Advances in immunotherapy and biomarker-driven treatment have rapidly reshaped the management of gastric and gastroesophageal junction (GEJ) adenocarcinoma.¹ At the 13^th APGCS, an international panel of medical oncologists and surgeons discussed two challenging clinical cases spanning localized mismatch repair deficient (dMMR) gastric cancer and gastric cancer with limited peritoneal metastatic disease.² The panel explored the incorporation of immune checkpoint inhibitors (ICIs) into perioperative treatment, management after an exceptional response to neoadjuvant chemoimmunotherapy, the role of conversion surgery, and postoperative maintenance strategies.² These evolving treatment approaches highlight the importance of integrating emerging evidence with tumor biology, patient characteristics, and multidisciplinary decision-making to optimize individualized care.²

Case 1: Perioperative management of localized dMMR GEJ adenocarcinoma

The discussion opened with a 73-year-old man with a history of metastatic hormone-sensitive prostate cancer who presented with iron deficiency anemia.² Endoscopic evaluation identified a large ulcerating tumor involving the gastric cardia and distal GEJ.² Computed tomography (CT) demonstrated irregular mural thickening of the gastric fundus and proximal body with associated serosal irregularity and enlarged perigastric lymph nodes.² Staging laparoscopy confirmed cT4aN1M0 disease without overt peritoneal metastases, and peritoneal cytology was negative.² Molecular profiling revealed mismatch repair deficiency (dMMR) with loss of MLH1 and PMS2, a PD-L1 combined positive score (CPS) of 25, and HER2-negative status, confirming a a highly immunogenic tumor profile.²

The panel evaluated optimal perioperative strategies, weighing upfront surgery against perioperative fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) chemotherapy, chemotherapy combined with ICIs, or dual immune checkpoint blockade.² Prof. So noted that despite the absence of overt metastatic disease, the patient had high-risk locally advanced disease, favoring a combination of chemotherapy and immunotherapy.² He also emphasized the need to address the patient’s symptomatic anemia and assess for ongoing tumor bleeding, noting that local control measures, including radiotherapy, may be required if bleeding persists during systemic treatment.²

Dr. Shiu considered perioperative FLOT to be relatively intensive for a 73-year-old patient and suggested that a less intensive chemoimmunotherapy approach could be considered, such as a FOLFOX-based regimen with an ICI or a durvalumab-containing regimen, followed by reassessment of treatment response.² Dr. Luna agreed that while evidence for perioperative ICI integration in localized disease is maturing, a chemotherapy doublet + immunotherapy approach represents a pragmatic middle ground.²

Debate focused on whether chemotherapy could be omitted entirely in favor of dual ICI.² Dr. Ng cautioned against omitting chemotherapy, emphasizing that adequate tumor downstaging remains essential in bulky cT4 disease to ensure complete surgical resection.² He favored perioperative FLOT chemotherapy with immunotherapy for fit patients, reserving doublets with an ICI for those with reduced performance status.² Conversely, Dr. Shiu argued that T4 disease alone should not rule out dual ICI prior to surgery, citing emerging trial data that demonstrate rapid, profound biological responses in dMMR tumors treated with dual checkpoint blockade.³

While the panel agreed on incorporating immunotherapy into perioperative care, opinions on chemotherapy backbone intensity varied, reflecting the need to balance high-risk local staging against patient fitness and emerging trial data.^2,4

Management after pCR following neoadjuvant chemoimmunotherapy

The patient subsequently received CAPOX + pembrolizumab but developed severe abdominal pain after the second treatment cycle.² CT revealed pneumoperitoneum, and emergency surgery confirmed gastric perforation, necessitating total gastrectomy with D2 lymphadenectomy.² Histopathological examination demonstrated a pathological complete response (pCR), with no viable tumor cells in the stomach (score 0) or in any of the 45 resected lymph nodes (0/45).² Resection margins and omentectomy specimens were negative for malignancy, and postoperative restaging showed no evidence of residual or metastatic disease.²

The panel discussed optimal postoperative management following an exceptional pathological response.² Dr. Sudoyo favored continuation of immunotherapy, emphasizing that the absence of radiologically detectable disease does not exclude residual micrometastatic disease.² He suggested continuation of ICI ± additional chemotherapy depending on postoperative recovery to reduce the recurrence risk.²

The occurrence of gastric perforation during neoadjuvant treatment was highlighted as a rare but severe complication.² Prof. So emphasized multidisciplinary collaboration for prompt intervention, while Dr. Ng stressed patient education regarding new or worsening symptoms during treatment.² Dr. Shiu added that gastric perforation should not automatically be interpreted as treatment failure, advocating for prompt multidisciplinary assessment to distinguish treatment-related complications from disease progression.² He also noted that the availability of subsequent systemic treatment options upon recurrence varies across healthcare systems.²

The patient’s subsequent course provided further context for postoperative decision-making.² Pembrolizumab monotherapy was initially planned for one year; however, the patient developed grade 4 immune-mediated myositis requiring intravenous immunoglobulin, high-dose methylprednisolone and rituximab.² Immunotherapy was permanently discontinued, and the patient transitioned to surveillance.² He remained free of recurrent disease for more than one year post-surgery.² The case highlighted the potential for durable disease control following a pCR while underscoring the need to balance the potential benefits of continued immunotherapy against the risk of serious immune-related toxicity.²

