Quality of Life in Locally Advanced Carcinoma Rectum Patients During Various Phases of NACRT: An Indian Perspective

Abstract

In low- and middle-income countries (LMICs) including India, cancer patients have a poor prognosis because of late diagnosis and cases already grown to advanced stages, low cancer awareness and skewed cancer care facilities. In India, the incidence of colorectal cancer (CRC) is ranked the 4th most common (6.4%) in males and the 5th most common (3.4%) in females. The improvement in the cure rate of rectal cancer has increased life expectancy, and assessment of the quality of life (QoL) in these patients has become a fundamental requirement. Little is known about how the patients perceive these adverse effects during curatively intended radiotherapy. Although studies have investigated the various adverse effects that can occur with radiotherapy and chemotherapy in carcinoma rectum patients, these have not yet been critically appraised and synopsized to form a comprehensive review of their prevalence and effects on QoL. The study was designed to explore the QoL issues in locally advanced carcinoma rectum patients during various phases of neoadjuvant concurrent chemo-radiotherapy (NACCRT). The study was performed over a period of 2 years at a single super speciality cancer hospital in North India. Patients were selected as per the inclusion criteria and followed up with a standard questionnaire incorporating various aspects depicting QoL. The interview technique was used for collecting QoL data at four points, at baseline, midway during treatment, at the end of treatment and 4 weeks after completion of NACCRT, using EORTC QLQ C30, for QLQ CR29. Special care was taken to avoid observer bias in cases of language issues, and interpreters’ services were utilised, and compared with the baseline pre-treatment scores, patients reported a statistically significant and large clinically meaningful change in the global health status, social functioning, fatigue (FACIT-F), appetite loss, anxiety, sore skin and male and female sexual function at the post-treatment time point. Statistically significant changes with moderate clinically meaningful changes were reported for the functional scales—physical, role and emotional functioning of the QLQ C30 questionnaire and body image and weight of the CR29 questionnaire. Similar moderate clinical changes were found in the symptom scales—fatigue, nausea and vomiting, insomnia, constipation and diarrhoea of QLQ C30 and stool frequency, embarrassment with bowel function, impotence and dyspareunia. These parameters returned to almost the pre-treatment values after 4 weeks of completion of NACRT. Since QoL is a relatively subjective variable, differences in human race, culture, education and social environment will have impacts on the results. International cooperation is needed to study the QoL in patients with multiple cultural backgrounds. The existing QoL questionnaire tools have been designed with Western countries in mind, and we did face multiple social issues. We suggest that many similar multicentre studies shall be required to essentially tap the accurate QoL-related issues keeping in mind the diverse social, economic, racial and educational backgrounds. As we deal with the ever-increasing cancer menace and better life expectancy, QoL issues shall be a major determinant of treatment success besides primary treatment. These factors should form an integral part of treatment modality, and adequate counselling must be performed prior to initiation of care.

Introduction

Cancer is globally recognized as one of the major causes of morbidity and mortality. It is the second leading cause of death (16%) following cardiovascular diseases (31%). According to the WHO, approximately 70% of cancer deaths take place in low- and middle-income countries (LMICs) [1].

In LMICs including India, cancer patients have a poor prognosis because of late diagnosis and cases already grown to advanced stages, low cancer awareness and skewed cancer care facilities. In India, the incidence of colorectal cancer (CRC) is ranked the 4th most common (6.4%) in males and the 5th most common (3.4%) in females. The mortality in males due to colorectal carcinomas is 6.9% [2].

Studies have revealed increasing relative overall 5-year survival rates over the years (1975–1977) from 45 to 70%. The authors in the study have concluded that tri-modality treatment has reaped benefits with improved overall survival with respect to single or dual modality. This effect was confirmed by a propensity score matching analysis (hazard ratio, 0.72; P = 0.01) [3].

