Table 2.
Studies focusing on Single Symptom in Colorectal Cancer Survivors (N = 29)
| Author(s)/ Yearref# |
Aim | Study Design/ Country |
Setting/Sample (mean age, sex, ethnicity) |
Primary Symptom Measures |
Cancer Related Factorsa |
Findings Regarding Symptom Experiences |
|---|---|---|---|---|---|---|
| A. Peripheral Neuropathy (n = 9) | ||||||
| Lu et al., (2019)45 | To examine the relationships among restriction of daily activity, mood, and QOL in CRC after CTx. | Cross-sectional design. Taiwan |
103 survivors with CRC in inpatient settings (100% both colon and rectal; 61-70 y.o; 44.7% females; Asian) | -Neuropathic pain symptoms inventory (NPSI) | -Stage II (5.8%), III (60.2%). -CTx ‘Oxaliplatin’(100%) |
Time to assess symptoms: After CTx, but specific time point was not addressed. Severity of neuropathic pain: 13.66 out of total 100 points (mild). Risk factors of neuropathic pain: Restrictive daily activity, negative mood status. Impacts of neuropathic pain: QOL |
| Soveri et al.,(2019)39 | To examine the long-term neuropathy after CTx. | Cross-sectional design. Finland |
144 survivors with CRC in outpatient clinics (62% colon, 38% rectual; 61 y.o.; 58% females; Finlandian) | - Chemotherapy-Induced Peripheral Neuropathy (EORTC CIPN20) questionnaires. | -Stage II (77%), III (11%). -CTx ‘Oxaliplatin’ (100%), RTx (34%) |
Time to assess symptoms: At median 4.2 years after CTx. Neuropathy: 69% of survivors reported long-term sensory neuropathy including pain and peripheral tingling severity. Risk factors of neuropathy: CTx (Oxaliplatin) Impacts of neuropathy: QOL, specifically physical functioning and role functioning QOL. |
| Vatandoust et al., (2014)42 | To explore the frequency of persistent peripheral neuropathy after CTx. | Cross-sectional design. Australia |
27 survivors with CRC in two cancer centers (78% colon, 18.5% rectal; 3.7% both colon and rectal; 66 y.o.;33.3% females; Australian) | -Neuropathy: Survivors answered a 12-item questionnaire (NTX-12). | -Stage III (70.4%), IV (29.6%) -CTx ‘Oxaliplatin’ (100%) |
Time to assess symptoms: At median 3 years after CTx. Severity: Grade 2 and 3 assessed by NTX-12 were prevalent. Risk factors of neuropathy: Dose of Oxaliplatin, a history of regular alcohol use. |
| Velasco et al., (2014)29 | To define early predictors of neuropathy after CTx. | Prospective design. Spain |
200 survivors with CRC at four cancer centers (100% both colon and rectal; 63.6 y.o.; 40% females; Europeans) | -Neuropathy: Total Neuropathy Scale (TNS) | -CTx ‘Oxaliplatin’ (100%) |
Time to assess symptoms: At 1 month after CTx. Symptoms of neuropathy: Severity: 4.1 (mild, 0-28 score). Neuropathy: Severity and frequency decreased over time from baseline, but persistent over time. Risk factors of neuropathy: CTx, previous dose of Oxaliplatin. |
| Mols et al., (2013)32 | To examine the neuropathy after CTx | Cross-sectional design. Netherlands |
500 survivors with CRC registered in Dutch cancer registry (67% colon, 33% rectal; 66.7 y.o; 42% females; European) | -Neuropathy: EORTC QLQ Chemotherapy-Induced Peripheral Neuropathy 20. | -Years since diagnosis (5.5 y.o.) -Stage I (5%), II (14%), III (70%), IV (8%) -Surgery (46%), CTx (5%), Surgery+RTx (24%), Surgery+CTx (22%),Surgery+CTx+ RTx (9%) |
Time to assess symptoms: 2 to 11 years after diagnosis. Neuropathy: 20% of survivors reported neuropathy including sensory, motor and autonomic neuropathy; 10.1 (mean severity of neuropathy including sensory, motor and autonomic neuropathy) in 0-100 scale. Risk factors of neuropathy: CTx, Oxaliplatin-based CTx was significantly associated with severity of neuropathy. Impacts of neuropathy: QOL. |
| Tofthagen et al., (2013)41 | To examine the neuropathy after CTx. | Cross-sectional design. USA. |
