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Overview and Recommendations
Background
- •Gastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer death. Surgical resection with curative intent is the mainstay for localized disease, with the goal of R0 resection and adequate lymphadenectomy. The management is stage-dependent: early gastric cancer (T1) may be amenable to endoscopic resection or limited surgery, while locally advanced disease (T2-4 or N+) requires D2 gastrectomy with perioperative chemotherapy.
- •The paradigm has shifted from surgery alone to multimodality therapy. In the West, perioperative chemotherapy (MAGIC trial: ECF; FLOT regimen) improved overall survival (HR 0.75). In Asia, adjuvant S-1 (ACTS-GC) and neoadjuvant DOS followed by S-1 (PRODIGY) have become standards. The four pillars of modern management are adequate surgery, perioperative systemic therapy, lymphadenectomy, and ERAS.
- •Key surgical approaches include distal gastrectomy, total gastrectomy, and proximal gastrectomy. Lymphadenectomy extent (D1 vs D2) impacts outcomes: D2 dissection improves disease-specific survival compared with D1 (HR 0.807; NNT = 10). At least 16 lymph nodes should be assessed for adequate staging.
- •Laparoscopic gastrectomy has been validated in multiple randomized controlled trials (KLASS-01, KLASS-02, LOGICA, CLASS-02) as oncologically noninferior to open surgery, with equivalent 5-year overall survival and fewer early and late complications. Robotic gastrectomy offers technical advantages in lymph node dissection, particularly in narrow spaces.
- •Function-preserving techniques are emerging for early gastric cancer. Pylorus-preserving gastrectomy (PPG) for middle-third cT1N0 tumors reduces bile reflux, gallstone formation, and nutritional deficiencies. Sentinel node navigation surgery (LSNNS) allows stomach preservation in 74.8% of patients with cT1N0 tumors ≤3 cm, with 3-year disease-specific survival of 99.1%.
- •Enhanced recovery after surgery (ERAS) protocols have become standard of care. ERAS shortens hospital stay by ~1.8 days, reduces overall complications (OR 0.63), and improves 3-year overall survival in stage III gastric cancer (; HR 0.57). Core elements include prehabilitation, opioid-sparing analgesia, early oral feeding, and selective omission of abdominal drains.
Evaluation
- •Suspect gastric cancer in patients with dyspepsia, weight loss, early satiety, iron deficiency anemia, or hematemesis. Upper endoscopy with biopsy is the diagnostic gold standard; obtain multiple biopsies from the tumor and surrounding mucosa.
- •Stage with contrast-enhanced CT of chest, abdomen, and pelvis to assess T stage, nodal involvement, and distant metastases. Endoscopic ultrasound (EUS) is essential for accurate T and N staging, especially for early tumors where endoscopic resection or limited surgery may be considered.
- •Assess HER2, MSI, and PD-L1 status on biopsy specimens to guide perioperative and systemic therapy decisions. HER2-positive tumors benefit from trastuzumab; MSI-high tumors are highly responsive to immune checkpoint inhibitors.
- •For early gastric cancer (cT1N0), evaluate eligibility for endoscopic resection (differentiated type, ≤2 cm, no ulceration) or sentinel node navigation (tumor ≤3 cm). If not eligible, proceed to laparoscopic gastrectomy with D1+ lymphadenectomy.
- •For locally advanced disease (cT2-4 or N+), multidisciplinary discussion is essential. Consider neoadjuvant chemotherapy: FLOT (docetaxel 50 mg/m², oxaliplatin 85 mg/m², leucovorin 200 mg/m², 5-FU 2600 mg/m² as 24h infusion) every 2 weeks for 4 cycles in the West; DOS (docetaxel 50 mg/m², oxaliplatin 100 mg/m², S-1 80-120 mg/day) in Asia.
- •Assess patient fitness for surgery: performance status (ECOG 0-2), nutritional status (NRS-2002), and frailty (Geriatric 8 score). Use preoperative risk stratification tools such as the Comprehensive Inflammatory-Metabolic Index (CIMI) to predict complications (AUC 0.748).
- •Preoperative imaging should include assessment of left gastric vein (LGV) anatomy on CT. Type C LGV (dorsal to splenic artery) predicts a 17.9% risk of postoperative pancreatic fistula (POPF) vs 1.7% for other types.
- •Consider staging laparoscopy for patients at high risk of peritoneal metastases: signet ring histology, diffuse type, advanced T stage (T3/T4), or suspicious findings on CT. Laparoscopy can detect occult peritoneal disease and avoid unnecessary laparotomy.
- •For metastatic disease (stage IV), surgery is reserved for palliation of obstruction or bleeding. Systemic therapy is primary; trastuzumab plus chemotherapy for HER2-positive, nivolumab plus chemotherapy for PD-L1 CPS ≥5, and apatinib for third-line therapy.
- •Also consider fertility preservation in young patients with early gastric cancer. Pylorus-preserving gastrectomy or sentinel node navigation may be appropriate to maintain reproductive potential and long-term quality of life.
Management
- •For early gastric cancer (cT1N0, ≤3 cm): offer laparoscopic sentinel node navigation surgery (LSNNS) if available; stomach preservation achieved in 74.8% of patients. If not eligible, perform laparoscopic distal gastrectomy with D1+ lymphadenectomy. For middle-third tumors, consider pylorus-preserving gastrectomy (PPG) to reduce bile reflux and nutritional deficiencies.
- •For locally advanced gastric cancer (cT2-4 or N+): administer perioperative chemotherapy. In the West, use FLOT (docetaxel 50 mg/m², oxaliplatin 85 mg/m², leucovorin 200 mg/m², 5-FU 2600 mg/m² as 24h infusion) every 2 weeks for 4 cycles before and 4 cycles after surgery. In Asia, neoadjuvant DOS (docetaxel 50 mg/m², oxaliplatin 100 mg/m², S-1 80-120 mg/day) followed by D2 gastrectomy and adjuvant S-1 for 1 year.
