Abstract
Purpose:
Colorectal cancer (CRC) incidence and mortality are increasing among young adults (YAs) aged 18–39. This study compared quality of life (QOL) between YA and older adult CRC survivors in the ColoCare Study.
Methods:
Participants were grouped by age (years) as follows: 18–39 (YA), 40–49, 50–64, 65+. Functional QOL (physical, social, role, emotional, cognitive) and global QOL were assessed with the EORTC-QLQ-C30 at enrollment, 3, 6, and 12-months. Average scores were compared between groups over time using longitudinal mixed-effect modeling. Proportions with clinically meaningful QOL impairment were calculated using age-relevant thresholds and compared between groups over time using logistic regression with mixed effects.
Results:
Participants (N=1,590) were n=81 YAs, n=196 aged 40–49, n=627 aged 50–64, and n=686 aged 65+. Average physical function was better among YAs than participants aged 50–64 (p=0.010) and 65+ (p<0.001), and average social function was worse among YAs than aged 65+ (p=0.046). Relative to YAs, all age groups were less likely to report clinically meaningful social dysfunction (aged 40–49 OR=0.13, 95%CI=0.06–0.29; aged 50–64 OR=0.10, 95%CI=0.05–0.21; aged 65+ OR=0.07, 95%CI=0.04–0.15) and role dysfunction (aged 40–49 OR=0.36, 95%CI=0.18–0.75; aged 50–64 OR=0.41, 95%CI=0.22–0.78; aged 65+ OR=0.32, 95%CI=0.17–0.61). Participants aged 40–49 were also less likely to report physical dysfunction (OR=0.42, 95%CI=0.19–0.93).
Conclusion:
YA CRC survivors reported better physical and worse social function compared to older CRC survivors, and YA CRC survivors were more likely to report clinically meaningful social, role, and physical disfunction. Future work should further investigate QOL using age-relevant benchmarks to inform best practices for CRC survivorship care.
Keywords: Cancer survivors, colorectal cancer, patient-reported outcomes, quality of life, young adult
Introduction
Colorectal cancer (CRC) accounts for more than 151,000 new cancer diagnoses and 52,000 cancer-related deaths among adults in the United States each year [1]. In recent decades, CRC incidence and mortality rates have decreased among adults aged 50 years and older, due in part to uptake of CRC screening [2]. However, these improvements have not extended to young adults (YAs) aged 18–39, for whom CRC incidence rates have increased by 3–6% each year and mortality rates have worsened [3, 4].
Cancer is a uniquely challenging experience for YAs, because common cancer-related life disruptions occur simultaneously with the rapid social and emotional development that characterizes this life stage (e.g., establishment of independence, development of romantic relationships, educational and career achievements) [5, 6]. As a result, YAs report significant cancer-related impacts on their quality of life (QOL), or overall well-being, as well as on various subdomains of functional QOL (e.g., social function, physical function) [7–9]. However, very few studies have evaluated QOL among the growing population of YA CRC survivors. As an exception, one study retrospectively assessed QOL in 50 YA gastrointestinal cancer survivors, the majority of whom had CRC, and noted impairments in occupational function and coping abilities during cancer treatment [10]. In a subsequent cross-sectional study of 196 YA CRC survivors [11], average scores for overall QOL and various QOL subdomains (i.e., physical, social, emotional, and functional well-being) all fell below known cutoffs that indicate clinically low QOL. Other studies have assessed QOL among patients with CRC diagnosed up to age 50 and found similar QOL impairments [12, 13]. However, a major limitation of prior published studies is the use of cross-sectional and/or retrospective designs, which limits the generalizability of findings. Moreover, we are not aware of any studies that have directly compared QOL between YA CRC survivors and older adult CRC survivors.
To address these limitations, the goals of this study were to prospectively characterize functional QOL among newly diagnosed YA CRC survivors and compare functional QOL between YA and older adult CRC survivors over one year. This study leveraged data from the international ColoCare Study, a multi-site study that aims to investigate multilevel factors associated with CRC survivorship via a large cohort of adult CRC survivors with prospectively collected biospecimen and patient-reported outcomes data [14]. We hypothesized that YAs would report greater impairment in functional QOL than older adult CRC survivors over time.
Method
Participants and Procedures
Details of the ColoCare Study design and eligibility criteria have been described previously (ClinicalTrials.gov NCT02328677) [14–16]. Briefly, participants were 1) at least 18 years old, 2) newly diagnosed with stage 0-IV CRC (colon or rectum), 3) able to read and speak English (US sites), Spanish (US sites), or German (German site), and 4) without mental or physical diagnoses that could limit their ability to consent to or participate in the study. Participants were recruited across seven sites in the ColoCare Study: Moffitt Cancer Center (Tampa, FL, USA), University of Tennessee Health Science Center (Memphis, TN, USA), Washington University School of Medicine (St Louis, MO, USA), Huntsman Cancer Institute (Salt Lake City, UT, USA), Cedars-Sinai Medical Center (Los Angeles, CA, USA), Fred Hutchinson Cancer Center (Seattle, WA, USA), and University of Heidelberg (Heidelberg, Germany). The study protocol was approved by the ethics committee of each recruitment site. Eligible patients interested in participating provided written informed consent. All attempts were made to enroll participants shortly after their CRC diagnosis and prior to them undergoing surgery or treatment. Data were collected at enrollment (baseline) and at 3-, 6-, and 12-months post-enrollment. The assessments from baseline to 6-months corresponded to time when patients are expected to be receiving active cancer treatment, and the assessment at 12-months corresponded to time when patients are expected to have finished treatment [17, 18]. Data collected across sites were centrally harmonized according to standardized operating procedures. For this analysis, we included participants enrolled between December 2009 and March 2021 who completed at least one QOL questionnaire between enrollment and 12-months.