The improvement in the cure rate of rectal cancer has increased life expectancy, and assessment of the quality of life (QoL) in these patients has become the fundamental requirement. Little is known about how the patients themselves perceive these adverse effects during the course of curatively intended radiotherapy. Although studies have investigated the various adverse effects that can occur with radiotherapy and chemotherapy in carcinoma rectum patients, these have not yet been critically appraised and synopsized to form a comprehensive review of their prevalence and effects on QoL.

The Core Quality of Life Questionnaire developed by the European Organization for Research and Treatment of Cancer (EORTC QLQ C30) is an instrument for assessing health-related QoL in cancer patients. This instrument is reliable, validated, and feasible to use in research and is the questionnaire most widely used in cancer clinical trials worldwide. The cross-cultural adaptability of the EORTC QLQ C30 has been evaluated with testing in more than 24 countries [4].

The QLQ C30 is a 30-item general cancer instrument that evaluates 5 domains of QOL (physical, role, cognitive, emotional and social), 9 symptom scales (fatigue, nausea/vomiting, pain, dyspnoea, sleep disturbance, appetite loss, constipation, diarrhoea and financial impact) and a global QOL score. Each domain is assessed by 2 to 5 questions, and responses are scored on a 4-point Likert scale, with higher scores representing better QOL. Higher scores on symptom items represent worse symptoms. The validity and reliability of the QLQ C30 have been well documented.

The 29-item QLQ CR29, by contrast, represents an update to the QLQ CR38 and consists of 6 scales and 11 single items. Questions regarding anorectal and urinary function were added in constructing the QLQ CR29, and intrusive questions on sexual symptoms and enjoyment that were on the original 38-item measure were eliminated [5].

Though neoadjuvant concurrent chemo-radiotherapy (NACCRT) has been found to have OS benefit, there has been associated issue related to QoL The literature on this aspect post-treatment limited especially in the Indian subcontinent.

Therefore, this prospective study was carried out at our centre to evaluate the impact of NACCRT on QoL which was evaluated utilising a validated questionnaire.

Aims and Objectives

The study was designed to explore the QoL issues in locally advanced carcinoma Rectum patients during various phases of NACCRT.

Material and Methods

The study was performed over a period of 2 years at a single super speciality cancer hospital in north India. Patients were selected as per the inclusion criteria and followed up with a standard questionnaire incorporating various aspects depicting QoL.

The interview technique was used for collecting QoL data at four points, at baseline, midway during treatment, at the end of treatment and 4 weeks after completion of NACCRT, using EORTC QLQ C30, for QLQ CR29. Special care was taken to avoid observer bias in cases of language issues, and interpreters’ services were utilised.

We assessed general cancer-related QoL using the EORTC QLQ C30. The core questionnaire, the QLQ C30, is the product of more than a decade of collaborative research. Following its general release in 1993, the QLQ C30 has been used in a wide range of cancer clinical trials, by a large number of research groups; it has additionally been used in various other, non-trial studies.

The QLQ C30 is a 30-item general cancer instrument that evaluates 5 domains of QoL (physical, role, cognitive, emotional and social), 9 symptom scales (fatigue, nausea/vomiting, pain, dyspnoea, sleep disturbance, appetite loss, constipation, diarrhoea and financial impact) and a global QoL score. The validity and reliability of the QLQ C30 have been well documented. The 29-item QLQ CR29, by contrast, represents an update to the QLQ CR38 and consists of 6 scales and 11 single items. Questions regarding anorectal and urinary function were added in constructing the QLQ CR29, and intrusive questions on sexual symptoms and enjoyment that were on the original 38-item measure were eliminated. The colorectal cancer module is a supplementary questionnaire module to be employed in conjunction with the QLQ C30. The QLQ CR29 incorporates 4 multi-item scales and 19 single items assessing a range of symptoms and problems common among patients with colorectal cancer. The scoring approach for the QLQ CR29 is identical in principle to that for the function and symptom scales/single items of the QLQ C30.