- •Perform D2 lymphadenectomy (removal of perigastric nodes plus nodes along celiac axis, splenic artery, common hepatic artery, and left gastric artery). Aim for at least 16 lymph nodes. Use indocyanine green (ICG) fluorescence to improve nodal yield, especially after neoadjuvant therapy (mean difference 9.3 nodes) and in obese patients (mean difference 10.94 nodes).
- •For patients who undergo upfront surgery without neoadjuvant therapy and have T3+ or node-positive disease: administer adjuvant chemoradiation (45 Gy with 5-FU/leucovorin) per INT-0116. However, after D2 dissection, adjuvant chemotherapy alone (S-1 or SOX) is preferred based on CRITICS and ARTIST 2 data.
- •For stage III node-positive disease after D2: use S-1 (80-120 mg/day, 4 weeks on/2 weeks off for 1 year) plus docetaxel (JACCRO GC-07) to improve 3-year relapse-free survival from 50% to 66% (NNT=6). Alternatively, SOX (S-1 80-120 mg/day days 1-14, oxaliplatin 130 mg/m² day 1, every 3 weeks for 6 months) is effective (ARTIST 2).
- •For HER2-positive advanced disease: add trastuzumab (8 mg/kg loading, then 6 mg/kg every 3 weeks) to chemotherapy (capecitabine/cisplatin or 5-FU/oxaliplatin). After trastuzumab failure, anbenitamab plus chemotherapy improves PFS (HR 0.25) and OS (HR 0.29).
- •For MSI-high advanced disease: use pembrolizumab or nivolumab plus chemotherapy. Anti-PD-1 regimens yield OS HR 0.34 in MSI-high vs 0.85 in MSS (P interaction = 0.003).
- •Intraoperative management: use a pancreas-contactless technique to reduce POPF (from 7.6% to 0% in open gastrectomy). Perform intraoperative air-leak test for anastomotic integrity. Have a low threshold for conversion to open if bleeding is not rapidly controlled laparoscopically.
- •Postoperative ERAS: initiate early oral feeding (clear liquids on POD 1, soft diet by POD 3-4), multimodal opioid-sparing analgesia (subcostal TAP block, acetaminophen, COX-2 inhibitors), early mobilization, and selective omission of abdominal drains. Discharge criteria: tolerating oral intake, pain controlled with oral analgesics, afebrile, ambulating independently.
- •Monitor for complications: pancreatic fistula (POPF) - manage with drainage, nil per os, parenteral nutrition, somatostatin analogues; anastomotic leak - endoscopic stenting or percutaneous drainage; reoperation for large defects. Use preoperative LGV anatomy to stratify POPF risk.
- •Avoid: non-dihydropyridine CCBs (diltiazem, verapamil) - exacerbate gastroparesis; routine abdominal drainage - increases complications (OR 0.53 for omission); routine radiotherapy after D2 dissection - no benefit (ARTIST 2); ELFE, FAMTX, or FEMTX regimens - no survival benefit; adjuvant nivolumab/ipilimumab for ypN+/R1 after neoadjuvant chemo - inferior to chemotherapy (VESTIGE).
- •Refer to medical oncology for perioperative therapy and management of advanced disease. Refer to radiation oncology if adjuvant chemoradiation is indicated (inadequate lymphadenectomy or R1 resection). Refer to palliative care for symptom management in advanced disease.
- •For young patients with early gastric cancer: consider pylorus-preserving gastrectomy or sentinel node navigation to preserve fertility and long-term quality of life. Discuss fertility preservation options preoperatively.
- •Long-term surveillance: clinical follow-up with history, physical exam, and contrast-enhanced CT every 3-6 months for first 2 years, then every 6-12 months. Endoscopy as indicated for symptoms. Monitor nutritional status with NRS-2002 every 2 weeks for first 3 months; oral nutritional supplements if needed, target 25-30 kcal/kg/day and protein 1.0-1.5 g/kg/day.
Board Review — High Yield
- •MAGIC trial, Perioperative ECF chemotherapy improved overall survival (HR 0.75) compared to surgery alone for resectable gastric cancer.
- •D2 lymphadenectomy, Improves disease-specific survival over D1 (HR 0.807); at least 16 lymph nodes required for adequate staging.
- •KLASS-01, Laparoscopic distal gastrectomy noninferior to open for stage I gastric cancer (5-year OS 94.2% vs 93.3%).
- •S-1 plus docetaxel (JACCRO GC-07), For stage III after D2, improves 3-year RFS from 50% to 66% (NNT=6).
- •ERAS (GISSG1901), Reduces complications, hospital stay, and improves 3-year survival in stage III gastric cancer (HR 0.57).
- •Sentinel node navigation (SENORITA), For cT1N0 tumors ≤3 cm, detection rate 97.5%, accuracy 99%; stomach preservation in 74.8%.
- •Pylorus-preserving gastrectomy (KLASS-04), For middle-third early gastric cancer, reduces bile reflux, gallstone formation, and nutritional deficiencies.
- •ICG fluorescence, Increases lymph node yield by 6.9 nodes (mean), especially after neoadjuvant therapy and in obese patients.
- •CRITICS trial, After D2, adjuvant chemotherapy alone superior to chemoradiation (5-year OS 57.9% vs 45.5%; adjusted HR 1.62).
- •VESTIGE trial, Nivolumab/ipilimumab inferior to chemotherapy for ypN+/R1 after neoadjuvant chemo (median DFS 11.4 vs 20.8 months; HR 1.55).