Measures
Patient and clinical data.
Patient and clinical data were collected via electronic medical record systems, chart abstraction, patient questionnaires, and internal data warehouses. Data across sites were collated by the ColoCare Study data warehouse team. For this study, participants were categorized according to their age at diagnosis as follows: 18–39 (i.e., YA), 40–49, 50–64, and 65+ years.
Functional QOL.
QOL was assessed with the functional subscales (i.e., physical, social, role, emotional, and cognitive function) and the global QOL subscale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) [19]. Raw scores for each scale were converted to scores ranging from 0–100 [20], with higher scores indicating better functioning and better global QOL. We used established thresholds to determine the proportion of participants with clinically meaningful QOL dysfunction/impairment for each domain. Recognizing that YAs may have different functional expectations than older patients and thus different clinical thresholds, we applied the following age-relevant thresholds to indicate QOL dysfunction/impairment for YAs: physical function ≤97, social function ≤92, role function ≤92, emotional function ≤71, and global QOL ≤71 [21]. A YA-specific threshold for cognitive function has not been established, and thus we used the general cancer threshold of ≤75 [22]. General cancer thresholds were applied for older adult participants (i.e., aged 40–49, 50–64, 65+) as follows: physical function ≤83, social function ≤58, role function ≤58, emotional function ≤71, and cognitive function ≤75 [22]. A general cancer threshold has not been established for global QOL. Thus, like past studies, we applied a threshold of ≤66, which was derived from population normative data across 13 European countries, Canada, and the Unites States [23].
Statistical Analyses
Analyses were performed using R version 4.3.0, and statistical significance was indicated by p<0.05. We used descriptive statistics to characterize each age group’s characteristics at baseline, each age group’s average functional QOL scores by domain at each timepoint, and the proportion of participants within each age group reporting clinically meaningful QOL dysfunction/impairment at each timepoint. Then, we compared the functional QOL outcomes between YA and older adult (i.e., aged 40–49, 50–64, 65+) CRC survivors in two primary ways.
First, we considered the QOL domain scales as continuous outcomes and used independent-samples t-tests to cross-sectionally compare average QOL domain scores by age group at each timepoint. We also used mixed-effect modeling to examine changes in average QOL domain scores by age group over time. Mixed-effect modeling accounts for correlations between repeated assessments, accounts for individual trajectories over time, and uses all available data (vs. listwise deletion) [24]. A mixed-effect model for each outcome assessed the effect of time in months (reference=0, baseline), the effect of age group (reference=YA), and the interaction of time and age group on average scores. Significant effects were considered large if the ratio of the estimated coefficient to the standard error (SE) was >0.8 or <−0.8.[25]
Next, we considered the QOL domain scales as categorical outcomes and used chi-square analyses to cross-sectionally compare the proportion of participants with clinically meaningful QOL dysfunction/impairment (vs. within normal range) by age group at each timepoint. We also used logistic regression with mixed effects to examine changes in the proportion of participants with clinically meaningful QOL dysfunction/impairment by age group over time. A logistic regression model for each outcome assessed the effect of time in months (reference=0, baseline), the effect of age group (reference=YA), and the interaction of time and age group on the proportion of participants with clinically meaningful QOL dysfunction/impairment. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and significance was indicated by the exclusion of the value 1.0 within the 95% CI. ORs ranging from 0.7–0.9 and 1.1–1.5 were considered small; from 0.2–0.7 and 1.5–5.0 were considered medium; and <0.2 and >5.0 were considered large.[26] Models did not include covariates due to model complexity, and missing data were not imputed.
Results
Participant Characteristics
In total, 1,590 participants were included in the analyses (n=81 YAs aged 18–39, n=196 aged 40–49, n=627 aged 50–64, n=686 aged 65+). Table 1 shows the patient and clinical characteristics of the overall sample and for each age group. Across age groups, approximately half of participants were male (56.9%), and most were White (90.2%) and non-Hispanic (95.7%). More than two-thirds (68.7%) were categorized as having an overweight or obese body mass index (37.7% and 31.0%, respectively), and half (49.5%) had a history of smoking. Approximately half were diagnosed with colon cancer (55.1%) and half were diagnosed with advanced disease (50.3% with stage III or IV).
Table 1.
Participant characteristics overall and by age group.
