A Phase III, Prospective, Multicenter, Randomized Controlled Trial of the Prognostic Impact of Laparoscopic Staging Laparoscopy in Patients With Clinical Stage III Gastric Cancer
Phase: NA
Conditions: Gastric Cancer (GC), Gastric Adenocarcinoma
Sponsor: Tianjin Medical University Cancer Institute and Hospital

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A Prospective, Multicenter, Randomized Controlled Phase III Study on the
Prognostic Impact of Laparoscopic Staging in Patients with Clinical Stage III
Gastric Cancer
I. Basic Study Information
II. (I) Study Title
A Prospective, Multicenter, Randomized Controlled Phase III Study on the
Prognostic Impact of Laparoscopic Staging in Patients with Clinical Stage III
Gastric Cancer
(II) Protocol Number
CGCA202501
(III) Study Period
Enrollment Period: December 1, 2025 – December 31, 2026
Intervention
Period:
From
randomization
to
treatment
completion
(as
determined per each center's treatment protocol)
Followup Period: From treatment completion to December 31, 2029 (minimum
3year followup)
(IV) Sponsor
Tianjin Medical University Cancer Institute & Hospital
(V) Principal Investigator
Professor Liang Han, Department of Gastric Oncology, Tianjin Medical
University Cancer Institute & Hospital
Participating Institutions
See Appendix

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Study Summary
Study Title
A Prospective, Multicenter, Randomized Controlled Phase III
Study on the Prognostic Impact of Laparoscopic Staging in
Patients with Clinical Stage III Gastric Cancer
Study
Objectives
Primary Objective:
To compare 3year Overall Survival (OS) between the two
groups.
Secondary Objectives:
To evaluate the detection rate of peritoneal metastasis by
laparoscopic staging in the experimental group.
To evaluate the R0 resection rate after conversion surgery in
both groups.
To compare the surgical conversion rate (change from original
treatment plan) between the two groups.
Study Design
Prospective, multicenter, randomized controlled Phase III
clinical study, 1:1 randomization
Experimental Group: Peritoneal metastasis (CY+ or P+),
cT4aN+, or M1: Systemic therapy + NIPS ± HIPEC or
HIPEC ；No
peritoneal
metastasis,
cT3N+:
Systemic
neoadjuvant therapy.
Control Group: Systemic therapy alone.
Inclusion
Criteria
1.
Pathologically
confirmed:
Histologically
proven
adenocarcinoma of the stomach or gastroesophageal junction
(Siewert type II/III).
2. Definitive pathological markers: Documented status of
HER2, MMR, CPS (PDL1) score, and Claudin 18.2.
3. Clinical stage: cT3/4aN+M0 based on contrastenhanced CT,
endoscopic ultrasound, or MRI (AJCC 8th edition):
cT3: Tumor invades through the muscularis propria into the
subserosa.
cT4a: Tumor penetrates the visceral peritoneum.
cN+:
Regional
lymph
node
metastasis
(intraabdominal
regional nodes such as perigastric, celiac, or common hepatic

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artery lymph nodes: shortaxis diameter > 8 mm; other nodes
such as retroperitoneal or paraaortic lymph nodes: shortaxis
diameter > 10 mm).
No evidence of peritoneal metastasis on imaging modalities
other than laparoscopic exploration.
4. Age: 18 to 75 years, regardless of sex.
5. Performance status: ECOG score 0–2 (fully active to
ambulatory and capable of selfcare but unable to work).
6. Life expectancy: Estimated survival ≥6 months.
7.
Surgical
fitness:
Adequate
cardiopulmonary
functional
reserve and no contraindications to anesthesia.
8. Informed consent: Voluntary participation with written
informed consent obtained.
Exclusion
Criteria
1. Gastric outlet obstruction: Requiring gastrojejunostomy due
to obstructive symptoms.
2. Distant metastasis: Evidence of peritoneal, mesenteric, or
omental metastasis and/or obvious ascites on imaging, or distant
organ metastasis.
3. Other malignancies: History of or concurrent other malignant
tumors (except curatively treated basal cell carcinoma of the
skin).
4. Organ dysfunction: Severe cardiac insufficiency (NYHA
class III–IV), hepatic dysfunction ChildPugh class C, or
creatinine clearance < 30 mL/min.
5. Contraindications to laparoscopy: History of severe
intraabdominal adhesions, coagulation disorders (INR > 1.5 or
platelet count < 50 × 10⁹/L), or severe intestinal obstruction.
6. Special populations: Pregnant or lactating women, or those