Deep Dive — Evidence Details
Indications by Stage
- ▸D2 gastrectomy + perioperative chemotherapy is standard for locally advanced disease.
- ▸LSNNS is a stomach-preserving option for select early gastric cancer.
Surgical management of is stage-dependent. For early gastric cancer (cT1N0, ≤3 cm), laparoscopic sentinel node navigation surgery (LSNNS) allows stomach preservation in 81% of patients, with 3-year disease-specific survival of 99.1% vs. 99.5% for standard [18]A1b. For locally advanced (T2-4, N+), D2 gastrectomy with perioperative chemotherapy is standard. The MAGIC trial established perioperative ECF ( , , fluorouracil) improving OS (HR 0.75) [7]A1b. PRODIGY showed neoadjuvant DOS ( , , S-1) followed by D2 surgery and adjuvant S-1 improved PFS (HR 0.70) [10]A1b[13]A1b. After upfront surgery, adjuvant chemoradiation (INT-0116) reduces relapse (HR 1.51) [14]A1b. For metastatic disease, surgery is palliative only. Pearl: For locally advanced gastric cancer, D2 gastrectomy with perioperative chemotherapy (MAGIC-style ECF/X or PRODIGY-style DOS) is the evidence-based standard; adjuvant chemoradiation is an alternative for patients who did not receive neoadjuvant therapy, but after D2 dissection, adjuvant chemotherapy alone may be preferred based on CRITICS data.
Operative Techniques
- ▸Minimally invasive gastrectomy has randomized-trial evidence addressing **5-year OS and DFS**, but the supplied meta-analysis abstract does not provide pooled estimates [29].
- ▸Robotic gastrectomy may reduce blood loss and severe complications but generally requires longer operating time and greater resources [131,133,143].
- ▸ICG fluorescence can support lymphatic mapping, hepatic-perfusion assessment during ALHA management, and structured robotic-program implementation [72,130].
- ▸CVQ and CT-based radiomics are emerging tools for assessing or predicting lymphadenectomy quality and difficulty, but neither replaces pathological assessment [141,144].
- ▸PPG and CLEAN-NET should be restricted to carefully selected early-stage disease because evidence for broader oncologic application remains limited [137,140].
- ▸Prehabilitation and perioperative prediction tools may improve risk stratification and adjuvant-treatment delivery, but most supporting evidence is observational or requires validation [25,132,139].
Surgical approach and oncologic principles
Gastrectomy should be selected according to tumor location, clinical stage, resectability, patient fitness, institutional expertise, and the requirement for an oncologically appropriate lymphadenectomy. Minimally invasive gastrectomy (MIG), encompassing laparoscopic and robotic approaches, is an established alternative to open gastrectomy for appropriately selected resectable disease; randomized-trial meta-analytic evidence evaluating 5-year overall survival (OS), stage-specific OS, and 5-year disease-free survival (DFS) addresses long-term oncologic safety, although the supplied abstract does not provide the pooled estimates [29]A1a. In advanced gastric cancer, laparoscopic gastrectomy has been evaluated across Japanese and Italian centers using severe morbidity, mortality, R0 resection, and lymph-node yield as principal quality outcomes, emphasizing that safe adoption depends on standardized technique and institutional experience [135].
For post-chemotherapy cStage IVb disease undergoing curative-intent resection, minimally invasive surgery (MIS) has been compared with open surgery in a multicenter retrospective cohort with propensity-score matching; this evidence supports MIS as a selectively assessable option rather than a universal substitute for systemic therapy or open surgery [52]B3b. Conversion surgery remains a treatment strategy for initially unresectable stage IV gastric or gastroesophageal-junction cancer that becomes resectable after systemic therapy, and the role of first-line nivolumab-based treatment in selecting such patients has been examined in propensity-matched real-world data [136].
Laparoscopic and robotic gastrectomy
Robotic gastrectomy can be used for radical gastrectomy and lymphadenectomy, but available comparative evidence indicates a trade-off between technical capability and resource use. A meta-analysis of 17 studies involving 31,573 patients reported longer operative time with robotic versus open gastrectomy, with a weighted mean difference of 93.4 minutes, while blood loss was lower by a weighted mean difference of 86.71 mL; the supplied abstract does not report all postoperative and oncologic endpoints [133]. A propensity-score-matched study of advanced gastric cancer compared 154 robotic and 154 laparoscopic cases and assessed severe morbidity, postoperative inflammation, delivery of adjuvant chemotherapy, recurrence patterns, OS, and relapse-free survival; the abstract reports that robotic surgery independently reduced severe complications, but does not provide the effect estimate or complete survival results [131].
In patients aged ≥75 years, a retrospective comparison of robotic and laparoscopic gastrectomy included 316 elderly patients—233 laparoscopic and 83 robotic—and reported longer operative time with robotic surgery in both elderly and non-elderly cohorts; the abstract does not provide the complete complication and survival estimates [143]. Robotic surgery may therefore be considered when enhanced instrument articulation, visualization, or dissection ergonomics are valuable, but its use should be balanced against longer operating time and higher cost reported in the comparative literature [131][133][143].
A randomized trial in robot-assisted distal gastrectomy compared a laparoscopic-like 3-arm + 2-port configuration with the traditional 4-arm + 1-port configuration during Billroth II reconstruction with Braun anastomosis and D2 lymphadenectomy. The trial evaluated operative time, blood loss, lymph-node yield, and postoperative outcomes, but the supplied abstract does not report the comparative results [33]A1b. Port configuration should consequently be individualized to the robotic platform, surgeon ergonomics, target anatomy, and the planned reconstruction [33]A1b.