| Overall (N=1,590) |
YAs age 18–39 (n=81) |
Age 40–49 (n=196) |
Age 50–64 (n=627) |
Age 65+ (n=686) |
|
|---|---|---|---|---|---|
| Age at diagnosis, M (SD) | 61.50 (12.70) | 34.12 (4.40) | 45.12 (2.86) | 57.37 (4.21) | 73.19 (5.97) |
| Sex, n (%) | |||||
| Female | 685 (43.1) | 43 (53.1) | 95 (48.5) | 264 (42.1) | 283 (41.3) |
| Male | 905 (56.9) | 38 (46.9) | 101 (51.5) | 363 (57.9) | 403 (58.7) |
| Race, n (%) | |||||
| White | 1,434 (90.2) | 75 (92.6) | 172 (87.8) | 545 (86.9) | 642 (93.6) |
| Black | 95 (6.0) | 2 (2.5) | 12 (6.1) | 52 (8.3) | 29 (4.2) |
| Other | 54 (3.4) | 4 (4.9) | 11 (5.6) | 27 (4.3) | 12 (1.7) |
| Missing | 7 (0.4) | 0 (0.0) | 1 (0.5) | 3 (0.5) | 3 (0.4) |
| Ethnicity, n (%) | |||||
| Hispanic | 63 (4.0) | 5 (6.2) | 13 (6.6) | 29 (4.6) | 16 (2.3) |
| Non-Hispanic | 1,521 (95.7) | 76 (94.3) | 183 (93.4) | 594 (94.7) | 668 (97.4) |
| Missing | 6 (0.4) | 0 (0.0) | 0 (0.0) | 4 (0.6) | 2 (0.3) |
| Smoking status, n (%) | |||||
| Never smoker | 730 (45.9) | 50 (61.7) | 116 (59.2) | 278 (44.3) | 286 (41.7) |
| Former smoker | 584 (36.7) | 20 (24.7) | 46 (23.5) | 215 (34.3) | 303 (44.2) |
| Current smoker | 204 (12.8) | 8 (9.9) | 28 (14.3) | 108 (17.2) | 60 (8.7) |
| Missing | 72 (4.5) | 3 (3.7) | 6 (3.1) | 26 (4.1) | 37 (5.4) |
| BMI category, n (%) | |||||
| Underweight (<18.5) | 34 (2.1) | 4 (4.9) | 5 (2.6) | 7 (1.1) | 18 (2.6) |
| Healthy (18.5–24.9) | 422 (26.5) | 34 (42.0) | 63 (32.1) | 154 (24.6) | 171 (24.9) |
| Overweight (25.0–29.9) | 600 (37.7) | 26 (32.1) | 64 (32.7) | 251 (40.0) | 259 (37.8) |
| Obesity (≥30.0) | 493 (31.0) | 10 (12.3) | 58 (29.6) | 194 (30.9) | 231 (33.7) |
| Missing | 41 (2.6) | 7 (8.6) | 6 (3.1) | 21 (3.3) | 7 (1.0) |
| Stage at diagnosis, n (%) | |||||
| 0 | 64 (4.0) | 2 (2.5) | 3 (1.5) | 21 (3.3) | 36 (5.2) |
| I | 278 (17.5) | 11 (13.6) | 22 (11.2) | 99 (15.8) | 148 (21.6) |
| II | 387 (24.3) | 16 (19.8) | 37 (18.9) | 140 (22.3) | 192 (28.0) |
| III | 554 (34.8) | 27 (33.3) | 86 (43.9) | 228 (36.4) | 215 (31.3) |
| IV | 247 (15.5) | 20 (24.7) | 38 (19.4) | 117 (18.7) | 72 (10.5) |
| Missing | 60 (3.8) | 5 (6.2) | 10 (5.1) | 22 (3.5) | 23 (3.4) |
| Disease site, n (%) | |||||
| Colon | 876 (55.1) | 50 (61.7) | 95 (48.5) | 318 (50.7) | 415 (60.5) |
| Rectum | 689 (43.3) | 27 (33.3) | 96 (49.0) | 300 (47.8) | 264 (38.5) |
| Missing | 25 (1.6) | 4 (4.9) | 5 (2.6) | 9 (1.4) | 7 (1.0) |
| Surgery, n (%) | |||||
| Yes | 1,432 (90.1) | 72 (88.9) | 173 (88.3) | 564 (90.0) | 623 (90.8) |
| No | 100 (6.3) | 4 (4.9) | 17 (8.7) | 40 (6.4) | 39 (5.7) |
| Missing | 58 (3.6) | 5 (6.2) | 6 (3.1) | 23 (3.7) | 24 (3.5) |
| Neoadjuvant therapy, n (%) | |||||
| Yes | 973 (61.2) | 42 (51.9) | 92 (46.9) | 347 (55.3) | 492 (71.7) |
| No | 548 (34.5) | 32 (39.5) | 97 (49.5) | 254 (40.5) | 165 (24.1) |
| Missing | 69 (4.3) | 7 (8.6) | 7 (3.6) | 26 (4.1) | 29 (4.2) |
| Adjuvant therapy, n (%) | |||||
| Yes | 836 (52.6) | 25 (30.9) | 87 (44.4) | 293 (46.7) | 431 (62.8) |
| No | 613 (38.6) | 46 (56.8) | 96 (49.0) | 268 (42.7) | 203 (29.6) |
| Missing | 141 (8.9) | 10 (12.3) | 13 (6.6) | 66 (10.5) | 52 (7.6) |
Note: BMI, body mass index calculated as kg/m2; YA, young adult. Percentages may not sum to 100 due to rounding
Average QOL Domain Scores by Age Groups
Table 2 shows the means and standard deviations for each functional QOL domain and global QOL by age group at each timepoint. Table 3 shows the results of mixed-effect models examining changes in average functional QOL scores by age group over time.
Table 2.
Means (standard deviations) for QOL domain scores at each timepoint by age group.