In relation to the clinical significance of QLQ C30 and QLQ CR29, a change of 5–10 points between time points is considered to be a small clinically meaningful change, a change of 10–20 points is considered to be a moderate clinically meaningful change and a change of greater than 20 points is classified as a large clinical meaningful change (Osoba et al. 1998 [6]; Guren et al. 2003 [7].

The sample size was calculated by assuming at the most 5% risk, with a minimum of 80% power and 5% significance level (significant at 95% confidence level, Z = 1.96).With the assumption of a 95% confidence level, 0.85 probability of success and a margin of error (confidence interval) of ± 12%, the sample size was calculated as 35. The formula used for the same is as follows: Sample Size Formula = (Z-score) ² * P*(1-P)/(margin of error) ².

Only those patients were part of the study who were histologically confirmed to be locally advanced non-metastatic adenocarcinoma of the rectum and were of stages III and IV with no prior history of receiving radiation. The patients who had a KPS score [8] of < 80%, and pregnant ladies, age more than 70 years, were excluded. Also, recurrent cases of carcinoma rectum, early stages of operable carcinoma rectum and patients with deranged biochemical parameters were excluded.

With respect to the administration of RT, multiple RT fields were used to include the tumour or tumour bed with a 2- or 5-cm margin, pre-sacral nodes and the internal iliac nodes. The external iliac nodes were included for T4 tumours involving anterior structures; the inclusion of the inguinal nodes for tumours invading the distal anal canal was considered. In long-course RT, recommended doses of RT of typically 45 to 50 Gy in 25 to 28 fractions to the pelvis were used using 3 or 4 fields by 3D-conformal technique. Capecitabine (CA) was administered concomitantly with RT at a dose of 825 mg/m² twice daily (bid) during the whole period of RT without giving weekend breaks.

Surgery was performed after 8–10 weeks after the response assessment by the surgical oncologist at our hospital. The pathological assessment was performed as per the CAP protocol [9]. The post-operative specimen was analysed in detail for tumour size, nodal stage, pathological response, margin status including circumferential resection margin and tumour regression grade (TRG) score using Mendard’s scoring [10].

Results

The study included 35 patients of which 22 were males, while 13 were female patients. The mean (SD) of age (years) was 45.43 (14.34). The median (IQR) of age (years) was 46.00 (34–55.5). The age (years) ranged from 22 to 70.

Most of the patients were males and consumed a mixed diet. This is similar to other studies which also had male preponderance and consumed mixed diet. Approximately 90% of our patients had bleeding per rectum as the main complaint, while 8.6% had predominant symptoms such as altered bowel habits (Table 1).

Table 1.

Clinico-demographic treatment profile of the patient

Basic details	Mean ± SD || median (IQR) || min–max || frequency (%)
Age (years)	45.43 ± 14.34 || 46.00 (34.00–55.50) || 22.00–70.00
Gender
Male	22 (62.9%)
Female	13 (37.1%)
Residence (rural)	35 (100.0%)
Diet
Non-vegetarian	6 (17.1%)
Vegetarian	29 (82.9%)
Addictions
Bidi	4 (11.4%)
Gutka	1 (2.9%)
Nil	30 (85.7%)
Comorbidities
Nil	30 (85.7%)
BPH	1 (2.9%)
CVA	1 (2.9%)
Hypertension	1 (2.9%)
Neurocystecercosis	1 (2.9%)
T2DM	1 (2.9%)
Presenting symptoms
Bleeding P/R	31 (88.6%)
Altered bowel habits	3 (8.6%)
Mucus discharge P/R	1 (2.9%)
Location
Upper 1/3rd	2 (5.7%)
Middle 1/3rd	9 (25.7%)
Lower 1/3rd	24 (68.6%)
Histological type
Well differentiated	6 (17.1%)
Moderately differentiated	22 (62.9%)
Poorly differentiated	1 (2.9%)
Mucinous	4 (11.4%)
Signet ring cell	2 (5.7%)
CEA	11.08 ± 37.49 || 3.25 (1.94–5.16) || 0.60–221.80
KRAS
Wild-type	28 (80.0%)
Mutated	7 (20.0%)
Total duration of treatment
≤ 6 Weeks	22 (62.9%)
> 6 Weeks	13 (37.1%)

Lower rectum tumour was the most common location followed by 1/4th of patients seeking medical attention which had mid-rectal involvement, while a small percentage (5.7%) had upper rectum tumour (Table 1).

