Clinical efficacy of neoadjuvant chemotherapy combined with radical gastrectomy in elderly patients with advanced gastric cancer

Abstract

BACKGROUND

Neoadjuvant chemotherapy combined with radical gastrectomy is a safe and effective treatment for elderly patients with advanced gastric cancer. Despite the increased risk of pulmonary complications, such as pleural effusion and pulmonary infection, postoperative recovery time and survival outcomes are similar to younger patients.

AIM

To investigate the safety and efficacy of neoadjuvant chemotherapy combined with radical gastrectomy in elderly patients with advanced gastric cancer by comparing treatment-related complications, surgical outcomes, and long-term survival between elderly patients (≥ 65 years) and younger patients (< 65 years).

METHODS

The clinical data of 148 patients with advanced gastric cancer in elderly patients who received neoadjuvant chemotherapy in our hospital from January 2015 to October 2023 were retrospectively analyzed, and these patients were divided into young and middle-aged groups (111 patients) and elderly groups (37 patients), and their clinicopathology and prognosis were compared.

RESULTS

Neoadjuvant chemotherapy induced anemia (χ² = 0.235, P = 0.628), leukopenia (χ² = 0.613, P = 0.434), neutropenia (χ² = 0.011, P = 0.918) and thrombocytopenia (χ² = 0.253, P = 0.628) in both groups. Hematological complications, nausea (χ² = 0.092, P = 0.762), vomiting (χ² = 0.166, P = 0.683), diarrhea (χ² = 0.015, P = 0.902) and mucositis (χ² = 0.199), and there was no significant difference in the incidence of nonhematological complications (P = 0.766). Between the old group and the young and middle-aged groups, no significant differences were observed in operative time (t = 0.270, P = 0.604), intraoperative blood loss (t = 1.140, P = 0.250), or R0 removal rate (χ² = 0.105, P = 0.750). Although the incidence of postoperative complications was higher in the old group (37.8%) compared to the young and middle-aged groups (25.2%), this difference did not reach statistical significance (χ² = 2.172, P = 0.141). However, the elderly group demonstrated significantly higher incidences of pleural effusion (χ² = 7.007, P = 0.008) and pulmonary infection (χ² = 10.204, P = 0.001) than the young and middle-aged groups. When examining survival outcomes, neither the 3-year progression-free survival (t = 0.494, P = 0.482) nor the 3-year overall survival (t = 0.013, P = 0.908) showed significant differences between the elderly group and the young and middle-aged groups.

CONCLUSION

Neoadjuvant chemotherapy combined with radical gastrectomy is safe and effective in elderly patients with advanced gastric cancer, but there are more pulmonary complications (specifically pleural effusion and pulmonary infection) during the perioperative period.

Key Words: Gastric neoplasms; Tumor adjuvant therapy; Elderly people; Postoperative complications; Survival prognosis

Core Tip: Neoadjuvant chemotherapy combined with radical gastrectomy is a safe and effective treatment for elderly patients with advanced gastric cancer. Despite the increased risk of pulmonary complications, such as pleural effusion and pulmonary infection, postoperative recovery time and survival outcomes are similar to younger patients. Hematological and non-hematological complications related to chemotherapy are generally manageable. While age-related factors may affect chemotherapy tolerance, the combination therapy significantly improves surgical resectability and prognosis. Close monitoring of renal function and attention to pulmonary and cardiovascular issues are crucial for optimizing treatment outcomes in elderly gastric cancer patients.

INTRODUCTION

Recently, large-scale prospective studies have demonstrated that neoadjuvant chemotherapy followed by radical gastrectomy significantly improves both overall and disease-free survival rates in patients with advanced gastric cancer[1-3]. This combination approach has consequently emerged as a standard treatment protocol for locally advanced gastric cancer. However, China’s aging demographic trend has led to an annual increase in elderly gastric cancer patients[4]. Elderly individuals typically present with comorbidities, diminished tolerance to chemotherapy and surgical interventions, and heightened susceptibility to treatment-related complications compared to their younger counterparts[5-7]. Currently, research specifically addressing the safety profile of neoadjuvant chemotherapy combined with radical surgery in elderly gastric cancer patients remains limited and inconclusive[8].