| Timepoint | Age Group | n | Physical Function | Social Function | Role Function | Emotional Function | Cognitive Function | Global QOL |
|---|---|---|---|---|---|---|---|---|
| Baseline (Month 0) |
18–39 | 56 | 92.36 (14.02)a | 71.73 (29.11)a | 80.30 (29.59)a | 65.87 (24.99)a | 83.93 (21.55) | 68.75 (21.16)a |
| 40–49 | 145 | 86.90 (18.35)b | 67.24 (30.90) | 73.10 (30.06) | 63.68 (26.96)a | 81.61 (23.55) | 63.22 (22.00)a | |
| 50–64 | 492 | 85.13 (20.55)b | 71.87 (29.32) | 75.12 (30.90) | 63.84 (27.01)a | 82.11 (23.03) | 62.61 (24.02)a,b | |
| 65+ | 549 | 80.43 (21.91)a,b | 76.71 (27.45) | 74.47 (30.78) | 70.17 (26.15)a | 84.49 (19.60) | 62.10 (23.23)a,b | |
| Month 3 | 18–39 | 37 | 86.13 (14.35)a | 66.67 (29.13)a | 68.47 (32.58)a | 76.35 (24.57) | 81.08 (22.62) | 65.99 (20.54)a |
| 40–49 | 110 | 81.90 (21.47)a | 66.06 (30.37) | 65.15 (33.30) | 73.18 (24.35) | 80.45 (24.20) | 63.56 (23.05)a | |
| 50–64 | 374 | 79.68 (20.66)a,b | 66.44 (30.74) | 64.26 (33.34) | 70.57 (25.45) | 81.42 (22.27) | 63.56 (20.41)a | |
| 65+ | 438 | 77.84 (21.05)a,b | 77.55 (26.55)b | 71.78 (31.21) | 80.77 (19.92) | 86.27 (18.30) | 65.79 (20.41)a | |
| Month 6 | 18–39 | 43 | 84.65 (16.94)a | 72.48 (29.07)a | 71.71 (31.82)a | 69.96 (25.01)a | 76.74 (24.70) | 68.80 (20.98)a |
| 40–49 | 97 | 83.52 (17.47) | 67.87 (29.29) | 68.73 (32.65) | 68.73 (26.76)a | 74.57 (26.25)a | 65.72 (20.41)a | |
| 50–64 | 345 | 80.36 (21.30)a | 69.23 (29.97) | 67.30 (31.61) | 69.58 (25.25)a | 80.38 (22.52) | 63.52 (21.53)a | |
| 65+ | 380 | 76.70 (20.65)a,b | 73.88 (28.32) | 72.27 (29.96) | 76.52 (23.43) | 82.50 (19.39) | 64.37 (21.29)a | |
| Month 12 | 18–39 | 39 | 88.38 (15.43)a | 75.64 (29.58)a | 73.08 (33.47)a | 73.72 (22.90) | 81.20 (23.63) | 73.50 (18.02) |
| 40–49 | 83 | 83.94 (21.36) | 69.31 (31.37) | 72.69 (32.36) | 68.60 (26.78)a | 75.61 (25.42) | 66.77 (23.55) | |
| 50–64 | 292 | 84.97 (19.29) | 77.68 (26.58) | 77.55 (28.80) | 75.29 (22.25) | 80.46 (22.43) | 69.45 (20.56) | |
| 65+ | 340 | 82.19 (20.87)a,b | 82.50 (25.00) | 80.42 (27.44) | 81.44 (21.02) | 84.76 (19.01) | 71.29 (20.25) |
Note: QOL, quality of life.
Average score was below age-relevant threshold indicating clinically meaningful QOL dysfunctional/impairment.
Average score is significantly different from YA average score based on independent samples t-test at the given timepoint with p<0.05.
Table 3.
Results of mixed-effect models examining changes in average QOL domain scores by age group over time.
| Physical Function |
Social Function |
Role Function |
Emotional Function |
Cognitive Function |
Global QOL |
|
|---|---|---|---|---|---|---|
| (Intercept) | 89.44 (84.69–94.19)*** | 68.98 (62.47–75.48)*** | 77.00 (69.90–84.10)*** | 68.65 (63.07–74.24)*** | 82.20 (77.30–87.10)*** | 66.93 (61.98–71.88)*** |
| Time (vs. 0, baseline) | −0.17 (−0.69–0.35) | 0.56 (−0.21–1.34) | −0.46 (−1.34–0.41) | 0.46 (−0.17–1.08) | −0.30 (−0.84–0.24) | 0.46 (−0.13–1.06) |
| Age Group (vs. YA) | ||||||
| 40–49 | −3.09 (−8.68–2.50) | −0.93 (−8.60–6.74) | −5.35 (−13.71–3.00) | −0.60 (−7.20–5.99) | −0.37 (−6.15–5.42) | −2.58 (−8.41–3.26) |
| 50–64 | −6.60 (−11.62-−1.59)** | 0.42 (−6.46–7.29) | −6.62 (−14.13–0.88) | −3.04 (−8.95–2.87) | −0.74 (−5.93–4.45) | −4.65 (−9.88–0.58) |
| 65+ | −10.44 (−15.43-−5.45)*** | 6.96 (0.12–13.80)* | −4.27 (−11.73–3.19) | 4.72 (−1.16–10.60) | 2.40 (−2.76–7.56) | −4.38 (−9.58–0.82) |
| Time x Age Group | ||||||
| Time x 40–49 | −0.09 (−0.71–0.52) | −0.52 (−1.45–0.41) | 0.42 (−0.63–1.46) | −0.24 (−0.99–0.50) | −0.19 (−0.84–0.45) | −0.23 (−0.94–0.48) |
| Time x 50–64 | 0.06 (−0.49–0.61) | −0.18 (−1.01–0.64) | 0.61 (−0.32–1.53) | 0.29 (−0.37–0.95) | 0.1 (−0.47–0.67) | −0.03 (−0.66–0.59) |
| Time x 65+ | 0.14 (−0.40–0.68) | −0.27 (−1.09–0.54) | 0.78 (−0.14–1.70) | 0.19 (−0.47–0.84) | 0.23 (−0.33–0.80) | 0.12 (−0.50–0.74) |
|
| ||||||
| N (ID) | 1586 | 1586 | 1587 | 1588 | 1588 | 1589 |
| AIC | 32816.43 | 36408.23 | 34150.43 | 33139.80 | 35636.79 | 33547.91 |
| R2 (fixed) | 0.02 | 0.00 | 0.03 | 0.01 | 0.02 | 0.01 |
| R2 (total) | 0.58 | 0.42 | 0.57 | 0.58 | 0.48 | 0.47 |
Note: Each column reflects a separate mixed-effect model. YA, young adult aged 18–39; QOL, quality of life.
p<0.05
p<0.01
p<0.001.
Physical function.