The most common histology in our subset of patients was moderately differentiated, while poorly differentiated was the least common variety (11.4%) (Table 1).

The mean (SD) pre-op CEA was 11.08 (37.49). The median (IQR) of CEA was 3.25 (1.94–5.16). The CEA ranged from 0.6 to 221.8

Social Impact (Table 2)

Table 2.

QLC 30 QOL indicators

QLQ C30	Pre-treatment	Mid-treatment	Post-treatment	Follow-up
Global health status	84.23 ± 6.15	73.34 ± 7.61	63.09 ± 11.25	83.57 ± 7.26
Physical functioning	93.77 ± 8.79	89.97 ± 10.24	79.94 ± 11.77	96.69 ± 6.74
Role functioning	89.37 ± 11.57	84.03 ± 12.81	70.97 ± 14.59	92.74 ± 9.40
Emotional functioning	77.74 ± 9.63	71.57 ± 12.94	57.91 ± 16.08	85.94 ± 7.06
Cognitive functioning	100.00 ± 0.00	100.00 ± 0.00	100.00 ± 0.00	100.00 ± 0.00
Social functioning	91.80 ± 10.26	78.94 ± 12.20	63.54 ± 10.64	93.71 ± 10.86
Fatigue	11.63 ± 10.65	17.60 ± 10.40	28.91 ± 12.54	3.77 ± 7.03
Nausea and vomiting	1.46 ± 4.83	9.20 ± 9.46	17.34 ± 8.46	3.40 ± 6.90
Pain	20.66 ± 8.91	22.54 ± 10.47	25.31 ± 10.74	8.26 ± 8.62
Dyspnoea	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00
Insomnia	26.43 ± 15.68	34.03 ± 12.84	39.80 ± 13.80	21.69 ± 15.89
Appetite loss	8.49 ± 14.63	23.60 ± 17.19	35.91 ± 9.66	5.66 ± 12.62
Constipation	0.94 ± 5.58	9.43 ± 15.13	0.00 ± 0.00	0.00 ± 0.00
Diarrhoea	0.00 ± 0.00	1.89 ± 7.77	13.26 ± 20.09	0.00 ± 0.00
Financial difficulties	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00

1. Global health status decreased from a maximum of 84.23 at the pre-treatment time point to a minimum of 63.09 at the post-treatment time point and then increased to 83.57 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 99.3, p < 0.001) and had a large clinically meaningful change.

2. Physical functioning decreased from 93.77 at the pre-treatment time point to a minimum of 79.94 at the post-treatment time point and then increased to 96.69 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 89.0, p < 0.001) with moderate impact.

3. Role functioning decreased from 89.37 at the pre-treatment time point to a minimum of 70.97 at the post-treatment time point and then increased to 92.74 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 83.1, p < 0.001) with a moderate clinically meaningful change.

4. Fatigue increased from 11.63 at the pre-treatment time point to a maximum of 28.91 at the post-treatment time point and then decreased to 3.77 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 88.6, p < 0.001) and had a moderate clinically meaningful change.

Gastrointestinal Symptoms

1. Constipation increased from 0.94 at the pre-treatment time point to a maximum of 9.43 at the mid-treatment time point and then decreased to 0.00 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 27.4, p < 0.001) and a moderate clinically meaningful change.

