Clinicopathological profile and survival impact of neoadjuvant chemotherapy in gastric and GE junction cancers undergoing D2 gastrectomy: Outcomes from a tertiary centre in North India

INTRODUCTION

This study aimed to evaluate clinicopathological characteristics and survival outcomes following D2 gastrectomy and assess the impact of neoadjuvant chemotherapy on survival in gastric and gastroesophageal junction adenocarcinoma in a tertiary care centre in North India.

MATERIAL AND METHODS

This retrospective and prospective observational study was conducted at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, between 2018 and 2022. Sixty patients with histologically proven gastric or gastroesophageal junction adenocarcinoma undergoing D2 gastrectomy were included. Clinicopathological characteristics, operative outcomes, and survival data were analysed. Patients with metastatic or unresectable disease, recurrent gastric cancer, non-adenocarcinoma histology, previous gastric surgery, or incomplete clinical and follow-up data were excluded from the study. D2 lymphadenectomy was performed according to Japanese Gastric Cancer Association (JGCA) guidelines.^[1] Survival analysis was performed using Kaplan–Meier methodology, and survival curves were generated for overall survival analysis.

RESULTS

Baseline characteristics: Baseline patient and tumour characteristics are shown in Table 1. A total of 60 subjects were included in the final analysis. The mean age of patients having stomach malignancy was 57.88±10.22 years. Epigastric discomfort affected the majority of patients, with 23 (38.33%) reporting it, while 20 (33.33%) experienced vomiting.

Subtotal gastrectomy was done in 40 patients (66.67%), total gastrectomy in 13 patients (21.67%), and upper partial gastrectomy in 7 patients (11.66%). In our study, most of the patients had antropyloric growth. Antro-pyloric growth was observed in 31 patients (51.67%).

Most patients presented with advanced disease, with stage IIIA accounting for the largest subgroup. T4 tumours were observed in 46.7% of patients, while nodal involvement was identified in 65%. Median lymph node retrieval was 21, with ≥16 nodes retrieved in 81.6% of cases. Lymph vascular invasion and perineural invasion were observed in 88.3% and 50% of patients, respectively.

In our study, 12 patients (20%) had lost their follow-up. Thus, we had 48 patients for survival analysis. We included all these patients from Jan 2018 to April 2022 for survival analysis. The overall 3-year and 4-year survival rates were 65% and 52%, respectively [Figure 1]. For tumour stages I, II, and III, the four-year overall survival rates were 100%, 91%, and 77%, respectively [Figure 2]. Overall T and N stage-specific survival rates are mentioned in Table 2.

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Figure 1: Overall, 3-year and 4-year survival

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Figure 2: Four-year overall survival rates for tumour stages I, II, and III.

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In our study, out of 60 patients, 25 (41.7%) received neoadjuvant chemotherapy—19 with the FLOT regimen and 6 with CapOx—while 35 (58.3%) underwent upfront surgery. Among those not receiving neoadjuvant therapy, 28 presented in emergency settings due to bleeding or obstruction, and 7 declined chemotherapies. Adjuvant CapOx therapy was administered to 21 patients, with a compliance rate of 60%. Postoperative morbidity occurred in 28.3% of patients, with no perioperative mortality. The overall 1-year, 3-year, and 4-year survival rates were 81%, 65%, and 52%, respectively, and disease-free survival at 1 and 3 years was 77.1% and 47.1%. Patients who underwent neoadjuvant therapy demonstrated improved outcomes, achieving overall survival rates of 85%, 70%, and 55% at 1, 3, and 4 years, respectively, compared with 78%, 60%, and 48% in the upfront surgery cohort [Figure 3].

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Figure 3: Overall survival NACT vs upfront surgery. NACT: Neoadjuvant chemotherapy

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DISCUSSION

Total gastrectomy or subtotal gastrectomy with D2 lymph node dissection is the standard recommended procedure for carcinoma of the stomach.^[2-4] There is increasing global consensus on performing a D2 lymphadenectomy for gastric cancer due to the long-term results of large Western studies with Eastern data.^[5-8] However, there is a scarcity of data from the Kashmir Valley, a high-incidence area of gastric cancer, regarding the outcome of D2 lymphadenectomy for a curative gastrectomy.^[9]

In the present study, most patients presented with advanced-stage disease, with stage III disease accounting for 51.7% of the cohort. Similar observations have been reported from Indian studies by Nandi et al. and Franklyn et al., where delayed presentation and absence of routine screening contributed to diagnosis at advanced stages.^[10,11] The high burden of advanced disease in the Kashmir Valley highlights the need for improved awareness and early detection strategies in this high-risk population.