Average scores indicated clinically meaningful physical dysfunction for YAs and participants aged 65+ at all timepoints, for participants aged 40–49 at 3-months, and for participants aged 50–64 at 3-months and 6-months. Cross-sectionally, YAs had better average physical function than participants aged 40–49 at baseline (t(127)=2.25, p=0.026), better average physical function than participants aged 50–64 at baseline (t(83)=3.43, p=0.001) and 3-month (t(52)=2.49, p=0.016), and better average physical function than participants aged 65+ at all timepoints: baseline (t(83)=5.65, p<0.001), 3-months (t(50)=3.23, p=0.002), 6-months (t(57)=2.85, p=0.006), 12-month (t(55)=2.28, p=0.027). In longitudinal analysis, there was a main effect of age group such that average physical function was better among YAs than participants aged 50–64 (B=−6.60, p=0.010, coefficient/SE=−2.58, large effect) and 65+ (B=−10.44, p<0.001, coefficient/SE=−4.10, large effect).
Social function.
Average scores indicated clinically meaningful social dysfunction for YAs at all timepoints, whereas average scores for participants in all other age groups were within normal range. Cross-sectionally, YAs had worse average social function than participants aged 65+ at 3-months (t(41)=−2.20, p=0.034). In longitudinal analyses, there was a main effect of age group such that average social function was worse among YAs than participants aged 65+ (B=6.96, p=0.046, coefficient/SE=2.00, large effect).
Role function.
Average scores indicated clinically meaningful role dysfunction for YA participants at all timepoints, whereas average scores for participants in all other age groups were within normal range. There were no cross-sectional differences in average role function between age groups at any timepoint (ps>0.05), and there were no effects of time, age group, nor the interaction of time and age group on average role function in longitudinal analyses (ps>0.05).
Emotional function.
Average scores indicated clinically meaningful emotional dysfunction for all age groups at baseline, for YAs and participants aged 40–49 and 50–64 at 6-months, and for participants aged 40–49 at 12-months. There were no cross-sectional differences in average emotional function between age groups at any timepoint (ps>0.05), and there were no effects of time, age group, nor the interaction of time and age group on average emotional function in longitudinal analyses (ps>0.05).
Cognitive function.
Average scores for cognitive function were within the normal range for all age groups at all timepoints, with the exception of participants aged 40–49 at 6-months. There were no cross-sectional differences in average cognitive function between age groups at any timepoint (ps>0.05), and there were no effects of time, age group, nor the interaction of time and age group on average cognitive function in longitudinal analyses (ps>0.05).
Global QOL.
Average scores for global QOL indicated clinically meaningful QOL impairment for all age groups at baseline, 3-months, and 6-months. Cross-sectionally, YAs had better average global QOL at baseline than participants aged 50–64 (t(72)=2.03, p=0.046) and 65+ (t(69)=2.22, p=0.030). There were no effects of time, age group, nor the interaction of time and age group on average global QOL in longitudinal analyses (ps>0.05).
Proportions with Clinically Meaningful QOL Impairment by Age Groups
Figure 1 shows the proportions of participants with clinically meaningful QOL dysfunction/impairment by domain and age group at each timepoint, as calculated using age-relevant thresholds. Table 4 shows the results of logistic regression models with mixed effects examining changes in the proportion of participants with clinically meaningful QOL dysfunction/impairment by age group over time for each QOL domain.
Figure 1.
Bar graphs showing the proportion of participants reporting clinically meaningful QOL dysfunction/impairment by age group at each timepoint. Noted group differences represent results of chi-square analyses with *p<0.05, **p<0.01, ***p<0.001.
Table 4.
Results of logistic regression models with mixed effects examining changes in the proportion of participants with clinically meaningful QOL domain scores by age group over time.
| Physical Function |
Social Function |
Role Function |
Emotional Function |
Cognitive Function |
Global QOL |
|
|---|---|---|---|---|---|---|
| (Intercept) | 1.01 (0.52–1.96) | 3.30 (1.71–6.38)*** | 0.97 (0.53–1.77) | 1.08 (0.55–2.10) | 0.36 (0.17–0.75)** | 1.19 (0.65–2.20) |
| Time (vs. 0, baseline) | 1.02 (0.93–1.11) | 0.90 (0.83–0.98)* | 1.03 (0.95–1.11) | 0.95 (0.87–1.04) | 1.00 (0.92–1.10) | 0.97 (0.90–1.05) |
| Age Group (vs. YA) | ||||||
| 40–49 | 0.42 (0.19–0.93)* | 0.13 (0.06–0.29)*** | 0.36 (0.18–0.75)** | 0.89 (0.41–1.95) | 0.99 (0.41–2.35) | 0.50 (0.24–1.03) |
| 50–64 | 0.55 (0.27–1.12) | 0.10 (0.05–0.21)*** | 0.41 (0.22–0.78)** | 1.11 (0.55–2.24) | 1.09 (0.50–2.38) | 0.63 (0.33–1.20) |
| 65+ | 0.83 (0.41–1.68) | 0.07 (0.04–0.15)*** | 0.32 (0.17–0.61)*** | 0.54 (0.27–1.10) | 0.72 (0.33–1.56) | 0.71 (0.38–1.36) |
| Time x Age Group | ||||||
| Time x 40–49 | 1.00 (0.90–1.10) | 1.09 (0.99–1.21) | 0.96 (0.87–1.06) | 1.05 (0.94–1.16) | 1.07 (0.96–1.20) | 0.99 (0.90–1.10) |
| Time x 50–64 | 0.99 (0.91–1.09) | 1.09 (0.99–1.19) | 0.96 (0.88–1.04) | 0.98 (0.90–1.08) | 1.01 (0.92–1.12) | 0.98 (0.90–1.07) |
| Time x 65+ | 0.98 (0.89–1.07) | 1.07 (0.98–1.18) | 0.95 (0.87–1.04) | 1.00 (0.91–1.1.00) | 0.97 (0.88–1.07) | 0.97 (0.89–1.05) |
|
| ||||||
| N (ID) | 1586 | 1588 | 1586 | 1587 | 1588 | 1589 |
| AIC | 4746.33 | 4016.57 | 4246.76 | 4683.51 | 4128.66 | 4799.69 |
| R2 (fixed) | 0.01 | 0.04 | 0.02 | 0.02 | 0.02 | 0.01 |
| R2 (total) | 0.50 | 0.45 | 0.41 | 0.50 | 0.55 | 0.42 |
Note: Each column reflects a separate logistic regression model with mixed-effects. YA, young adult aged 18–39; QOL, quality of life.
p<0.05
p<0.01
p<0.001.