111 survivors with CRC from the cancer center (100 % both colon and rectal; 61 y.o.; females 53%; 98% Caucasian) | -Neuropathy: Chemotherapy Induced Peripheral Neuropathy Assessment Tool - |
-Stage III (67%), IV (32%) -CTx regimen (100%): Oxaliplatin |
Time to assess symptoms: On average after 3 years of CTx: Neuropathy: Frequency: 89%, Severity: 68.7 (0 to 248 scale, higher indicates severe). Risk factors of neuropathy: Poor sleep, depression, Oxaliplatin-based CTx. Impact of neuropathy: Poor QOL. |
| Argyriou et al., (2012)19 | To examine the peripheral neuropathy after CTx. | Prospective design. Greece |
150 survivors with CRC in outpatient settings (100% both colon and rectal; 63.3 y.o; 40% females; European) | -Neuropathy: Total Neuropathy Scale (TNS) | -Not specified. -CTx regimen (100%): Oxaliplatin (FOLFOX-4 or XELOX) |
Time to assess symptoms: At within 1 month after CTx: Neuropathy: Frequency: 71.5%, Severity: 6.5 (mild in 0-28 point severity scale). Severity and frequency decreased over time from baseline, but persistent over time. Risk factors of neuropathy: Using FOLFOX is associated with higher severity of neuropathy, compared to the group with XELOX. |
| Kidwell et al., (2012)36 | To examine the long-term neuropathy after CTx | Cross-sectional design. USA |
92 survivors with CRC registered in Long-Term Survivors study (71.7% colon, 28.3% rectal: 50-59 y.o as majority; 34.8% females; Not specified) | -Neuropathy: Survivors answered a 12-item questionnaire (NTX-12) | -Not specified -CTx ‘Oxaliplatin’ (100%) |
Time to assess symptoms: At the time of follow-up (29 ± 4 months post-oxaliplatin): Neuropathy: Frequency: 79.2%, Severity: 4.66 (0-48 score). Risk factors of neuropathy: CTx. |
| Park et al., (2011)38 | To describe the neuropathy. | Cross-sectional design. Australia |
22 survivors with CRC from the medical registry of oncology hospital (60 y.o.; 37.5% females, Australian) | -Neuropathy: Total Neuropathy Scale (TNS) | -Stage III (58%), IV (42%) -CTx (100%) |
Time to assess symptoms: At a median of 25 months post-oxaliplatin: Neuropathy: Frequency: 79.2%, Severity: 4.1 (mild, 0-28 score). Risk factors of neuropathy: Previous dose of CTx, duration of CTx more than 3 months. |
| B. Psychological Distress (i.e., Depression and Anxiety) (n = 7) | ||||||
| Mols et al. (2018)18 | To assess frequency, risk factors and impacts of anxiety and depression. | Prospective longitudinal design (across a 4-year time period). Netherlands |
2625 survivors with CRC from Cancer registry (colon 61%, rectal 39%; 69 y.o.; 45% females; 100% Caucasian European) | -Psychological distress: HADS | -Stage I (30%), II (36%), III (38%), IV (4%) -Surgery (100%), CTx (29%), RTx (31%) |
Time to assess symptoms: Mean 5 years after diagnosis. Psychological distress: Severity and frequency (approx. 20%) of depression and anxiety were significantly higher in CRC survivors compared to the general population (approx. 10%). Mean severity of anxiety (4.6), depression (4.4). Risk factors of psychological distress: single or non-married, low education level, comorbid condition, younger age, and female. Impacts of psychological distress: Lower global QOL, lower physical, role cognitive, emotional, and social functioning QOL. Even years after diagnosis and treatment, anxiety and depression and their negative effect on HRQOL are still high in CRC survivors. |
| Trudel-Fitzgerald et al. (2018)27 | To examine psychological distress and its’ impact on life style. | Prospective longitudinal design USA |
372 women with CRC from Nurses’ Health Study cohort (50% colon, 50% rectal; 66 y.o.; 100% females) | -Depression: Mental Health Index-5 -Anxiety: Self-report Crown Crisp Index |
-Cancer stage (75% women with 0-II). |
