, and identifying predictors of the three most prevalent moderate to severe symptoms.
Methods
This secondary data analysis examined patient-reported symptom burden data using the MD Anderson Symptom Inventory collected for clinical purposes from January to December 2023. Sex differences in symptom burden were compared using t-tests. Multivariate logistic regressions identified predictors of the three most prevalent moderate to severe symptoms.
Results
Among 2550 survivors (mean age 61.9 ± 12.1 years; 69.9% female, 36.4% breast cancer), the average time in survivorship care was 4.04 ± 4.00 years. Over 75% of survivors reported experiencing ≥ 1 symptom, and 45% reported ≥ 1 moderate-severe symptom. The three most prevalent moderate to severe symptoms were fatigue (25%), sleep disturbance (24%), and problems remembering (15%). Compared with males, females reported significantly more symptoms (p < 0.05) and more moderate to severe symptoms (p < 0.01). Female survivors and those under the age of 65 were more likely to report moderate to severe fatigue, sleep disturbance, and problems remembering (all p < 0.01).
Conclusion
The high prevalence of persistent symptoms among cancer survivors in this sample supports the need for routine symptom assessments in survivorship care. Age and sex are important considerations in tailoring supportive interventions. As the population of cancer survivors grows, understanding symptom burden across diagnoses is critical to inform effective supportive care strategies.
Keywords: Cancer, Patient-reported outcomes, Survivorship, Symptom burden
Introduction
Over 18 million people currently living in the United States are cancer survivors, and the number of survivors is projected to exceed 22 million by 2035 [1]. Despite efforts aimed at improving survivorship care, cancer survivors continue to report unmet supportive care needs across multiple domains, including psychological, social, physical, and cognitive functioning. Cancer survivors frequently experience persistent symptoms that negatively impact quality of life (QOL) long after treatment completion [2]. Symptoms most frequently reported by survivors across cancer diagnoses include fatigue, sleep disturbance, and cognitive impairment [3]. Cancer survivors are transitioned out of oncology care after completing treatment. Survivorship care is provided across a range of health care settings. Common locations include comprehensive cancer centers, academic medical centers, primary care settings, shared-care or coordinated models between the oncology and primary care teams, specialty survivorship clinics or community-based practices [4, 5]. Addressing cancer survivors’ symptom burden is a critical component for optimizing health and promoting well-being.
The National Standards for Cancer Survivorship Care recommend ongoing assessment of the physical, psychological, and social effects of cancer and its treatment following completion of therapy [4]. These assessments should incorporate ongoing evaluation and management of both physical and psychosocial symptoms. Because cancer symptoms are experiential phenomena and inherently subjective, these are most accurately assessed through patient self-report, and patient-reported outcome (PRO) instruments are frequently used to capture this information. Furthermore, PRO instruments integrated into the electronic health record (EHR) capture substantially higher rates of symptom prevalence compared with clinician documentation alone, suggesting that EHR‑embedded PROs provide valuable insights for cancer survivorship care [6]. Since survivorship care is often shared among oncology, primary care, and specialty providers, a common understanding of prevalent symptoms helps standardize assessments and supports consistent monitoring and continuity of care.
The Survivorship Program at a National Cancer Institute (NCI) designated cancer center successfully implemented electronic PROs into clinical practice to guide supportive care for cancer survivors [7]. In this survivorship program, patients are transitioned from oncologist-directed follow-up care to diagnosis specific survivorship care clinics at defined intervals following the completion of treatment. Transitions are guided by clinical practice algorithms and occur at a point in the patient’s care trajectory when the risk of primary cancer recurrence or relapse has stabilized [8]. Advanced practice providers typically see patients in the survivorship clinic annually. Clinic visits focus on the provision of comprehensive survivorship care, including surveillance for cancer recurrence, management of late and long-term treatment effects, symptom management, cancer prevention, and risk reduction strategies, and addressing psychosocial concerns.
The Survivorship Program’s implementation of PROs yielded a large database, providing a unique opportunity to assess the symptom burden of a diverse sample of cancer survivors. Understanding the prevalence and severity of the most common symptoms experienced by cancer survivors is crucial to informing symptom management practices among healthcare providers in diverse care settings. The purpose of this study was to examine the symptom burden reported by cancer survivors who received care in survivorship clinics over a one-year period. The specific aims were to (1) describe symptom severity and the severity of symptom interference with life activities, (2) compare symptom severity by sex and cancer diagnosis, and (3) identify predictors of the three most prevalent moderate to severe symptoms.