Physical function.
The largest proportion of YAs reported clinically meaningful physical dysfunction at 6-months (74%), and at least 34% of YAs reported physical dysfunction at every timepoint (Figure 1A). Cross-sectionally, physical dysfunction was more prevalent among YAs than participants aged 40–49 at 3-months (X2(2)=10.93, p=0.001) and 6-months (X2(2)=14.80, p<0.001), more prevalent among YAs than participants aged 50–64 at 3-months (X2(2)=4.68, p=0.031) and 6-months (X2(2)=14.16, p<0.001), and more prevalent among YAs than participants aged 65+ at 6-months (X2(2)=6.97, p=0.008). In longitudinal analyses, there was a main effect of age group such that participants aged 40–49 were less likely to report physical dysfunction than YAs (OR=0.42, 95%CI 0.19–0.93, medium effect).
Social function.
The largest proportion of YAs reported clinically meaningful social dysfunction at 3-months (76%), and at least 46% of YAs reported social dysfunction at every timepoint (Figure 1B). Cross-sectionally, social dysfunction was more prevalent among YAs than participants aged 40–49 at baseline (X2(2)=19.10, p<0.001), 3-months (X2(2)=19.84, p<0.001), and 6-months (X2(2)=10.83, p=0.001). Social dysfunction was more prevalent among YAs than participants aged 50–64 at all timepoints: baseline (X2(2)=45.96, p<0.001), 3-months (X2(2)=24.57, p<0.001), 6-months (X2(2)=14.95, p<0.001), 12-months (X2(2)=12.67, p<0.001). Finally, social dysfunction was more prevalent among YAs than participants aged 65+ at all timepoints: baseline (X2(2)=55.90, p<0.001), 3-months (X2(2)=57.92, p<0.001), 6-months (X2(2)=23.20, p<0.001), 12-months (X2(2)=23.26, p<0.001). In longitudinal analyses, there was a main effect of age group such that, relative to YAs, participants in all other age groups were less likely to report social dysfunction (40–49: OR=0.13, 95%CI 0.06–0.29, large effect; 50–64: OR=0.10, 95%CI 0.05–0.21, large effect; 65+: OR=0.07, 95%CI 0.04–0.15, large effect). There was also a main effect of time, such that all participants were less likely to report social dysfunction over time (OR=0.90, 95%CI 0.83–0.98, small effect).
Role function.
The largest proportion of YAs reported clinically meaningful role dysfunction at 3-months (68%), and at least 41% of YAs reported role dysfunction at every timepoint (Figure 1C). Cross-sectionally, role dysfunction was more prevalent among YAs than participants aged 40–49 at all timepoints: baseline (X2(2)=4.15, p=0.042), 3-months (X2(2)=13.07, p<0.001), 6-months (X2(2)=9.25, p=0.002), 12-months (X2(2)=8.90, p=0.003). Role dysfunction was more prevalent among YAs than participants aged 50–64 at all timepoints: baseline (X2(2)=8.86, p=0.003), 3-months (X2(2)=11.99, p=0.001), 6-months (X2(2)=7.79, p=0.005), 12-months (X2(2)=18.73, p<0.001). Finally, role dysfunction was more prevalent among YAs than participants aged 65+ at all timepoints: baseline (X2(2)=7.58, p=0.006), 3-months (X2(2)=25.07, p<0.001), 6-months (X2(2)=18.17, p<0.001), 12-months (X2(2)=22.17, p<0.001). In longitudinal analyses, there was a main effect of age group such that, relative to YAs, participants in all other age groups were less likely to report role dysfunction (40–49: OR=0.36, 95%CI 0.18–0.75, medium effect; 50–64: OR=0.41, 95%CI 0.22–0.78, medium effect; 65+: OR=0.32, 95%CI 0.17–0.61, medium effect).
Emotional function.
The largest proportion of YAs reported clinically meaningful emotional dysfunction at baseline (55%), and at least 35% of YAs reported emotional dysfunction at every timepoint (Figure 1D). There were no cross-sectional differences in the proportion reporting emotional dysfunction between age groups at any timepoint (ps>0.05), and there were no effects of time, age group, nor the interaction of time and age group on the likelihood of reporting emotional dysfunction in longitudinal analyses (ps>0.05).
Cognitive function.
The largest proportion of YAs reported clinically meaningful cognitive dysfunction at 6-months (37%), and at least 28% of YAs reported cognitive dysfunction at every timepoint (Figure 1E). There were no cross-sectional differences in the proportion reporting cognitive dysfunction between age groups at any timepoint (ps>0.05), and there were no effects of time, age group, nor the interaction of time and age group on the likelihood of reporting cognitive dysfunction in longitudinal analyses (ps>0.05).
Global QOL.