Gastric cancer represents one of the most prevalent malignancies worldwide, with particularly high incidence and mortality rates among older populations[9]. The accelerating demographic shift toward an aging society has created an urgent need for effective treatment approaches for elderly patients with advanced gastric cancer. While conventional radical gastrectomy remains the primary therapeutic intervention, the clinical reality presents significant challenges - elderly patients frequently have multiple comorbidities that increase both operative risk and postoperative complication rates[10-12]. This clinical scenario underscores the critical importance of developing and evaluating therapeutic strategies that optimize both safety and efficacy for this vulnerable patient population. Neoadjuvant chemotherapy, that is, the preoperative administration of chemotherapy drugs to reduce the tumor volume and kill small metastases, thereby improving the surgical resection rate and overall survival (OS) rate of patients, is considered an important means to improve the prognosis of patients with advanced gastric cancer. Studies have shown that neoadjuvant chemotherapy can significantly improve the pathological complete response rate of patients with gastric cancer and reduce postoperative recurrence[13-15]. However, owing to the degeneration of physiological function and the existence of multiple complications in elderly patients, the implementation of neoadjuvant chemotherapy has a high risk, which may lead to a series of adverse reactions, affecting patients’ quality of life and treatment compliance[16]. Therefore, how to balance the potential benefits and risks of neoadjuvant chemotherapy and optimize individualized treatment plans is the focus and difficulty of current research.

To analyze the efficacy of neoadjuvant chemotherapy combined with radical gastrectomy in the treatment of elderly patients with advanced gastric cancer, explore its application value and safety in elderly patients, and provide more clinical evidence for improving the OS rate and quality of life of elderly patients with gastric cancer.

MATERIALS AND METHODS

Research subjects

A retrospective analysis was performed on patients with advanced gastric cancer in elderly patients who received neoadjuvant chemotherapy combined with radical gastrectomy in our hospital from January 2015 to October 2023. This study complied with the Hippocratic Oath, and have obtained patient informed consent for treatment and approved by the Human Ethics Committee of Tangdu Hospital of Air Force Medical University, No. 2024070385.

Inclusion criteria: (1) Gastric cancer was confirmed by biopsy pathology, clinical stage II or III, and immunohistochemistry revealed Her2 (-); (2) Neoadjuvant chemotherapy combined with radical gastrectomy; (3) At least 18 years of age; and (4) Complete clinicopathological data.

Exclusion criteria: (1) Distant metastasis; (2) Gastric stump cancer or other malignant tumors; (3) Receiving neoadjuvant therapy other than chemotherapy; and (4) Incomplete clinical data or serious complications (such as severe cardiopulmonary dysfunction). In this study, patients < 65 years old were defined as the young and middle-aged group, and patients ≥ 65 years old were defined as the elderly group.

Treatment plan

Patients routinely receive 2 or more cycles of neoadjuvant chemotherapy, which mainly includes the sex-determining region Y-box regimen and fluorouracil, leucovorin, and oxaliplatin regimen. After 2-3 cycles of neoadjuvant chemotherapy, patients routinely undergo hematology, computed tomography, and digestive endoscopy to assess their disease status. Adverse reactions during neoadjuvant chemotherapy were graded according to the National Cancer Institute Common Toxicity Criteria (V3.0). Patients with grade 3 or above serious adverse reactions are given necessary medical care. Surgical timing and approach were established through comprehensive evaluation by a multidisciplinary team. Tumor response following neoadjuvant chemotherapy was evaluated using the tumor regression grade (TRG) classification in accordance with the American Cancer Society Gastric Cancer Staging System, 8^th edition. The Clavien-Dindo grading system provided the framework for assessment of postoperative complications. Determination of adjuvant chemotherapy protocols following surgery was based on each patient's general condition and previous response to chemotherapeutic agents.