Methods
Study design and population
This secondary data analysis examined patient-reported symptom burden in adult cancer survivors who received care at one of six diagnosis specific survivorship clinics at an NCI-designated comprehensive cancer center. The participating clinics included the breast, head and neck, genitourinary, lymphoma, thoracic, and thyroid survivorship clinics. As part of standard survivorship care, all cancer survivors receive a request to complete a PRO instrument (MD Anderson Symptom Inventory [MDASI]) through the EHR patient portal seven days prior to their scheduled survivorship clinic visit.
Data were retrieved from an existing, IRB approved Survivorship Program PRO database. Variables included de-identified demographic, clinical, and MDASI results from cancer survivors receiving care across six survivorship clinics during 2023. The inclusion criteria for study cases were complete and evaluable MDASI within 7 days of the scheduled clinic visit. Some patients completed more than one MDASI in 2023 to correspond with multiple survivorship clinic visits. Only the first completed MDASI was included in the dataset so that each completed MDASI represented a unique individual. From January 1 to December 31, 2023, 7912 cancer survivors received a request to complete the MDASI prior to their scheduled clinic visit. Data were available for 34% (n = 2693) who completed the MDASI within 7 days of their scheduled clinic visit. Data from non-responders were not available in the PRO database; thus, comparisons of demographic or clinical characteristics between responders and non-responders were not performed.
Study variables
Demographic and clinical characteristics Age at MDASI completion, sex assigned at birth, race/ethnicity, diagnosis, and time (years) patients had received care in survivorship clinics prior to MDASI completion were abstracted from the Survivorship Program’s PRO database. Variables were further categorized into groups for regression modeling. Age was categorized as younger (< 65 years) and older adults (≥ 65 years) according to the American Society of Clinical Oncology’s recommendations to improve evidence guiding the treatment and management focused on older adults [9]. Years in survivorship care was grouped based on the distribution of the sample and the pattern of decreasing follow-up visits in survivorship care [10].
Symptom burden. The MDASI is a valid and reliable cancer-specific, patient-reported questionnaire used to assess the presence and severity of symptoms and the severity of symptom interference with life activities over the past 24 h [11]. The instrument consists of 13 symptom items and 6 symptom interference items. Symptom and symptom interference items are rated on a numeric scale from 0 to 10, where 0 = “not present/did not interfere” and 10 = “as bad as you can imagine/interfered completely.” Higher scores indicate higher severity of symptoms and symptom interference. Symptoms were considered present when rated ≥ 1. The number of symptoms present per case was calculated by summing the number of symptoms rated ≥ 1 per case. To better understand the prevalence of moderate to severe symptom and interference, each symptom and interference item was also coded as not present = 0, 1–3 = mild, 4–10 = moderate to severe. The MDASI demonstrated excellent internal consistency in the current sample (Cronbach’s α = 0.89 for symptoms; 0.94 for interference items).
Data analysis
Means, frequencies, percentages, and standard deviations were calculated for demographic and clinical variables. Symptom and symptom interference items are reported as means and standard deviation (SD) for continuous variables or as frequencies (%) for variables grouped by severity (not present, mild, or moderate to severe). The effect of sex differences (female versus male) on symptom severity and interference were analyzed using the Welch’s t-test. Multivariable logistic regressions were conducted to examine clinical and demographic predictors of moderate to severe fatigue, sleep disturbance and problems remembering (scores 4–10 versus 0–3). Each model included age (< 65 versus ≥ 65 years), sex (female versus male), race/ethnicity (Non-Hispanic White versus racial/ethnic minority), and years of survivorship care in the specialized setting (< 1 year versus 1–4 years versus ≥ 5 years) as predictors. Logistic regression assumptions were evaluated prior to modeling. Because all predictors were categorical, the assumption of linearity in the logit was not applicable. Independence of observations was ensured by including only the first completed MDASI per survivor. Multicollinearity was assessed using tolerance and variance inflation factors (VIF) derived from a parallel linear regression specifying the same predictors; all values indicated negligible collinearity (all VIF ≤ 1.04, all tolerance ≥ 0.96), and no evidence of complete or quasi-complete separation was observed. Model fit was evaluated using the Hosmer–Lemeshow goodness-of-fit test, the omnibus likelihood-ratio test, and the Cox & Snell and Nagelkerke pseudo-R² statistics; overall classification accuracy was also examined. Results are reported as odds ratio (ORs) with 95% confidence interval (CIs). Statistical significance was defined as p <.05. There was no data imputation for missing data. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 24.0 (IBM Corp., Armonk, NY, 2020).
