Long-term health-related quality of life in patients with gastric cancer after total or distal gastrectomy: a propensity score-matched cohort study

Abstract

Background:

Surgical resection remains the cornerstone of treatment for locally advanced gastric cancer (LAGC) and is accompanied by potential deterioration in patients’ health-related quality of life (HRQOL). As an important indicator of the psychosocial burden, HRQOL has become an essential endpoint to evaluate the efficacy and impact of cancer treatment. We examined longitudinal changes in HRQOL among patients with LAGC receiving total gastrectomy (TG) or distal gastrectomy (DG) over time.

Materials and methods:

The patients in this study were from a prospective observational study (NCT04408859) conducted during 2018–2022. We used the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and the stomach module questionnaire to evaluate HRQOL at baseline and at postoperative months 1, 3, 6, and 12. We used linear mixed models to analyze longitudinal changes in HRQOL between groups and correlations with follow-up time.

Results:

A total of 219 patients were included. After propensity score matching, 186 patients were ultimately analyzed. Compared with the DG group, patients in the TG group reported significantly poorer global health status, physical functioning, and role functioning and more severe fatigue, insomnia, appetite loss, pain, and financial problems. Gastric-specific symptoms, dysphagia, chest and abdominal pain, reflux, restricted eating, and anxiety were more common and severe in the TG group. Most scales showed deterioration at months 1 and 3 after surgery, with gradual recovery thereafter, except the scales for global health status, pain, chest and abdominal pain, and reflux, which improved continually compared with baseline. TG was associated with worsening in at least six HRQOL domains for each measure after baseline, compared with DG.

Conclusions:

In contrast with DG, TG had an adverse impact on postoperative HRQOL scales in patients with LAGC. Different HRQOL scales had various recovery trajectories after surgery. Effects of the gastrectomy scope on patients’ HRQOL should be considered together with sound oncology principles.

Introduction

Highlights

• Total gastrectomy had an adverse impact on postoperative HRQOL in patients with gastric cancer.

• The scope of gastrectomy was a key risk factor for deterioration in HRQOL domains.

• Effects of gastrectomy scope on patients’ HRQOL should be considered together with sound oncology principles.

Gastric cancer (GC) is one of the most common malignant tumors worldwide, especially in East Asia¹. Current estimates show that China accounts for nearly half of the annual new cases and deaths globally. Approximately 90% of patients with GC are in an advanced stage at the time of initial consultation and diagnosis². Despite the increasing use of effective innovative chemotherapy and immunotherapy regimens, gastrectomy remains the mainstay of treatment for all stages of GC^3,4. Today, the extent of gastrectomy is determined according to tumor location, tumor site, and clinical stage⁵. However, the optimal resection therapy (total or subtotal) for GC remains controversial⁶. For patients with GC, distal gastrectomy (DG) shortens the duration of surgery and postoperative hospital stay and reduces postoperative complications. Total gastrectomy (TG) can reduce gastric remnant cancer but can increase postoperative diet restrictions, dysphagia, and reflux symptoms^7–9. Moreover, post-gastrectomy symptoms, including reflux, early satiety, nausea and pain, are more common in those who undergo TG¹⁰.

Treatments (chemotherapy, radiotherapy, and gastrectomy) influence patients’ lives because of associated toxicity, radiation-related effects, and reconstruction of the digestive tract^11,12. With advances in treatment, the survival of patients with locally advanced gastric cancer (LAGC) has been continuously improving in the past decades. Patients’ health-related quality of life (HRQOL) has increasingly become a focus of researchers’ attention and an important determinant in the optimal management of patients with malignancy¹³. HRQOL reflects the subjective feelings of individual patients. Although most oncologists regard HRQOL as an important clinical indicator, only 50% measure patient HRQOL in clinical practice¹⁴. HRQOL has previously been confused with functional results, and tools for measuring multiple dimensions of HRQQL have not been validated until recently.

Whether the scope of gastrectomy affects the HRQOL of patients with GC remains controversial^15–17. Most past studies have used a cross-sectional design and have lacked reference populations or pretreatment measurements^17,18. Hence, we performed a retrospective study to explore the impact of the scope of gastrectomy on patient HRQOL and evaluate the longitudinal changes in HRQOL among patients with LAGC over time.

Materials and methods

Patients and study design

The patients in this study were identified from a prospective observational study of patients with LAGC at the Department of Gastrointestinal Surgery of Peking University Cancer Hospital between April 2018 and January 2022. Ethical approval for this study (NCT04408859) was provided by the Research Ethics Committee of Peking University Cancer Hospital & Institute on 16 January 2018. Written informed consent was obtained from each participant. The study is reported in line with the strengthening the reporting of cohort studies in surgery (STROCSS) criteria¹⁹ (Supplemental Digital Content 1, http://links.lww.com/JS9/A808). According to the tumor location, clinical stage, and judgment of the surgeon, we determined the extent of gastric resection for the TG or DG groups combined with D2 lymph node dissection.