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unable to interrupt breastfeeding.
7. Mental status: Cognitive impairment or psychiatric disorders
that preclude compliance with followup.
Efficacy
Evaluation
and Outcome
Measures
Efficacy Evaluation and Outcome Measures
1. Efficacy Evaluation:
Detection
rate
of
peritoneal
metastasis
by
laparoscopic
exploration
R0 resection rate after conversion surgery
Surgical conversion rate (change from original treatment plan)
1year, 2year, and 3year overall survival (OS) rates
2. Followup Observation:
3year followup period
3. Assessment Methods:
Laboratory examinations
Imaging examinations
Sample Size
A total of 968 patients are planned for enrollment, with 484
patients in the experimental group and 484 patients in the
control group, including a 20% dropout rate.
Treatment
Regimen
Experimental Group:
Patients undergoing laparoscopic exploration found to have
peritoneal metastasis (CY+ or P+), cT4aN+, cT4bN+, or M1
disease are recommended to receive:
Systemic therapy + NIPS ± HIPEC or HIPEC alone
In cases without peritoneal metastasis and for patients with
cT3N+:

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Systemic neoadjuvant therapy, with imaging evaluation every
3–4 cycles followed by planned surgery
Nota bene: For the experimental group, systemic therapy +
NIPS ± HIPEC or HIPEC is also recommended following
conversion therapy surgery.
NIPS Dosing (reference: PHOENIXGC study [10]):
Intraperitoneal paclitaxel 20 mg/m² + IV paclitaxel 50 mg/m²
(days 1, 8); q3w
Or nabpaclitaxel: IP nabpaclitaxel 80 mg/m² + IV nabpaclitaxel
180 mg/m² (day 1); q3w
HIPEC Dosing:
Paclitaxel 40–100 mg/m² recommended
If combined with NIPS: 2–4 HIPEC sessions recommended
If HIPEC alone: 4 sessions recommended
Control Group:
No laparoscopic exploration
Upfront systemic therapy without intraperitoneal drug
administration
Systemic Therapy (applicable to both groups):
Treatment regimen selected based on molecular marker testing
results and in accordance with gastric cancer treatment
guidelines
No limit on the number of neoadjuvant or conversion therapy
cycles

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Imaging evaluation required every 3–4 cycles
Surgical Treatment (applicable to both groups):
Surgery performed according to each center's treatment
assessment and plan
Intraoperative exploration determines:
1. If R0 resection is achievable: D2 or D2+ radical
gastrectomy
2. If partial response achieved but R0 resection remains
infeasible: Conclude exploration, continue conversion therapy
with original regimen or secondline therapy
Postsurgery, maintenance therapy with the original regimen
recommended until disease progression
Study
Timeline
Patient enrollment is planned to be completed within 1–2 years,
with a followup period of 3 years starting from the enrollment
of the last patient.
II. Study Background
Study Background
According to the latest epidemiological data, gastric cancer is the fifth most
common malignancy worldwide, with approximately 960,000 new cases and
720,000 deaths in 2022 [1]. In China, gastric cancer ranks fifth in incidence and
third in mortality [2]. A largescale national realworld study including 220,000
patients showed that advances in early diagnosis and staging techniques and the
application of novel therapies have significantly improved 5year survival rates

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in gastric cancer patients, while also revealing substantial gaps in treatment
standardization across hospitals in China [3]. Among surgical gastric cancer
cases, clinical stage III accounts for approximately 70% (China Gastrointestinal
Surgery Alliance data). These patients present with tumor invasion depth
reaching the subserosa or penetrating the serosa, with regional lymph node
metastasis. Conventional treatment strategies rely on clinical staging (based on
CT/MRI imaging), which has a detection rate of only 20%–30% for peritoneal
micrometastases (diameter <5 mm) [4]. Thinslice contrastenhanced CT is the
most commonly used preoperative modality for detecting peritoneal metastasis.
Although CT has high specificity for diagnosing peritoneal metastasis, its
sensitivity is only approximately 50%, and 10%–30% of advanced gastric
cancer patients with no evidence of peritoneal metastasis on preoperative CT
are found to have occult peritoneal metastasis during intraoperative exploration
[5].
Diagnostic laparoscopy + peritoneal cytology + peritoneal nodule biopsy is the
most reliable method for peritoneal staging. It has high sensitivity and
specificity, particularly for detecting clinically occult peritoneal metastasis, and
allows relatively accurate assessment of the Peritoneal Cancer Index (PCI) and
response to neoadjuvant therapy. Cohort studies including all stages of gastric
cancer have shown that 14%–17% of patients have macroscopically visible
peritoneal metastases, and up to 41% have positive cytology [6]. The core
purpose of laparoscopic staging is to precisely identify peritoneal metastasis,
thereby enabling targeted intraperitoneal therapy in addition to systemic
treatment. However, there is currently no highlevel evidence regarding the
prognostic impact of laparoscopic staging. The 2025 CSCO Gastric Cancer
Diagnosis and Treatment Guidelines classify diagnostic laparoscopy staging as

