D2 Gastrectomy With or Without Para-Aortic Lymph Node Dissection After Chemoimmunotherapy for Gastric Cancer (PAN-SELECT)

D2 Lymphadenectomy With Versus Without Para-Aortic Lymph Node Dissection in Gastric Cancer Patients With Radiologic Regression of Para-Aortic Lymph Nodes After Chemoimmunotherapy: A Single-Center Randomized Exploratory Trial

Some patients with gastric cancer have enlarged para-aortic lymph nodes, also called No. 16 lymph nodes, at diagnosis. After standard chemoimmunotherapy, these lymph nodes may shrink to less than 10 mm on imaging, but it is uncertain whether microscopic cancer remains and whether surgically removing these nodes improves disease control. This single-center randomized exploratory trial will enroll 32 patients whose suspicious No. 16a2 and/or No. 16b1 lymph nodes have regressed to less than 10 mm after 2 to 8 cycles of standard chemoimmunotherapy and who have no disease progression or new distant metastases. Participants will be assigned 1:1 to curative-intent gastrectomy with standard D2 lymphadenectomy either with or without para-aortic lymph node dissection. The main outcome is progression-free survival at 2 years after randomization.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Procedure: Gastrectomy with D2 lymphadenectomy plus para-aortic lymph node dissection; Procedure: Gastrectomy with standard D2 lymphadenectomy

Detailed Description

PAN-SELECT is a prospective, open-label, parallel-group, single-center randomized exploratory trial. The study evaluates whether adding dissection of the No. 16a2 and No. 16b1 para-aortic lymph nodes to curative-intent gastrectomy and standard D2 lymphadenectomy improves outcomes in a response-selected population with gastric or eligible esophagogastric junction adenocarcinoma.

At initial diagnosis, eligible candidates must have radiologic evidence of involvement of No. 16a2 and/or No. 16b1 lymph nodes, defined by a short-axis diameter of at least 10 mm together with metastatic morphology, and no other distant metastases. Candidates receive 2 to 8 cycles of an immune checkpoint inhibitor combined with chemotherapy as routine clinical care outside the randomized intervention. The specific agents, doses, modifications, and number of cycles are selected by the multidisciplinary team according to current clinical practice and are recorded by the study.

After completion of the planned preoperative systemic therapy, chest, abdominal, and pelvic contrast-enhanced computed tomography is performed. Written informed consent for PAN-SELECT is obtained only after the first planned post-treatment reassessment confirms that all previously suspicious No. 16a2 and No. 16b1 lymph nodes have a short-axis diameter of less than 10 mm, there is no progression according to RECIST version 1.1 and clinical assessment, there is no new distant metastasis, curative-intent R0 resection appears feasible, and the patient is fit for either study operation.

After all randomization criteria are verified, an independent statistician-generated sequence using simple randomization with a fixed seed assigns participants 1:1 to one of two groups. The experimental group undergoes gastrectomy with standard D2 lymphadenectomy plus systematic dissection of No. 16a2 and No. 16b1 para-aortic lymph nodes. The active comparator group undergoes gastrectomy with standard D2 lymphadenectomy without planned systematic No. 16 dissection. Robotic, laparoscopic, and open approaches are permitted. Surgery is planned 2 to 6 weeks after the last preoperative systemic treatment, after treatment-related toxicity has recovered and the participant is clinically fit.

Participants and surgeons are not masked because the surgical fields differ. Radiologic progression and recurrence are independently assessed by two radiologists who are not involved in clinical decision-making and are unaware of treatment assignment; disagreement is resolved by a third radiologist or multidisciplinary review. Pathology reporting includes ypTNM stage, Becker or College of American Pathologists tumor regression grade, margin and R0 status, and regional lymph node station-specific counts. In the experimental group, the No. 16 specimen is submitted separately and the number of examined and metastatic No. 16 lymph nodes is recorded.

