Investigating the Quality of Life and its Associated Factors in Patients with Colorectal Cancer.

INTRODUCTION
Colorectal cancer, with an annual incidence of more than one million cases, is one of the most common cancers worldwide.[1] Comprising the second and third most common cancers in women and men, respectively.[2] Thanks to timely diagnosis and treatment, the mortality rate of this disease has significantly decreased in recent decades, increasing the 5–10 survival rate in these patients from 55% to 62%.[2]
Gender, genetic determinants, and environmental factors seem to play an important role in the development of colon cancer. Among other risk factors are the male gender, inflammatory bowel disease (IBD), African-American race, obesity, sedentary lifestyle, and meat consumption.[3] The increase in the life-expectancy of patients with colorectal cancer following recent therapeutic advances has boosted the expectations of these patients for having a satisfactory quality of life (QoL), as an essential determinant of overall health.[4] The factors affecting the QoL of colorectal cancer patients can be divided into five categories, including socio-demographic, health-related, cancer-related, surgery-related, and lifestyle-related factors.[5] Studies have shown that gender has a minimal impact on the QoL of patients with colorectal cancer.[6] There is controversy regarding the effects of age, with some studies negating a role for age in affecting QoL, while others noting that advanced age is a negative predictor of QoL.[5] Among health-related factors are the comorbidities of cancer patients, such as urination problems, cardiac diseases, and depression.[7] Disease stage and tumor location constitute cancer-related factors that affect the type and modality of treatment, length of treatment, presenting signs and symptoms, and finally, the patient’s QoL. Patients who are diagnosed in stage I disease have lower life-expectancy and QoL compared to patients who are in the last stage of the disease.[8] Of patients with colon cancer, approximately 41% show the involvement of the proximal colon; 22% have distal colon engagement, and 28% of tumors are identified in the rectum. However, the site of cancer may vary depending on age and gender.[1]
Colorectal cancer patients, who undergo surgery generally experience a decrease in their QoL due to psychological and physiological factors, showing recovery within around three months. However, returning to the normal condition may take longer in elderly patients. Patients with colorectal cancer frequently carry a stoma, which alone can decrease QoL in these patients compared to patients whose sphincter is preserved after surgery.[9]
Therefore, to improve the QoL of these patients, the factors influencing this entity should initially be identified. Although factors such as age and gender cannot be modified, there are also modifiable factors that can improve the QoL of these individuals. Psychological factors are among the determinants that can be enhanced by psychotherapy and medicinal treatment, which can improve the QoL of these patients.[5] Considering those mentioned above and the importance of colorectal cancer as the third most common neoplasm in populations,[10] as well as insufficient studies on the QoL of these patients in Iran, this study aimed to determine the QoL of individuals diagnosed with colorectal cancer and its associated factors in Isfahan province.