The eligibility criteria for this cohort were as follows: age 18–80 years; diagnosed with gastric adenocarcinoma via endoscopic biopsy; clinical tumor stages II–III with cT2-4aN0-3M0 (Eighth Edition of the American Joint Committee on Cancer Staging Manual) confirmed by endoscopic ultrasound or enhanced abdominal computed tomography; Grade I or II American Society of Anesthesiologists (ASA) score; and written informed consent. Treatment was not limited to laparoscopy or open surgery.

The following patients were excluded from the analysis: pregnant or breastfeeding women; patients with a history of other malignant diseases, unstable angina, myocardial infarction, cerebral infarction, or cerebral hemorrhage within 6 months; patients receiving neoadjuvant chemotherapy; and patients with missing data for eight or more questionnaire items.

Follow-up

All enrolled patients were followed-up at baseline (pre-operation) and postoperative months 1, 3, 6, and 12. HRQOL data were gathered using the validated Chinese edition of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and the stomach module questionnaire (EORTC QLQ-STO22)^20,21. All questionnaires were administered online by a trained coordinator via the ‘Wenjuanxing’ platform, a professional platform in China for questionnaire surveys. Patient characteristics and clinical information were collected from the original electronic patient files.

HRQOL measurement

The EORTC QLQ-C30, a general scale suitable for the global assessment of patients, has good reliability and validity^20,22. The structured questionnaire for cancer self-management includes 30 questions and a total of 15 scales representing various aspects or dimensions of HRQOL; the global status scale includes five functional scales (physical, role, emotional, cognitive, and social) and three multi-item symptom scales (fatigue, pain, nausea and vomiting). The remaining six items are single-item scales that describe cancer-related symptoms (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). As a supplement to the EORTC QLQ-C30 scale, the EORTC QLQ-STO22 was used to evaluate gastric-specific symptoms in patients undergoing various treatments¹⁶. The QLQ-STO22 comprises 22 questions that assess five multi-item symptom scales (dysphagia, eating restriction, chest and abdominal pain, reflux, and anxiety) and four single-item symptom scales (dry mouth, body image, hair loss, and abnormal taste). Scores on all scales were translated into the centesimal system for unified quantification. A high score represents good functioning, a strong global status, or severe symptoms. A 10-point difference in the mean score was considered a clinical improvement or deterioration, according to previous studies^23–25.

Propensity score matching

Propensity score matching (PSM) was applied to create comparable groups to decrease selection bias and confounding factors in the comparisons of HRQOL. A multivariate logistic regression model was used to calculate propensity scores for each patient. We selected covariates [age, sex, body mass index [BMI], ASA score, comorbidities, and clinical T-stage and N-stage] based on significant differences in the univariate logistic regression model and clinical significance. A 0.05 caliper width was used, and nearest neighbor matching was performed in a 1:1 ratio without replacement²⁶.

Statistical analysis

We used the chi-squared (χ ²) analysis or Fisher’s exact test for categorical variables and the Student t-test or Mann–Whitney U test for continuous variables in comparisons of the baseline characteristics and clinical outcomes between groups. The questionnaire scores were calculated in accordance with EORTC guidelines²⁷. We used a linear mixed model (LMM) to analyze longitudinal changes in HRQOL between groups and for comparisons of different follow-up times. The treatment group, time, baseline scores, and the interaction of group and time were included as fixed effects after standardized transformation in the model. The patients were enrolled as a random effect, and first-degree autoregressive covariance was chosen as the covariance structure for the residuals. Cohen’s d values with 95% confidence intervals (CIs) were derived from the beta estimate of the LMM as the effect sizes, which were used to evaluate the effects and standardize the comparisons between domains²⁸. Bonferroni correction was applied to correct for multiple comparisons. Cohen’s d values range of 0.0–0.2, 0.2–0.5, 0.5–0.8, and 0.8–1.0 indicated no, small, moderate, and large effect sizes, respectively. To evaluate the effect of baseline characteristics on HRQOL deterioration after surgery, logistic regression models were performed to estimate the association between worsening in ≥6 HRQOL domains and age, sex, BMI, ASA score, comorbidities, clinical T-stage and N-stage, gastrectomy scope, and surgical method. The outcomes are presented as odds ratios (ORs) and 95% CIs. A P value <0.05 was considered to indicate statistical significance. Statistical analysis was performed using IBM SPSS version 25.0 (IBM Corp., Armonk, New York, USA).

Results

Baseline clinical characteristics and postoperative outcomes

A total of 113 patients were excluded because of age >80 years (n=3), non-adenocarcinoma (n=9), clinical stage I and IV (n=52), ASA score >II (n=7), history of other malignant diseases (n=7), and neoadjuvant chemotherapy (n=35). Of the 219 patients who met the inclusion criteria, 108 (49.3%) underwent TG and 111 (50.7%) received DG (Fig. 1). More patients in the TG group were at an advanced clinical stage and had positive lymph nodes (Table 1). After matching, 186 patients were distributed equally between the two groups. No significant differences were observed in baseline characteristics between the TG and DG groups (Table 1). Results of comparisons of surgical indicators and short-term outcomes after PSM are shown in Table 2. Patients in the TG group had a longer operative time, a more frequent open approach, greater blood loss, and more extended postoperative stays than those in the DG group. Postoperative complications were comparable between the two groups (Table 2).