Lymphatic mapping and dissection quality
Indocyanine-green (ICG) near-infrared lymphography may assist tumor localization and lymph-node dissection during robotic gastrectomy. A structured implementation study introduced robotic gastrectomy stepwise, beginning with subtotal and progressing to total gastrectomy after formal training, and evaluated perioperative outcomes and the diagnostic accuracy of ICG-guided lymphography; this low-level evidence supports protocolized training and staged case selection during program development [72]C4.
The quality of minimally invasive lymphadenectomy can be assessed intraoperatively using the anatomy-based Critical View of Quality (CVQ), which evaluates completeness across five nodal stations. In a retrospective series of 260 laparoscopic or robotic distal gastrectomies, CVQ was correlated with lymph-node yield and used to develop a computer-vision model for automated video assessment; CVQ is therefore a potential quality-assurance adjunct, but it is not established as a substitute for pathology or long-term oncologic endpoints [144]. Preoperative CT-based radiomics of suprapancreatic adipose tissue has also been investigated to predict high-difficulty lymph-node dissection, defined as suprapancreatic dissection time exceeding the 75th percentile, with a training cohort of 134 and validation cohort of 58 patients; this may support operative planning but remains retrospective and single-center evidence [141].
When an aberrant left hepatic artery (ALHA) is encountered, preservation or ligation should account for oncologic requirements and hepatic perfusion. A prospective, non-randomized multicenter study of 50 minimally invasive gastrectomy patients used temporary ALHA clamping followed by intravenous ICG and near-infrared fluorescence assessment of left-lobe perfusion, categorizing patients according to absent, partial, or preserved fluorescence; the reported algorithm is investigational and should not replace individualized vascular and oncologic judgment [130].
Function-preserving and limited resections
Pylorus-preserving gastrectomy (PPG) is a function-preserving option for selected early tumors, particularly when oncologically appropriate. In patients aged ≥75 years with cT1N0M0 disease, a retrospective comparison of laparoscopic PPG and laparoscopic distal gastrectomy with Billroth I reconstruction evaluated CT-based bone mineral density and vertebral fractures at 1, 3, and 5 years; PPG was associated with more favorable long-term bone-health outcomes in the reported cohort, although selection bias limits generalization [140]. CLEAN-NET, a non-exposure laparoscopic and endoscopic cooperative technique, has been evaluated in only 19 patients with clinically cT1N0 disease and selective limited nodal assessment; its long-term oncologic validity remains uncertain and it should not be generalized to node-positive or advanced disease [137]C.
Perioperative optimization and recovery
Operative planning should incorporate risk reduction and postoperative treatment continuity. Multimodal prehabilitation involving medical, physical, nutritional, and psychological optimization has been studied in esophagogastric cancer surgery, with pulmonary complications and resilience to major postoperative events as outcomes [139]. A multimodal deep-learning model was developed in 5,237 patients to predict postoperative complications and long-term survival, while the NUTRISCORE nomogram was developed in 391 patients receiving postoperative CAPEOX/XELOX/SOX after curative laparoscopic D2 gastrectomy to predict grade 3/4 neutropenia across cycles 2–8; these tools may support selection and adjuvant-treatment planning but require external validation before routine use [25]C4[132]. For proximal gastric or gastroesophageal operations involving minimally invasive esophagectomy, early postoperative CT has been studied for suspected anastomotic leakage, but this evidence is not directly transferable to standard gastrectomy [138].
| Technique or adjunct | Evidence and reported findings | Practical implication |
|---|---|---|
| MIG versus open gastrectomy | Randomized-trial meta-analysis assessed 5-year OS, stage-specific OS, and 5-year DFS [29]A1a | Use MIG when oncologic resection is feasible and expertise is available |
| Robotic gastrectomy | Longer operative time than open surgery: 93.4 minutes; lower blood loss: 86.71 mL [133] | Balance potential technical benefits against time, cost, and training requirements |
| Robotic versus laparoscopic surgery | Propensity-matched advanced-cancer study reported independently fewer severe complications with robotic surgery; complete estimates unavailable in the supplied abstract [131] | Consider selectively; survival benefit is not established from the supplied data |
| ICG lymphography | Used for lymphatic mapping and ALHA perfusion assessment; ALHA study included 50 patients [72]C4[130] | Apply as an adjunct to anatomy-based dissection and vascular judgment |
| CVQ and radiomics | CVQ evaluates five nodal stations; radiomics predicted high-difficulty suprapancreatic dissection [141][144] | Support quality assurance and preoperative planning, pending validation |
| PPG/CLEAN-NET | PPG studied in elderly cT1N0M0 disease; CLEAN-NET included 19 cT1N0 patients [137]C[140] | Reserve for rigorously selected early cancers |
Fertility-Sparing Surgery
- ▸PPG preserves pyloric function and reduces nutritional deficiencies.
- ▸Indicated for cT1N0M0 middle-third tumors ≥4 cm from pylorus.
For young patients with early , function-preserving approaches minimize long-term morbidity. Pylorus-preserving (PPG) is indicated for cT1N0M0 middle-third tumors ≥4 cm from pylorus [32]A1b. By preserving the hepatic branch of the vagus nerve and infrapyloric vessels, PPG reduces gallstone formation, bile reflux, and postoperative nutritional deficiencies (KLASS-04 trial) [32]A1b. These benefits are critical for preserving fertility and pregnancy outcomes. PPG is technically demanding; advances in minimally invasive surgery and ICG imaging facilitate safe implementation [32]A1b. If postoperative pathology reveals advanced disease, standard adjuvant therapy is sufficient without additional resection [32]A1b. Pearl: For young patients with cT1N0M0 gastric cancer in the middle third, pylorus-preserving gastrectomy should be the preferred function-preserving approach, as it reduces postoperative nutritional deficiencies and bile reflux, supporting long-term quality of life and potentially fertility.