Results
Sample characteristics
The final sample included 2550 cancer survivors after excluding MDASIs that were completed more than seven days before the scheduled survivorship clinic visit (n = 22), MDASIs subsequently completed after the first in 2023 (n = 93), and unevaluable MDASIs (n = 28). Cancer survivors completed the MDASIs a mean of 2.49 (SD = 2.45) days prior to the scheduled clinic visit. Demographic and clinical characteristics are displayed in Table 1. The mean age was 61.88 (SD = 12.06) years. Among survivors, 70% (n = 1782) were female and 70% (n = 1784) were non-Hispanic White. Hispanic individuals comprised 13% (n = 341) of the sample. Cancer survivors were drawn from the following survivorship clinics: breast (n = 929, 36%), thyroid (n = 741, 29%), head and neck (n = 328, 13%), lymphoma (n = 198, 8%), genitourinary (n = 198, 8%), and thoracic (n = 80, 3%).The mean time patients had been receiving care in the survivorship clinic prior to completing the first MDASI survey in 2023 was 4.04 (SD = 4.00) years.
Table 1.
Sample Characteristics (N = 2550)
| Outcomes | Mean (SD) or n (%) |
|---|---|
| Age | 61.88 (12.06) |
| Sex assigned at birth | |
| Female | 1782 (69.9%) |
| Male | 766 (30.0%) |
| Declined to answer | 2 (0.1%) |
| Race | |
| Non-Hispanic white | 1784 (70.0%) |
| Hispanic | 341 (13.4%) |
| Non-Hispanic black | 193 (7.6%) |
| Asian/Pacific islander | 187 (7.3%) |
| Other/multiracial | 35 (1.4%) |
| Declined to answer | 10 (0.4%) |
| Survivorship clinic | |
| Breast | 929 (36.4%) |
| Thyroid | 741 (29.1%) |
| Head/neck | 328 (12.9%) |
| Lymphoma | 274 (10.7%) |
| Genitourinary | 198 (7.8%) |
| Thoracic | 80 (3.1%) |
| Years since 1 st Survivorship Clinic Visit | 4.04 (4.00) |
| Years in survivorship care groups | |
| <1 year | 605 (23.7%) |
| 1–4 years | 990 (38.8%) |
| ≥5 years | 955 (37.5%) |
SD, standard deviation
Symptom burden
Over 75% (n = 1931) of survivors reported at least one symptom present and approximately 41% (n = 1040) reported five or more symptoms present. Approximately half of survivors (n = 1149, 45%) reported at least one moderate to severe symptom (Fig. 1). Table 2 displays the means (SD) and frequencies of severity ratings (none, mild, moderate to severe) for symptom and symptom interference items. The mean symptom severity scores ranged from 2.08 (SD = 2.51) for fatigue to 0.11 (SD = 0.72) for vomiting. The three most prevalent moderate to severe symptoms across cancer diagnoses were fatigue (n = 646, 25%), sleep disturbance (n = 613, 24%), and problems remembering (n = 379, 15%). The distribution of moderate to severe symptoms (percentages) reported across cancer diagnoses is visualized as a heat map in Fig. 2. Symptom interference scores were available for all survivorship clinics except genitourinary (n = 198). The mean scores for the symptom interference items ranged from 1.12 (SD = 2.11) for work (including work around the house) to 0.70 (SD = 1.70) for relations with other people. Survivors most frequently reported moderate to severe symptom interference for work (n = 308, 13%) and general activity (n = 298, 13%).
Fig. 1.
Number of symptoms present and moderate to severe symptoms per survivor (N = 2550). Present, symptoms rated ≥ 1; Moderate to severe, symptoms rated 4–10
Table 2.