Figure 1.

STROBE (Strengthening the Reporting of Observational studies in Epidemiology) flow diagram illustrating the eligibility screening of patients with locally advanced gastric cancer receiving total or distal gastrectomy in a propensity score-matched observational cohort study. ASA, American Society of Anesthesiologists; BMI, body mass index; DG, distal gastrectomy; LAGC, locally advanced gastric cancer; TG, total gastrectomy.

Table 1.

Baseline characteristics before and after propensity score matching of locally advanced gastric cancer patients treated with total gastrectomy or distal gastrectomy.

	Original cohort			Matched cohort*
	TG (n=108)	DG (n=111)	P † value	TG (n=93)	DG (n=93)	P † value
Age			0.67			0.76
≥65	37 (34.3)	35 (31.5)		31 (33.3)	33 (35.5)
<65	71 (65.7)	76 (68.5)		62 (66.7)	60 (64.5)
Sex			0.64			1.00
Male	79 (73.1)	78 (70.3)		69 (74.2)	69 (74.2)
Female	29 (26.9)	33 (29.7)		24 (25.8)	24 (25.8)
ASA score			0.39			0.64
I	14 (13.0)	19 (17.1)		11 (11.8)	9 (9.7)
II	94 (87.0)	92 (82.9)		82 (88.2)	84 (90.3)
Preoperative BMI			0.22			1.00
≥25	43 (40.2)	35 (32.1)		36 (38.7)	36 (38.7)
<25	64 (59.8)	74 (67.9)		57 (61.3)	57 (61.3)
Comorbidity			0.25			0.37
≥1	41 (38.0)	34 (30.6)		39 (41.9)	33 (35.5)
None	67 (62.0)	77 (69.4)		54 (58.1)	60 (64.5)
Tumor size			0.07			0.45
≥4	47 (43.5)	35 (31.5)		39 (41.9)	34 (36.6)
<4	61 (56.5)	76 (68.5)		54 (58.1)	59 (63.4)
Differentiation			0.47			0.14
Well	61 (56.5)	68 (61.2)		49 (52.7)	59 (63.4)
Poor	47 (53.5)	43 (38.8)		44 (47.3)	34 (36.6)
Clinical T-stage			0.14			0.33
T2	17 (15.7)	29 (26.1)		16 (17.2)	21 (22.6)
T3	56 (51.9)	47 (42.3)		49 (52.7)	39 (41.9)
T4	35 (32.4)	35(31.5)		28 (30.1)	33 (35.5)
Clinical N-stage			0.04			0.58
N0	25 (23.1)	44 (39.6)		24 (25.8)	31 (33.3)
N1	41 (38.0)	39 (35.1)		34 (36.6)	34 (36.6)
N2	29 (26.9)	19 (17.1)		26 (28.0)	19 (20.4)
N3	13 (12.0)	9 (8.1)		9 (9.7)	9 (9.7)
Clinical TNM stage			0.04			0.55
II	35 (32.4)	51 (45.9)		33 (35.5)	37 (39.8)
III	73 (67.6)	60 (54.1)		60 (64.5)	56 (62.4)
Anemia			0.83			1.00
Yes	23 (21.3%)	25 (22.5)		23 (24.7)	23 (24.7)
No	85 (78.7)	86 (77.5)		70 (75.3)	70 (75.3)
CEA			0.66			0.35
>5	20 (18.5)	23 (20.9)		17 (18.3)	22 (23.9)
≤5	88 (81.5)	87 (79.1)		76 (81.7)	70 (76.1)

Values are presented as number (%).

^*Cohort matched on age, sex, BMI, ASA score, comorbidity, Clinical T and N stages.

^†The bold italic P value indicates a statistical difference.

ASA, American Society of Anesthesiologists; BMI, body mass index; CEA, carcinoembryonic antigen; DG, distal gastrectomy; TG, total gastrectomy; TNM, tumor–node–metastasis staging.

Table 2.

Comparisons of surgical outcomes and postoperative complications of patients after PSM sorted by gastrectomy scope.

	TG (n=83)	DG (n=83)	P value*
Operative time (min)	248.2 (67.1)	221.3 (65.6)	<0.01
Type of surgery			0.01
Open	41 (44.1)	25 (26.9)
Laparoscopic	52 (55.9)	68 (73.1)
Estimated blood loss (ml)	104.3 (142.1)	61.0 (56.1)	<0.01
No. of harvested lymph node	32.5 (10.1)	30.6 (11.3)	0.22
Radical resection			0.16
R0	91 (97.8)	91 (100.0)
R1	2 (2.2)	0 (0)
Postoperative stay (day)	11.4 (6.9)	8.6 (4.7)	<0.01
Postoperative complications			0.34
None	81 (87.1)	85 (91.4)
≥1	12 (12.9)	8 (8.6)
Clavien–Dindo grade			0.79
None-I	85 (91.4)	86 (92.5)
≥II	8 (8.6)	7 (7.5)
Mortality in 30 days	0	0
Postoperative active hemorrhage	2	0
Intra-abdominal abscess	0	2
Gastroplegia	0	2
Anastomotic leakage	5	0
Anastomotic stenosis	0	1
Duodenal stump fistula	1	2
Ileus	1	0
Gastroparesis	0	2
Wound infection	1	0
Pulmonary infection	6	4

Values are presented as number (%) or mean (SD).

