Validation of the Taiwan Chinese version of the EORTC QLQ-CR29 to assess quality of life in colorectal cancer patients

Traditional Chinese (Mandarin) language used in Taiwan is linguistically different from the Simplified Chinese used in Mainland China. The translation and pilot study were conducted during the years 2007 and 2008, shortly after the introduction of the updated English version of colorectal cancer-specific module QLQ-CR29. Fifty-seven Taiwanese patients were enrolled as part of the multi-national validation study [5]. The Taiwan Chinese EORTC QLQ-CR29 was developed using a standard procedure of translation and back-translation [8], after which the questionnaire was reviewed and approved by the EORTC Quality of Life Group.

Patient recruitment began on November 1, 2015 and ended on March 31, 2016 at Cathay General Hospital. Patients over 18 years of age with pathology-proved colon or rectum cancer were invited during the enrollment period. Patients’ status was categorized into the active treatment or follow-up group. Pre-operative patients or patients under chemotherapy constituted the active treatment group, and these patients were interviewed before surgery or after the first day of chemotherapy. Follow-up patients were those who had completed surgery, chemotherapy, or any adjuvant therapy for at least six months, and their interviews were conducted during returning visits at outpatient clinics. Exclusion criteria included disagreement to participate, concurrent secondary malignancy, concurrent engagement in another quality-of-life study, and declaration of critical illness. Study purpose and privacy protection policy were effectively explained with written consent obtained from all participants.

The EORTC QLQ-C30 core questionnaire is a quality-of-life measuring instrument for cancer patients, and the Taiwan Chinese (Traditional Chinese) version has been validated and descripted previously [9, 10]. The clinical applicability for breast cancer, lung cancer, head and neck cancer, gastric cancer, and esophageal cancer has been demonstrated [9‐13]. The QLQ-C30 consists of a global health status/quality of life, five multi-item functional scales and several multi-item symptomatic scales or single items. With linear transformation, seven- and four-level Likert scales (seven for the global health status/quality of life scale and four for the others) were converted to a 0 to 100 score with 100 representing the best global health, functional status, or worst symptom depending on the measuring characteristic of each multi-item scale or single item [14].

The EORTC QLQ-CR29 is a 29-item colon and rectum cancer site-specific supplemental module that aims to enhance the sensitivity and specificity for colorectal cancer quality of life measures [4, 5]. The original English version comprises 4 multi-item scales (body image, urinary frequency, blood and mucus in stool, and stool frequency) and 17 functional/symptomatic single-items (anxiety, weight, sexual interest, urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, flatulence, fecal incontinence, sore skin, embarrassment, stoma care problem, impotence or dyspareunia), with higher scores indicating better functional or worse symptomatic status. Of these 21 scales or items, only body image, anxiety, weight, and sexual interest are functional domain scales/items, and all the remaining are symptomatic. One item (Q18) of the QLQ-CR29 is an indicator of colostomy/ileostomy construction, and different contents are designed for patients with/without a stoma in stool frequency, flatulence, fecal incontinence, sore skin, and embarrassment. Separate items are arranged for patients with a stoma (Q19-Q25) and those without it (Q19-Q24). The stoma care problem is only eligible to patients with a colostomy/ileostomy (Q25). Moreover, sexual interest, impotence, and dyspareunia items are only applicable to the corresponding gender (Q26-Q27 for male and Q28-Q29 for female). Permission to use the QLQ-C30 and QLQ-CR29 was obtained in advance from the EORTC Quality of Life Department.

Additional measures were rated by two investigators (MHS and CCH, both of who are qualified colorectal surgeons) to assess patients’ performance status and colonic transit time in the week prior to administering the questionnaires. Eastern Cooperative Oncology Group (ECOG) Performance Status, evaluates a patient’s level of functioning, and is widely used in cancer research, with Grade 0 representing fully active and Grade 5 representing dead status [15]. Bristol Stool Scale is adopted from Lewis et al. [16], which categorizes the form of stool representing colonic transit time. In brief, Type 1 and 2 indicate stool constipation, while Type 5-7 indicate diarrhea.

Internal consistency reliability was evaluated for multi-item scales, and a referable reliability was indicated by Cronbach’s alpha coefficient greater than 0.70 [17]. For multi-item scales, both convergent and discriminant validity were evaluated by item-scale correlations. Convergent validity was indicated by item and item-own scale correlation greater than 0.40, and item and item-own scale correlation greater than item-other scale correlations demonstrated discriminant validity [18]. A subset of follow-up patients was re-assessed within 7-14 days for the test-retest reliability (reproducibility) by evaluating the correlation coefficients between repeated measures during December 2017.

Known-groups comparisons, which compared patients of different treatment conditions, ECOG Performance Status, and Bristol Stool Scale, were conducted for the purpose of evaluating clinical validity. We postulated that patients under active treatment may suffer from disease burden or treatment adverse effects, and higher symptomatic and lower functional scores were discernable. Patients with higher degree of diarrhea according to the Bristol Stool Scale may have worse diarrhea-related symptoms, and patients with better ECOG Performance Status may report higher functional and lower symptomatic scores. Additional comparisons regarding the presence of a stoma, the type of adjuvant therapy, and different surgical procedures were evaluated as well.