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Class IB evidence, with no support from Phase III studies. The 2025 CACA
Integrated Gastric Cancer Diagnosis and Treatment Guidelines indicate that
indications for laparoscopic exploration remain controversial.
The clinical challenge of peritoneal metastasis in gastric cancer lies in its high
incidence and extremely poor prognosis. The peritoneum, as a metastatic site, is
protected by the plasmaperitoneal barrier, which limits penetration of
systemically administered drugs, leading to poor efficacy of conventional
systemic chemotherapy. Current intraperitoneal treatment modalities mainly
include three categories:
1. Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Chemotherapy
solution at approximately 42°C is perfused intraoperatively or postoperatively,
leveraging thermal cytotoxicity and drug synergy to inhibit metastasis. A
Chinese multicenter retrospective study showed that in gastric cancer patients
with peritoneal metastasis, 3year OS was 18.4% (95% CI, 12.3%–24.5%) in the
HIPEC + chemotherapy group vs. 10.1% (95% CI, 5.4%–14.8%) in the
chemotherapyalone group [7].
2. Intraperitoneal Port Chemotherapy: A chemotherapy port is implanted for
regular perfusion of roomtemperature drugs (e.g., paclitaxel, cisplatin). This
method is convenient but carries risks of catheterrelated complications [8].

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3. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): Drugs are
aerosolized for uniform distribution within the abdominal cavity, providing
excellent coverage of small lesions but requiring specialized equipment and
with limited clinical application [9].
Neoadjuvant Intraperitoneal and Systemic Chemotherapy (NIPS), as an
innovative approach, achieves high local drug concentrations via direct
intraperitoneal administration (e.g., paclitaxel concentration in the peritoneal
cavity can reach 1000 times that in plasma), combined with systemic
chemotherapy to control distant metastases. The Japanese PHOENIXGC study
[10] demonstrated that the NIPS group (IP + IV paclitaxel plus S1) had a
median survival extension of 3.4 months compared to the control group
(cisplatin plus S1) (17.7 months vs. 14.3 months, P=0.022), and 3year survival
rate increased by 15.9% (21.9% vs. 6.0%). The Chinese DRAGON01 study [11]
confirmed that the NIPS group achieved a median OS of 19.4 months, 5.5
months longer than the IV chemotherapyalone group, with a 21.9% increase in
conversion surgery rate (57% vs. 35.1%), and patients with R0 resection
achieved a median OS of 35.5 months. Compared with other methods, NIPS
offers advantages including proven efficacy, high safety, broad applicability,
and operational flexibility, providing a new therapeutic option for patients with
peritoneal metastasis.
This study aims to determine, through a multicenter randomized controlled
design, the impact of precision treatment guided by laparoscopic staging on
overall survival (OS), surgical conversion rate, and peritoneal metastasis rate in
patients with clinical stage III gastric cancer, thereby providing evidence for
precision staging and treatment decisionmaking.

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References
[1] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022:
GLOBOCAN estimates of incidence and mortality worldwide for 36
cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229263.
[2] Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China,
2022. J Natl Cancer Cent. 2024;4(1):4753.
[3] Chen Y, Jia K, Xie Y, et al. The current landscape of gastric cancer and
gastroesophageal junction cancer diagnosis and treatment in China: a
comprehensive
nationwide
cohort
analysis.
J
Hematol
Oncol.
2025;18(1):42.
[4] Jacquet P, Sugarbaker PH. Peritonealplasma barrier. Cancer Treat Res.
1996;82:5363.
[5] Kim SJ, Kim HH, Kim YH, et al. Peritoneal metastasis: detection with 16 or
64detector row CT in patients undergoing surgery for gastric cancer.
Radiology. 2009;253(2):407415.
[6] Thomassen I, van Gestel YR, van Ramshorst B, et al. Peritoneal
carcinomatosis of gastric origin: a populationbased study on incidence,
survival and risk factors. Int J Cancer. 2014;134(3):622628.
[7] Lei Z, Wang J, Li Z, et al. Hyperthermic intraperitoneal chemotherapy for
gastric cancer with peritoneal metastasis: A multicenter propensity
scorematched cohort study. Chin J Cancer Res. 2020;32(6):794803.
[8] Kobayashi D, Kodera Y. Intraperitoneal chemotherapy for gastric cancer
with peritoneal metastasis. Gastric Cancer. 2017;20(Suppl 1):111121.
[9] Solaß W, Hetzel A, Nadiradze G, Sagynaliev E, Reymond MA. Description
of a novel approach for intraperitoneal drug delivery and the related
device. Surg Endosc. 2012;26(7):18491855.
[10] Ishigami H, Fujiwara Y, Fukushima R, et al. Phase III Trial Comparing
Intraperitoneal and Intravenous Paclitaxel Plus S1 Versus Cisplatin Plus