Follow-up visit

A comprehensive, standardized follow-up protocol was implemented for all patients. During the first two years post-surgery, patients underwent thorough clinical evaluations every 3 months to 4 months, which included physical examination, laboratory tests (complete blood count, liver and kidney function tests, tumor markers including carcinoembryonic antigen, carbohydrate antigen 19-9, and cancer antigen 72-4), and imaging studies (abdominal and pelvic computed tomography, chest radiography). For patients in their third to fifth post-operative years, these comprehensive assessments were conducted at 6-month intervals. After the fifth year, annual evaluations were deemed sufficient for long-term surveillance. Follow-up data were meticulously collected through both in-person outpatient consultations and structured telephone interviews with patients or their family members. The final follow-up data collection was completed in February 2024, providing a minimum potential follow-up period of 4 months for the most recently recruited patients. Progression-free survival (PFS) was precisely defined as the interval between the date of surgical intervention and the first documented evidence of disease recurrence, metastasis, or death from any cause. OS was calculated as the time from the date of surgery until death from any cause or until the final follow-up date for patients who remained alive.

Observation indices

The outcome measures were comprehensively categorized to evaluate the safety and efficacy of neoadjuvant chemotherapy combined with radical gastrectomy in elderly patients with gastric cancer. Neoadjuvant chemotherapy parameters included the specific regimen administered (sex-determining region Y-box, fluorouracil, leucovorin, and oxaliplatin, or other protocols), number of treatment cycles completed, and treatment-related complications categorized according to the National Cancer Institute Common Toxicity Criteria (V3.0). Dose modifications and treatment delays due to adverse events were also documented, along with pre- and post-neoadjuvant clinical staging assessments to evaluate initial response. Surgical and postoperative pathological indicators encompassed the interval between completion of neoadjuvant chemotherapy and surgery, surgical approach (laparoscopic, open, or conversion), extent of gastrectomy, quantified intraoperative blood loss, operative time, incision length, lymph node harvest, and achievement of R0 resection. Detailed tumor regression grade according to the 8^th edition of the American Cancer Society Gastric Cancer Staging System was recorded, as well as comprehensive pathological assessment including tumor characteristics and tumor-node-metastasis staging. Postoperative recovery parameters monitored included complications classified by the Clavien-Dindo grading system, with specific attention to anastomotic leakage, wound infection, pneumonia, pleural effusion, and other potential complications. Time to first flatus, liquid intake, solid food intake, and duration of hospital stay were recorded to assess recovery trajectory. Long-term oncological outcomes focused on progression-free and OS, patterns of recurrence, and the impact of postoperative adjuvant chemotherapy on survival outcomes, with particular emphasis on comparative analysis between elderly and young/middle-aged groups.

Comorbidity assessment

Comorbidities were systematically assessed and documented for all patients through comprehensive evaluation of medical history, physical examination, and thorough review of medical records. The assessment included cardiovascular diseases (hypertension, coronary artery disease, congestive heart failure, arrhythmias, and cerebrovascular disease), pulmonary diseases (chronic obstructive pulmonary disease, asthma, and other chronic respiratory conditions), endocrine disorders (diabetes mellitus and thyroid disorders), renal diseases (chronic kidney disease and renal insufficiency), and other significant conditions including liver disease, previous malignancies, autoimmune disorders, and neurological conditions. The presence and severity of each comorbidity were recorded according to standard clinical diagnostic criteria and classified as present or absent. For patients with multiple comorbidities, all conditions were documented individually, and the assessment was performed by the treating physician team and verified through multidisciplinary consultation when necessary.

Statistical analysis

SPSS 26.0 statistical software was used for data analysis. The statistical data were analyzed via Fisher’s exact test or the χ² test. The PFS and OS curves were drawn via the Kaplan-Meier method. P < 0.05 was considered statistically significant.

RESULTS

Baseline data

A comprehensive analysis included 148 patients in total, with 37 elderly patients (average age 68 years, range 65-76 years) and 111 young and middle-aged patients (average age 54 years, range 28-64 years). Prior to neoadjuvant chemotherapy, clinical staging in the elderly group revealed stage II disease in 4 patients (10.8%) and stage III disease in 33 patients (89.2%). Similarly, in the young and middle-aged group, 13 patients (11.7%) presented with stage II disease, while 98 patients (88.3%) had stage III disease. Comparison of baseline characteristics between the elderly group and the young and middle-aged group showed no statistically significant differences (all P > 0.05), as detailed in Table 1.

Table 1 Comparison of baseline data between two groups of gastric cancer patients (cases).