DG, distal gastrectomy; TG, total gastrectomy.

^*The bold italic P value indicates a statistical difference.

Five and three patients dropped out of our study before and after PSM, respectively. Data for these patients were preserved and analyzed with the patients’ permission because the LMM had a good ability to address missing data²⁹. The overall questionnaire completion rates were 98.4% (baseline), 88.7% (postoperative month 1), 85.7% (month 3), 82.9% (month 6), and 72.1% (month 12) after matching (Supplementary Table S1, Supplemental Digital Content 2, http://links.lww.com/JS9/A809). No significant differences were observed in response rates between the two groups for each measure (Supplementary Table S1, Supplemental Digital Content 2, http://links.lww.com/JS9/A809). Moreover, to check whether the lost data were missing at random and would affect the results of our analyses, we compared the basic characteristic between these groups. As shown in Supplementary Table S2 (Supplemental Digital Content 2, http://links.lww.com/JS9/A809), no statistical difference in baseline features was observed between the two groups, indicating that the dropout of patients did not cause attrition bias.

Longitudinal changes in HRQOL between groups

Changes in the trajectories of HRQOL scores (mean with 95% CI) in the EORTC QLQ-C30 and EORTC QLQ-STO22 questionnaires in the TG and DG groups throughout this longitudinal study are presented in Figures 2 and 3. Compared with patients in the DG group, patients in the TG group reported significantly poorer global health status (P=0.003), physical functioning (P=0.001), and role functioning (P=0.003) and more severe fatigue (P=0.004), insomnia (P=0.014), appetite loss (P=0.001), pain (P=0.023), and financial problems (P=0.039; Fig. 2). Gastric-specific symptoms such as dysphagia (P=0.001), chest and abdominal pain (P=0.012), reflux (P=0.001), eating restriction (P=0.004), and anxiety (P=0.001) were more common and severe in the TG group than in the DG group (Fig. 3). Moreover, significant differences were observed between groups for some measures, as shown in Figures 2 and 3. At baseline, patients in the TG group had better performance on the scales of social function, cognitive function, nausea and vomiting, chest and abdominal pain, reflux symptoms, and abnormal taste than those in the DG group. Dysphagia symptoms were more severe in the TG group at postoperative month 1. A similar situation was observed for the scales of global health status, role function, constipation, dysphagia, and eating restriction at month 3 after gastrectomy. Furthermore, all of the nine scales (global health status, physical function, role function, constipation, dysphagia, reflux symptoms, dry mouth, eating restriction, and anxiety) showed worse performance in the TG group than in the DG group at postoperative month 6. Finally, dysphagia and reflux symptoms remained more common in the TG group than in the DG group at the end of the measurement.

Figure 2.

Mean scores with 95% confidence intervals over time in the health-related quality of life (HRQOL) questionnaire, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, stratified by treatment group. P _overall represents statistical values for the longitudinal comparison between groups that underwent total gastrectomy or distal gastrectomy. Between-group differences in HRQOL scores at each follow-up were also analyzed using a linear mixed model. *Significant difference with P<0.05. DG, distal gastrectomy; TG, total gastrectomy.

Figure 3.

Mean scores with 95% confidence intervals over time in the health-related quality of life (HRQOL) questionnaire, the European Organization for Research and Treatment of Cancer Quality of Life stomach module questionnaire 22, stratified by treatment group. P _overall represents statistical values for the longitudinal comparison between groups that underwent total gastrectomy or distal gastrectomy. Between-group differences in HRQOL scores at each follow-up were also analyzed using a linear mixed model. *Significant difference with P<0.05. DG, distal gastrectomy; TG, total gastrectomy.

Overall HRQOL trends in the entire cohort

The comparison of all of the 24 domains in the EORTC QLQ-C30 and STO22 questionnaires between baseline and follow-up time points is shown in Table 3. The trajectories of the 24 scales were divided into four classes. The scales of global health status, pain, chest and abdominal pain, and reflux symptoms were continually improved compared with the baseline. A total of 11 scales first presented deteriorating values but later improved. However, the trajectories were not the same for these 11 scales. Physical function, role function, social function, and dysphagia showed rapid deterioration in the first month after surgery and relatively slow recovery thereafter. The scales for emotional function, appetite loss, nausea/vomiting, diarrhea, abnormal taste, and eating restrictions showed slow stepwise deterioration at months 1 and 3 postoperatively; the scales then returned to pretreatment levels at 12 months after surgery except for the scale for diarrhea, which remained low (Table 3). The remaining eight scales (cognitive function, dyspnea, insomnia, constipation, financial problems, dry mouth, body image, anxiety, and hair loss) showed less fluctuation and remained relatively stable during follow-up (Supplementary Fig. S1, Supplemental Digital Content 2, http://links.lww.com/JS9/A809).