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S1 in Patients With Gastric Cancer With Peritoneal Metastasis:
PHOENIXGC Trial. J Clin Oncol. 2018;36(19):19221929.
[11] Yan C, Lu S, Zhu ZG. Clinical value and implementation strategy of
neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) for
gastric
cancer
peritoneal
metastasis.
Chin
J
Gastrointest
Surg.
2025;28(05):481486.
[12] Li HJ, Chen XL, Hu JK. Application and clinical value of the "West China
FourStep Method" of laparoscopic exploration in diagnosing peritoneal
metastasis
of
gastric
cancer.
Chin
J
Gastrointest
Surg.
2025;28(05):508513.
[13] Ikoma N, Chen HC, Wang X, et al. Patterns of Initial Recurrence in Gastric
Adenocarcinoma in the Era of Preoperative Therapy. Ann Surg Oncol.
2017;24(9):26792687.
III. Study Objectives
(I) Primary Objective
1. To compare 3year Overall Survival (OS) between the two groups.
(II) Secondary Objectives
1. To evaluate the detection rate of peritoneal metastasis by laparoscopic
staging in the experimental group.
2. To evaluate the R0 resection rate after conversion surgery in both groups.
3. To compare the surgical conversion rate (change from original treatment
plan) between the two groups.
IV. Study Design
(I) Overall Design

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Study Type: Prospective, randomized controlled, multicenter Phase III
clinical study
Group Allocation: Parallel assignment, Experimental group (n=[484]) vs.
Control group (n=[484])
Interventions:
Experimental Group: Laparoscopic exploration reveals peritoneal
metastasis (CY+ or P+), cT4aN+, cT4bN+, or M1: Systemic therapy + NIPS ±
HIPEC or HIPEC. No peritoneal metastasis, cT3N+: Systemic neoadjuvant
therapy. Specific drug regimens and surgical plans are determined according to
guidelines (CSCO, CACA) and each center's experience.
Control Group: No laparoscopic exploration. Systemic therapy
recommended based on imaging staging. Each center develops specific drug
regimens and surgical plans according to current guidelines (CSCO, CACA)
and their own experience.
(II) Randomization Method
1. Stratification Factor: Study center (to avoid center bias)
2. Randomization Method: 1:1 ratio between experimental and control groups
using a random number table.
(III) Blinding Design
Investigator Unblinded: Surgeons are aware of group assignment
(experimental group requires laparoscopic exploration).
Outcome Assessor Blinded: An independent thirdparty team assesses OS.
Statistical Analysis Blinded: Grouping information is concealed during
statistical analysis.
(IV) Study Period

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Patient Enrollment Period: All clinical research centers are expected to
complete patient enrollment within one year of study initiation.
Followup Period: The enrollment of the first patient marks the start of
followup. The primary endpoint followup ends 3 years after the last patient's
surgery.
V. Study Flowchart
VI. Study Population
All patients who meet all inclusion criteria and none of the exclusion criteria are
eligible for enrollment in this study.
(I) Inclusion Criteria
1. Pathologically confirmed: Histologically proven adenocarcinoma of the
stomach or gastroesophageal junction (Siewert type II/III).

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2. Definitive pathological markers: Documented status of HER2, MMR, CPS
(PDL1) score, and Claudin 18.2.
3. Clinical stage: cT3/4aN+M0 based on contrastenhanced CT, endoscopic
ultrasound, or MRI (AJCC 8th edition):
cT3: Tumor invades through the muscularis propria into the subserosa.
cT4a: Tumor penetrates the visceral peritoneum.
cN+: Regional lymph node metastasis (intraabdominal regional nodes such
as perigastric, celiac, or common hepatic artery lymph nodes: shortaxis
diameter > 8–10 mm; other nodes such as retroperitoneal or paraaortic lymph
nodes: shortaxis diameter > 10 mm).
No evidence of peritoneal metastasis on imaging modalities other than
laparoscopic exploration.
4. Age: 18 to 75 years, regardless of sex.
5. Performance status: ECOG score 0–2 (fully active to ambulatory and capable
of selfcare but unable to work).
6. Life expectancy: Estimated survival ≥6 months.
7. Surgical fitness: Adequate cardiopulmonary functional reserve and no
contraindications to anesthesia.
8. Informed consent: Voluntary participation with written informed consent
obtained.
(II) Exclusion Criteria
1. Gastric outlet obstruction: Requiring gastrojejunostomy due to obstructive
symptoms.
2. Distant metastasis: Evidence of peritoneal, mesenteric, or omental metastasis
and/or obvious ascites on imaging, or distant organ metastasis.