Time to assess symptoms: At baseline and mean 4 years after diagnosis. Psychological distress: Frequency: Depression (12%), and anxiety (26%). Impacts of psychological distress: Unhealthier lifestyle scores throughout follow-up. Treating psychological symptoms early in the cancer trajectory may not solely reduce psychological distress but also promote healthier lifestyle. |
| Akyol et al. (2015)44 | To examine psychological distress and impacts of psychological distress. | Cross-sectional design. Turkey |
105 survivors with CRC from university cancer center (colon 67%, rectal 33%; 53 y.o.; 31% females; 100% Turkish) | -Psychological distress: HADS |
-Stage I (51%) II (24%), III or IV (25%) -Having current stoma (29%) |
Time to assess symptoms: After surgery (specific time point was not addressed). Psychological distress: Frequency (Depression, 44%; anxiety, 29%), Severity (Depression 6.5; anxiety 8.0) Risk factors of psychological distress: Gender (being female), advanced cancer stage Impacts of psychological distress: Low global QOL, physical functioning, sexual function, sexual problems with partners, financial problems. |
| Zhang et al. (2015)43 | To explore the influence of self-efficacy and demographic, disease-related, and psychological factors on symptoms. | Cross-sectional design. China |
252 survivors with CRC from outpatient clinics (colon 50%, rectal 50%; 53 y.o.; 34% females; 100% Chinese) | -Psychological distress: HADS | -Stage II (42%), III (58%). -Surgery (100%), CTx (100%) |
Time to assess symptoms: After post-surgical adjuvant CTx (specific time point was not addressed). Psychological distress: Severity (Depression 4.0; anxiety 6.0) Risk factors of psychological distress: Age ≥60 years, female, suburban residence, body mass index (<18.5), and stage III cancer, marital status of single or divorced. Greater self-efficacy was associated with milder symptoms severity and less symptom interference with daily life. |
| Abu-Helalah et al.,(2014)46 | To examine psychological well-being in CRC survivors. | Cross-sectional design. Jordan |
241 survivors with CRC from outpatient clinics (colon 60%, rectal 23%, colon and rectal, 17.4%; 56.7 y.o; 47.7% females; 100% Jordanish) | -Psychological distress: HADS | -Stage I (10.9%), II (38%), III (38%), IV (13.1%) -Surgery (98%), CTx (88%), RTx (25%) |
Time to assess symptoms: After cancer treatments (specific time point was not addressed). Psychological distress: Depression severity 4.4, Anxiety severity 3.9. Of note, 5.4% of participants had severe anxiety and 5.4% of them had severe depression. |
| Gray et al. (2014)34 | To examine the risk factors and impacts of anxiety and depression. | Cross-sectional design. Scotland |
496 survivors with CRC from colorectal oncology and surgical outpatient clinics (colon 55%, rectal 32%; 66 y.o.; 45% females, 100% Caucasian European) | -Psychological distress: HADS | -Stage I &II (71%), III & IV (19%) -Surgery (91%), CTx (78%), RTx (97%), Stoma (31%) |
Time to assess symptoms: Less than 2 years from diagnosis, and after cancer treatments (specific time point was not addressed). Psychological distress: Depression severity 4.07, Anxiety severity 5.32. Risk factors of psychological distress: Poor self-reported cognitive functioning, bowel symptoms, poor physical and social functioning. Impacts of psychological distress: High negative life and emotional impact, difficulties, functional impairments. |
| Dunn et al. (2013)21 | To examine the risk factors and impacts of psychological distress. | Prospective longitudinal design. Australia |
1703 women with CRC from urban cancer (median 60 y.o. [range 20-80]; mean 40% females) | -Composite score of psychological distress: Brief Symptom Inventory-18 | -Cancer stage (55% 0-II/35% with III, IV) -Surgery (54%), Surgery+RTx or CTx (43%) |