Table 3.

The comparison in all 24 domains of questionnaires between baseline and follow-up measurement point.

		1st month		3rd month		6th month		12th month
Domain	Baseline	CD* (95% CI)	P †	CD* (95% CI)	P †	CD* (95% CI)	P †	CD* (95% CI)	P †
Global health status	Ref	0.27 (0.12–0.42)	<0.01	0.34 (0.16–0.52)	<0.01	0.34 (0.15–0.53)	<0.01	0.63 (0.43–0.83)	<0.01
Physical function	Ref	−0.68 (−0.83 to −0.56)	<0.01	−0.56 (−0.72 to −0.39)	<0.01	−0.57 (−0.75 to −0.39)	<0.01	−0.42 (−0.61 to −0.22)	<0.01
Role function	Ref	−0.60 (−0.75 to −0.46)	<0.01	−0.45 (−0.63 to −0.28)	<0.01	−0.43 (−0.62 to −0.25)	<0.01	−0.26 (−0.45 to −0.06)	0.01
Fatigue	Ref	0.68 (0.54–0.83)	<0.01	0.64 (0.47–0.80)	<0.01	0.54 (0.36–0.72)	<0.01	0.35 (0.16–0.54)	<0.01
Dyspnea	Ref	−0.05 (−0.24 to 0.13)	0.58	−0.13 (−0.33 to 0.07)	0.20	−0.12 (−0.32 to 0.09)	0.26	−0.24 (−0.45 to −0.03)	0.03
Insomnia	Ref	0.10 (−0.07 to 0.27)	0.24	−0.01 (−0.18 to 0.18)	0.98	0.03 (−0.15 to 0.21)	0.76	0.10 (−0.09 to 0.29)	0.31
Appetite loss	Ref	0.23 (0.06 to 0.39)	0.01	0.57 (0.39 to 0.75)	<0.01	0.41 (0.22 to 0.60)	<0.01	0.01 (−0.19 to 0.21)	0.89
Nausea /vomiting	Ref	0.25 (0.07–0.42)	0.01	0.53 (0.34–0.72)	<0.01	0.25 (0.06–0.45)	0.01	−0.08 (−0.29 to 0.12)	0.43
Constipation	Ref	0.04 (−0.11 to 0.20)	0.59	0.08 (−0.09 to 0.25)	0.36	−0.08 (−0.26 to 0.10)	0.10	−0.20 (−0.39 to −0.01)	0.04
Diarrhea	Ref	0.19 (0.03–0.35)	0.02	0.48 (0.31–0.66)	<0.01	0.46 (0.28–0.64)	0.28	0.27 (0.08–0.46)	0.01
Pain	Ref	−0.19 (−0.35 to −0.02)	0.03	−0.31 (−0.49 to −0.14)	<0.01	−0.31 (−0.49 to −0.13)	<0.01	−0.33 (−0.52 to −0.14)	<0.01
Emotional function	Ref	−0.16 (−0.31 to −0.02)	0.03	−0.20 (−0.37 to −0.02)	0.03	−0.12 (−0.31 to 0.06)	0.19	−0.09 (−0.29 to 0.10)	0.36
Cognitive function	Ref	0.16 (0.01–0.31)	0.04	−0.01 (−0.22 to 0.13)	0.64	0.01 (−0.16 to 0.21)	0.82	0.05 (−0.15 to 0.24)	0.63
Social function	Ref	−0.39 (−0.54 to −0.25)	<0.01	−0.38 (−0.55 to −0.20)	<0.01	−0.30 (−0.49 to −0.12)	<0.01	−0.23 (−0.43 to −0.04)	0.02
Financial problems	Ref	0.03 (−0.09 to 0.15)	0.64	−0.06 (−0.21 to 0.08)	0.39	−0.12 (−0.28 to 0.04)	0.13	−0.11 (−0.28 to 0.06)	0.20
Dysphagia	Ref	0.51 (0.35 to 0.68)	<0.01	0.15 (−0.03 to 0.34)	0.10	0.06 (−0.13 to 0.24)	0.06	−0.03 (−0.23 to 0.16)	0.74
Chest and abdominal pain	Ref	−0.31 (−0.46 to −0.16)	<0.01	−0.40 (−0.58 to −0.22)	<0.01	−0.42 (−0.60 to −0.23)	<0.01	−0.50 (−0.70 to −0.30)	<0.01
Reflux symptoms	Ref	−0.11 (−0.27 to 0.05)	0.20	−0.09 (−0.28 to 0.09)	0.33	−0.16 (−0.35 to 0.03)	0.10	−0.31 (−0.51 to −0.10)	<0.01
Dry mouth	Ref	−0.08 (−0.25 to 0.10)	0.38	−0.07 (−0.26 to 0.12)	0.48	−0.17 (−0.37 to 0.03)	0.09	−0.39 (−0.60 to −0.19)	<0.01
Abnormal taste	Ref	0.26 (0.05–0.47)	<0.01	0.61 (0.37–0.85)	<0.01	0.55 (0.30–0.80)	<0.01	0.19 (−0.07 to 0.46)	0.29
Eating restriction	Ref	0.25 (0.10–0.40)	<0.01	0.36 (0.19–0.53)	<0.01	0.30 (0.12–0.49)	<0.01	0.09 (−0.11 to 0.28)	0.39
Body image	Ref	−0.10 (−0.25 to 0.06)	0.21	0.13 (−0.05 to 0.31)	0.16	0.04 (−0.16 to 0.22)	0.72	0.20 (−0.01 to 0.40)	0.06
Anxiety	Ref	0.13 (−0.01 to 0.27)	0.07	0.16 (−0.01 to 0.32)	0.06	0.06 (−0.12 to 0.23)	0.54	0.07 (−0.12 to 0.25)	0.50
Hair loss	Ref	0.12 (−0.01 to 0.28)	0.14	−0.10 (−0.28 to 0.08)	0.29	−0.05 (−0.24 to 0.14)	0.58	−0.08 (−0.28 to 0.12)	0.45