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3. Other malignancies: History of or concurrent other malignant tumors (except
curatively treated basal cell carcinoma of the skin).
4. Organ dysfunction: Severe cardiac insufficiency (NYHA class III–IV),
hepatic dysfunction ChildPugh class C, or creatinine clearance < 30 mL/min.
5. Contraindications to laparoscopy: History of severe intraabdominal
adhesions, coagulation disorders (INR > 1.5 or platelet count < 50 × 10⁹/L), or
severe intestinal obstruction.
6. Special populations: Pregnant or lactating women, or those unable to
interrupt breastfeeding.
7. Mental status: Cognitive impairment or psychiatric disorders that preclude
compliance with followup.
(III) Discontinuation/Withdrawal Criteria
1. Poor compliance: Failure to complete ≥50% of protocolspecified followup
visits or examinations.
2. Severe AE: Occurrence of studyrelated Grade 3 or higher adverse events
(e.g., intestinal perforation due to laparoscopic exploration).
3. Voluntary withdrawal: Patient submits a written request to withdraw from
the study.
VII. Sample Size Calculation
(I) Assumptions
Based on realworld multicenter data from China [3], the 3year OS in the control
group is estimated at 48%. The experimental group is expected to achieve a
10% improvement in 3year OS. Sample size calculation uses a two independent
samples survival comparison (Logrank test, approximated as comparison of two
proportions). Significance level α = 0.05 (twosided), power = 80% (β = 0.2).
Calculation Formula:

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Where:
p₁ = 0.48 (control group)，p₂ = 0.58 (experimental group)，Zα/2 = 1.96
(α=0.05, twosided)，Zβ = 0.84 (β=0.2)，p₁(1p₁) = 0.48 × 0.52 = 0.2496，
p₂(1p₂) = 0.58 × 0.42 = 0.2436，p₁(1p₁) + p₂(1p₂) = 0.2496 + 0.2436 = 0.4932，
(p₁ p₂)² = (0.48 0.58)² = 0.01，(Zα/2 + Zβ)² = (1.96 + 0.84)² = 2.80² = 7.84，n
= 7.84 × 0.4932 / 0.01 = 3.866688 / 0.01 = 386.67
Therefore, approximately 387 patients are required per group, totaling 774
patients.Considering a 20% dropout rate, the total sample size is adjusted:
Rounded up, the total sample size is 968 patients, with 484 patients per group.
(II) Interim Analysis
An interim analysis will be conducted by the Independent Data Monitoring
Committee (IDMC) for efficacy and safety assessment when 50% of events
(approximately 484 OS events) have occurred.
VIII. Treatment Regimen
(I) Experimental Group
Patients undergoing laparoscopic exploration found to have peritoneal
metastasis (CY+ or P+), cT4aN+, cT4bN+, or M1 disease are recommended to
receive: Systemic therapy + NIPS ± HIPEC or HIPEC. In cases without
peritoneal metastasis and for patients with cT3N+, systemic neoadjuvant
therapy is recommended, with specific drug regimens and planned surgery
determined according to guidelines (CSCO, CACA) and each center's
experience. Notably, for the experimental group, systemic therapy + NIPS ±
HIPEC or HIPEC is also recommended following conversion therapy surgery.

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Laparoscopic Exploration Procedure (West China FourStep Method
recommended) [12]:
1. Exploration of anterior abdominal wall and visceral surfaces: Patient in
supine position. Follow a clockwise, "O"shaped route to sequentially explore
bilateral diaphragmatic domes, ligamentum teres hepatis, falciform ligament,
and anterior abdominal wall. Follow an "S"shaped route to sequentially explore
the liver, transverse colon, left abdominal wall, left paracolic gutter, descending
colon, lower abdominal wall, small intestine, right abdominal wall, right
paracolic gutter, and ascending colon.
2. Exploration of pelvic cavity and visceral surfaces: Patient in
Trendelenburg position. Sequentially explore the pelvic cavity and visceral
surfaces, focusing on bilateral iliac fossae, bladder base, and peritoneal
reflection; in female patients, also examine bilateral adnexa and uterine fundus
for suspicious lesions.
3. Exploration of mesentery and small intestine: Patient returned to supine or
reverse Trendelenburg position. Explore the transverse colon, small intestinal
mesentery, and mesenteric root.
4. Exploration of stomach and perigastric region: Patient remains supine.
Explore the primary gastric lesion and perigastric involvement, focusing on the
lesser omentum, hepatorenal recess, and other adjacent structures for tumor
invasion. A 10 mm trocar is placed at the umbilicus under general anesthesia;
the laparoscope is inserted to sequentially examine the liver surface, pelvic
cavity, peritoneum, perigastric area, and omentum.
Peritoneal Biopsy: For suspicious nodules (diameter ≥2 mm), biopsy from at
least two sites is recommended. For highrisk biopsy sites such as the
diaphragmatic dome, if peritoneal metastasis is highly suspected, photographic
documentation may suffice without biopsy.