Wilcoxon rank sum test was used for comparing group means since most quality-of-life scores were skewed and not normally distributed. All tests were two-sided, and a P-value less than 0.05 was considered as statistically significant. Sample size was calculated by G*Power3 [19] and was estimated as follows: assuming the standard deviation was 20, in order to detect a difference of 10 to 15 scores between two groups, the number needed in each group was 51 and 23, respectively, under the two-sided Z test with 80% power and α level of 0.05. Consequently a total of 50 patients in each group were a prerequisite for the validation purpose. The presuming quality-of-life score difference as well as standard deviation were estimated from our previous validation study for the QLQ-BR23, QLQ-STO22, and the suggestion of Osoba et al. [9, 10, 20].

During the enrollment period, 108 colorectal cancer patients (53 from the active treatment and 55 from the follow-up group) were successfully interviewed. There were 63 males and 45 females, with the mean age being 63.7 years (range: 22.2~ 89.1, SD: 13.2). Among them, 20 (18.5%) patients were presented with an obstructive lesion during initial diagnosis. The response rate was 88% for the active treatment and 87% for the follow-up group (refusers: 7 for active treatment and 8 for the follow-up group), with no significant difference (Fisher’s exact test, P = 0.21). Of the 53 patients in active treatment, 20 were planned for surgery and 33 for chemotherapy. Descriptive statistics are listed in Table 1. There was no difference in demographic and clinical features except more female patients in the follow-up group, and more stage IV and chemotherapy patients in the active treatment group (P < 0.05). There was no difference in terms of the ECOG Performance Status and the Bristol Stool Scale between these two groups. The distributions of the EORTC QLQ-C30 and QLQ-CR29 scale scores are detailed in Table 2.

Table 2 also displays reproducibility (test-retest reliability) for multi−/single- item scales of the EORTC QLQ-C30 and QLQ-CR29. A subset of 30 follow-up patients were approached, and 20 completed repeated measures between the first and second assessments within 7-14 days. Most scales indicated moderate to high correlation coefficients (0.51-1), augmenting the reproducibility of the measuring instruments. Exceptions were cognitive function (r = 0.48), pain (r = 0.11), dyspnea (r = 0.29), and financial difficulty (r = 0.47) from the QLQ-C30, as well as anxiety (r = 0.47), weight (r = 0.48), sexual interest (r = 0.47), blood and mucus in stool (r = 0.34), urine incontinence (r = 0.11), bloating (r = 0.40), dry mouth (r = 0.09), fecal incontinence (r = 0.47), and embarrassment (r = 0.50) scales from the QLQ-CR29. It is noteworthy that test-retest reliability was performed for the same follow-up group separately during December 2017.

Table 3 exhibited the reliability of the Taiwan Chinese version of the EORTC QLQ-C30 and QLQ-CR29. Convergent validity was indicated by item-own scale correlation (corrected for overlap) above 0.40 for all multi-item scales, and discriminant validity was convinced as the item own scale correlation was higher than item-other scale correlations for all multi-item scales. Cronbach’s alpha coefficient indicated good internal consistency reliability (> 0.70) for the QLQ-C30 and the QLQ-CR29 except cognitive function (0.45) and pain (0.61), both of which were from the QLQ-C30.

Table 4 presented the results of clinical validity. Follow-up patients reported a higher functional score in global health status/quality of life than those undergoing active treatment (P = 0.005). On the other hand, worse blood and mucus in stool was reported by patients in the active treatment group (19 versus 4, P < 0.001). The EORTC QLQ-CR29 recognized this as a colorectal cancer-specific symptom.

When ECOG Performance Status was used for partitioning, better global health status/quality of life (P < 0.05, QLQ-C30); better role function (P < 0.05, QLQ-C30); better physical function (P < 0.01, QLQ-C30); improved sexual interest (P < 0.01, QLQ-CR29); fewer complaints of fatigue (P < 0.01, QLQ-C30); lesser constipation, pain, and appetite loss (P < 0.05, QLQ-C30); and lesser problems with urinary frequency (P < 0.01, QLQ-CR29) were observed for ECOG Performance Status Grade 0 patients compared with patients having Grades 1-3. Types 5 and 6 patients on the Bristol Stool Scale experienced less appetite loss, and had better social function compared to Types 1 to 4 patients on the Bristol Stool Scale (P < 0.05, QLQ-C30).

Further comparisons evaluating the impacts of colostomy/ileostomy construction, adjuvant therapy, and surgical methods upon quality of life are detailed in Table 5. Stoma construction inevitably hampered quality of life in sore skin and fecal incontinence (P < 0.05, QLQ-CR29), while less insomnia (P < 0.05, QLQ-C30) was also revealed for the stoma group. Minimally invasive surgery benefited colorectal cancer patients with better social function, and fewer buttock pain and nausea/vomiting symptoms (P < 0.05). Adjuvant therapy deteriorated quality of life with worse hair loss and compromised social function (P < 0.01).