The largest proportion of YAs reported clinically meaningful global QOL impairment at 3-months (62%), and at least 46% of YAs reported global QOL impairment at every timepoint (Figure 1F). Cross-sectionally, global QOL impairment was more prevalent at 3-months among YAs than participants aged 40–49 (X2(2)=4.19, p=0.041), 50–64 (X2(2)=4.77, p=0.029), and 65+ (X2(2)=6.56, p=0.010). Global QOL impairment was also more prevalent at 12-months among YAs than participants aged 50–64 (X2(2)=3.93, p=0.047) and 65+ (X2(2)=5.08, p=0.024). There were no effects of time, age group, nor the interaction of time and age group on the odds of reporting global QOL impairment in longitudinal analyses (ps>0.05).
Discussion
To our knowledge, this was one of the first studies to prospectively assess functional QOL among YA CRC survivors aged 18–39 over the first year of CRC diagnosis and treatment and to compare clinically relevant functional QOL outcomes between YA and older adult (i.e., aged 40–49, 50–64, 65+) CRC survivors. When functional QOL outcomes were considered as continuous variables, YAs reported worse average social function than participants aged 65+ (large effect) and better average physical function than participants aged 50–64 and 65+ (large effects). However, when age-relevant clinical thresholds were applied to determine the proportion of participants within each age group reporting clinically relevant QOL impairment/dysfunction, many more differences between age groups emerged. YA CRC survivors were more likely to report clinically relevant social and role dysfunction than participants in all other age groups (large and medium effects, respectively), and YAs were more likely to report physical dysfunction than participants aged 40–49 (medium effect).
Among the YAs, average scores for physical, social, role, and emotional function as well as global QOL all fell below the age-relevant thresholds indicating QOL dysfunction or impairment at most or all timepoints. These findings are consistent with a prior cross-sectional study of YA CRC survivors [11], in which average scores for QOL and various QOL domains (e.g., physical, social, emotional, and functional well-being) fell below cutoffs indicating QOL impairment [27, 28]. YAs in our study also appeared to have worse average scores for social and role function as compared to normative data for YAs in the general population across 13 European countries, Canada, and the Unites States [23]. In our study, social and physical function emerged as significantly different between YAs and older adult CRC survivors at baseline, and differences persisted over time. Given the significant social development and expectations during young adulthood (e.g., establishment of independence, development of romantic relationships, educational and career achievements) [5, 6] as well as the potential impacts of cancer treatments on aspects of health that are highly relevant to YAs (e.g., fertility, early menopause), it is unsurprising that YAs reported worse average social dysfunction over the first year of CRC diagnosis and treatment than CRC survivors aged 65+. Similarly, in a prior analyses of a subset of ColoCare participants 1–5 years post-diagnosis, we found that younger CRC survivors had sustained financial hardship compared to older CRC survivors [29]. In addition, our finding that YAs reported better average physical function than survivors aged 50–64 and 65+ makes sense in the context of better overall health and fewer comorbid conditions among YAs generally [30]. Contrary to expectations, we only observed differences in average global QOL between age groups in cross-sectional analyses, with YAs reporting better global QOL than participants aged 50–64 and 65+ at baseline. This highlights the importance of assessing various functional domains of QOL in addition to global QOL to gain a more nuanced understanding of potential QOL dysfunction among YAs.
The high rates of functional QOL impairment seen among YAs in this study (e.g., up to 74% with physical dysfunction, up to 76% with emotional dysfunction, up to 68% with role dysfunction) are similar to rates of functional impairment reported in other studies among cancer survivors in general. For example, a recent national investigation of more than 50,000 cancer survivors showed that rates of physical and emotional impairment among cancer survivors have increased from 57% in 1999 to 70% in 2018 and are now almost twice the prevalence of functional impairment in the general population [31]. This underscores the importance of screening YA CRC survivors for functional QOL impairment and offering supportive services, as the majority may endorse impairments throughout the first year of CRC diagnosis and treatment. However, the rates of functional QOL impairment among YAs in our sample would have been underestimated if we had applied general cancer thresholds instead of age-specific thresholds. Thus, it is critical to also consider functional QOL impairments in the context of the individual’s developmental life stage to prevent patients who may be suffering from falling through the cracks.
Results of this study should be interpreted within scope of its limitations. The subsample of YAs was small relative to the subsamples of participants in other age groups, and participants were primarily White and non-Hispanic. These factors may limit the generalizability of findings to the broader population of YA CRC survivors and to more racially and ethnically diverse populations. Detailed data regarding participants’ treatment regimens were not available to further characterize the sample. Findings from this study are limited to the initial 12-months post-CRC diagnosis and may not generalize to longer-term QOL. In addition, these analyses did not explore how patient and clinical characteristics (e.g., socioeconomic status, disease stage, detailed treatment regimens) may have affected functional QOL outcomes and differences between age groups [32]. This should be explored in future work to gain a more nuanced understanding of functional QOL among subpopulations of YA CRC survivors. However, findings from this study are supported by this study’s many strengths; this study leveraged data from a large, international cohort study and used a well-validated QOL measure to assess various domains of functional QOL in addition to global QOL. We considered the QOL domains as both continuous outcomes and categorical outcomes; moreover, we applied validated age-relevant thresholds to determine the proportion of participants with clinically meaningful functional QOL impairments. Future studies with larger samples of more racially and ethnically diverse YA CRC survivors are needed to replicate and extend these findings.
Conclusion
This was one of the first studies to prospectively assess functional QOL among YA CRC survivors and to compare functional QOL outcomes between YA and older adult CRC survivors over time. Among CRC survivors, YAs reported better average physical function and worse average social function compared to older adults. Age-relevant thresholds revealed high proportions of YAs with functional QOL impairment (up to 76%), and YA CRC survivors were more likely to report clinically relevant physical, social, and role dysfunction than older adult CRC survivors. These domains of functional QOL could indicate potential targets for the development or adaptation of supportive care interventions for YA CRC survivors, and early intervention has the potential to improve longer-term outcomes. Future work should further investigate functional QOL outcomes using age-relevant benchmarks and appropriate interventions to improve functional QOL outcomes among YA CRC survivors to inform best practices for CRC survivorship care.
