The key points of normothermic intraperitoneal and systemic treatment for gastric cancer with peritoneal metastasis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 ZHU Zhenggang

Department of Surgery, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory of Stomach Neoplasmas, Shanghai 200025, P. R. China;

Corresponding?author：

ZHU Zhenggang, Email: zzg1954@hotmail.com

Keywords：

gastric cancer; peritoneal metastasis; normothermic intraperitoneal and systemic treatment

DOI：

10.7507/1007-9424.202605010

Video：

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Gastric cancer is one of the major malignant tumors in China, with a high incidence and mortality rate. Once peritoneal metastasis occurs in patients with gastric cancer, the prognosis is extremely poor, with an median survival time of approximately 6 to 9 months. In recent years, normothermic intraperitoneal and systemic treatment (NIPS) has achieved favorable outcomes in the treatment of gastric cancer with peritoneal metastasis and is being gradually promoted and applied. Combining the newly released “Asian consensus on normothermic intraperitoneal and systemic treatment for gastric cancer with peritoneal metastasis” and multiple prospective clinical studies at home and abroad, this article analyzes several key points for the clinical implementation of NIPS therapy, mainly including: the importance of combined administration of systemic therapy and intraperitoneal therapy; the necessity of attaching importance to laparoscopic examination; applicable population and indications for NIPS therapy; selection of intraperitoneal medications for NIPS and surgical indications after conversion therapy for peritoneal metastasis. It aims to further promote the clinical application of NIPS in the treatment of gastric cancer with peritoneal metastasis and gradually improve the therapeutic efficacy through academic discussion and exchange.

Citation： ZHU Zhenggang. The key points of normothermic intraperitoneal and systemic treatment for gastric cancer with peritoneal metastasis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2026, 33(5): 597-602. doi: 10.7507/1007-9424.202605010 Copy