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Peritoneal Free Cancer Cell Cytology Procedure:
(1) Lavage Fluid Collection: It is recommended to use >250 ml of warm
saline for sequential irrigation, avoiding direct irrigation of the primary tumor
and protecting the serosal surface. The irrigation sequence may proceed from
bilateral diaphragmatic domes, suprahepatic, subhepatic, greater omentum,
bilateral paracolic gutters, to the uterovesical and rectouterine pouches.
Collect >100 ml of lavage fluid from the bilateral subphrenic spaces, subhepatic
space, and pouch of Douglas for cytological examination. If sufficient ascites
(>200 ml) is present, ascitic fluid may be directly collected for examination.
PCI Score: The abdominal cavity is divided into 13 regions: Central, Right
Upper, Epigastrium, Left Upper, Left Flank, Left Lower, Pelvis, Right Lower,
Right Flank (9 regions), and Proximal Jejunum, Distal Jejunum, Proximal Ileum,
Distal Ileum (4 regions). Peritoneal lesion size score (LS) is graded as follows:
LS 0: No tumor seen; LS 1: Tumor size ≤0.5 cm; LS 2: Tumor size 0.5–5 cm;
LS 3: Tumor size >5 cm or confluent. Each region is assigned a score of 0–3
based on the intraoperative lesion size. A total of 13 regions are examined
intraoperatively, and the LS score for each region is determined. The total PCI
score (range 0–39) is the sum of LS scores for all 13 regions.

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(II) Stage Determination
Clinical stage is revised based on exploration findings. If peritoneal
metastasis (CY+ or P+) or micrometastases to other organs (e.g., liver
metastases) are detected, the patient is classified as M1. Systemic therapy +
NIPS or HIPEC or NIPS+HIPEC is recommended. For T4b, refer to the CSCO
2025 guidelines; advanced firstline conversion therapy is recommended.
(1) Intraperitoneal Therapy
HIPEC Therapy
Drainage Catheter Placement: Two drainage catheters placed in the upper
abdomen (tip positioned in the left subphrenic space and hepatorenal recess)
serve as inflow catheters. Two drainage catheters placed in the lower abdomen
(tip positioned in bilateral pelvic floors) serve as outflow catheters. Catheters
are generally placed along the anterior axillary line. Inflow catheters should
ideally be positioned near tumor deposits, and outflow catheters away from
tumorbearing areas.
Temperature Setting: 43°C.
Perfusion Duration: 60 minutes.

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Perfusate Volume: Sufficient to achieve abdominal filling and maintain
unobstructed circulation.
Perfusate: Normal saline.
Drug and Dosage: Paclitaxel, 40–100 mg/m², is recommended.
Timing: First HIPEC session to begin within 24 hours postexploration.
Temperature: 43°C, Duration: 60 minutes. A minimum interval of 24 hours
between HIPEC sessions is required.
Treatment Course: If combined with NIPS, 2–4 HIPEC sessions are
recommended; if HIPEC alone, 4 sessions are recommended.
Intraoperative Medication: Intravenous sedatives may be administered
during treatment if the patient is intolerant, with dosage adjusted according to
patient response. Fluid resuscitation should be guided by vital sign monitoring.
Intraoperative Monitoring: During HIPEC, monitor blood pressure, body
temperature, pulse, urine output, respiration, oxygen saturation, and check for
inflow catheter blockage and outflow patency. Record these parameters in the
CRF at time 0, 30 minutes, 60 minutes during perfusion, and 1 hour
postperfusion. If symptoms such as profuse sweating or tachycardia (>100 bpm)
occur, hypovolemia should be ruled out, and fluid resuscitation intensified. If
respiratory or oxygen saturation abnormalities occur, monitor anesthetic drugs
and perfusate volume, and consider discontinuing treatment if necessary.
NIPS Therapy
Subcutaneous Implantation of Intraperitoneal Chemotherapy Port
The subcutaneous implantation site for the intraperitoneal chemotherapy
port is typically at McBurney's point in the right lower quadrant. Depending on
the patient's subcutaneous fat thickness, some adipose tissue may be excised.
The base of the port is secured to the anterior rectus sheath with a single suture
through a fixation hole. The intraperitoneal catheter is placed into the pelvic
cavity. Strict aseptic technique should be maintained throughout the procedure

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to prevent postoperative wound infection.。
NIPS Dosing: Reference PHOENIXGC study [10] dosing. Experimental group
receives: Intraperitoneal paclitaxel 20 mg/m² and intravenous paclitaxel 50
mg/m² (days 1, 8); q3w. Alternatively, nabpaclitaxel: Intraperitoneal
nabpaclitaxel 80 mg/m² and intravenous nabpaclitaxel 180 mg/m² (day 1); q3w.
(3) Systemic Therapy (applicable to both experimental and control groups):
Treatment regimen is selected based on molecular marker testing results and in
accordance with gastric cancer treatment guidelines (including NCCN, CSCO,
CACA guidelines) or participation in clinical trials. Detailed treatment regimens
and doses should be recorded. There is no limit on the number of neoadjuvant
or conversion therapy cycles; imaging evaluation is required every 3 to 4 cycles.
(4) Surgical Treatment (applicable to both experimental and control groups):
Surgery is performed according to each center's treatment assessment and plan.
Intraoperative exploration will determine the following: 1) If R0 resection is
achievable, D2 or D2+ radical gastrectomy is performed; 2) If partial response
is achieved but R0 resection remains infeasible, the procedure is concluded, and
conversion therapy with the original regimen or secondline therapy is continued.
Postsurgery, maintenance therapy with the original regimen is recommended
until disease progression.