The primary estimand is the between-group difference in 2-year progression-free survival under the intention-to-treat principle. The sample size of 32 participants is based on single-center feasibility and the precision needed for preliminary estimates rather than a formal superiority or noninferiority hypothesis test. Results will be used to estimate effect size, event rates, surgical safety, protocol adherence, and recruitment feasibility for a future multicenter confirmatory trial.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hao Xu, MD, PhD; Phone Number: +86-25-68306505; Email: hxu@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • The First Affiliated Hospital with Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 to 75 years.
• Histologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma limited to Siewert type III or Siewert type II disease not requiring a transthoracic combined operation.
• Human epidermal growth factor receptor 2 (HER2)-negative disease, defined as immunohistochemistry 0 or 1+, or immunohistochemistry 2+ with negative fluorescence in situ hybridization, or HER2 status unknown.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• At initial diagnosis, thin-section contrast-enhanced computed tomography shows at least one No. 16a2 and/or No. 16b1 lymph node with a short-axis diameter of at least 10 mm and metastatic morphology, such as a round shape, irregular border, central necrosis, clustering, or abnormal enhancement, confirmed by two radiologists or gastric cancer multidisciplinary team physicians with relevant experience.
• Regional lymph node metastases are permitted, but imaging shows no peritoneal, hepatic, pulmonary, osseous, or other distant metastasis apart from the eligible No. 16a2 and/or No. 16b1 lymph nodes.
• Completion of 2 to 8 cycles of an immune checkpoint inhibitor combined with chemotherapy as routine clinical care before randomization, with the agents, doses, modifications, and number of cycles determined by the multidisciplinary team and completely documented.
• At the first reassessment after completion of the planned preoperative systemic therapy, all previously suspicious No. 16a2 and No. 16b1 lymph nodes have a short-axis diameter of less than 10 mm.
• No disease progression according to RECIST version 1.1 and clinical assessment, and no new distant metastasis at the post-treatment reassessment.
• The gastric primary tumor and regional disease are considered resectable with curative intent and an R0 resection is expected; the participant is considered medically and technically eligible for either assigned operation.
• Toxicities related to the last preoperative systemic therapy have recovered to Common Terminology Criteria for Adverse Events version 5.0 grade 1 or lower or to the pretreatment baseline. Controlled immune-related endocrine events requiring only stable replacement therapy are permitted.
• Adequate major organ function, cardiopulmonary reserve, and acceptable anesthetic risk for gastrectomy and possible para-aortic lymph node dissection.
• Ability and willingness to complete study follow-up and provide written informed consent after post-treatment eligibility is confirmed.

Exclusion Criteria:

• Disease progression, a new distant metastasis, or any suspicious para-aortic lymph node with a short-axis diameter of 10 mm or greater at the post-treatment reassessment.
• Curative-intent R0 resection is not considered feasible, or the participant cannot tolerate both assigned surgical strategies.
• Previous radical gastric cancer surgery or para-aortic operation expected to substantially alter the planned lymphadenectomy, or severe intra-abdominal adhesions or another condition that prevents safe completion of the assigned surgery.
• Uncontrolled active infection, severe cardiac, pulmonary, hepatic, or renal dysfunction, coagulopathy, or another disease that materially increases perioperative risk.
• Preoperative treatment toxicity has not recovered to the allowed level, or an unstable immune-related adverse event requires high-dose systemic immunosuppression.
• Pregnancy or breastfeeding, or inability to comply with clinically required contraception or follow-up.
• Another active malignancy within the previous 5 years, except a cured malignancy with a low risk of recurrence as determined by the investigator and applicable ethics requirements.
• Concurrent participation in another interventional study that may interfere with evaluation of the primary outcome.
• Any other condition that, in the investigator's judgment, makes participation inappropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: D2 plus PAND; Participants undergo curative-intent gastrectomy with standard D2 lymphadenectomy plus systematic para-aortic lymph node dissection of No. 16a2 and No. 16b1. The No. 16 specimen is submitted separately for pathological examination.	Procedure: Gastrectomy with D2 lymphadenectomy plus para-aortic lymph node dissection; Distal, proximal, or total gastrectomy is performed as appropriate for tumor location, with standard D2 lymphadenectomy and additional systematic dissection of No. 16a2 from the upper border of the celiac trunk to the lower border of the left renal vein and No. 16b1 from the lower border of the left renal vein to the upper border of the inferior mesenteric artery. Robotic, laparoscopic, or open surgery is permitted.
Experimental: D2 alone; Participants undergo curative-intent gastrectomy with standard D2 lymphadenectomy without planned systematic dissection of No. 16a2 or No. 16b1. Rescue removal or dissection is permitted only when an intraoperative finding requires treatment for safety or curative intent, and the reason and extent are recorded.	Procedure: Gastrectomy with standard D2 lymphadenectomy; Distal, proximal, or total gastrectomy is performed as appropriate for tumor location, with standard D2 lymphadenectomy and without planned systematic No. 16a2 or No. 16b1 dissection. Robotic, laparoscopic, or open surgery is permitted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival rate at 2 years	Progression-free survival is measured from randomization to the earliest of radiologic or clinical disease progression, postoperative local, regional, or distant recurrence, or death from any cause. Participants without an event are censored at the date of their last adequate disease assessment. The 2-year progression-free survival rate will be estimated by the Kaplan-Meier method.	From randomization to 2 years after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival rate at 2 years after surgery	Among participants who undergo R0 resection, recurrence-free survival is measured from surgery to the earliest of local, regional, or distant recurrence or death from any cause. Participants without an event are censored at the date of their last adequate disease assessment.	From surgery to 2 years after surgery
Overall survival	Overall survival is measured from randomization to death from any cause. Participants alive at the last follow-up are censored on that date.	From randomization through 5 years after surgery
Cumulative incidence of para-aortic lymph node region recurrence	Recurrence involving the No. 16a2 or No. 16b1 region is determined by imaging, pathology, or clinical evidence. The cumulative incidence will be estimated with death without para-aortic recurrence treated as a competing event, and recurrence patterns will be summarized.	From randomization through 5 years after surgery
R0 resection rate	The percentage of randomized participants with microscopically negative proximal, distal, and applicable circumferential or other resection margins.	At definitive postoperative pathological assessment, generally within 30 days after surgery
Pathological complete response rate	The percentage of participants with no residual viable tumor in the gastric primary tumor and all evaluated lymph nodes, defined as ypT0N0.	At definitive postoperative pathological assessment, generally within 30 days after surgery
Number of examined and metastatic regional lymph nodes	Regional lymph nodes will be recorded by station, including the number examined and the number with pathologically confirmed metastasis.	At definitive postoperative pathological assessment, generally within 30 days after surgery
Pathological positivity rate of No. 16 para-aortic lymph nodes in the experimental arm	Among participants assigned to D2 lymphadenectomy plus para-aortic lymph node dissection who have an evaluable No. 16 specimen, the percentage with at least one pathologically metastatic No. 16 lymph node and the numbers examined and metastatic will be reported.	At definitive postoperative pathological assessment, generally within 30 days after surgery
Operative time	Operative time in minutes, measured according to the institutional anesthesia and operative record, will be summarized by randomized group.	During the assigned surgery
Estimated intraoperative blood loss	Estimated blood loss in milliliters, as recorded in the operative and anesthesia records, will be summarized by randomized group.	During the assigned surgery
Postoperative length of hospital stay	The number of days from surgery to hospital discharge will be summarized by randomized group.	From surgery until discharge, generally within 30 days after surgery
Rate of Clavien-Dindo grade III or higher postoperative complications	The percentage of participants with at least one postoperative complication requiring surgical, endoscopic, or radiologic intervention, intensive care for organ dysfunction, or resulting in death, classified as Clavien-Dindo grade III or higher.	Within 30 days after surgery
All-cause postoperative mortality	The percentage of participants who die from any cause within 90 days after surgery.	Within 90 days after surgery

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Principal Investigator: Hao Xu, MD, PhD, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): October 31, 2031
• Study Completion (Estimated): December 31, 2034

Study Registration Dates

• First Submitted: October 28, 2026
• First Submitted That Met QC Criteria: October 28, 2026
• First Posted (Actual): November 3, 2026

Study Record Updates

• Last Update Posted (Actual): November 3, 2026
• Last Update Submitted That Met QC Criteria: October 28, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: Gastric Cancer; Chemoimmunotherapy; D2 Lymphadenectomy; Para-Aortic Lymph Node Metastasis; No. 16 Lymph Node; Para-Aortic Lymph Node Dissection; Randomized Exploratory Trial
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Surgical Procedures, Operative; Digestive System Surgical Procedures; Gastrectomy
• Other Study ID Numbers: FNMU-PAN-SELECT-2026-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Due to ethic restriction.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No