1.	Zhu Z, Kitayama J, Kim HH, et al. Asian consensus on normothermic intraperitoneal and systemic treatment for gastric cancer with peritoneal metastasis. Gastric Cancer, 2025, 28(5): 731-748.
2.	朱正綱, 北山丈二, 金炯浩, 等. 腹腔內常溫與全身聯合治療胃癌腹膜轉移的亞洲專家共識. 外科理論與實踐, 2025, 30(4): 277-294.
3.	Ishigami H, Fujiwara Y, Fukushima R, et al. Phase Ⅲ trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC Trial. J Clin Oncol, 2018, 36(19): 1922-1929.
4.	Yan C, Yang Z, Shi Z, et al. Intraperitoneal and intravenous paclitaxel plus S-1 for gastric cancer with peritoneal metastasis: a phase 3 randomized clinical trial. JAMA Oncol, 2026, 15: 39. doi: 10.1001/jamaoncol.2026.1347.
5.	Ajani JA, D’Amico TA, Bentrem DJ, et al. Gastric cancer, version 2. 2025, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2025, 23(5): 169-191.
6.	Kim IH, Kang SJ, Choi W, et al. Korean practice guidelines for gastric cancer 2024: an evidence-based, multidisciplinary approach (update of 2022 guideline). J Gastric Cancer, 2025, 25(1): 5-114.
7.	Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2025 (7th edition). Gastric Cancer, 2026, 29(2): 271-299.
8.	Wang FH, Zhang XT, Tang L, et al. The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer, 2023. Cancer Commun (Lond), 2024, 44(1): 127-172.
9.	Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet, 2021, 398(10294): 27-40.
10.	Rha SY, Oh DY, Ya?ez P, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol, 2023, 24(11): 1181-1195.
11.	Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet, 2010, 376(9742): 687-697.
12.	Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med, 2023, 29(8): 2133-2141.
13.	Shitara K, Lordick F, Bang YJ, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet, 2023, 401(10389): 1655-1668.
14.	van Hootegem SJM, Guchelaar NAD, van der Sluis K, et al. Staging laparoscopy for gastric cancer: European consensus. Br J Surg, 2025, 112(9): znaf144. doi: 10.1093/bjs/znaf144.
15.	Schena CA, Laterza V, De Sio D, et al. The role of staging laparoscopy for gastric cancer patients: current evidence and future perspectives. Cancers (Basel), 2023, 15(13): 3425. doi: 10.3390/cancers15133425.
16.	Boshier PR, Chia DKA, Thrumurthy SG, et al. Management of gastric cancer peritoneal metastasis: International Gastric Cancer Association GCPM Working Group consensus statements. Br J Surg, 2026, 113(4): znag027. doi: 10.1093/bjs/znag027.
17.	Butensky SD, Bansal VV, Su DG, et al. Consensus guideline for the management of gastric cancer with synchronous peritoneal metastases. Ann Surg Oncol, 2025. doi: 10.1245/s10434-025-17361-2.
18.	Huang B, Rampulla V, Ri M, et al. Staging laparoscopy with peritoneal lavage to identify peritoneal metastases and free intraperitoneal cancer cells in the management of locally advanced gastric cancer. Eur J Surg Oncol, 2022, 50(6): 108059. doi: 10.1016/j.ejso.2024.108059.
19.	Ostowari A, Chen KT, Hasjim BJ, et al. Underutilization of staging laparoscopy prior to neoadjuvant systemic therapy in gastric cancer. Ann Surg Oncol, 2026, 33(2): 1343-1349.
20.	Hu YF, Deng ZW, Liu H, et al. Staging laparoscopy improves treatment decision-making for advanced gastric cancer. World J Gastroenterol, 2016, 22(5): 1859-1868.
21.	Acs M, Piso P, Glockzin G. Peritoneal metastatic gastric cancer: local treatment options and recommendations. Curr Oncol, 2024, 31(3): 1445-1459.
22.	Lewis KA, Diggs LP, Badgwell BD. Educational review: updates on therapeutic strategies for gastric cancer with peritoneal metastasis. Ann Surg Oncol, 2025, 32(5): 3672-3687.
23.	Tajik F, Eyob B, Khan AM, et al. Iterative intraperitoneal chemotherapy in gastric cancer peritoneal carcinomatosis. Cancers (Basel), 2025, 17(2): 289-304.
24.	Kobayashi D, Kodera Y, Fukushima R, et al. Phase Ⅱ study of intraperitoneal administration of paclitaxel combined with S-1 and cisplatin for gastric cancer with peritoneal metastasis. Ann Surg Oncol, 2024, 31(2): 735-743.
25.	Seo WJ, Kim DW, Lee CM, et al. Intraperitoneal paclitaxel with systemic S-1 plus oxaliplatin for advanced or recurrent gastric cancer with peritoneal metastasis: a single-arm, multicenter phase Ⅱ clinical trial. Eur J Surg Oncol, 2025, 51(6): 109603. doi: 10.1016/j.ejso.2025.109603.
26.	Chia DKA, Sundar R, Kim G, et al. Outcomes of a phase Ⅱ study of intraperitoneal paclitaxel plus systemic capecitabine and oxaliplatin (XELOX) for gastric cancer with peritoneal metastases. Ann Surg Oncol, 2022, 29(13): 8597-8605.
27.	Miyatani K, Miyauchi W, Kono Y, et al. Successful treatment of peritoneal recurrence after gastric cancer surgery with intravenous and intraperitoneal paclitaxel combined with S-1 chemotherapy: a case report. Surg Case Rep, 2020, 6(1): 88. doi: 10.1186/s40792-020-00849-2.
28.	Jin ZJ, Lu S, Shi M, et al. Perioperative systemic and prophylactic intraperitoneal chemotherapy for type 4/large type 3 gastric cancer: DRAGON-10. Future Oncol, 2024, 20(36): 2833-2838.
29.	Rietveld PCS, Guchelaar NAD, Sassen SDT, et al. A clinical pharmacological perspective on intraperitoneal chemotherapy. Drugs, 2025, 85(7): 931-943.
30.	Tamura K, Kitayama J, Saga Y, et al. Combined intraperitoneal and systemic chemotherapy for peritoneal metastases: drug delivery concepts, pharmacokinetics, and clinical applications: a narrative review. Pharmaceutics, 2026, 18(2): 179-206.
31.	朱正綱. 紫杉醇與替吉奧聯合防治胃癌腹膜轉移的臨床療效. 中華胃腸外科雜志, 2015, 18(10): 979-982.
32.	Chen X, Wei Y, Chen X, et al. Hydrogel-based intraperitoneal drug delivery platforms for peritoneal metastasis: strategies, advances, and prospects. Drug Deliv, 2025, 33(1): 2576199. doi: 10.1080/10717544.2025.2576199.
33.	Yoshida K, Yamaguchi K, Okumura N, et al. Is conversion therapy possible in stage Ⅳ gastric cancer: the proposal of new biological categories of classification. Gastric Cancer, 2016, 19(2): 329-338.
34.	Han HS, Rha SY. From control to conversion: optimizing systemic therapy for curative-intent conversion surgery in metastatic gastric cancer. J Gastric Cancer, 2026, 26(1): 146-160.
35.	Yoshida K, Yasufuku I, Terashima M, et al. International retrospective cohort study of conversion therapy for stage Ⅳ gastric cancer 1 (CONVO-GC-1). Ann Gastroenterol Surg, 2021, 6(2): 227-240.
36.	Choo J, Sargsyan A, Khachatryan V, et al. Advances in the management of metastatic gastric cancer: current strategies and emerging therapeutics. Nat Rev Clin Oncol, 2026. doi: 10.1038/s41571-026-01134-1.