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(II) Control Group
No laparoscopic exploration is performed. No intraperitoneal drug
administration. Based on imaging staging, neoadjuvant therapy is recommended,
avoiding immediate surgery. Each center develops specific treatment plans
according to current guidelines (CSCO, CACA) and their own experience.
Participation in various clinical drug trials is permitted based on actual
circumstances.
Surgical Treatment: After neoadjuvant therapy, each center develops a surgical
treatment plan based on assessment results. Intraoperative exploration will
determine:
1) If R0 resection is achievable, D2 radical gastrectomy is performed;
2) If partial response is achieved but R0 resection remains infeasible, the
procedure is concluded, and conversion therapy with the original regimen or
secondline therapy is continued.
VIII. Study Endpoints
(I) Primary Endpoint
1. 3Year OS: Time from randomization to death from any cause.
(II) Secondary Endpoints
1. Peritoneal Metastasis Detection Rate in the Experimental Group:
Peritoneal metastasis detection rate = (Number of patients with peritoneal
metastasis detected by laparoscopic exploration / Total number of patients in the
experimental group) × 100%.

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2. R0 Resection Rate After Conversion Surgery in Both Groups:
Among
patients with peritoneal metastasis who receive conversion therapy, the
proportion of patients who undergo R0 resection.
3. Surgical Conversion Rate:
In this study, surgical conversion rate refers to
the proportion of patients for whom a definitive surgical treatment plan
(including surgical timing, procedure type, etc.) established at enrollment is
altered during the treatment course, preventing the planned surgery from being
performed as intended, thereby changing the treatment strategy.
Surgical
Conversion Rate = (Number of patients in the control or experimental group
whose original treatment plan was changed / Total number of patients in that
group) × 100%.
Changes to the original treatment plan include, but are not
limited to:
Abandoning surgery, switching to other treatments such as
chemotherapy alone, adiotherapy, targeted therapy, or immunotherapy;
Delaying surgery, administering other adjuvant therapies first, and reassessing
operability after disease improvement;
Changing the surgical approach, e.g.,
adjusting from planned radical surgery to palliative surgery.
IX. Followup Plan
(I) Followup Schedule
Phase
Time Point
Followup Content
Treatment
Period
Before each
treatment
cycle
Physical examination, blood routine,
liver/kidney function, tumor markers
(CEA/CA199),
recording of treatmentrelated adverse
reactions
PostSurgery /
Within 1
month
Baseline CT/MRI (chest/abdomen/pelvis),
wound healing assessment, etc.
End of

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Phase
Time Point
Followup Content
Treatment
Followup
Period
Years 12:
Every 3
months
Clinical examination, tumor markers,
chest/abdominal CT (every 6 months),
inquiry about symptoms of
recurrence/metastasis
Years 35:
Every 6
months
Clinical examination, tumor markers,
chest/abdominal CT (annually),
confirmation of survival status
PostTreatment
Annually
(after 5 years)
Survival status confirmation (telephone
followup)
(II) Endpoint Event Confirmation
OS Event: Confirmed through hospital medical records, death certificate, or
notification by family members.
X. Data Collection and Management
(I) Data Collection Tools
1. Electronic Case Report Form (eCRF): Data entered via EDC system,
including:
Baseline Data: Demographics, medical history, imaging reports, pathology
results
Treatment Records: Laparoscopic procedure details (experimental group),
surgical method, chemotherapy regimen, radiotherapy dose
Followup Data: Survival status, adverse events, quality of life scores, etc.
2. Imaging and Photographic Documentation
1. Retain all preoperative CT images for all enrolled patients.

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2. Preserve highquality intraoperative images of peritoneal metastasis sites
and complete unedited video recordings of the entire surgical procedure.
PCI scoring requires division into 13 regions. Retain images of metastatic
regions, ensuring that the PCI score can be clearly calculated from the retained
images and is consistent with the score recorded in the CRF.
Example: Preoperative cT4aN0M0, exploratory staging reveals peritoneal
metastasis, PCI 6, liver
metastasis?

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3. Postoperative Pathology Following D2 Lymph Node Dissection:
Postoperative TNM staging, number of lymph nodes dissected and number of
positive nodes per station, total number of nodes dissected, etc.
(II) Quality Control
Double Data Entry Verification: Key data (randomization date, endpoint event
dates) will be entered independently by two designated personnel. Consistency
rate must be ≥99%.
Database Lock: Following the final followup visit, the database will be locked
after review and confirmation by the IDMC.
XI. Quality Assurance
(I) Investigator Training