Acknowledgements:
The authors would like to gratefully acknowledge Sofia Cobos, MPH, Julaxis Love, and Devon Conant for their assistance with data collection. The authors would also like to gratefully acknowledge the colorectal cancer survivors who participated in this study.
Funding:
This study was supported in part by an Innovation Award via the Moffitt Cancer Center Department of Epidemiology (MPIs: Siegel, Oswald), institutional funds via the Moffitt Cancer Center AYA Program, Florida Department of Health Bankhead Coley Award (09BN-13, Siegel), and funding via the National Cancer Institute of the National Institutes of Health (U01CA206110, R01NR018762, R01CA189184, R01CA207371, R01CA254108). The ColoCare Study at the Heidelberg site was supported by the German Ministry of Education and Research projects 01KT1503 and 01KD2101D, the National Institutes of Health/National Cancer Institute (NHI/NCI) projects R01 CA189184 and U01 CA206110, the Stiftung LebensBlicke, the Matthias-Lackas Foundations, the Rahel-Goitein-Straus-Program, Medical Faculty Heidelberg University, and the Heidelberger Stiftung Chirurgie, Heidelberg University Hospital. This work was also supported in part by the Total Cancer Care Protocol and the Participant Research, Interventions, and Measurements Core at Moffitt Cancer Center, an NCI designated Comprehensive Cancer Center (P30CA076292). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Abbreviations:
- BMI
body mass index
- CI
confidence interval
- CRC
colorectal cancer
- EORTC-QLQ-C30
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire
- OR
odds ratio
- QOL
quality of life
- SE
standard error
- YA
young adult
Footnotes
Author contributions: LBO: conceptualization, funding acquisition, writing – original draft, writing – review and editing; AB: data curation, formal analysis, writing – original draft, writing – review and editing; XL: data curation, formal analysis, visualization, writing – original draft, writing – review and editing; EJ-B: project administration, writing – review and editing; GT: project administration, investigation, writing – review and editing; SF: project administration, writing – review and editing; BJS: data curation, writing – review and editing; JO: project administration, investigation, writing – review and editing; SH: project administration, writing – review and editing; IS: project administration, writing – review and editing; LCH: resources, writing – review and editing; KM: writing – review and editing; MGM: resources, writing – review and editing; DC: project administration, writing – review and editing; SAC: resources, writing – review and editing; MK: resources, writing – review and editing; EHW: resources, writing – review and editing; VD: project administration, writing – review and editing; NCL: project administration, writing – review and editing; JG: resources, writing – review and editing; ATT: conceptualization, funding acquisition, writing – review and editing; CIL: conceptualization, funding acquisition, writing – review and editing; DS: conceptualization, funding acquisition, writing – review and editing; MS: conceptualization, funding acquisition, writing – review and editing; BG: conceptualization, funding acquisition, writing – review and editing; JCF: conceptualization, funding acquisition, writing – review and editing; HSLJ: conceptualization, funding acquisition, writing – review and editing; CMU: conceptualization, funding acquisition, writing – review and editing; EMS: conceptualization, funding acquisition, writing – original draft, writing – review and editing.
Competing interests: Dr. Felder reports an advisory role for GSK and research funding from ViewRay and Natera. Dr. Cohen reports personal fees and grants from Pfizer and personal fees from Taiho, Bayer, Regeneron, Biomea, Eisai, Delcath, Isofol, and GSK. Dr. Gong reports advisory/consulting for Aveo, Basilea, Bayer, EMD Serono, Elsevier, Exelixis, HalioDx, Janssen, Pfizer, Inc, QED Therapeutics, Seagen, and Taiho. Dr. Jim reports grant funding from Kite Pharm and a consultant role for SBR Bioscience. Dr. Ulrich reports oversight over research funded by several pharmaceutical companies in her role as Cancer Center Director, but she has not received funding directly herself. The other authors have no competing interests to disclose.
Statements & Declarations
Ethics approval: This study was performed in line with the Declaration of Helsinki. Approval was granted by the ethics committee of each recruitment site: Moffitt Cancer Center (USF104189, USF108437), University of Tennessee Health Science Center (16–04626-FB), Washington University School of Medicine (201610032), Huntsman Cancer Institute (IRB_00077147), Cedars-Sinai Medical Center (Pro000464423, CR00012892), Fred Hutchinson Cancer Center (6407), and University of Heidelberg (300/2001, S-134/2016).
Consent to participate and publish: Informed consent to participate and to have de-identified and aggregate study data published was obtained from all individual participants included in this study.
Trial registration: NCT02328677, registered December 2014
Availability of data and code:
The ColoCare Study data and code are available from the corresponding author upon reasonable request and as described on the ColoCare website: (https://uofuhealth.utah.edu/huntsman/labs/colocare-consortium/). Our data sharing procedures have been updated and are available online: (https://uofuhealth.utah.edu/huntsman/labs/colocare-consortium/data-sharing/new-projects.php). For additional questions, please contact the ColoCare Study Administrator Team (colocarestudy_admin@hci.utah.edu).
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The ColoCare Study data and code are available from the corresponding author upon reasonable request and as described on the ColoCare website: (https://uofuhealth.utah.edu/huntsman/labs/colocare-consortium/). Our data sharing procedures have been updated and are available online: (https://uofuhealth.utah.edu/huntsman/labs/colocare-consortium/data-sharing/new-projects.php). For additional questions, please contact the ColoCare Study Administrator Team (colocarestudy_admin@hci.utah.edu).