CD, Cohen’s d; CI, confidence interval.

^*The CD value was taken from the β estimate in the linear mixed model after standardization of both outcome and predictor variables, and the baseline score of each domain was regarded as the reference in each comparison.

^†The bold italic P value indicates a statistical difference, statistical significance is set at P<0.0125 after a Bonferroni correction for multiple comparisons.

Risk factors among baseline characteristics for worsening HRQOL

At present, there was no uniform standard for the cutoff value of determining deterioration or not. We calculated the median of domains with deterioration for patients at each postoperative measurement, respectively. Then the value was regarded as the cutoff point for logistics regression analysis at each time point after operation. Univariable and multivariable logistic regression were performed to detect the risk factors for deterioration in ≥6 HRQOL domains during postoperative follow-up. The results showed that patients who underwent TG had a significantly greater probability of worsening at month 1 postoperatively in comparison with those who underwent DG; the same was true in patients with clinical T3 stage compared with those who had clinical T2 stage (OR, 3.40; 95% CI, 1.36–8.49 and OR, 3.71; 95% CI, 1.35–10.24, respectively; Table 4). Moreover, TG remained significantly associated with worsening ≥6 HRQOL domains at months 3, 6, and 12 after baseline compared with DG (OR, 3.42; 95% CI, 1.70–6.88; OR, 5.34; 95% CI, 2.60–10.98 and OR, 2.10; 95% CI, 1.06–4.17, respectively) in multivariable analysis (Supplementary Tables S3–S5, Supplemental Digital Content 2, http://links.lww.com/JS9/A809). In contrast, the effect of the clinical T-stage was no longer significant. Age, sex, BMI, ASA score, comorbidities, clinical N-stage, and surgical method were not found to be risk factors for worsening in ≥6 HRQOL domains after surgery for each measure.

Table 4.

Univariable and multivariable logistic regression of association between baseline characteristics and locally advanced gastric cancer patients reporting worse scores (>10 points) for ≥6 domains of questionnaires.

	HRQOL worsening at 1st month (118/162)*
	Univariable		Multivariable
Variables	OR (95% CI)	P †	OR (95% CI)	P †
Age		0.55
<60	Ref
≥60	1.24 (0.61–2.54)
Sex		0.58
Male	Ref
Female	0.79 (0.34–1.84)
BMI		0.06		0.10
<25	Ref		Ref
≥25	2.13 (0.98–4.62)		2.08 (0.87–5.00)
ASA score		0.12		0.41
I	Ref		Ref
II	0.30 (0.07–1.38)		0.51 (0.11–2.52)
Comorbidities		0.39
None	Ref
≥1	1.37 (0.67–2.83)
Clinical T-stage		0.03		0.04
T2	Ref		Ref
T3	3.40 (1.36–8.49)	0.01	3.71 (1.35–10.24)	0.01
T4	1.69 (0.69–4.14)	0.25	2.96 (0.95–9.27)	0.06
Clinical N-stage		0.16		0.26
N0	Ref		Ref
N1	2.08 (0.83–5.24)	0.12	1.83 (0.65–5.15)	0.25
N2	0.76 (0.31–1.87)	0.55	0.72 (0.23–2.21)	0.56
N3	0.78 (0.24–2.52)	0.68	0.60 (0.15–2.47)	0.48
Gastrectomy		0.02		0.02
Distal	Ref		Ref
Total	2.30 (1.13–4.70)		2.56 (1.16–5.65)
Surgical method		0.09		0.06
Open	Ref		Ref
Laparoscopy	1.85 (0.91–3.74)		2.17 (0.97–4.86)

ASA, American Society of Anesthesiologists; BMI, body mass index; CI, confidence interval; HRQOL, health-related quality of life; OR, odds ratio; Ref, reference.

^*Number of patients with worse score in ≥6 HRQOL domains/total number of eligible patients.