Means and frequencies of severity ratings for symptoms and symptom interference items (N = 2550)
| Severity ratings | 0–10 | Not Present (0) | Mild (1–3) | Moderate to severe (4–10) |
|---|---|---|---|---|
| Symptoms | Mean (SD) | n (%) | n (%) | n (%) |
| Fatigue | 2.08 (2.51) | 1152 (45.4%) | 742 (29.2%) | 646 (25.4%) |
| Sleep disturbance | 1.95 (2.53) | 1255 (49.4%) | 671 (26.4%) | 613 (24.1%) |
| Problems remembering | 1.48 (2.07) | 1285 (50.6%) | 874 (34.4%) | 379 (14.9%) |
| Drowsiness | 1.32 (2.10) | 1512 (59.6%) | 659 (26.0%) | 366 (14.4%) |
| Dry mouth | 1.20 (2.14) | 1659 (65.3%) | 542 (21.3%) | 338 (13.3%) |
| Neuropathy | 1.11 (2.06) | 1702 (67.0%) | 528 (20.8%) | 311 (12.2%) |
| Distress | 1.04 (1.94) | 1714 (67.6%) | 528 (20.8%) | 293 (11.6%) |
| Pain | 0.89 (1.98) | 1936 (76.5%) | 316 (12.5%) | 279 (11.0%) |
| Sadness | 0.82 (1.75) | 1852 (73.1%) | 463 (18.3%) | 220 (8.7%) |
| Shortness of breath | 0.72 (1.61) | 1976 (75.5%) | 430 (16.9%) | 193 (7.6%) |
| Lack of appetite | 0.44 (1.33) | 2176 (85.7%) | 245 (9.6%) | 118 (4.6%) |
| Nausea | 0.31 (1.17) | 2292 (90.2%) | 182 (6.4%) | 86 (3.4%) |
| Vomiting | 0.11 (0.72) | 2435 (96.0%) | 75 (3.0%) | 26 (1.0%) |
| Symptom Interference a | ||||
| Work (including work around the house) | 1.12 (2.11) | 1601 (68.6%) | 426 (18.2%) | 308 (13.2%) |
| General activity | 1.09 (2.06) | 1608 (69.0%) | 425 (18.2%) | 298 (12.8%) |
| Walking | 0.87 (1.95) | 1794 (76.9%) | 294 (12.6%) | 245 (10.5%) |
| Mood | 0.91 (1.86) | 1677 (71.9%) | 421 (18.0%) | 235 (10.1%) |
| Enjoyment of life | 0.87 (1.87) | 1715 (73.4%) | 393 (16.8%) | 227 (9.7%) |
| Relations with other people | 0.70 (1.70) | 1832 (78.6%) | 324 (13.9%) | 174 (7.5%) |
SD, standard deviation; aSeverity ratings for symptom interference items were not available for genitourinary cancer survivors (n = 198)
Fig. 2.
Heat map of the distribution (percentages) of moderate to severe symptomsa across cancer diagnoses. aSymptoms rated 4–10. The degree of darkness in the heat map represents the percentage of survivors who rated each symptom as moderate to severe (a darker color represents a higher percentage)
Sex differences
Table 3 displays the differences in the number of symptoms (present, moderate to severe) and severity ratings of symptoms and symptom interference items by sex. Compared to males, female survivors reported significantly more symptoms present (t(1467) = 2.76, p =0.006) and more moderate to severe symptoms (t(1695) = 5.38, p <0.001). Female survivors reported significantly higher severity in the presence of nine symptoms and four symptom interference items compared to males: fatigue (t(1680) = 6.46, p <0.001), sleep disturbance (t(1716) = 6.78, p <0.001), problems remembering (t(1594) = 2.88, p =0.004), neuropathy (t(1738) = 3.24, p =0.001), distress (t(1790) = 5.52, p <0.001), pain (t(1812) = 4.15, p <.001), sadness (t(1780) = 5.05, p <.001), nausea (t(2047) = 3.69, p <0.001), and vomiting (t(2289) = 2.95, p =0.003), symptom interference with work (t(2289) = 2.95, p =0.003), general activity (t(2289) = 2.95, p =0.003), walking (t(2289) = 2.95, p =0.003), and mood (t(2289) = 2.95, p =0.003). Female survivors reported significantly higher ratings of moderate to severe neuropathy (t(161) = 3.49, p =0.001). No significant differences were observed in ratings of moderate to severe symptom interference items. Figure 3 displays the percentages of females and males that rated each symptom moderate to severe.
Table 3.