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Unified training will be conducted prior to the study initiation meeting.
Training content includes: a. Each center designates 1–2 senior attending
radiologists to determine TNM staging based on contrastenhanced CT or MRI.
b. Standardized laparoscopic exploration procedure (refer to West China
FourStep Method [12]). c. eCRF completion requirements and timelines. d.
Endpoint event determination criteria (AJCC 8th edition staging update
interpretation), assessed by the previously designated senior attending
radiologists.
(II) Site Monitoring
Routine Monitoring: Onsite monitoring will be conducted quarterly to verify
informed consent signing, CRF completeness, and specimen storage compliance.
Source Data Verification: 20% of cases will be randomly selected to verify
consistency between source medical records (surgical reports, imaging reports)
and eCRF data.
(III) Independent Data Monitoring Committee (IDMC)
Composition: 3 clinical oncologists, 1 biostatistician, 1 ethicist (none involved
in this study).
Responsibilities: Review safety data every 6 months. Recommend suspension
of enrollment if the incidence of laparoscopyrelated serious adverse events
exceeds 5%.
XII. Ethical Considerations
(I) Informed Consent Process
1. Investigators will explain the following to patients in lay language:

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Purpose of laparoscopic exploration (detection of micrometastases) and risks
(bleeding/infection rate approximately 12%).
Fairness of randomization; both groups receive guidelinerecommended
treatment.
2. Patients are permitted to withdraw from the study at any stage without
affecting subsequent medical care.
(II) Risk Mitigation
Laparoscopic exploration will be performed by associate chief physicians or
higher who have experience with ≥50 laparoscopic gastric cancer surgeries.
Serious adverse events (e.g., intestinal perforation) must be reported to the
Ethics Committee and the sponsor within 24 hours.
(III) Ethical Review
The study protocol must be approved by the Ethics Committee of each
participating center (approval number must be recorded in the CRF).
Protocol amendments (e.g., sample size adjustment) require resubmission for
ethical review.
XIII. Statistical Analysis Plan
(I) Baseline Analysis
Continuous variables: Independent samples ttest (normal distribution) or
Wilcoxon ranksum test (skewed distribution).
Categorical variables: Chisquare test or Fisher's exact test.

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(II) Efficacy Analysis
1. Survival Analysis:
KaplanMeier method to plot OS curves; Logrank test for betweengroup
differences.
Cox proportional hazards model to analyze independent prognostic factors
(including laparoscopic staging, T/N stage, treatment regimen, etc.).
2. Peritoneal Metastasis Rate: Chisquare test to compare differences between
the experimental group (intraoperative detection) and the control group
(followup detection).
(III) Safety Analysis
Treatmentrelated adverse events will be graded according to CTCAE Version
5.0. Betweengroup comparisons will use Fisher's exact test.
(IV) Software Tools
Statistical analysis will be performed using SAS version 9.4. Survival curves
will be generated using GraphPad Prism version 9.
XIV. Study Timeline
Phase
Time Period
Key Tasks
Preparation
Phase
2025.06–2025.12
①Complete ethical reviews and center
contracts
②Train study team
③Set up EDC system
Enrollment
Phase
2026.01–2027.12
①Monthly investigator meetings
(online)
②Quarterly enrollment progress

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Phase
Time Period
Key Tasks
reports
Follow-up
Phase
2026.04–2028.12
①Complete follow-up assessments per
schedule
②Semi-annual study data backup
Analysis Phase
2029.01–2029.03
①Data cleaning and database lock
②Complete statistical analysis report
Reporting
Phase
2029.04–2029.06
①Draft and submit study manuscript
②Hold results dissemination meeting
XV. Risk Assessment and Mitigation
(I) Major Risks and Countermeasures
Risk Type
Specific Issue
Mitigation Measures
Slow Accrual
< 2 patients enrolled per
center per month
①Increase number of
collaborating centers (planned
expansion to 20)
②Develop patient education
video (explaining advantages
of laparoscopy)
Missing Data
Follow-up dropout
rate > 20%
①Establish dedicated follow-
up team (telephone/home
visits)
②Analyze reasons for
dropout
Laparoscopic
Complications
Intraoperative bleeding
requiring conversion to
open surgery
①Preoperative coagulation
assessment
②Prepare hemostatic devices
(ultrasonic shears/vascular
clips)
Treatment
Heterogeneity
Significant inter-center
variation in
chemotherapy regimens
①Develop core chemotherapy
drug list (e.g., XELOX/SOX
regimens prioritized)

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Risk Type
Specific Issue
Mitigation Measures
②Periodic review of
treatment records
XVI. Post-Trial Provisions
(I) Data Archiving
- Original data (CRFs, imaging materials) will be stored in a biorepository
designated by the sponsor for 15 years.
- Anonymized data may be made available to academic institutions for
secondary analysis (subject to a data sharing agreement).
(II) Patient Follow-up
- After study conclusion, patients may opt to continue in each center's routine
follow-up system to provide ongoing survival status information.
(III) Results Dissemination
- Study results will be disseminated promptly through academic conferences
(e.g., ASCO/HICCO) and peer-reviewed journal publication.