1. Zhu Z, Kitayama J, Kim HH, et al. Asian consensus on normothermic intraperitoneal and systemic treatment for gastric cancer with peritoneal metastasis. Gastric Cancer, 2025, 28(5): 731-748.
2. 朱正綱, 北山丈二, 金炯浩, 等. 腹腔內常溫與全身聯合治療胃癌腹膜轉移的亞洲專家共識. 外科理論與實踐, 2025, 30(4): 277-294.
3. Ishigami H, Fujiwara Y, Fukushima R, et al. Phase Ⅲ trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC Trial. J Clin Oncol, 2018, 36(19): 1922-1929.
4. Yan C, Yang Z, Shi Z, et al. Intraperitoneal and intravenous paclitaxel plus S-1 for gastric cancer with peritoneal metastasis: a phase 3 randomized clinical trial. JAMA Oncol, 2026, 15: 39. doi: 10.1001/jamaoncol.2026.1347.
5. Ajani JA, D’Amico TA, Bentrem DJ, et al. Gastric cancer, version 2. 2025, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2025, 23(5): 169-191.
6. Kim IH, Kang SJ, Choi W, et al. Korean practice guidelines for gastric cancer 2024: an evidence-based, multidisciplinary approach (update of 2022 guideline). J Gastric Cancer, 2025, 25(1): 5-114.
7. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2025 (7th edition). Gastric Cancer, 2026, 29(2): 271-299.
8. Wang FH, Zhang XT, Tang L, et al. The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer, 2023. Cancer Commun (Lond), 2024, 44(1): 127-172.
9. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet, 2021, 398(10294): 27-40.
10. Rha SY, Oh DY, Ya?ez P, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol, 2023, 24(11): 1181-1195.
11. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet, 2010, 376(9742): 687-697.
12. Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med, 2023, 29(8): 2133-2141.
13. Shitara K, Lordick F, Bang YJ, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet, 2023, 401(10389): 1655-1668.
14. van Hootegem SJM, Guchelaar NAD, van der Sluis K, et al. Staging laparoscopy for gastric cancer: European consensus. Br J Surg, 2025, 112(9): znaf144. doi: 10.1093/bjs/znaf144.
15. Schena CA, Laterza V, De Sio D, et al. The role of staging laparoscopy for gastric cancer patients: current evidence and future perspectives. Cancers (Basel), 2023, 15(13): 3425. doi: 10.3390/cancers15133425.
16. Boshier PR, Chia DKA, Thrumurthy SG, et al. Management of gastric cancer peritoneal metastasis: International Gastric Cancer Association GCPM Working Group consensus statements. Br J Surg, 2026, 113(4): znag027. doi: 10.1093/bjs/znag027.
17. Butensky SD, Bansal VV, Su DG, et al. Consensus guideline for the management of gastric cancer with synchronous peritoneal metastases. Ann Surg Oncol, 2025. doi: 10.1245/s10434-025-17361-2.
18. Huang B, Rampulla V, Ri M, et al. Staging laparoscopy with peritoneal lavage to identify peritoneal metastases and free intraperitoneal cancer cells in the management of locally advanced gastric cancer. Eur J Surg Oncol, 2022, 50(6): 108059. doi: 10.1016/j.ejso.2024.108059.
19. Ostowari A, Chen KT, Hasjim BJ, et al. Underutilization of staging laparoscopy prior to neoadjuvant systemic therapy in gastric cancer. Ann Surg Oncol, 2026, 33(2): 1343-1349.
20. Hu YF, Deng ZW, Liu H, et al. Staging laparoscopy improves treatment decision-making for advanced gastric cancer. World J Gastroenterol, 2016, 22(5): 1859-1868.
21. Acs M, Piso P, Glockzin G. Peritoneal metastatic gastric cancer: local treatment options and recommendations. Curr Oncol, 2024, 31(3): 1445-1459.