Sex differences in the number of symptoms (present, moderate to severe) and severity ratings of symptoms and symptom interference items
| Severity ratings | Presenta | Moderate to severeb | ||||
|---|---|---|---|---|---|---|
| Female | Male | p | Female | Male | p | |
| Symptoms | ||||||
| Number of symptoms (out of 13) | 4.09 (3.58) | 3.67 (3.53) | 0.006 | 1.67 (2.50) | 1.15 (2.11) | < 0.001 |
| Fatigue | 2.28 (2.61) | 1.62 (2.22) | < 0.001 | 5.86 (1.56) | 5.66 (1.55) | 0.190 |
| Sleep disturbance | 2.15 (2.64) | 1.47 (2.18) | < 0.001 | 5.86 (1.75) | 5.71 (1.57) | 0.337 |
| Problems remembering | 1.56 (2.12) | 1.31 (1.91) | 0.004 | 5.56 (1.57) | 5.67 (1.54) | 0.549 |
| Drowsiness | 1.36 (2.14) | 1.23 (2.00) | 0.163 | 5.68 (1.53) | 5.74 (1.61) | 0.766 |
| Dry mouth | 1.16 (2.14) | 1.28 (2.12) | 0.187 | 5.96 (1.84) | 5.79 (1.77) | 0.430 |
| Neuropathy | 1.19 (2.16) | 0.93 (1.77) | 0.001 | 6.03 (1.84) | 5.31 (1.50) | 0.001 |
| Distress | 1.17 (2.05) | 0.75 (1.63) | < 0.001 | 5.66 (1.63) | 5.71 (1.55) | 0.833 |
| Pain | 0.98 (2.10) | 0.66 (1.65) | < 0.001 | 6.00 (1.80) | 5.67 (1.48) | 0.149 |
| Sadness | 0.93 (1.85) | 0.58 (1.47) | < 0.001 | 5.67 (1.65) | 5.81 (1.49) | 0.590 |
| Shortness of breath | 0.69 (1.60) | 0.79 (1.64) | 0.149 | 5.50 (1.47) | 5.55 (1.50) | 0.838 |
| Lack of appetite | 0.45 (1.36) | 0.39 (1.26) | 0.292 | 5.57 (1.72) | 5.71 (1.55) | 0.688 |
| Nausea | 0.36 (1.28) | 0.19 (0.88) | < 0.001 | 5.72 (1.85) | 6.00 (1.60) | 0.584 |
| Vomiting | 0.13 (0.80) | 0.06 (0.47) | 0.003 | 6.27 (2.16) | 5.50 (2.38) | 0.578 |
| Symptom Interference | ||||||
| Work (including work around the house) | 1.20 (2.17) | 0.89 (1.90) | 0.001 | 5.84 (1.73) | 5.92 (1.95) | 0.779 |
| General activity | 1.15 (2.11) | 0.91 (1.90) | 0.010 | 5.75 (1.70) | 5.89 (1.68) | 0.563 |
| Walking | 0.93 (2.01) | 0.67 (1.74) | 0.002 | 5.86 (1.69) | 6.20 (1.81) | 0.283 |
| Mood | 0.99 (1.96) | 0.66 (1.52) | < 0.001 | 5.72 (1.74) | 5.53 (1.58) | 0.514 |
| Enjoyment of life | 0.90 (1.90) | 0.81 (1.79) | 0.343 | 5.84 (1.79) | 5.86 (1.54) | 0.914 |
| Relations with other people | 0.74 (1.74) | 0.61 (1.58) | 0.095 | 5.80 (1.72) | 6.09 (2.01) | 0.451 |
SD, standard deviation;
aSymptom and symptom interference items rated ≥ 1;
bSymptom and interference items rated 4–10
Symptom interference scores were missing for the genitourinary cancer survivors (n = 198)
Fig. 3.
Moderate to severea symptoms by sex (Percentages). aSymptoms rated 4–10
Predictors of the three most prevalent moderate to severe symptoms
Table 4 displays the results of the logistic regressions examining the predictors of the three most prevalent moderate to severe symptoms (fatigue, sleep disturbance, and problems remembering). Each model was statistically significant (fatigue: χ²[5] = 51.16, p <0.001; sleep disturbance: χ²[5] = 59.48, p <0.001; problems remembering: χ²[5] = 44.78, p <0.001) and demonstrated adequate calibration on the Hosmer–Lemeshow goodness-of-fit test (fatigue: χ²[8] = 5.94, p =0.65; sleep disturbance: χ²[8] = 4.77, p =0.78; problems remembering: χ²[8] = 8.77, p =0.36). The models accounted for a modest proportion of variance (Nagelkerke R² = 0.029, 0.035, and 0.031, respectively) and correctly classified 74.6%, 75.9%, and 85.1% of cases. Younger survivors (< 65 years) had 47% higher odds of reporting moderate to severe fatigue (p <0.001), 49% higher odds of reporting moderate to severe sleep disturbance (p <0.001), and 80% higher odds of reporting moderate to severe reporting problems remembering (p <0.001) compared to older survivors. Compared to males, female survivors had 75% higher odds of reporting moderate to severe fatigue (p <0.001), 82% higher odds of reporting moderate to severe sleep disturbance (p <0.001), and 41% higher odds of reporting moderate to severe problems remembering (p =0.010). No significant differences by race/ethnicity or years in survivorship care were observed for these moderate to severe symptoms.
Table 4.