MATERIALS AND METHODS
This cross-sectional study was conducted in 2021 on patients diagnosed with colorectal cancer registered in the cancer registry system in 2015 in Isfahan province, Iran. The exclusion criteria included the diagnosis of colorectal cancer in 2015, data registration in the cancer registry system of the Isfahan University of Medical Sciences, being alive, and willingness to participate in the study. Also, incomplete data file and lack of a contact route to the patient or his/her family to recollect missing information were considered as exclusion criteria.
The sample size required was calculated as 400 using a formula designed for estimating the mean value in a population with a confidence interval of 95%, study power of 80%, the standard deviation of 3.6 and the range of 6.6 for the QoL score in patients with colorectal cancer, and an error rate of 0.8. To obtain this sample size, those fulfilling our inclusion criteria among 887 patients diagnosed with colorectal cancer and registered in the cancer registry system of the Isfahan University of Medical Sciences in 2015 were enrolled.
Patients’ data were gathered through phone calls or during their periodic visits, including demographic information such as age and sex, time of diagnosis, comorbidities, disease stage, presence of a colostomy, and past medical history of treatment including chemotherapy, surgery, or both. The QLQ-C29 and QLQ-C30 questionnaires were then provided to the patients. Those who were able to complete the questionnaires responded to the queries independently, while patients who were unable to do so received assistance from the researcher.
The QLQ-C30 questionnaire is a 30-item tool designed to evaluate the QoL of cancer patients by assessing the impact of the disease and treatments on patients’ daily living in five performance dimensions (physical, role, emotional, cognitive, and social), as well as overall life quality, symptoms (fatigue, nausea, vomiting, and pain), and six independent items. The responses were recorded on a four-option Likert scale from 1 to 4. The final score ranged from 0 (i.e., the poorest health status) to 100 (the best health status) in the performance dimension. Regarding symptoms and overall health, the total score also ranged from 0 (no symptoms; the best health status) to 100 (most severe symptoms and the poorest health status).[11]
The QLQ-C29 questionnaire contains 29 queries and aims to measure the QoL of patients with colorectal cancer. This tool assesses the symptoms (digestive, urinary, etc.), performance (e.g., sexual function), and body image of colorectal cancer patients. This questionnaire contains separate questions for patients carrying a stoma, as well as specific items to ascertain the sexual function of men and women. The responses are evaluated on a four-point Likert scale from 1 to 4. The final score ranged from 0 (i.e., the poorest health status) to 100 (i.e., the best health status) for the performance dimension and from 0 (no symptoms) to 100 (most symptoms) for the symptom dimension. The queries of the questionnaire evaluate the patient’s condition within the past week, except for sexual performance, which is related to the past 4 weeks. The reliability of the QLQ-C30 questionnaire has been estimated as 0.8 for the whole instrument and from 0.6 to 0.9 for its dimensions, verifying its internal consistency (i.e., reliability).[11] The reliability and validity of the QLQ-C30 and QLQ-C29 questionnaires have been confirmed by Safaei and Khazanli.[6] These classifications were based on percentage score thresholds, where a QoL score below 50% was considered poor or unsatisfactory, scores between 50% and 66% were defined as moderate, and scores above 66% were deemed satisfactory.
The demographic and clinical data obtained from the questionnaires were entered into SPSS 26 software. The t-test, one-way analysis of variance (ANOVA), and Pearson correlation were used to analyze the data at a significance level of P < 0.05.

RESULTS
In this study, 400 patients with colorectal cancer were enrolled, with a mean age of 66.3 ± 14.2 years (range, 25–100 years). According to Figure 1, the lowest frequency was observed in the age group of < 50 years, and the highest frequency was in the age group of 50–69 years. In terms of gender distribution, 218 (54.5%) of the patients were men, and 182 (45.5%) of them were women. The mean ages of men and women were 67.96 ± 14.7 and 64.3 ± 13.2 years, respectively, indicating that male patients were significantly older [P = 0.01, Figure 1].
Of the patients, 110 (27.5%) carried an ostomy, and 282 (70.5%) had a history of surgery. Regarding disease stage, 142 (35.5%), 139 (34.8%), 82 (20.5%), and 37 (9.3%) patients were in stages I, II, III, and IV, respectively.
The mean score of overall QoL in the patients studied was 65.53 ± 19.3, corresponding to a percentage score of 54.61 ± 16.1% of the maximum of 100%. According to this, QoL was satisfactory in 46 (11.5%) patients, moderate in 153 (38.3%) individuals, and poor in 201 (50.2%) patients.
The mean scores of QoL in the dimensions of performance and symptoms were obtained as 34.31 ± 12.7 and 19.75 ± 5.95, respectively, corresponding to the respective percentage scores of 47.65 ± 17.6% and 44.89 ± 13.53%. Based on these results, 38 (9.5%), 131 (32.8%), and 231 (57.8%) of the patients performed unsatisfactory, moderately, and satisfactory, respectively. However, symptoms were severe in 10 (2.5%), moderate in 141 (35.3%), and mild in 249 (62.3%) of the patients.
The mean overall health and QoL score was 4.62 ± 1.3 out of a maximum score of seven, corresponding to a QoL percentage score of 66 ± 19.1%. According to this, the overall health and QoL were satisfactory in 124 (31%), moderate in 208 (52%), and poor in 68 (17%) of the patients [Figure 2].
Table 1 shows the means ± standard deviations of the overall QoL score in the two dimensions of performance and symptoms based on demographic and clinical characteristics. There was no significant difference in the QoL score between males and females. However, the overall QoL score showed substantial differences in separate age groups, as well as based on having an ostomy or not, history of surgery, and disease stage. In this sense, the QoL score falls as one gets older and the disease stage advances. Patients who had a history of surgery or ostomy, however, showed better QoL scores—possibly from improved general health at the time of surgery, effective treatment, or symptom relief. Regarding the overall health status and life quality during the past week, the mean scores for overall health status and QoL were 4.62 ± 1.34 and 4.5 ± 1.37, respectively, with a maximum score of seven. This indicates a significant difference in overall health status and QoL across various demographic and clinical variables, except for gender.
As shown in Figure 3, mean QoL scores in the five dimensions of physical, role, cognitive, emotional, and social performance were 10.3 ± 4.29, 5.78 ± 2.53, 5.62 ± 2.38, 6.36 ± 2.53, and 6.25 ± 2.70, respectively. There was no significant difference in these scores between the two genders. Regarding the history of surgery, there was a significant difference in the physical and role-playing dimensions, but not other QoL dimensions, among the patients. There was also a significant difference in the mean score of QoL in all dimensions in terms of the age group, ostomy status, and disease stage.
According to the LQL-CR29 questionnaire, the mean QoL score was 48.7 ± 14.4, corresponding to a percentage score of 45.1 ± 13.3 out of 100, based on the maximum obtainable score. Table 2 displays the symptoms and physical and psychological problems observed in the studied patients. The most common urinary problem among the patients was frequent daytime urination. Also, the most frequent problem related to defecation was abdominal bloating. Regarding treatment side effects, the most encountered problem was the loss of taste. Regarding psychological issues, concern over the health status was the most prominent observation. Finally, anal sores and discomfort during intercourse were the most common complaints related to the colostomy sac and sexual dimension, respectively [Table 3].