22. Lewis KA, Diggs LP, Badgwell BD. Educational review: updates on therapeutic strategies for gastric cancer with peritoneal metastasis. Ann Surg Oncol, 2025, 32(5): 3672-3687.
23. Tajik F, Eyob B, Khan AM, et al. Iterative intraperitoneal chemotherapy in gastric cancer peritoneal carcinomatosis. Cancers (Basel), 2025, 17(2): 289-304.
24. Kobayashi D, Kodera Y, Fukushima R, et al. Phase Ⅱ study of intraperitoneal administration of paclitaxel combined with S-1 and cisplatin for gastric cancer with peritoneal metastasis. Ann Surg Oncol, 2024, 31(2): 735-743.
25. Seo WJ, Kim DW, Lee CM, et al. Intraperitoneal paclitaxel with systemic S-1 plus oxaliplatin for advanced or recurrent gastric cancer with peritoneal metastasis: a single-arm, multicenter phase Ⅱ clinical trial. Eur J Surg Oncol, 2025, 51(6): 109603. doi: 10.1016/j.ejso.2025.109603.
26. Chia DKA, Sundar R, Kim G, et al. Outcomes of a phase Ⅱ study of intraperitoneal paclitaxel plus systemic capecitabine and oxaliplatin (XELOX) for gastric cancer with peritoneal metastases. Ann Surg Oncol, 2022, 29(13): 8597-8605.
27. Miyatani K, Miyauchi W, Kono Y, et al. Successful treatment of peritoneal recurrence after gastric cancer surgery with intravenous and intraperitoneal paclitaxel combined with S-1 chemotherapy: a case report. Surg Case Rep, 2020, 6(1): 88. doi: 10.1186/s40792-020-00849-2.
28. Jin ZJ, Lu S, Shi M, et al. Perioperative systemic and prophylactic intraperitoneal chemotherapy for type 4/large type 3 gastric cancer: DRAGON-10. Future Oncol, 2024, 20(36): 2833-2838.
29. Rietveld PCS, Guchelaar NAD, Sassen SDT, et al. A clinical pharmacological perspective on intraperitoneal chemotherapy. Drugs, 2025, 85(7): 931-943.
30. Tamura K, Kitayama J, Saga Y, et al. Combined intraperitoneal and systemic chemotherapy for peritoneal metastases: drug delivery concepts, pharmacokinetics, and clinical applications: a narrative review. Pharmaceutics, 2026, 18(2): 179-206.
31. 朱正綱. 紫杉醇與替吉奧聯合防治胃癌腹膜轉移的臨床療效. 中華胃腸外科雜志, 2015, 18(10): 979-982.
32. Chen X, Wei Y, Chen X, et al. Hydrogel-based intraperitoneal drug delivery platforms for peritoneal metastasis: strategies, advances, and prospects. Drug Deliv, 2025, 33(1): 2576199. doi: 10.1080/10717544.2025.2576199.
33. Yoshida K, Yamaguchi K, Okumura N, et al. Is conversion therapy possible in stage Ⅳ gastric cancer: the proposal of new biological categories of classification. Gastric Cancer, 2016, 19(2): 329-338.
34. Han HS, Rha SY. From control to conversion: optimizing systemic therapy for curative-intent conversion surgery in metastatic gastric cancer. J Gastric Cancer, 2026, 26(1): 146-160.
35. Yoshida K, Yasufuku I, Terashima M, et al. International retrospective cohort study of conversion therapy for stage Ⅳ gastric cancer 1 (CONVO-GC-1). Ann Gastroenterol Surg, 2021, 6(2): 227-240.
36. Choo J, Sargsyan A, Khachatryan V, et al. Advances in the management of metastatic gastric cancer: current strategies and emerging therapeutics. Nat Rev Clin Oncol, 2026. doi: 10.1038/s41571-026-01134-1.

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The key points of normothermic intraperitoneal and systemic treatment for gastric cancer with peritoneal metastasis

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