Predictors of reporting moderate to severea fatigue, sleep disturbance, and problems remembering
| Predictors | B | SE | OR | 95% CI | p-value |
|---|---|---|---|---|---|
| Fatigue | |||||
| Age < 65 years (reference: Age ≥ 65) | 0.382 | 0.095 | 1.465 | 1.216–1.765 | < 0.001 |
| Female (reference: Male) | 0.559 | 0.110 | 1.749 | 1.410–2.169 | < 0.001 |
| Non-Hispanic White (reference: Racial/ethnic minority) | 0.097 | 0.102 | 1.102 | 0.903–1.344 | 0.340 |
| < 1 year in survivorship care (reference: ≥5 years) | 0.008 | 0.120 | 1.008 | 0.797–1.275 | 0.947 |
| 1–4 years in survivorship care | −0.064 | 0.107 | 0.938 | 0.761–1.156 | 0.549 |
| Sleep Disturbance | |||||
| Age < 65 years (reference: Age ≥ 65) | 0.400 | 0.097 | 1.492 | 1.233–1.804 | < 0.001 |
| Female (reference: Male) | 0.597 | 0.114 | 1.817 | 1.454–2.270 | < 0.001 |
| Non-Hispanic White (reference: Racial/ethnic minority) | −0.085 | 0.102 | 0.918 | 0.752–1.121 | 0.401 |
| < 1 year in survivorship care (reference: ≥5 years) | −0.040 | 0.122 | 0.961 | 0.757–1.220 | 0.743 |
| 1–4 years in survivorship care | −0.165 | 0.109 | 0.848 | 0.685–1.049 | 0.129 |
| Problems Remembering | |||||
| Age < 65 years (reference: Age ≥ 65) | 0.586 | 0.119 | 1.797 | 1.423–2.270 | < 0.001 |
| Female (reference: Male) | 0.347 | 0.134 | 1.414 | 1.087–1.840 | 0.010 |
| Non-Hispanic White (reference: Racial/ethnic minority) | −0.151 | 0.120 | 0.860 | 0.679–1.088 | 0.209 |
| < 1 year in survivorship care (reference: ≥5 years) | 0.243 | 0.144 | 1.275 | 0.961–1.691 | 0.092 |
| 1–4 years in survivorship care | 0.002 | 0.132 | 1.002 | 0.773–1.299 | 0.988 |
SE, standard error; OR, odds ratio; CI, confidence interval; aSymptoms rated 4–10
Discussion
This study used an NCI-designated cancer center’s Survivorship Program’s PRO database to examine the symptom burden reported by cancer survivors treated across six diagnosis specific survivorship clinics. Over 75% of survivors in our sample reported at least one symptom present, although the low mean severity scores for symptom and interference items reflected mild severity levels. Survivors reported highest severity of symptom interference with work and general activity. The identification of moderate to severe symptoms in 25% of the sample reinforces the importance of utilizing PROs to assess cancer survivors’ symptom burden throughout survivorship care. This information is particularly helpful to providers who may not specialize in cancer care, such as primary care providers who see cancer survivors in their practice.
The study findings contribute to the expanding body of research highlighting long-term fatigue as one of the most persistent and burdensome symptoms experienced by cancer survivors, often continuing for years following treatment completion [12, 13]. While the overall mean rating of fatigue in this sample was low, 25% of respondents reported ongoing moderate to severe fatigue. These findings underscore the critical need for ongoing evaluation and management of fatigue across all cancer types regardless of years since completing cancer treatment. Supporting this, a related study involving 206 cancer survivors receiving care in a survivorship clinic found significant reductions in fatigue from the initial visit to the one-year follow-up, although approximately 30% continued to experience moderate to severe fatigue [14]. Further prospective, longitudinal studies are warranted to evaluate persistent fatigue and potential moderate to severe symptom clusters in cancer survivors to mitigate the impact on quality of life.
Sleep disturbance was the second most prevalent moderate to severe symptom, reinforcing the existing evidence that sleep disturbances remain a persistent problem among cancer survivors [15]. However, it is important to note that the prevalence of sleep disturbance in cancer survivors may not be greater than that observed in the general population. A large comparative study involving female cancer survivors (n = 2067) and age-matched controls without a cancer history (n = 9717) found no significant difference in sleep disturbances after adjusting for age, prior depression, diabetes, hypertension, and menopausal status [16]. The comparable rates of moderate to severe fatigue (25.4%) and sleep disturbance (24.1%) observed in this study are also noteworthy, reflecting the co-occurrence of these symptoms in cancer survivors [17]. Sleep disturbance is associated with adverse health outcomes including increased risk of cardiovascular disease and decreased neurocognitive functioning [18]. Therefore, routine assessment of sleep disturbance should be a key component of survivorship care.