Sentinel Lymph Node Mapping
- ▸SNNS is a stomach-preserving strategy for selected EGC patients, whereas ICG fluorescence is also used to enhance standard and D2 lymphadenectomy. [155][30]
- ▸Intraoperative sentinel-node pathology is central to deciding the extent of surgery; representative-section hematoxylin-eosin assessment was used in the SENORITA protocol, with permanent cytokeratin immunohistochemistry. [62]
- ▸Adequate lymphadenectomy is commonly assessed against **≥16 nodes** for proper and **≥30 nodes** for ideal retrieval. [30][66]
- ▸The FUGES-012 randomized trial reported superior 5-year overall and disease-free survival and lower cumulative recurrence with ICG-guided surgery, including **20.2% recurrence** in the ICG group. [57]
- ▸Fluorescence does not reliably establish nodal metastasis by itself and must not replace pathological examination. [67]
Scope and rationale
Sentinel lymph node mapping identifies the first draining lymph nodes or nodal basins from a gastric primary, with the aim of tailoring lymphadenectomy in selected early gastric cancer (EGC) while maintaining oncological safety. The approach is distinct from fluorescence-guided conventional lymphadenectomy: sentinel node navigation surgery (SNNS) seeks to support limited, stomach-preserving surgery, whereas indocyanine green (ICG) fluorescence lymphography is also used to improve visualization and completeness of standard or D2 dissection. [155][30]A1a
Technique and intraoperative assessment
Mapping has been performed with dual tracers, including a radioisotope and ICG, or with ICG fluorescence alone. In the SENORITA 2 prospective multicenter study, patients with non-curative endoscopic submucosal dissection underwent sentinel-basin mapping using either dual-tracer endoscopic submucosal injection or fluorescence imaging after ICG injection. This strategy was investigated because the reported incidence of lymph-node metastasis after non-curative endoscopic resection is approximately 5–10%, although standard management remains radical gastrectomy with systematic lymphadenectomy. [145]C
Intraoperative pathological examination is essential when the extent of surgery depends on sentinel-node status. In the SENORITA trial protocol, sentinel nodes were assessed intraoperatively with hematoxylin-eosin staining of a representative section through the largest nodal plane; permanent evaluation included hematoxylin-eosin staining and cytokeratin immunohistochemistry of sentinel-basin nodes. The study specifically evaluated the feasibility and accuracy of this intraoperative protocol. [62]C4
Evidence for stomach-preserving surgery
The multicenter randomized phase III SENORITA trial established the clinical basis for laparoscopic sentinel node navigation surgery with stomach preservation in selected EGC patients. A subsequent secondary analysis examined patients in whom stomach preservation failed or recurrence occurred, identifying clinicopathological factors associated with unsuccessful treatment; these findings emphasize that SNNS requires careful patient selection and cannot be regarded as universally interchangeable with standard gastrectomy. [58]A1b
A post hoc SENORITA analysis explored whether regional lymphadenectomy could omit sentinel-node navigation. Among 237 patients who underwent SNN, nodal metastases in sentinel and non-sentinel basins were analyzed according to longitudinal and circumferential tumor location. Because this was a post hoc analysis and not a replacement prospective validation of SNNS, regional lymphadenectomy without mapping remains an investigational simplification rather than a general standard. [60]C4
SNNS is also being extended to patients with non-curative ESD. SENORITA 2 was designed as a prospective multicenter feasibility study of sentinel-basin mapping in this setting, where most patients do not have nodal metastasis but the residual risk remains clinically relevant. [145]C
ICG-guided lymphadenectomy beyond sentinel surgery
ICG fluorescence can increase real-time lymphatic visualization during minimally invasive gastrectomy. A 2026 systematic review and meta-analysis compared ICG-guided with standard minimally invasive lymphadenectomy in randomized and non-randomized studies, evaluating total retrieved nodes, the proportion achieving ≥30 nodes (“ideal” lymphadenectomy), ≥16 nodes (“proper” lymphadenectomy), postoperative outcomes, recurrence, and mortality. [30]A1a
The FUGES-012 randomized trial provides long-term oncological evidence: among 258 per-protocol patients, 129 received ICG-guided surgery and 129 conventional surgery. At 5 years, overall survival and disease-free survival were superior in the ICG group, and cumulative recurrence was lower: 20.2% (26/129) in the ICG group. These results support potential oncological relevance, although the findings derive from a specific randomized cohort and should not be equated automatically with proof that ICG itself improves survival in all settings. [57]A1b
Additional systematic reviews consistently evaluate ICG as an adjunct to D2 or minimally invasive lymphadenectomy. Reviews have assessed its effect on nodal yield and perioperative outcomes across open, laparoscopic, and robotic approaches, while a robotic-surgery meta-analysis specifically examined fluorescent lymphography during robotic gastrectomy. [69]C4[68]B2a A separate meta-analysis compared near-infrared ICG-guided versus conventional D2 dissection and specifically assessed whether results differed between Eastern and Western cohorts. [65]B2a
After neoadjuvant chemotherapy, a systematic review of five studies involving 694 patients evaluated nodal yield, the proportion with ≥30 retrieved nodes, non-compliance, blood loss, hospital stay, operative time, and complications. This evidence addresses whether chemotherapy-associated lymphatic changes diminish ICG performance. [66]B2a A retrospective cohort study also examined long-term outcomes after neoadjuvant chemotherapy and laparoscopic radical gastrectomy, comparing ICG with non-ICG surgery using overlap weighting. [146]