DISCUSSION
QoL is a practical and reliable indicator for assessing health and disease in patients suffering from chronic conditions, particularly cancer.[11] Cancer patients struggle not only with the symptoms of their disease but also the side effects of treatment, and more importantly, they are predisposed to severe psychological problems such as anxiety and depression because these patients see themselves at the end of their lives. Several psychosocial therapies may improve cancer patients’ QoL. cognitive behavioral (CBT) support groups, and mindfulness-based stress-reduction (MBSR) have reduced anxiety, depression, and emotional upheaval in colon cancer survivors. Including them in regular treatment programs may enhance functional and emotional quality of life.[12] All these events together lead to a decline in the QoL of these patients in all aspects, including physical, psychological, emotional, social, role-playing, and cognitive dimensions. Therefore, the evaluation of QoL helps modify circumstances for these patients so that they can enjoy a more favorable and acceptable condition in all aspects. In this regard, this study aimed to investigate the QoL and its associated factors in patients diagnosed with colorectal cancer.
The findings of the present study showed that the QoL of colorectal cancer patients was considerably inferior compared to healthy people, and our patients attained an overall QoL score of 54.61 out of the maximal score of 100. Accordingly, the level of QoL was observed to be desirable in 11.5% of the patients and moderate in 38.3% of them. This was while over half of the patients had poor QoL. In a similar study in 1385 conducted on patients with colorectal cancer by Akhondi-Meybodi et al.,[13] the QoL score percentage was reported as 67.9%. The reason for the difference with our result may be related to factors such as the age of diagnosis and disease stage. In the recent study, the population under study comprised newly diagnosed patients. Also, Nikbakht et al.,[14] who investigated 120 patients with colorectal cancer, reported a mean QoL percentage score of 56%, which was close to the value obtained in our study. Padilla et al.[15] estimated the average QoL score of patients with colorectal cancer as 62%–84%.
The present study’s findings showed that age was an essential determinant of QoL in cancer patients, with older individuals reporting better QoL scores. However, gender did not significantly influence QoL. Other associated factors included disease stage, history of surgery, and carrying an ostomy. Also, our results indicated that patients with a history of surgery and those carrying an ostomy had lower QoL scores, like earlier studies. For instance, Sprangers et al.[16] reported lower QoL in patients with a stoma using the QLQ-C30 questionnaire. Marventano et al.[5] also found that surgery and advanced stage were associated with reduced QoL. Likewise, Mormont et al.[17] found poor education level and ostomy as leading causes of lowered quality of living.
It should be noted that patients with high disease severity were treated with chemotherapy alone, while patients with better disease status were treated with surgery alone. Therefore, in our study, the QoL score of patients with a history of surgery was better than that of patients with chemotherapy alone or combined with surgery.
Besides clinical characteristics, socioeconomic status (SES)—comprising income, educational attainment, and healthcare accessibility—exerts a considerable impact on the quality of life in cancer patients. A multitude of studies indicate that lower socioeconomic status is associated with heightened symptom load, constrained treatment alternatives, and diminished psychological support. While SES data were not included in our study, these factors undoubtedly influenced some of the observed inequalities in quality of life.[18]
Our findings indicate that the average QoL score across all categories (i.e., physical, role-playing, cognitive, emotional, and social) was similar for both men and women. Conversely, physical performance and role-playing ratings were markedly elevated in colorectal cancer patients with a surgical history compared to their counterparts without such a history. There was a substantial variation in the average QoL score across all parameters among all age groups, ostomy status, and illness stages.[15]
According to the findings of our study, patients with colorectal cancer did not perform well regarding the sexual dimension of QoL. In this regard, more than two-thirds of the patients had no desire to have intercourse. Also, more than half of the patients complained of experiencing pain and discomfort during sexual activities, which was in line with the results of Chao et al.[19] The findings of various studies indicate that patients with colorectal cancer face many problems, including physical and psychological conundrums, adversely affecting their QoL in multiple areas. However, factors such as the disease stage, undergoing surgery, carrying a fecal bag, and therapeutic interventions (such as chemotherapy) exacerbate the problems of patients.[13] Therefore, it is necessary to think of measures needed to improve the physiological and psychological adaptation of patients with their disease and help them cope with these problems.
Although our research concentrated on a primarily Iranian cohort, global literature indicates that racial and ethnic discrepancies markedly affect both healthcare access and health-related quality of life (HRQoL) among colon cancer patients. African American patients have been documented to present at more advanced stages of illness, encounter more complications, and have worse QoL ratings. Systemic inequities, cultural attitudes, and discrepancies in care must be taken into account when generalizing global quality of life results.[20]
The lack of information on various treatment methods limits our study. All these factors add to the general QoL, and these therapies are known to have significant effects on physical symptoms (e.g., tiredness, nausea), mental well-being, and functional ability. The absence of these factors might be a confusing element that reduces the interpretability of the reported correlations. Comprehensive treatment profiles should be included in future research to help better separate the impact of every modality on QoL.
The QoL decline in colorectal cancer patients, particularly those with advanced disease stages, ostomies, or a surgical history, is influenced by a combination of physical, psychological, and social stressors. Advanced disease stages require more aggressive therapies, leading to increased symptom burdens. Surgical interventions, particularly those causing permanent ostomies, significantly impact body image and daily living activities. Elderly patients often have slower recovery rates and are more susceptible to comorbid conditions, resulting in poorer emotional and social outcomes. Future research should use longitudinal methodologies and randomized clinical studies to evaluate the effectiveness of tailored treatments.