^†Bold P-values indicate statistical significance (P<0.05) according to the ordinal logistic regression analysis.

Discussion

As is well known, gastric cancer has a poor prognosis, even when curative resection has been performed. Common outcomes such as survival are well described in surgical series, but little is known about the HRQOL effects of the disease and the treatments³⁰. In recent years, HRQOL has become a critical component in the assessment of the clinical benefit of medical interventions among patients with cancer. It has been suggested that the HRQOL represents the functional effect of a disease and its treatment, in other words, how it is perceived and the extent to which it affects the life of a patient¹⁶. Gastrectomy is not only the mainstay of treatment for LAGC but also one of the main determinants of patient HRQOL. Moreover, considering the high likelihood of tumor recurrence, it is imperative that the benefits of surgery should surpass its detriments in terms of patient HRQOL³¹. Overall, gastrectomy itself is widely accepted as a cause of deterioration in patients’ HRQOL^13,15,32. However, the effects associated with the scope of gastrectomy remain controversial. Munene et al. found no significant difference in HRQOL between partial gastrectomy and TG using the Functional Assessment of Cancer Therapy-Gastric questionnaire¹⁵. A cohort study conducted by Goh et al.¹⁶ showed that compared with patients receiving DG, those who received TG had more severe eating restrictions and dysphagia, although global health status and function were similar. However, different conclusions were reported in other studies^17,18,33. Park et al.¹⁷ observed that patients who received TG showed improvement in physical function, role function, fatigue, pain, and reflux, but long-term HRQOL associated with eating restrictions, anxiety, abnormal taste, and body image declined. Moreover, HRQOL was negatively correlated with tumor stage and TG, especially for patients with advanced GC, because TG causes the aggravation of upper gastrointestinal symptoms¹⁸. A multivariate analysis revealed that patients with LAGC who underwent DG and minimally invasive surgery had better HRQOL compared with patients who underwent TG and open surgery³³. Therefore, whereas the extent of gastrectomy should abide by sound oncologic principles, its effect on the patient’s HRQOL should be considered.

We observed that the extent of gastrectomy and clinical T-stage were risk factors for the deterioration of HRQOL. At present, few reports are available on the progression of gastric cancer and associated changes in HRQOL. From the limited studies, we found that most of them thought that tumor progression might lead to the deterioration of patients’ HRQOL^13,34–36. Later clinical stage and loss of appetite may lead to a decline in postoperative quality of life among patients with GC^36,37. The progression of cancer leads to a poor prognosis and high mortality. Tumor-directed therapies and their side-effects potentially deteriorated the patients’ general condition¹³. Patients with advanced gastric cancer have complications that affect HRQOL, such as obstructions or bleeding due to ulcerations and huge mass lesions. They complained of more symptoms than patients with early stages of gastric cancer and consequently showed a poorer HRQOL³⁴. Similar situation was observed in esophageal and rectal cancer^38,39. However, some scholars thought surgical interventions have not shown positive effects on alleviating the post-gastrectomy burden of patients and the clinical factors related to cancer progression had a rather small effect on post-gastrectomy HRQOL, curability of the cancer and surgical safety should be prioritized⁴⁰. It is valuable to perform further studies on this topic.

In this study, a laparoscopic approach did not show benefits in reducing the postoperative deterioration of HRQOL; this finding may be attributable to the fact that the advantages of laparoscopic surgery are apparent in the short term rather than after a long period after surgery. Studies showed the laparoscopic gastrectomy with D2 lymphadenectomy for LAGC has similar safety and shows benefits in terms of lower complication rate, faster recovery, and less pain compared with open surgery^41,42. However, it remains doubtful whether these advantages of laparoscopy are equivalent to the benefits of quality of life. Misawa et al.⁴³ showed no benefit of the laparoscopic approach was observed in terms of physical functioning. Moreover, a randomized controlled trial, comparing quality of life after laparoscopic versus open gastrectomy for patients with predominantly advanced gastric cancer, found no significant differences were observed between the laparoscopic and open groups for all functional and symptom scales tested at all time points⁴⁴. In order to explore the effect of laparoscopic surgery on patients’ quality of life, it is necessary to increase the frequency of perioperative follow-up time in further study. In addition to the above considerations, factors such as sex, chemotherapy cycles, the neutrophil–lymphocyte ratio, mental state, living environment, and income level are reported to be related to HRQOL and should be considered when making clinical decisions^45–48. In clinical treatment, clinicians should choose an appropriate treatment plan, address uncomfortable symptoms, and provide psychological counseling to improve patients’ HRQOL.