Clinical indicators	Number of cases	Middle aged and young group (n = 111)	Elderly group (n = 37)	χ2 value	P value
Gender				0.062	0.803
Female	26	20	6	-	-
Male	122	91	31	0.885	0.347
Underlying disease
No	105	81	24	-	-
Yes	43	30	13	-	-
BMI (kg/m2), mean ± SD	-	22.9 ± 4.3	21.9 ± 2.7	1.369	0.245
Tumor site				0.997	0.607
Upper part of stomach	94	69	25
Middle part of stomach	19	16	3
Lower part of stomach	35	26	9
Clinical stages				0.022	0.882
Phase II	17	13	4
Phase III	131	98	33
Neoadjuvant chemotherapy regimen				4.214	0.239
FOLFOX	81	66	15
SOX	55	37	18
XELOX	7	5	2
FLOT	5	3	2
Neoadjuvant chemotherapy cycle				0.225	0.635
< 3	73	56	17
≥ 3	75	55	20
Operation				0.580	0.446
Laparoscope	80	58	22
Openness	68	53	15
Postoperative chemotherapy				0.379	0.538
No	46	33	13
Yes	102	78	24

BMI: Body mass index; FOLFOX: Fluorouracil, leucovorin, and oxaliplatin; SOX: Sex-determining region Y-box; XELOX: Capecitabine and oxaliplatin; FLOT: Fluorouracil, leucovorin, oxaliplatin, taxotere.

Complications of neoadjuvant chemotherapy

In the elderly group, 36 patients (97.3%) completed 2 or more cycles of neoadjuvant chemotherapy, and 20 patients (54.1%) received 3 or more cycles of neoadjuvant chemotherapy. In the young and middle-aged groups, 105 patients (94.6%) completed 2 or more cycles of neoadjuvant chemotherapy, and 55 patients (49.5%) received 3 or more cycles of neoadjuvant chemotherapy. Among the hematological complications caused by neoadjuvant chemotherapy, anemia (21.6% vs 18.0%, χ² = 0.235, P = 0.628), leukopenia (43.2% vs 36.0%, χ² = 0.613, P = 0.434), neutropenia (29.7% vs 30.6%, χ² = 0.011, P = 0.918) and thrombocytopenia (10.8% vs 8.1%, χ² = 0.253, P = 0.615) were not statistically significant. Among the nonhematological complications of neoadjuvant chemotherapy, nausea (35.1% vs 32.4%, χ² = 0.092, P = 0.762), vomiting (16.2% vs 13.5%, χ² = 0.166, P = 0.683) and diarrhea (18.9% vs 18.0%, χ² = 0.015, χ² = 0.015) were observed in the elderly group and the young and middle-aged groups. There was no significant difference in the incidence of mucositis (13.5% vs 10.8%, χ² = 0.199, P = 0.766). Adverse reactions were effectively alleviated in all patients after adjusted chemotherapy and symptomatic supportive treatment, as shown in Table 2.

Table 2 Comparison of common terminology criteria for adverse events grading of complications in neoadjuvant chemotherapy between two groups of gastric cancer patients (cases).

Non hematological complications	Middle aged and young group (n = 111)	Elderly group (n = 37)	χ2 value	P value
New hematological complications
Level 3-4	3	4	-	0.066
Anemia	20	8	0.235	0.628
Level 1-2	18	7	-	-
Level 3-4	2	1	-	-
Leukopenia	40	16	0.613	0.434
Level 1-2	40	16	-	-
Level 3-4	0	0	-	-
Neutropenia	34	11	0.011	0.918
Level 1-2	33	9	-	-
Level 3-4		2	-	-
Thrombocytopenia	9	4	0.253	0.615
Level 1-2	9	3	-	-
Level 3-4	0	1	-	-
Non hematological complications
Level 3-4	14	9	2.900	0.089
Nausea	36	13	0.092	0.762
Level 1-2	28	10	-	-
Level 3-4	8	3	-	-
Vomit	15	6	0.166	0.683
Level 1-2	10	4	-	-
Level 3-4	5	2	-	-
Diarrhea	20	7	0.015	0.902
Level 1-2	16	5	-	-
Level 3-4	4	2	-	-
Mucositis	12	5	0.199	0.766
Level 1-2	9	3	-	-
Level 3-4	3	2	-	-