Time to assess symptoms: At post diagnosis, 1, 2,3,4,5 years follow-up. Psychological distress: Percentages of overall psychological distress among all participants were 44% at T1, 40% at T3, and 42% at T6 (depression and anxiety frequency: 42% at T6 in both symptoms) Risk factors of higher psychological distress: Short-term survivorship (< 2 years) compared to long-term survivorship (<5 years), younger age, lower education, poor socioeconomic advantage, late disease stage and poor social support. |
| C. Fatigue (n = 6) | ||||||
| Agasi-Idenburg et al. (2017)35 | To identify and compare symptom clusters including fatigue | Cross-sectional design. Netherlands |
1698 survivors with CRC from cancer registry and 2 urban hospitals (colon 59%, rectal 42%; 65 y.o.; 45% females) | -Fatigue: Fatigue Assessment Scale. | -Stage I (46%), II (54%) -Surgery (63%), Surgery + RTx (27%), Surgery + CTx (5%), Surgery+CTx+ RTx (5%) |
Time to assess symptoms: Mean 5 to 10 years after diagnosis. Identified symptom cluster including fatigue: An emotional symptom cluster (anxiety, fatigue, and depression); a pain symptom cluster (pain and insomnia); and a dyspnea only cluster. Risk factors of fatigue: Psychological distress. |
| Wei & Li (2017)31 | To evaluate the relationship between fatigue and nutritional status after surgery | Cross-sectional design. China |
70 survivors with CRC after surgery from a tertiary hospital (colon 63%, colorectal 37%; 67 y.o.; 29% females; 100% Chinese) | -Fatigue: Cancer Fatigue Scale. | -Stage II (71%), III (26%), IV (3%) -Surgery (100%), CTx or RTx (0%) |
Time to assess symptoms: At 24 hours after surgery Fatigue: 100% survivors reported fatigue (20% with severe fatigue) after surgery. Severity of fatigue increased after surgery. Risk factors of fatigue: Previous nutritional status, low white blood cells and low serum calcium levels. |
| Vardy et al. (2016)28 | To examine the severity and duration of fatigue | Prospective-longitudinal design. Canada & Australia |
362 survivors with CRC from multiple cancer registries (colon 69%, rectal 31%; 59 y.o.; 37% females; 100% Caucasian) | -Fatigue: FACT-Fatigue | -Stage I (46%), II (77%), III (76%), IV (20%) -CTx (98%) |
Time to assess symptoms: At baseline before CTx. 6, 12, and 24 months after CTx. Fatigue: Frequency of fatigue at baseline (52%). This increased over time: 70% at 6 months, 44% at 12 months, 39% at 24 months. Mean severity of fatigue increased over time: 67 (baseline), 65 (at 6 months), 71 (at 12 months), 75 (at 24 months). Risk factors of fatigue: Baseline fatigue, receiving chemotherapy, cognitive and affective symptoms, poorer QOL at baseline, and comorbidities. Impacts of fatigue: Poor QOL, affective and cognitive symptoms. |
| Li, Liu & Lu(2014)23 | To examine fatigue in post-surgical CRC survivors | Prospective longitudinal design (baseline, 2 or 3 days after surgery, 3 weeks after surgery). China |
96 survivors with CRC from a tertiary cancer center (colon 56%, rectal 44%; 60 y.o.; 21% females; 100% Chinese) | -Fatigue: Cancer Fatigue Scale | -Stage I (13%), II (76%), III (4%) -Surgery (100%), CTx (92%) |
Time to assess symptoms: At 3 weeks after the surgery (20.4 ±3.3). Fatigue: Fatigue increased at after 2 or 3 days of surgery, then decreased 3 weeks after surgery (mean severity at 3 weeks: 20.4). Tailored intervention based on the survivors’ characteristics at different periods may be required to alleviate fatigue. |
| Thong et al. (2013)40 | To examine the fatigue in short-term and long-term CRC survivors | Cross-sectional design. Netherlands |