2. Diarrhoea increased from a minimum of 0.00 at the pre-treatment time point to a maximum of 13.26 at the post-treatment time point and then decreased to 0.00 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 32.5, p < 0.001) and a moderate clinically meaningful change.

3. Bloated feeling increased from a minimum of 0.00 at the pre-treatment time point to a maximum of 0.94 at the mid-treatment time point and then decreased to 0.00 at the 4-week follow-up time point. This change was not statistically significant (Friedman test, χ2 = 3.0, p = 0.392).

4. Flatulence increased from a minimum of 0.00 at the pre-treatment time point to a maximum of 2.83 at the post-treatment time point and then decreased to 0.00 at the 4-week follow-up time point. This change was not statistically significant (Friedman test, χ2 = 7.2, p = 0.066).

5. Blood and mucus in stool increased from 0.49 at the pre-treatment time point to a maximum of 2.40 at the mid-treatment time point and then decreased to 0.00 at the 4-week follow-up time point. This change was not statistically significant (Friedman test, χ2 = 5.5, p = 0.141).

6. Stool frequency increased from a minimum of 0.00 at the pre-treatment time point to a maximum of 12.31 at the post-treatment time point and then decreased to 0.00 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 31.9, p < 0.001) and had a moderate clinically meaningful change.

7. Nausea and vomiting increased from a minimum of 1.46 at the pre-treatment time point to a maximum of 17.34 at the post-treatment time point and then decreased to 3.40 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 69.6, p < 0.001) and a moderate clinically meaningful change.

8. Appetite loss increased from 8.49 at the pre-treatment time point to a maximum of 35.91 at the post-treatment time point and then decreased to 5.66 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 68.3, p < 0.001) and had a large clinically meaningful change.

9. Abdominal pain increased from a minimum of 0.00 at the pre-treatment time point to a maximum of 0.94 at the mid-treatment time point and then decreased to 0.00 at the 4-week follow-up time point. This change was not statistically significant (Friedman test, χ2 = 3.0, p = 0.392).

10. Weight decreased from a maximum of 99.06 at the pre-treatment time point to a minimum of 81.06 at the post-treatment time point and then increased to 99.06 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 39.9, p < 0.001) and had a moderate clinically meaningful change

11. Embarrassed with bowel movements increased from a minimum of 0.00 at the pre-treatment time point to a maximum of 14.14 at the post-treatment time point and then decreased to 0.00 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 31.7, p < 0.001) had a moderate clinically meaningful change.

Urogenital Symptoms (Table 3)

Table 3.

QLQ CR29

QLQ CR29	Pre-treatment	Mid-treatment	Post-treatment	Follow-up
Anxiety	59.26 ± 16.56	59.23 ± 14.49	52.46 ± 18.88	72.66 ± 12.62
Weight	99.06 ± 5.58	91.49 ± 16.78	81.06 ± 21.80	99.06 ± 5.58
Body image	98.74 ± 4.44	94.66 ± 8.17	84.60 ± 8.52	97.80 ± 5.20
Male sexual function	51.55 ± 30.53	25.73 ± 27.17	7.50 ± 14.15	49.91 ± 44.58
Female sexual function	33.31 ± 27.35	10.15 ± 15.85	00.00 ± 0.00	20.38 ± 21.64
Urinary frequency	0.00 ± 0.00	1.46 ± 4.83	4.37 ± 7.54	0.00 ± 0.00
Urinary incontinence	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00
Dysuria	0.00 ± 0.00	2.83 ± 9.37	8.49 ± 14.63	0.00 ± 0.00
Abdominal pain	0.00 ± 0.00	0.94 ± 5.58	0.00 ± 0.00	0.00 ± 0.00
Buttock pain	0.00 ± 0.00	2.83 ± 9.37	2.86 ± 12.48	0.94 ± 5.58
Bloated feeling	0.00 ± 0.00	0.94 ± 5.58	0.94 ± 5.58	0.00 ± 0.00
Blood and mucus in stool	0.49 ± 2.87	2.40 ± 7.18	1.91 ± 6.73	0.00 ± 0.00
Dry mouth	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00
Hair loss	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00
Trouble with taste	0.00 ± 0.00	0.00 ± 0.00	0.94 ± 5.58	0.00 ± 0.00
Flatulence	0.00 ± 0.00	0.94 ± 5.58	2.83 ± 9.37	0.00 ± 0.00
Faecal incontinence	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00
Sore skin	0.00 ± 0.00	6.60 ± 13.39	28.29 ± 11.72	0.00 ± 0.00
Stool frequency	0.00 ± 0.00	7.09 ± 13.45	12.31 ± 15.17	0.00 ± 0.00
Embarrassed with bowel movements	0.00 ± 0.00	6.60 ± 13.39	14.14 ± 16.57	0.00 ± 0.00
Impotence	34.73 ± 30.01	59.09 ± 25.25	78.91 ± 21.91	31.91 ± 40.55
Dyspareunia	66.69 ± 27.35	89.85 ± 15.85	100.00 ± 0.00	79.62 ± 21.64