Operation and postoperative recovery

In the young and middle-aged groups, 34 patients (30.6%) had undergone surgery within 4 weeks from the last chemotherapy, 52 patients (46.8%) had undergone surgery at 4-6 weeks, and 25 patients (22.5%) had undergone surgery at more than 6 weeks. In the elderly group, there were 7 patients (18.9%) within 4 weeks, 21 patients (56.8%) between 4 and 6 weeks, and 9 patients (24.3%) above 6 weeks. In the young and middle-aged groups, 58 patients (52.3%) underwent laparoscopic surgery, and 53 patients (47.7%) underwent open surgery. In the elderly group, 22 patients (59.5%) underwent laparoscopic surgery, and 15 patients (40.5%) underwent open surgery, with no significant difference between the two groups (χ² = 0.580, P = 0.446). Total gastrectomy was performed in 73 patients (65.8%), distal gastrectomy in 14 patients (12.6%) and proximal gastrectomy in 24 patients (64.9%), 7 patients (18.9%) and 6 patients (16.2%) in the elderly group, with no significant difference (χ² = 1.181, P = 0.554).

There were no significant differences in operation duration, intraoperative blood loss or incision length between the young and middle-aged groups (273 ± 68 minutes vs 260 ± 66 minutes, t = 0.270, P = 0.604; 163 ± 37 mL vs 171 ± 42 mL, t = 1.140, P = 0.250; 10 ± 8 cm vs 9 ± 8 cm, t = 0.946, P = 0.332). There was no significant difference in the time of first liquid intake between the young and middle-aged groups and the old group [(4.6 ± 2.1) days vs (4.3 ± 1.8) days, t = 0.139, P = 0.710]. Ninety patients in the young and middle-aged groups (81.1%) recovered and were discharged from the hospital within 12 days after surgery, whereas 28 patients in the elderly group (75.7%) were not significantly different between the two groups (χ² = 0.502, P = 0.479).

Pathological examination revealed that the average number of dissected lymph nodes was 23.7 ± 9.1, and the R0 resection rate was 91.0%. There was an R0 of 25.4 ± 8.9 in the elderly group, and the R0 removal rate was 89.2%, which was not statistically significant (t = 0.026, P = 0.871; χ² = 0.105, P = 0.750). A complete response (polymerase chain reaction) was achieved in 1 patient (2.7%) in the elderly group and 4 patients (3.6%) in the young and middle-aged groups. For the TRG classification, 16 cases (43.2%) were grade 0-2, and 21 cases (56.8%) were grade 3. In the young and middle-aged groups, 47 patients (42.3%) had grade 0-2 disease, and 64 patients (57.7%) had grade 3 disease. In terms of the postoperative pathological stage, 20 patients (54.1%) were in the 0-II stage, and 17 patients (45.9%) were in the III-IV stage. There were 46 patients (41.4%) with stage 0 to II disease and 65 patients (58.6%) with stage III to IV disease in the young and middle-aged groups, with no significant difference (χ² = 0.101, P = 0.992; χ² = 4.825, P = 0.306).

In the whole group, 42 patients (28.4%) had postoperative complications, and the incidence of postoperative complications was 25.2% in the young and middle-aged groups and 37.8% in the elderly group, with no statistical significance (χ² = 2.172, P = 0.141). The incidence of pleural effusion and pulmonary infection in the old group was significantly greater than that in the young and middle-aged groups (16.2% vs 3.6%, χ² = 7.007, P = 0.008; 27.0% vs 7.2%, χ² = 10.204, P = 0.001), and there was no significant difference in the incidence of other complications (all P > 0.05), as shown in Table 3.

Table 3 Comparison of Clavien-Dindo grading for postoperative complications in two groups of gastric cancer patients (cases).