Comparative tracers and adjuncts
The FUTURE-01 randomized trial compared carbon nanoparticle suspension injection with ICG in potentially resectable cT1–4a, N0/+ M0 gastric cancer. Ninety patients formed the modified intention-to-treat population, including 46 carbon-nanoparticle and 44 ICG patients; the study evaluated lymphatic mapping, nodal dissection, and postoperative node sorting. [61]A1b A randomized study also evaluated combined ICG and endoscopic ultrasound for intraoperative lymph-node assessment, but its sample was small at 26 patients, limiting generalizability. [64]A1b
ICG has been investigated for detecting metastatic rather than merely fluorescent nodes. A systematic review and meta-analysis of oesophageal and gastric cancer studies evaluated the accuracy of ICG-guided lymphadenectomy for metastatic-node detection and concluded that the usefulness of fluorescence for identifying metastasis remains uncertain. Fluorescence should therefore not replace pathological examination. [67]C4
Small or early-stage studies continue to refine implementation. A 30-patient randomized pilot trial evaluated ICG-guided versus standard laparoscopic D2 dissection, with nodal yield as the primary endpoint and metastatic-node ratio, morbidity, mortality, and operative outcomes as secondary endpoints. [156]C A retrospective Western robotic-gastrectomy series described stepwise introduction of robotic surgery, using ICG lymphography to support lymphadenectomy and tumor localization. [72]C4
ICG labeling has also been combined with neurophysiological monitoring to preserve perigastric vagal nerves during laparoscopic distal gastrectomy for early distal gastric cancer; the randomized trial initially enrolled 285 patients with cT1N0M0 disease. This is a nerve-preservation application rather than sentinel-node mapping, but it illustrates the broader role of fluorescence navigation. [59]A1b Similarly, fluorescence imaging has been used to assess liver perfusion after temporary aberrant left hepatic artery clamping and to guide preservation or ligation decisions in minimally invasive gastrectomy. [130] ICG fluorescence has also been tested for real-time proximal-margin identification in a randomized trial of 422 patients undergoing laparoscopic distal gastrectomy; the ICG group had fewer positive initial proximal margins (0% vs 5.5%). [56]A1b
Practical limitations
SNNS is most relevant to carefully selected EGC patients and specialized centers with validated mapping, basin dissection, and rapid pathology protocols. ICG-guided lymphadenectomy may improve visualization and nodal retrieval, but evidence remains heterogeneous across tracer protocols, injection methods, surgical platforms, neoadjuvant-treatment populations, and Eastern versus Western practice. Sentinel mapping should therefore be viewed as a structured, pathology-dependent strategy, while ICG fluorescence is best considered an adjunct—not a substitute for oncologically appropriate lymphadenectomy or definitive histopathology. [30]A1a[62]C4[65]B2a[66]B2a[67]C4[155]
| Application | Evidence and clinical role |
|---|---|
| Sentinel node navigation | Stomach-preserving surgery in selected EGC; requires validated mapping and intraoperative pathology. [58]A1b[62]C4[155] |
| Non-curative ESD | Prospective feasibility evaluation of sentinel-basin mapping using dual tracer or ICG fluorescence. [145]C |
| Standard/D2 lymphadenectomy | Real-time lymphatic visualization, with outcomes including total yield, ≥16-node, and ≥30-node rates. [30]A1a[65]B2a[69]C4 |
| Neoadjuvant chemotherapy | Evidence evaluates whether ICG remains effective after chemotherapy and its association with nodal yield and long-term outcomes. [66]B2a[146] |
| Robotic gastrectomy | Fluorescence lymphography may facilitate structured implementation and nodal dissection. [68]B2a[72]C4 |
Adjuvant Therapy Triggers
- ▸S-1 +/- docetaxel is standard for Asian D2-resected stage II/III.
- ▸Adjuvant radiotherapy is not indicated after D2 dissection.
Postoperative therapy is guided by pathology. For Asian patients with D2-resected stage II/III, S-1 monotherapy (80-120 mg/day, 4 weeks on/2 weeks off for 1 year) is standard (ACTS-GC, 5-year OS 71.7% vs. 61.1%) [77]A1b. For node-positive stage III, adding to S-1 improves 3-year RFS from 50% to 66% (HR 0.632; NNT=6) [12]A1b. SOX (S-1 plus 130 mg/m² q3 weeks) for 6 months is an alternative [73]A1b. For Western patients, perioperative FLOT or postoperative chemoradiation (45 Gy with FU/LV) is standard [14]A1b. After D2 surgery, chemotherapy alone is preferred (CRITICS: 5-year OS 57.9% vs. 45.5% with chemoradiation) [5]A1b. Do not use adjuvant nivolumab/ipilimumab in ypN+/R1 patients (VESTIGE: inferior DFS) [19]B2b. Pearl: For patients with D2-resected, node-positive stage III gastric cancer, the addition of docetaxel to S-1 yields a 3-year relapse-free survival benefit of 16 percentage points (NNT = 6) and should be considered the new standard in Asia, while routine radiotherapy after D2 dissection is not supported by current evidence.
Intraoperative Considerations and Complications
- ▸Laparoscopic and open gastrectomy showed comparable pooled 5-year overall and disease-free survival in T4a disease, with procedure-specific interactions requiring careful interpretation [157].
- ▸Robotic or laparoscopic port configuration, visceral adiposity, and splenic-hilar anatomy should be incorporated into operative planning [33,158,161].
- ▸Spleen-preserving No. 10 dissection is supported only in carefully selected proximal tumors and experienced centers; tumors with macroscopic type 4 morphology or size ≥8 cm were excluded from the phase II trial [164].
- ▸Prehabilitation of at least 7 days, CT-based body composition, energy-expenditure dynamics, and modified transferrin saturation may improve perioperative risk assessment [151,159,165].