Problems remembering was the third most prevalent moderate to severe symptom in our sample. Problems remembering may be a subjective indication of cancer-related cognitive impairment, a common side effect experienced by an increasing number of cancer survivors [19]. Often referred to as “chemo brain” or “radiation fog”, cancer-related cognitive impairment describes the decline in patients’ cognitive functions, such as perception, attention, language, thinking, learning and memory, action planning, understanding, reasoning and problem solving [20]. Approximately 25% of survivors may continue to experience cancer-related cognitive impairment up to 20 years following the completion of cancer treatment [21, 22]. Close to 15% of cancer survivors in this study reported problems remembering. This study did not include objective measures of cognitive impairment, so it is not clear if problems remembering points to cancer-related cognitive decline in this sample. To further investigate this, it may be helpful to include subjective and objective measure of cognitive impairment in future studies as subjective and objective measures do not always correlate [23].
Survivors’ symptom burden interferes with multiple aspects of daily life. Over 25% of survivors in this study reported their symptoms interfered with work, general activity, mood, or enjoyment of life. Participants of a recent qualitative study that explored the return to daily life activities after cancer treatment described how symptoms including fatigue and difficulty concentrating interfered with daily tasks such as taking long car rides, eating at restaurants, or socializing [24]. Returning to work after completing cancer treatment is particularly challenging due to fatigue and impaired cognitive function, two of the most bothersome symptoms identified in the present study [25]. Survivors frequently underestimate how their symptoms will interfere with work and how long it will take for them to adjust and learn how to manage these symptoms [26, 27].
Managing symptom burden in survivorship care requires a multi-disciplinary approach. In a study of 2508 survivors, participants reported dissatisfaction with their healthcare providers’ management of burdensome symptoms including fatigue and concentration problems, with over 40% reporting their providers never asked about fatigue [27, 28]. Knowledge of how the effects of cancer treatment interfere with the patient’s daily life may facilitate identifying appropriate resources. In the primary care setting for example, providers not familiar with common symptoms experienced by cancer survivors may be prompted to ask more specific symptom-related questions by first asking the patient to describe their daily challenges and how their quality of life has changed after completing cancer treatment [29]. By becoming familiar with the most common symptoms experienced during survivorship, healthcare providers can educate patients on what to expect and help patients set realistic goals for returning to daily activities and work. Survivors may also benefit from referrals to supportive services such as psychologists and occupational therapists [24].
Consistent with previous studies, female survivors in this study reported significantly higher symptom burden compared to males. Explanations for sex and gender differences in cancer survivors are rooted in both biological (sex) reasons and in the broader social constructs (gender), which encompass roles, social functioning, identity, norms, and relationships [30]. Sex differences in disease prevalence, clinical presentation, and treatment response originate from the genetic distinctions between male and female [31]. Significant sex differences were observed in this study with female survivors reporting higher severity of nine symptoms present (rated ≥ 1). However, these differences are reduced to one symptom, neuropathy, when moderate to severe symptoms (rated 4–10) were examined. Female survivors reported significantly higher severity of moderate to severe neuropathy than males in this study, which may be explained by the higher representation of female and breast cancer survivors in our sample. Although specific therapy-related data was not available in the Survivorship Database, breast cancer is treated almost exclusively in females and frequently with taxanes. Chemotherapy-induced peripheral neuropathy is a common side-effect of taxanes such as paclitaxel and docetaxel [3].
Oertelt-Prigione et al. [30] suggest that while the prevalence of physical symptoms might be primarily related to biological differences, gender roles and social functioning may transcend biology in the symptom experience. Female cancer survivors reported experiencing more severe symptoms than males and higher severity for symptom interference. These findings may be explained by role-based gender differences in the recognition, expression and reporting of symptoms [32, 33]. Women are generally socialized to express health concerns and engage with care proactively, whereas men may be influenced by norms of stoicism or reluctance. Women tend to seek care earlier and more often, whereas masculinity norms may keep men from seeking help [34, 35]. Cultural norms may encourage men to underreport symptoms and women to be more expressive of them. Socialization often encourages women to articulate distress and emotions, leading to more frequent reporting of physical symptoms [36].