Non hematological complications	Middle aged and young group (n = 111)	Elderly group (n = 37)	χ2 value	P value
Clavien-Dindo grading			2.926	0.232
Level 0	83	23	-	-
Level 1-2	21	12	-	-
Level 3-4	7	2	-	-
Postoperative complications
Pleural effusion	4	6	7.007	0.008
pulmonary infection	8	10	10.204	0.001
pneumothorax	1	1		0.439
Acute respiratory distress syndrome	3	0		0.573
Gastroparesis	2	-	-	1
Intestinal obstruction	3	0	-	0.573
Complications of anastomotic site	3	1	-	1.000
Abdominal bleeding	l	0	-	1.000
Wound infection	3	0	-	0.573
Cardiovascular and cerebrovascular related complications	4	3	-	0.264

Long-term prognosis

As of February 2022, the median follow-up time for all patients was 40 months. In the whole group, patients who received postoperative adjuvant chemotherapy had significantly better OS than did those who did not receive adjuvant chemotherapy (t = 6.652, P = 0.010) (Figure 1A). The 3-year PFS rates of the young and middle-aged groups and the elderly group were 54.3% and 63.5% (t = 0.494, P = 0.482), respectively, and the 3-year OS rates were 63.1% and 66.1% (t = 0.013, P = 0.908), respectively, with no statistical significance, as shown in Figure 1B and C.

Figure 1 Long-term prognosis. A: Survival curves of patients with gastric cancer who received adjuvant chemotherapy and those who did not; B: Progression-free survival curve of gastric cancer patients in young and middle-aged group and elderly group; C: Survival curve of gastric cancer patients in young and middle-aged group and elderly group.

DISCUSSION

Neoadjuvant chemotherapy combined with radical gastrectomy can significantly increase the R0 resection rate and improve the prognosis of patients with advanced gastric cancer[17]. With the extension of life expectancy and the development of an aging society, nearly 70% of new cases and more than 75% of deaths from gastric cancer in China in recent years have been elderly patients with gastric cancer. For postoperative adjuvant chemotherapy for gastric cancer, a previous meta-analysis revealed that the incidence of serious adverse events after postoperative chemotherapy in elderly patients over 65 years old was significantly greater than that in middle-aged and young patients[18-20]. However, studies on neoadjuvant chemotherapy combined with radical gastrectomy for gastric cancer are rare, and conflicting research data exist concerning whether neoadjuvant chemotherapy increases the incidence of complications in elderly patients; thus, it is difficult for clinicians to make evidence-based medical decisions on the treatment of elderly patients with advanced gastric cancer.

Chemotherapy-related adverse reactions are important for evaluating the safety of chemotherapy[21-23]. In terms of palliative chemotherapy for gastric cancer, a relevant meta-analysis revealed that the incidence of grade 3-4 complications of chemotherapy in elderly patients with metastatic esophageal, esophagogastric junction and gastric cancer was significantly greater than that in middle-aged and young patients[24]. With respect to adverse reactions related to neoadjuvant chemotherapy. The complications of gastric cancer patients over 70 years old and those under 70 years old after neoadjuvant therapy were mainly different in terms of overall grade 3-4 hematological complications, gastrointestinal complications and general complications. However, most elderly individuals can complete the scheduled neoadjuvant chemotherapy, indicating that the adverse reactions of elderly individuals to neoadjuvant chemotherapy are well tolerated under the premise of close monitoring. With age, decreased renal function leading to decreased metabolism of platinum drugs may be the reason for the relatively high incidence of neoadjuvant chemotherapy-related adverse reactions in elderly patients[25]. Therefore, the renal function of elderly patients should be closely monitored, and attention should be given to chemotherapy-related complications during neoadjuvant chemotherapy.

The significantly higher incidence of pleural effusion and pulmonary infection in elderly patients observed in our study can be attributed to multiple age-related physiological changes and risk factors that collectively compromise respiratory function and recovery capacity. Age-related pulmonary function decline represents a fundamental contributing factor. Elderly patients typically experience progressive deterioration in lung mechanics, including reduced lung capacity, decreased respiratory muscle strength, impaired gas exchange efficiency, and diminished cough reflex. These changes result in inadequate clearance of respiratory secretions and increased susceptibility to atelectasis and pneumonia following major abdominal surgery. The physiological stress of radical gastrectomy, combined with the effects of general anesthesia and postoperative pain, further compromises already diminished respiratory reserve in elderly patients. Compromised immune function significantly contributes to increased infection risk in elderly patients. Age-related decline in both innate and adaptive immunity results in reduced ability to mount effective inflammatory responses against pathogens, delayed pathogen clearance, and impaired tissue repair mechanisms. This immunological vulnerability is further exacerbated by the immunosuppressive effects of neoadjuvant chemotherapy, creating a synergistic effect that predisposes elderly patients to postoperative infections, particularly pulmonary infections.