1. . a) Urinary frequency increased from a minimum of 0.00 at the pre-treatment time point to a maximum of 4.37 at the post-treatment time point and then decreased to 0.00 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 20.2, p < 0.001) and had no clinically meaningful change.

2. Dysuria increased from a minimum of 0.00 at the pre-treatment time point to a maximum of 8.49 at the post-treatment time point and then decreased to 0.00 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 20.2, p < 0.001) with minuscule impact.

3. Impotence increased from 34.73 at the pre-treatment time point to a maximum of 78.91 at the post-treatment time point and then decreased to 31.91 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 46.3, p < 0.001) and had a moderate clinical effect.

4. Dyspareunia increased from a minimum of 66.69 at the pre-treatment time point to a maximum of 100.00 at the post-treatment time point and then decreased to 79.62 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 20.7, p < 0.001) and affected moderately.

5. Male sexual function decreased from a maximum of 51.55 at the pre-treatment time point to a minimum of 7.50 at the post-treatment time point and then increased to 49.91 at the 4-week follow-up time point. This change was statistically significant (Friedman test, χ2 = 40.3, p < 0.001) and had a large clinically meaningful change.

6. Female sexual function also reduced from a maximum of 33.31 at the pre-treatment time point to a minimum of 0.00 at the post-treatment time point and then increased to 20.38 at the 4-week follow-up time point. This change was statistically significant (Friedman Test: χ2 = 20.7, p < 0.001) and had a large clinically meaningful change.

Discussion

Colorectal cancer is one of the leading cancers in the world and one of the most common causes of death. The incidence of rectal cancer has gradually increased in Indian subcontinent causes, which have been postulated to be multifactorial [11].

Management of rectal cancer is unique and complexed by the tumour location and the presence of vital surrounding structure which may sometimes suffer collateral damage as a part of treatment.

As we deal with primary management at times, its effect on social, physical, and psychological well-being often remains under evaluation. This has been the main cause as to why the literature discussing the impact of NACCRT as a primary modality on QoL especially along the course of management is limited.

The mean age of rectal cancer patients in our study is 45 years, with males constituting 62.9% and females 37.1%. This was similar to a study done at a tertiary cancer hospital in India in which the mean age was 47.2 years and 65% were males [12]. In another study, the median age of presentation was 43.4 years [13].

The commonest presenting complaints in our patients were bleeding P/R (88%) followed by altered bowel habits. This was similar to another study where rectal bleeding in combination with a change in bowel habits was the most common symptom combination (51% of all cancers and 71% of those presenting with rectal bleeding) [14].

QoL is also known to be an independent predictor of survival and response to therapy in cancer patients [15]. Broun et al. found that a 10-point increase in baseline global QoL scores (EORTC QLQ C30) was associated with a 7% decreased risk of death [16].