- ▸Use standardized complication definitions and actively prevent, detect, and manage duodenal stump leakage, infection, anastomotic complications, and other Clavien–Dindo grade ≥II events [149,150,162].
- ▸Several supplied studies provide methods but not quantitative results in the available abstracts; conclusions should therefore avoid claims of superiority [86,138,150,158,160,162].
Operative approach and technical planning
Minimally invasive gastrectomy should be selected according to tumor extent, reconstruction requirements, surgeon expertise, and the patient’s physiological and anatomical risk profile. In T4a gastric cancer, pooled evidence from 13 studies—including 2 randomized trials and 11 non-randomized cohorts—found no significant overall difference between laparoscopic and open gastrectomy in 5-year overall survival (HR 0.95, 95% CI 0.85–1.07) or disease-free survival (HR 0.91, 95% CI 0.79–1.04), although outcomes varied according to gastrectomy type and the abstract reports an interaction requiring procedure-specific interpretation [157]. These findings support laparoscopic resection in appropriately selected T4a patients when complete oncologic resection and safe handling of the serosa can be achieved, but they do not eliminate concerns regarding technical difficulty or peritoneal dissemination [157].
For patients undergoing robotic distal gastrectomy with D2 lymphadenectomy and Billroth II reconstruction with Braun anastomosis, a randomized trial compared a conventional 4-arm + 1-port configuration with a laparoscopic-like 3-arm + 2-port configuration; the trial evaluated operative time, blood loss, lymph-node yield, and postoperative outcomes [33]A1b. Port selection should therefore be considered part of operative planning rather than a purely cosmetic modification, particularly when maintaining adequate instrument triangulation and access for lymphadenectomy and reconstruction [33]A1b.
Obesity, overweight status, and high visceral adiposity can increase the technical difficulty of minimally invasive gastrectomy [158]. A systematic review and meta-analysis specifically assessed whether robotic gastrectomy offers advantages over laparoscopy in these populations, using East Asian comparative cohorts and categorical BMI or CT-defined adiposity measures; the supplied abstract does not provide the pooled quantitative results, so a definitive superiority claim cannot be made [158]. CT-derived body composition should nevertheless be incorporated into preoperative risk assessment because muscle and fat parameters have been systematically evaluated as predictors of postoperative complications after radical gastrectomy [159].
Robotic assistance may be particularly relevant for technically demanding splenic-hilar dissection. The No. 10 nodal station is bordered by terminal splenic vessels and the pancreatic tail, creating a narrow working space [161]. In a propensity-score-matched comparison of 35 robotic and 35 laparoscopic cases, robotic surgery was associated with lower reported blood loss, although the supplied abstract does not provide the complete comparative outcome set [161]. A multicentre phase II trial also evaluated laparoscopic or robotic spleen-preserving No. 10 dissection during total gastrectomy for cT2–4a proximal tumors involving the greater curvature without obvious No. 10 metastasis; macroscopic type 4 tumors and large type 3 tumors measuring ≥8 cm were excluded [164]. These selection criteria emphasize that spleen preservation and splenic-hilar dissection require careful patient selection and experienced teams [164].
Risk modification before and during surgery
Nutritional, functional, hematologic, and body-composition assessment should be integrated into operative planning. A systematic review of randomized trials evaluated unimodal and multimodal prehabilitation interventions lasting at least 7 days before gastric cancer resection, supporting structured optimization of physical and nutritional reserve, although the supplied abstract does not provide intervention-specific pooled effects [151]. Modified transferrin saturation, adjusted for sex and anemia status, was investigated as a predictor of Clavien–Dindo grade ≥II complications after curative gastrectomy and was compared with the conventional 20% transferrin-saturation threshold [165]. Resting-energy-expenditure dynamics measured preoperatively and on postoperative day 1 were also incorporated into a machine-learning model for predicting Clavien–Dindo grade ≥II complications [89]B2b. These tools may assist risk stratification but should complement, rather than replace, clinical judgment [89]B2b[165].
Major postoperative complications
Complication reporting should use standardized definitions and severity grading. The Korean Quality Improvement Platform in Surgery task force developed a consensus-based gastrectomy-specific classification after 10 formal meetings involving experts from 14 high-volume hospitals, incorporating international literature, guidelines, and randomized-trial evidence [149]. Standardization is important for comparing approaches and identifying preventable events [149].
Duodenal stump leakage is a high-consequence complication after gastrectomy and has historically been associated with postoperative mortality [162]C. The multinational STARDUST study analyzed consecutive gastrectomy patients treated from 2019 to 2022 across 24 high-volume European centers, focusing on incidence, 90-day mortality, and treatment strategies; the supplied abstract does not report the final rates or comparative management results [162]C. Intraoperatively, secure closure, avoidance of devascularization or excessive tension, and meticulous inspection of the stump are therefore essential [162]C.
Healthcare-associated infections after gastrointestinal cancer surgery include, but are not limited to, surgical-site infection. A prospective Romanian tertiary-center study followed 211 adults for 30 days after elective gastric or colorectal cancer surgery and evaluated infection incidence, microbiology, antimicrobial resistance, and risk factors [150]C. The study specifically examined neoadjuvant radiotherapy as a potential independent risk factor, but the supplied abstract does not provide the final effect estimate [150]C.
Postoperative complications may also affect long-term outcomes. A large Korean national cohort evaluated pulmonary, wound, gastrointestinal, urinary, and bleeding complications within 30 days after gastrectomy and their association with subsequent cardiovascular disease in patients without prior cardiovascular disease [166]. In addition, a multicentre study developed and externally validated a multimodal deep-learning model in 5,237 patients from 11 Chinese centers, with validation across six prospective clinical-trial datasets, to predict Clavien–Dindo grade ≥II complications and long-term survival [25]C4. These findings reinforce the importance of prevention, early detection, and rapid treatment because complications can compromise recovery and oncologic therapy delivery [25]C4[166].