Our findings revealed notable age-related differences in patient-reported moderate to severe symptoms. Younger survivors (< 65 years) in our sample were significantly more likely to report moderate to severe fatigue, sleep disturbance, and problems remembering than those aged ≥ 65 years. These results align with prior studies showing that younger cancer survivors frequently report a greater symptom burden and poorer QOL than older survivors [37]. For example, younger breast cancer survivors have been found to experience more fatigue, cognitive difficulties, sleep disturbance, and psychological distress than their older counterparts, and a population-based study found that survivors under 50 were nearly three times more likely than those over 65 to report ongoing pain, insomnia, and distress [37–40]. Similarly, a large American Cancer Society cohort identified younger age as an independent risk factor for elevated symptom burden one year after treatment (aOR = 2.3 for younger vs. older age) [41]. Fatigue and sleep disturbance are consistently among the most prevalent severe symptoms in younger survivors, and cognitive concerns such as memory or concentration problems are also reported more frequently [37]. In one study, breast cancer survivors under 50 demonstrated more pronounced subjective cognitive impairment than older survivors in the first two years post-treatment [42]. Taken together, younger survivors emerge as a subgroup at greater risk for persistent fatigue, insomnia, and cognitive difficulties after therapy.
Several factors may explain this heightened symptom burden in younger survivors, including more aggressive treatment regimens, greater psychosocial stressors such as work and caregiving responsibilities, and higher expectations for post-treatment recovery [43, 44]. Older survivors may underreport symptoms if they perceive them as part of normal aging and often display resilience and coping strategies that preserve QOL despite chronic issues [45]. For example, lower levels of fatigue reported by older cancer survivors may be influenced by adjusted expectations regarding energy levels as one ages or a tendency to normalize fatigue as part of aging [27]. Cancer diagnoses at younger ages or the more aggressive treatments they often require may also contribute to more pronounced long-term side effects [46]. These findings underscore the importance of age-tailored survivorship care. Younger survivors may benefit from targeted interventions such as fatigue management, cognitive rehabilitation, and sleep hygiene, while older survivors should continue to receive active monitoring and support, recognizing that a uniform approach may overlook distinct age-related needs.
This study has several important limitations that impact the generalizability of study findings. First, the data used in this study were originally collected as part of standard clinical care for cancer survivors receiving care in a survivorship clinic. The study team used an established Survivorship Program database and did not directly collect data from survivors. Thus, the analysis was limited to the data available in the database, a common limitation of secondary data analysis. Only 34% of eligible survivors completed the MDAI within 7 days of their survivorship clinic visit, and this represents a potential selection bias. In addition, clinical and demographic characteristics of individuals who did not complete the MDASI were not captured in the PRO database. Consequently, the extent to which the sample is representative cannot be assessed as comparisons between the responders and non-responders could not be performed. No data were available specifying cancer treatment type (e.g., chemotherapy, radiation, etc.), limiting our analyses and conclusions. The data were also collected in a single comprehensive cancer institution and may not represent cancer survivors who receive survivorship care in other healthcare settings. While a secondary analysis approach has inherent limitations, use of an established cancer survivorship database enabled access to a large, heterogeneous sample of cancer survivors representing six cancer diagnoses, enhancing generalizability of findings. However, this heterogeneity in disease stage, treatment modality and treatment intensity may have also increased variability, potentially complicating the interpretation of the symptom burden results. Future subgroup analysis will help identify and account for differences within this sample. Even so, the data from this large study provides guidance to healthcare providers regarding the typical prevalent symptoms that cancer survivors may experience regardless of diagnosis or time in survivorship care.
Conclusion
In summary, our findings underscore the value of using PROs in detecting persistent symptoms and guiding survivorship care. Symptom burden in cancer survivors is common leading to impairment in QOL. Fatigue, sleep disturbance, and problems remembering were identified as the most prevalent moderate to severe symptoms experienced by survivors. Age and sex-related differences for symptom severity align with existing literature and reinforce the observation that female and younger cancer survivors are more likely to experience moderate to severe symptoms, highlighting the need for individualized supportive care. Further studies are needed to evaluate the longitudinal symptom burden in cancer survivors and to inform targeted interventions to improve the trajectory of their health and QOL.
Author contributions
Conceptualization: all authors. Data curation: GT, EC, KG, JR, and EH. Formal Analysis: GT, EC, and EH. Methodology: GT, EC, and EH. Supervision: JD, AF, MR, and EH. Writing of the original draft: GT and EH. Writing, reviewing, & editing of the manuscript: all authors. All authors critically revised the manuscript and approved the final version.
Funding
Authors GT, KA, and EH received research support for this study from the Argyros Family Foundation.
Data availability
The data supporting the findings of this study are not publicly available, but they can be accessed upon reasonable request by contacting the corresponding author.
Declarations
Competing interests
The authors declare no competing interests.
Ethical approval
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of the University of Texas MD Anderson Cancer Center, protocol number 2024-0043.
Consent to Participate
As a retrospective study using an existing IRB approved database, the IRB granted an informed consent exemption.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
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Data Availability Statement
The data supporting the findings of this study are not publicly available, but they can be accessed upon reasonable request by contacting the corresponding author.