Some authors proposed a theory according to which QoL could have a direct influence on tumour behaviour and survival; others suggested that QoL had a direct influence on therapy adherence and consequently on survival. Moreover, a recent 18-month trial suggested that baseline QoL influenced CRC patient’s survival [17].

Compared with the baseline pre-treatment scores, patients reported a statistically significant and large clinically meaningful change in the global health status, social functioning, fatigue (FACIT-F), appetite loss, anxiety, sore skin and male and female sexual function at the post-treatment time point (Fig. 1).

Fig. 1.

FACIT subscale over time

Statistically significant changes with moderate clinically meaningful changes were reported for the functional scales—physical, role and emotional functioning of the QLQ C30 questionnaire and body image and weight of the CR29 questionnaire (Figs. 2 and 3).

Fig. 2.

QOL 30 index changes over time

Fig. 3.

QOL 29 indices over time

Similar moderate clinical changes were found in the symptom scales—fatigue, nausea and vomiting, insomnia, constipation and diarrhoea of QLQ C30 and stool frequency, embarrassment with bowel function, impotence and dyspareunia. These parameters returned to almost the pre-treatment values after 4 weeks of completion of NACRT (Fig. 2).

Statistically significant with small clinically meaningful changes were found in the pain and dysuria. Symptoms of scales like bloated feeling, flatulence, blood and mucus in stool, trouble with taste, abdominal pain, buttock pain and urinary frequency showed no statistically significant changes throughout the course of NACCRT (Fig. 4).

Fig. 4.

Effect of NACCRT on urogenital system

These findings corresponded to the findings of the study by Birsen Yucel et al. where, compared to pre-RT, at the end of RT, the global health status score (p < 0.001), nausea/vomiting (p < 0.001) and appetite loss scores (p < 0.001) were significantly poorer. Compared to the end of RT and at 1 and 6 months post-RT, global health status, all functional and all symptom scores were significantly improved (p < 0.001).

The median age in this study was 57 years as compared to 46 years in our study, which may explain the relatively better tolerance to nausea and vomiting and hence moderate clinically significant scores[18].

Social functioning scores were lower in CRC survivors compared to controls from the general population (Rusell et al. 2015) [19].

It has been hypothesized that younger cancer patients are a vulnerable group in terms of poorer survival and more severe psychosocial effects. Younger patients view cancer as greater threat to their lives and manifest poorer mental health than older patients. This explains to some extent, the larger clinically meaningful changes in the social functioning and anxiety subscales in our study [20].

A study by MG Guren et al. reported a similar finding, where at the end of radiotherapy, mean scores of diarrhoea, fatigue and appetite loss had significantly increased (p < 0.01) compared with pre-treatment scores, and at the end of radiotherapy, diarrhoea, fatigue, appetite loss, physical function, social function and global QoL were significantly worse than the population-based norms. Diarrhoea, fatigue and appetite loss increased transiently during pelvic radiotherapy [7].

In the study by Joseph M. Herman et al., global QoL showed a statistically significant and borderline clinically significant decrease during CRT (− 9.50, p = 0.0024) but returned to baseline 1 month after the end of treatment (− 0.33, p = 0.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting + 9.94, p < 0.0001; and diarrhoea + 16.67, p = 0.0022), urinary (dysuria + 13.33, p < 0.0001; and frequency + 11.82, p = 0.0006) or fatigue (+ 16.22, p < 0.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (p = 0.0236) and sexual function (p = 0.0047) remained persistently diminished after therapy [21].

Salvatore Pucciarelli et al. in their study revealed physical/social functioning, fatigue and body image showed a decrease just after NACCRT and returned to baseline levels at 1 year after treatment. Male sexual problems were greatly impaired throughout the study period (p < 0.001) with major clinically meaningful changes between baseline and 1 year after treatment [22].

In the study done by Tung et al., they showed that depression and fatigue measurements were higher in patients receiving treatment as compared to those who have finished their treatment.