CONCLUSION
The findings of the present study showed that patients with colorectal cancer were deprived of a desirable QoL, and more than two-thirds of the patients were in desperate physical and psychological conditions. Various factors were identified to profoundly affect QoL, such as age, history of surgery, having a colostomy sac, and disease stage. Therefore, these patients are required to receive special physical, psychological, and social support and to be provided with the necessary measures to be able to enjoy a better life quality. Meanwhile, considering the limitations of this study, such as the lack of studying all potential factors affecting QoL, the lack of the control group, and not following up with the patients, more studies are suggested to be conducted in this field.

Author contributions
ET, SB, and MS participated in the research concept and design. ET, SB, FR, ZR, and MS participated in the performance of research and analytic tools. ET, MR, and MS participated in writing the first draft and validation. ET, SB, MR, and MS participated in data analysis. All authors reviewed and confirmed the final manuscript.

Ethics approval and consent to participate
This study was approved by the ethics committees of Isfahan university of medical sciences (Ethics code: IR.MUI.MED.REC.1400.765). The methods were carried out in agreement with the principles and propositions established in declaration of Helsinki for all human subjects. Written and verbal informed consent obtained from all participants. In the case of adults with cognitive decline, the legal guardian/family or an appropriate representative gave informed consent to participate on their behalf.

Competing interest
The authors declare no conflict of interest.

Availability of data and materials
The datasets used and analyzed during the present study are available from the corresponding author on reasonable request.