Case 2: Navigating conversion surgery in gastric cancer with limited peritoneal metastatic disease

The second case involved a 46-year-old woman with a history of Helicobacter pylori-associated gastric ulcer who presented with persistent epigastric pain six months after eradication therapy.² Upper gastrointestinal endoscopy revealed a large ulcer with irregular margins in the proximal gastric body mucosa, with histopathology-confirmed gastric adenocarcinoma.² Diagnostic laparoscopy demonstrated limited peritoneal disease (peritoneal carcinomatosis index [PCI] 2) with trace ascites and peritoneal nodules; histology confirmed metastatic adenocarcinoma.² Molecular profiling showed proficient mismatch repair (pMMR), PD-L1 CPS of 70, and HER2-negative disease (cT3N2M1).²

The panel discussed the optimal approach to this limited peritoneal metastatic presentation.² Dr. Ibrahim favored aggressive upfront systemic treatment, given the patient’s young age and poor prognosis.^2,5 He considered chemotherapy + immunotherapy, e.g. CAPOX or FOLFOX + ICI, or an intensive regimen such as FLOT/DOS + ICI for suitable patients, followed by multidisciplinary reassessment for conversion surgery or intraperitoneal treatment if robust response was achieved.²

Prof. So recommended against upfront surgery, favoring a bidirectional approach incorporating systemic and intraperitoneal chemotherapy, reserving conversion surgery for patients achieving significant downstaging and sustained disease control.² Dr. Sudoyo concurred with an upfront systemic therapy and surgical reassessment guided by treatment response and patient preferences.²

The patient was enrolled in a clinical trial evaluating CAPOX, nivolumab, and intraperitoneal paclitaxel.² Peritoneal cytology converted to negative from cycle 3 onwards, and CT after 6 months of bidirectional therapy demonstrated stable disease without progression.² The panel evaluated whether this degree and duration of response justified conversion surgery.²

Dr. Shiu preferred a more cautious approach, emphasizing the need to establish sustained disease control before committing to conversion surgery.² He recommended repeat endoscopy and diagnostic laparoscopy to confirm both luminal and peritoneal disease clearance, noting that operating at 6 months may be premature given the high risk of recurrence in metastatic gastric cancer.² He proposed that continued disease control, potentially with immunotherapy for up to 1 year, may help identify patients with more favorable tumor biology who may derive greater benefit from conversion surgery.²

Dr. Luna echoed the need for individualized, multidisciplinary decision-making and noted that emerging evidence, including the DRAGON trial, may further clarify the role of multimodal treatment incorporating systemic and intraperitoneal chemotherapy with conversion surgery in selected patients.^2,6

Overall, the panel considered conversion surgery a potential option for highly selected patients with limited peritoneal metastatic disease who achieve sustained disease control following systemic and intraperitoneal therapy.^2,7 However, the optimal treatment duration and timing of surgery remain uncertain, underscoring the importance of careful patient selection, multidisciplinary reassessment, and integration of emerging evidence.^2,7

Post-conversion surgery management and the role of maintenance therapy

Dr. Walsh subsequently revealed that repeat diagnostic laparoscopy showed resolution of ascites and no visible peritoneal nodules, allowing the patient to undergo open total gastrectomy with D1+ lymphadenectomy.² Final pathological staging was ypT1N1, with metastatic disease identified in 1 of 29 lymph nodes.² The panel discussed the role of postoperative therapy following conversion surgery, particularly whether patients presenting with initial metastatic disease could be managed with surveillance after surgery or should continue systemic treatment to reduce the risk of recurrence.²

Dr. Ng favored continuing postoperative systemic therapy, emphasizing that patients who initially present with metastatic disease remain at risk of recurrence despite successful conversion surgery.^2,8 He suggested completing immunotherapy for up to 2 years alongside approximately 6 months of chemotherapy, while acknowledging that the optimal duration of postoperative treatment remains uncertain.²

Dr. Walsh concluded by sharing the patient’s clinical course.² She resumed maintenance therapy with capecitabine, nivolumab, and intraperitoneal paclitaxel, with intraperitoneal paclitaxel discontinued after cycle 23.² Nivolumab was continued to complete 2 years of therapy and was then discontinued.² At the time of the presentation, she had remained off treatment for 7 months, with the latest CT showing no evidence of disease progression.²

The case illustrated a multimodal treatment strategy incorporating systemic and intraperitoneal therapy, conversion surgery, and postoperative maintenance treatment in a highly selected patient with limited peritoneal metastatic gastric cancer.² The discussion highlighted the uncertainty surrounding the optimal duration of postoperative therapy and the need for prospective evidence to guide treatment selection and sequencing.²

Conclusion

The panel discussion highlighted the pivotal role of biomarker profiling and multidisciplinary collaboration in managing localized and oligometastatic gastric cancer.^2,9 Across two challenging cases, experts explored key considerations in integrating immunotherapy into perioperative treatment for dMMR disease, postoperative management following pCR, and the selection and timing of conversion surgery for patients with limited peritoneal metastases.² While advances in systemic therapy have expanded treatment options, the optimal sequencing and duration of therapy, including maintenance treatment, and the timing of surgical intervention remain areas of ongoing investigation.² Individualized treatment decisions based on tumor biology, disease burden, treatment response, patient fitness, and multidisciplinary assessment therefore remain central to optimizing outcomes.^2,9