The mean age of presentation in our study was 57.9 years, with a marked male predominance. Smoking was commonly observed among patients, consistent with previously reported Indian data suggesting tobacco exposure as an important associated risk factor in gastric malignancy.^[3] The antropyloric region was the most frequent tumour location in our cohort, observed in 51.7% of cases. This predominance of distal gastric tumours has also been documented in other Indian studies, including those by Pareekutty et al. and Sharma and Radhakrishnan.^[4,12] In contrast, Western literature has shown a gradual increase in proximal and gastroesophageal junction tumours.^[13]

The present study demonstrated acceptable perioperative outcomes following D2 gastrectomy. Postoperative morbidity occurred in 28.3% of patients, while no perioperative mortality was observed. Indian experiences, particularly in the Tata Memorial Hospital series by Shrikhande et al., have similarly demonstrated that D2 lymphadenectomy can be safely performed with acceptable complication rates in specialised and high-volume centres.^[14]

Adequate lymph node retrieval is essential for accurate staging and oncological clearance in gastric cancer surgery. In our study, the median lymph node yield was 21, with more than 16 lymph nodes retrieved in 81.6% of patients, meeting recommended oncological standards. Comparable lymph node yields have been reported in Indian studies evaluating D2 gastrectomy outcomes.^[12,14] Most patients in our series had advanced pathological disease, with T4 tumours identified in 46.7% and nodal involvement in 65% of patients. Although lymph vascular and perineural invasion were frequently observed, they did not demonstrate statistically significant prognostic impact in the present cohort, possibly due to the limited sample size. Survival outcomes were adversely affected by increasing tumour depth and nodal stage, with poorer survival observed in stage III and N3 disease.

Neoadjuvant chemotherapy demonstrated a favourable impact on survival outcomes in the present study. Patients receiving perioperative chemotherapy achieved improved 1-year, 3-year, and 4-year overall survival compared with those undergoing upfront surgery. Most patients in our cohort received the FLOT regimen, which was associated with acceptable tolerability and improved long-term outcomes. These findings are consistent with contemporary evidence supporting perioperative chemotherapy as a standard component of multimodal treatment for locally advanced gastric and gastroesophageal junction adenocarcinoma.^[15] Recent Indian studies have also reported encouraging outcomes with neoadjuvant and perioperative chemotherapy in gastric cancer. Janarthinakani et al. demonstrated improved survival trends in patients receiving neoadjuvant chemotherapy for locally advanced gastric cancer in a real-world Indian setting.^[16] Similarly, Ramaswamy et al. reported favourable pathological and survival outcomes with perioperative modified FLOT compared with EOX in resectable gastric cancer oesophageal junction adenocarcinoma.^[17] Our findings support the growing adoption of perioperative chemotherapy, particularly FLOT-based regimens, in the management of locally advanced gastric cancer in India.

TAKE HOME MESSAGE

This study demonstrates that D2 gastrectomy can be performed safely and effectively in specialised tertiary care centres with acceptable morbidity, no perioperative mortality, and adequate lymph node retrieval meeting oncological standards. Most patients in our cohort presented with advanced-stage disease, underscoring the urgent need for earlier diagnosis and improved awareness in high-incidence regions such as the Kashmir Valley. Importantly, patients receiving neoadjuvant chemotherapy, particularly FLOT-based regimens, achieved improved survival outcomes compared with upfront surgery, supporting the integration of perioperative chemotherapy into standard multidisciplinary management of locally advanced gastric and gastroesophageal junction adenocarcinoma. The present study adds valuable real-world evidence from North India and reinforces the role of standardised D2 lymphadenectomy combined with multimodal therapy in improving long-term oncological outcomes.