Strength of the Study

QOL plays an important role in the management of cancer patients; however, literature still seems to be sparse. Data pertaining to this topic is limited, and our study is one of the handful of studies across the nation. One of the strengths of our study has been a comparatively adequate representation of female patients. The study has comprehensively delved into QOL utilising two scales and deriving meaningful comprehensive relevant data including sexual health which has been a taboo for discussion, especially among Indian females.

Limitation of the Study

The total number of included patients was 35 which is a comparatively small number for impactful statistical analysis. Similarly, we found that the questionnaire was limited in the correct analysis due to the cultural, social and educational backgrounds of the patients. We are also limited by the fact that our QOL evaluation has been performed at 04 weeks post-treatment completion, and further studies shall be required to study the late effects.

Conclusion

Due to the burden of this disease and the higher survival rate, both for early diagnosis and new treatment, the QoL in survivors of CRC should be a priority for public health research. The knowledge about the determinants of QoL could help to identify survivors with special needs. Moreover, these findings may be useful for cancer clinicians in taking therapy and surveillance-related decisions in order to enhance the QoL of people with CRC. The limitations of a literature review of this nature are the lack of systematic research of articles and the lack of a gold standard for measuring QoL. Very heterogeneous instruments and different statistical analyses were used, making difficult a comparison across studies.

The importance of symptoms has been reported in many studies since they affect directly and indirectly QoL in CRC survival. In fact, the presence of diarrhoea, incontinence, fatigue and pain in addition to having direct effects on QoL influenced daily activities and hobbies and interfere with family and social life. Fixed factors such as age or sex have only a marginal role in QoL, and others are potentially modifiable. Therefore, a wide range of interventions has been developed to improve QoL in CRC survivors.

Clinically meaningful changes were reported for the functional scales—physical, role and emotional functioning. We can improve QoL by reducing psychological morbidity and facilitating crisis adaptation with educational programs, self-help groups, psychosocial interventions, cognitive behavioural therapy, coping and certain drugs.

Statistically significant with small clinically meaningful changes were found in the pain and dysuria. Symptoms of scales like bloated feeling, flatulence, blood and mucus in stool, trouble with taste, abdominal pain, buttock pain and urinary frequency showed no statistically significant changes throughout the course of NACCRT.

It has been observed that radiation therapy has a significant role in the QOL, and improvement in RT technique with a better organ-to-risk ratio may have a positive bearing on QOL.

Since QoL is a relatively subjective variable, differences in human race, culture, education and social environment will impact the results. International cooperation is needed to study the QoL in patients with multiple cultural backgrounds.

The existing QoL questionnaire tools have been designed with Western countries in mind, and we did face multiple social issues. We suggest that many similar multicentre studies shall be required to essentially tap the accurate QoL-related issues keeping in mind the diverse social, economic, racial and educational backgrounds. We believe that there is a need for the development of a self-administered questionnaire based on domains where importance has been given to the respondent’s satisfaction in different aspects of life.

The role of healthcare workers in QOL assessment and improvement cannot be underestimated. The science of QOL encompasses multiple factors which include various issues beyond treatment and has a bearing on patient satisfaction either directly or indirectly.

Author Contribution

Conceptualization: N.S., R.H. and M.T. Design: S.K.D., R.H. and M.T. Definition of intellectual content: R.H., N.S. and M.T. Literature search: S.K.D., R.H. and M.T. Clinical studies: S.K.D. and R.H. Experimental studies: R.H., N.S. and M.T. Data acquisition, data analysis and statistical analysis: S.K.D. and R.H. Manuscript preparation: S.K.D., R.H. and S.D. Manuscript editing and manuscript review: S.K.D., R.H. and S.D.

Data Availability

Full availability of data and materials can be provided on readers request.

Declarations

Ethics Approval

The manuscript has been read and approved by all the authors.

Conflict of Interest

The authors declare no competing interests.