3739 survivors with CRC (short-term survivors < 5 years: n = 2320, long-term survivors ≥ 5 years: n = 1419) from CRC registries (colon 50%, rectal 50%; 70 y.o.; females 55%; ethnicities not specified) | -Fatigue: Fatigue Assessment Scale | -Stage I (30%), II (37%), III (28%), IV (5%) -Surgery (50%), CTx (1%), RTx (0.1%), Surgery + CTx or RTx (49%) |
Time to assess symptoms: Mean 6 years after diagnosis. Fatigue: Frequency of fatigue (39%), higher than the general population (n=338) (39% vs. 22%, p<0.0001). Short-term survivors (<5 years post-diagnosis) had the highest mean fatigue scores compared with long-term survivors (≥5 years post-diagnosis) or the normative population (21±7 vs. 20±7 vs. 18±5, p<0.0001, respectively). Risk factors of fatigue: Psychological distress, having primary cancers prior to CRC, Surgery, CTx, and RTx |
| Mota et al. (2012)37 | To examine the frequency and risk factors of fatigue. | Cross-sectional design. Brazil |
159 survivors with CRC from four CRC outpatient clinics (colon 70%, rectal 30%; 60 y.o.; 46% females; 65% Caucasian) | -Fatigue: Piper Fatigue Scale. | -Stage I (9%), II (22%), III (25%), IV (45%), Cancer in remission (34%) -CTx and/or RTx (95%). |
Time to assess symptoms: Mean 5 years after diagnosis Fatigue: 26.8% survivors with 5.8 mean score. Risk factors of fatigue: Depression, poor performance status, and sleep disturbances. |
| D. Body Image Distress (n = 4) | ||||||
| Reese et al. (2018)25 | To assess body image distress over time and risk factors and Impacts of body image. | Prospective design USA |
141 survivors with CRC from urban cancer center (colon 74%, rectal 26%; 69 y.o.; 42% females; 83% Caucasian) | -Body image distress: Body Image Scale | -Mean 2.5 years -Stage I (30%), II (36%), III (38%), IV (4%) -Surgery (94%), CTx (75%), RTx (32%) |
Time to assess symptoms: Baseline and 6 months follow-up. Body image distress: Severity (0-10): 6.7 for survivors with colon cancer, 9.9 for survivors with rectal cancer, 6.0 for men, 9.6 for women. Risk factors of body image distress: Rectal cancer, being female. Impacts of body image distress: Lower sexual relationship, depression, poor QOL. |
| Benedict et al. (2016)30 | To examine body image and its correlates. | Cross-sectional design. USA |
70 women with CRC from urban cancer center (69% rectal, 29% anal; 55 y.o.; 100% females; 79% Caucasian) | -Body image distress: EORTC-C38 | -Stage I (31%), II (14%), III (41%) -Surgery (73%), CTx (11%), RTx (1%), CTx+RTx (71%) |
Time to assess symptoms: Mean 4 years after diagnosis (specific time point was not addressed). Body image distress: Average body image scores (69.2) indicated impairment. 86% reported body image distress. Risk factors of body image distress: Younger age, lower global health status, and greater severity of symptoms. Impacts of body image distress: Poor sexual relationships and sexual functioning. |
| Bullen et al. (2012)20 | To investigate body image as a predictor of psychological symptoms and QOL in CRC survivors after surgery. | Prospective design. Australia |
38 survivors with CRC from pre-surgical clinics (59 y.o.; 50% females; Caucasian) | -Body image distress: Body Image Ideals Questionnaire | -Surgery (100%) |
Time to assess symptoms: At 3 months after surgery. Risk factors of body image distress: Pre-existing body image distress, having stomas. Impacts of body image distress: Psychological distress, poor QOL. |
| Sharpe et al., (2011)26 | To examine the effect of having a stoma on body image distress. | Prospective design. Australia |
79 survivors with CRC from 7 hospitals (66 y.o; 40% females; Caucasian) | -Body image disturbance: Body image scale | -mean 10 years after cancer diagnosis. -Surgery (100%), CTx (40%), RTx (5%). |
Time to assess symptoms:
At baseline right after the surgery: 6.7 (group with stoma, n = 34), 3.3 in group with non-stoma (n = 65), total mean (5.5 out of 0-30 scale). At 6 months follow-up: 11.3(group with stoma, n = 34), 2.8 in group with non-stoma (n = 65), total mean (7.0 out of 0-30 scale). Risk factors of body image distress: Body image distress increased over time in group with stoma. Impacts of body image distress: Psychological distress. |
| E. Cognitive Impairment (n = 2) | ||||||
| Sales et al., (2019)15b | To examine the cognitive function differences by CTx groups. | Prospective, design. Group with CTx (n = 22) versus non-CTx (n= 47). Brazil |
69 survivors with CRC from cancer center (100% colon and rectal; 62.5 y.o.; 39.7% females; 58.8% Caucasian) | -Self-reported cognitive complaint questionnaires. Functional Magnetic Resonance Imaging (MRI). |
-Stage II (63.8%), III (36.2%) -CTx (100%, fluorouracil and oxaliplatin) |
Time to assess symptoms: Baseline and at 12 months after CTx. but frequency, severity, risk factors and impacts of neuropathy were not specified. Associations of cognitive impairment at baseline (pre-CTx) and 12 months after CTx by CTx groups: Using linear mixed models, patients with CRC who received CTx presented with a decline in executive cognitive function after 12 months compared with patients without CTx. There was not association of cognitive function with Apolipoprotein E genotyping. |
| Vardy et al., (2014)17b | To examine the cognitive function differences by CTx groups. | Prospective, longitudinal, design. Group with CTx (n = 173) versus non-CTx (n= 116), and healthy controls (HCs) (n = 72). Canada & Australia |
289 survivors with CRC from multiple cancer centers (colon 67%, rectal 33%; 59 y.o.; 37% females; 100% Caucasian) | -Cognitive function: FACT-Cognitive, Cambridge Neuropsychological Test Automated Battery (CANTAB) using Global Deficit Score | -Stage I (17.3%), II (36.7%), III (44.3%) -CTx (100%): Oxaliplatin (46%), fluorouracil (31.2%) |
Time to assess symptoms: At 6, 12, and 24 months after CTx. Frequency of cognitive impairment: 39%, and 46% at 6 and 12 months, respectively in CRC groups with and without CTx, compared with 6% and 13% in HCs. *Differences between CTx group (32%) vs. non-CTx group (16%) at 6 months, but not at 12 and 24 months. Severity of cognitive impairment (GDS more than 0.5 indicates impairment): 0.62, 0.57, 0.63, 0.56 (at baseline ‘pre-CTx’, 6, 12, and 24 months). This was significantly higher than HCs. Risk factors of cognitive impairment: Group, time, group-time interaction, female sex, and non-English primary language, previous higher cytokine levels, psychological distress, fatigue. Impacts of cognitive impairment: Psychological distress, fatigue, and poor QOL. |
| F. Insomnia (n = 1) | ||||||
| Coles et al. (2018)16b | To assess sleep disturbance and its correlates. | Cross-sectional design. USA |
613 survivors with CRC from Surveillance, Epidemiology, and End Results Program cancer registries (colon 61%, rectal 39%; 62 y.o.; 53% females; 55% Caucasian, 20% African-American) | -Sleep: Patient-Reported Outcomes Measurement Information System (PROMIS) | -Stage I (29%), II (31%), III (40%) -CTx (55%), RTx (19%) |
Time to assess symptoms: Mean 10 months after diagnosis. Mean scores of PROMIS: Sleep (50) Risk factors of sleep disturbances: Pain, anxiety, fatigue, multiple comorbid conditions, and retirement. Sleep disturbance screening may be warranted in individuals diagnosed with CRC. |
Note.
Abbreviation: CRC, colorectal cancer; CTx, Chemotherapy; EORTC, European Organization for Research and Treatment of Cancer; FACT, Functional Assessment of Cancer Therapy; HADS, Hospital Anxiety and Depression Scale; QOL, quality of life; RTx, Radiotherapy; YO, years old.
a
Only data available in the selected studies are presented in the table.
b
Denotes the studies excluded in meta-analyses (n = 3).