To a large extent, the HRQOL of patients undergoing gastrectomy is compromised in some domains. However, in our study, clear overall longitudinal trends of increasing global health status and decreasing reflux and pain were observed in the whole cohort after surgery (Table 3 and Supplementary Figure 1, Supplemental Digital Content 2, http://links.lww.com/JS9/A809). These trends indicated that gastrectomy could improve patients’ long-term global quality of life. Notably, consistent with the findings of previous studies, patients’ scores on most HRQOL scales decreased significantly at months 1 and 3 postoperatively and then gradually recovered thereafter^43,49,50. Scores for physical function, role function, social function, fatigue, and dysphagia remained slightly lower compared with baseline and the gastric-specific scales of chest and abdominal pain, reflux, and dry mouth showed better performance than baseline at 12 months after treatment. These digestive system symptoms, which are closely related to inadequate food intake, are considered to be an important factor in weight loss and poor body image^51,52. Previous studies suggest that fatigue is one of the most common symptoms in patients with various tumors^53–55. This phenomenon was also observed in our study. Fatigue greatly affects a patient’s ability to perform normal daily activities, leading to deteriorating quality of life. More targeted interventions may be necessary to reduce patients’ symptoms. Several studies have found that decreased functioning and severe symptoms may last for a long period after gastrectomy. Lee et al.⁵⁶ observed that HRQOL in patients undergoing DG was continuously affected by surgical factors even 5 years after surgery. Yu et al. showed that the domains of nausea, vomiting, anxiety, and abnormal taste only returned to preoperative levels at 5 years post-surgery. Changes in the scales of physical function, role function, fatigue, diarrhea, dysphagia, eating restrictions, and body image continue to be large⁵⁷. Given this, clinicians must inform patients in detail about the potential impact of the operation before treatment. Medical staff should cooperate with patients’ relatives to provide effective care and address uncomfortable symptoms in a timely manner to ensure that patients adapt to postoperative life and improve their quality of life^58,59.

Our study had several limitations. Firstly, we did not enroll patients with ASA III–IV because these patients were relatively rare in receiving gastrectomy in our hospital. The patients receiving neoadjuvant chemotherapy were also excluded for the reason that the follow-up times were different from those undergoing direct surgery. The conclusions of our study were not suitable for them. Secondly, bias was unavoidable because confounding factors in the cohort could not be randomly assigned in this observational study, even with PSM. Although PSM reduces the influence of confounding factors between groups, it significantly reduces sample size, potentially decreasing the efficiency of statistical analysis. Some missing follow-up data and lower compliance with questionnaire completion at 12 months postoperatively may have introduced selection bias. Moreover, a uniform standard for the cutoff value of effect size in HRQOL was not available; therefore, caution is needed in interpreting the results. Finally, collecting data from a healthy population could provide a reliable reference to detect differences in HRQOL for patients with LAGC.

Conclusion

This study showed that, compared with DG, TG had an adverse impact on the values of postoperative scales that assess HRQOL in patients with LAGC. Different HRQOL scales had various recovery trajectories after surgery. TG was a risk factor for deterioration in more HRQOL domains than DG at each postoperative follow-up time. To a certain extent, the effects of the scope of gastrectomy on patient HRQOL should be taken into consideration, together with sound oncologic principles.

Ethical approval

The study was reviewed and approved by the Research Ethics Committee of Peking University Cancer Hospital and Institute, Beijing, China (No. 2017KT33).

Consent

Written informed consent was obtained from the patient for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Sources of funding

This study was supported by the National Natural Science Foundation of China (No. 82073357), Joint funds for the Innovation of Science and Technology, Fujian Province (No. 2019Y9035). The Science Fund of Fujian Province Cancer Hospital (2022YNY01).

Author contribution

J.Y. and Z.W.: drafted the protocol, extracted the data, performed the statistical analyses, and drafted the article; Z.W.: performed the statistical analyses and directed statistical analyses; J.Y.: delivered and collected the questionnaire; H.Y., C.Z., J.X., and J.X.: drafted the protocol and participated in patient enrollment; H.L.: directed the writing; X.S. and Y.W.: directed the writing, review, and revision of the article; J.Y. and Z.W.: have contributed equally to this work and share first authorship. All authors contributed to the article and approved the submitted version.

Conflicts of interest disclosure

The authors declare that they have no conflicts of interest

Research registration unique identifying number (UIN)

Name of the registry: Long-Term Health-Related Quality of Life in Patients with Gastric Cancer after Total or Distal Gastrectomy: A Propensity Score-Matched Cohort Study the hyperlink: https://www.researchregistry.com/browse-theregistry#home/registrationdetails/646b982881680d00283427f9/

The unique identifying number of the study: researchregistry9061.

Guarantor

Dr Xiangqian Su, Department of Gastrointestinal Surgery IV, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing 100142, People’s Republic of China; Tel.: +86 010 881 211 22; E-mail: dr_sxq_pkuch@hotmail.com.

Dr Yu Wu, Department of Head and Neck Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian 350014, People’s Republic of China; Tel.: +86 059 162 752 345; E-mail: dr_wuyu@fjzlhospital.com

Provenance and peer review

Not commissioned, externally peer-reviewed.

Data availability statement

Data can be obtained upon scientifically sound request from the corresponding author at dr_sxq_pkuch@hotmail.com.

Supplementary Material

js9-109-3283-s001.pdf ^{(309.3KB, pdf)}

js9-109-3283-s002.docx ^{(215.7KB, docx)}