Neoadjuvant chemotherapy can easily lead to tissue edema and increase the difficulty of radical gastrectomy[26]. However, there was no significant difference in operative time, intraoperative blood loss or lymph node dissection between elderly gastric cancer patients after neoadjuvant chemotherapy and middle-aged and young patients, and the first postoperative liquid feeding time and postoperative hospital stay did not increase[27]. Therefore, age does not significantly increase the difficulty of radical gastrectomy after neoadjuvant chemotherapy or slow the postoperative recovery rate of patients. The common postoperative complications of patients with gastric cancer after neoadjuvant therapy include pulmonary infection, pleural effusion, abdominal hemorrhage and wound-related complications. Previous studies have shown that the incidence rates of postoperative complications and mortality in elderly patients undergoing radical gastrectomy are greater than those in middle-aged and young patients. There was no statistically significant difference in overall postoperative complications or the incidence of grade 3 to 5 complications between patients over 65 years of age and those under 65 years of age[28-31]. Overall postoperative complication rates were similar in the two groups in this study, but the incidence of pleural effusion and lung infection significantly increased in older patients, which may be due to poorer nutritional status and lung function in older patients[32-34]. Therefore, patients with postoperative pulmonary and cardiovascular complications in elderly patients with gastric cancer who receive neoadjuvant therapy combined with radical gastrectomy should be vigilant.

The tumor response after neoadjuvant therapy is significantly correlated with the prognosis of advanced gastric cancer patients[35]. A meta-analysis revealed that patients with gastric cancer who responded significantly to neoadjuvant therapy had significantly better OS than patients with a poor response. In this study, fewer than 50% of patients with TRGs ranging from 0-2 were in both groups. In recent years, the application of neoadjuvant chemotherapy combined with immunotherapy in patients with advanced gastric cancer has significantly increased the proportion of TRG grade 0--2 patients and the disease control rate, suggesting that neoadjuvant chemotherapy combined with immunotherapy is highly important for overcoming the bottleneck of neoadjuvant chemotherapy efficacy and further prolonging patients’ OS[36-40]. The results of this study indicate that the long-term efficacy of neoadjuvant therapy combined with radical gastrectomy in elderly patients with gastric cancer is no worse than that in middle-aged and young patients, which is consistent with the results of previous studies[41-43]. In addition, in this study, the prognosis of patients who received postoperative adjuvant chemotherapy was significantly better than that of nonrecipients[44]. Therefore, for patients receiving neoadjuvant therapy combined with radical gastrectomy, a full course of postoperative adjuvant chemotherapy is recommended to further improve patient prognosis.

There are several limitations to this study. First, the selection bias inherent in retrospective studies cannot be avoided. Second, the patients included in this study had a long time span, and most of them could not detect the mismatch repair status, and there were differences in the selection of neoadjuvant therapy during this period. In addition, there may be bias in the documentation of perioperative complications. Therefore, a large-scale prospective study is needed to further verify the results.

Limitation

We acknowledge that our study did not employ standardized comorbidity scoring systems such as the Charlson Comorbidity Index or the American Society of Anesthesiologists physical status classification system. The use of such validated scoring tools would have provided more objective quantification of comorbidity burden and enhanced the comparability of our results with other studies. This represents a limitation of our retrospective study design and will be addressed in future prospective investigations. The comorbidity data were used to inform treatment decision-making, perioperative risk stratification, and postoperative care protocols, with particular attention to patients with conditions that might affect surgical outcomes or chemotherapy tolerance.

CONCLUSION

Elderly patients with gastric cancer have good tolerance to neoadjuvant chemotherapy and do not significantly increase the incidence of related adverse reactions. The operative effect and overall postoperative complication rate of elderly patients are similar to those of middle-aged and young patients, the overall postoperative recovery speed is faster, and the long-term prognosis is good. Therefore, neoadjuvant chemotherapy combined with radical gastrectomy is safe and effective in elderly patients with gastric cancer, but the incidence of postoperative pleural effusion and pulmonary infection in elderly patients is significantly increased, and clinicians should pay attention to this combination.