Special situations and evidence boundaries
For remnant gastric cancer, a systematic review compared subtotal gastrectomy with completion total gastrectomy, addressing safety, feasibility, morbidity, and oncologic adequacy; the supplied abstract does not provide pooled estimates, so subtotal resection should not be considered universally equivalent to completion gastrectomy [86]C4. Evidence concerning delayed gastric conduit emptying after esophagectomy and CT diagnosis of anastomotic leakage after minimally invasive esophagectomy concerns esophageal surgery rather than standard gastrectomy and should not be directly extrapolated without clinical justification [160][138].
| Domain | Practical consideration | Evidence |
|---|---|---|
| Locally advanced disease | Select laparoscopic versus open resection based on oncologic and technical feasibility; pooled survival was similar in T4a disease | [157] |
| Port strategy | Compare conventional 4-arm + 1-port with laparoscopic-like 3-arm + 2-port robotic configurations according to exposure and reconstruction needs | [33]A1b |
| Adiposity | Assess BMI, visceral adiposity, muscle, and fat composition because these may influence technical difficulty and complications | [158][159] |
| Splenic hilum | Use experienced robotic or laparoscopic teams for No. 10 dissection; consider spleen preservation only in selected disease | [161][164] |
| Complication surveillance | Apply standardized definitions and monitor for stump leakage, infection, bleeding, pulmonary, gastrointestinal, and wound complications | [149][150]C[162]C[166] |
Postoperative Recovery and ERAS
- ▸ERAS reduces complications, hospital stay, and improves survival in stage III.
- ▸Avoid routine abdominal drains but consider selective omission.
Enhanced Recovery After Surgery (ERAS) is standard for surgery. Meta-analysis of 13 RCTs (n=1,915) shows ERAS shortens hospital stay (MD -1.82 days), reduces complications (OR 0.63), and accelerates flatus, oral intake, and ambulation [102]A1a. Key elements: prehabilitation for frail elderly (Geriatric 8 ≤14) reduces 30-day complications from 28.7% to 17.2% [107]A1b; multimodal opioid-sparing analgesia (subcostal TAP block, acetaminophen, COX-2 inhibitors) reduces fentanyl consumption by 500 μg over 72 hours [109]A1b; early oral feeding is safe [104]A1a; avoid routine abdominal drains (reduces complications, OR 0.53) [118]A1a, but selective omission is prudent (ADIGE: increased reoperation from 7.7% to 15%) [111]A1b. The GISSG1901 trial showed ERAS improves 3-year OS (86.56% vs. 80.11%) and DFS in stage III disease [110]A1b. Pearl: ERAS is not merely about faster discharge, the GISSG1901 trial showed it improves 3-year survival in stage III gastric cancer (NNT ≈ 7 to prevent one death), likely through reduced complications, attenuated inflammation, and earlier adjuvant chemotherapy [110]A1b.
| Component | Evidence Summary | Key Reference |
|---|---|---|
| Prehabilitation (frail patients) | Reduces 30-day complications from 28.7% to 17.2% | [107]A1b |
| Multimodal opioid-sparing analgesia | Reduces pain scores and fentanyl consumption by 500 μg/72 h | [109]A1b |
| Early oral feeding | Reduces hospital stay by 1.82 days; safe without increased complications | [104]A1a |
| Avoidance of routine drainage | Faster recovery, fewer complications (OR 0.53); ADIGE trial shows increased reintervention risk | [118]A1a[111]A1b |
| Psychosocial intervention | Improves 2-year DFS (HR 0.58) and OS (HR 0.52) | [106]A1b |
Outcomes by Stage and Approach
- ▸Adjuvant SOX improves 3-year DFS in stage II-III (NNT=11).
- ▸Nivolumab+chemo for CPS≥5 yields 5-year OS benefit (NNT=10).
For resectable stage II-III, adjuvant SOX (S-1 + 130 mg/m² q3 weeks) for 6 months yields 3-year DFS 74.3% vs. 64.8% with S-1 alone (NNT=11) [73]A1b. Neoadjuvant DOS improves PFS (HR 0.70) [10]A1b. For advanced/metastatic disease, first-line + chemotherapy in PD-L1 CPS≥5 gives 5-year OS 16% vs. 6% (HR 0.71; NNT=10) [120]A1b. In HER2+ disease after trastuzumab failure, anbenitamab + chemo improves PFS (HR 0.25) and OS (HR 0.29) [121]A1b. MSI-high status predicts exceptional immunotherapy benefit (OS HR 0.34) [128]A1a. Laparoscopic vs. open gastrectomy shows equivalent oncologic outcomes: LOGICA trial reported 1-year OS 76% vs. 78%, R0 95% both, lymph node yield 29 both [16]A1b. Pearl: Nodal response (ypN0) after preoperative therapy is a stronger predictor of survival than primary tumor response; patients with ypN+ disease have poor outcomes regardless of postoperative therapy [79]B3b.
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Backlinks
- ← Gastric Cancer Surveillance and Follow-up
- ← Gastric Cancer Radiation Management (Detailed)
- ← Gastric Cancer Radiation Management
- ← Gastric Cancer Systemic Therapy (Detailed)
- ← Gastric Cancer (Detailed)
- ← Gastric Cancer Palliative Care (Detailed)
- ← Gastric Cancer Recurrent and Metastatic Disease (Detailed)
- ← Gastric Cancer Recurrent and Metastatic Disease
- ← Gastric Cancer Palliative Care
- ← Gastric Cancer Surveillance and Follow-up (Detailed)