The efficacy of treatment options for patients with gastric cancer and peritoneal metastasis
Patients with peritoneal metastases of gastric cancer have a poor prognosis and median survival of 7 months. This study compared treatment options and outcomes based on the Peritoneal Cancer Index (PCI).
This retrospective analysis included patients with gastric cancer treated between August 2008 and December 2017 with synchronous peritoneal metastases only diagnosed by laparoscopy. The three treatments were as follows: (1) cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in combination with pre- and postoperative systemic chemotherapy (n = 58), (2) laparotomy/laparoscopy without CRS, but HIPEC in combination with pre- and postoperative systemic chemotherapy (n = 11), and (3) systemic chemotherapy only (n = 19).
A total of 88 patients aged 54.6 ± 10.9 years with mean PCI of 14.3 ± 11.3 were included. The PCI was significantly lower in group 1 (8.3 ± 5.7) than in group 2 (23.9 ± 11.1, p < 0.001) and group 3 (27.3 ± 9.3, p < 0.001). Mean time from diagnosis to laparoscopy was 5.2 ± 2.9 months. The median overall survival was 9.8 ± 0.7 for group 1, 6.3 ± 3.0 for group 2 and 4.9 ± 1.9 months for group 3 (p < 0.001). Predictors for deteriorated overall patient survival included > 4 cycles of preoperative chemotherapy (HR 4.49, p < 0.001), lymph-node metastasis (HR 3.53, p = 0.005), PCI ≥ 12 (HR 2.11, p = 0.036), and incompleteness of cytoreduction (HR 4.30, p = 0.001) in patients treated with CRS and HIPEC.
CRS and HIPEC showed convincing results in selected patients with PCI < 12 and complete cytoreduction. Prolonged duration (> 4 cycles) of preoperative intravenous chemotherapy reduced patient survival in patients suitable for CRS and HIPEC.
KeywordsPeritoneal metastases Gastric cancer Hyperthermic intraperitoneal chemotherapy Cytoreductive surgery Preoperative chemotherapy
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.
Informed consent or substitute for it was obtained from all patients included in the study.
- 4.Seyfried F, von Rahden BH, Miras AD, Gasser M, Maeder U, Kunzmann V, et al. Incidence, time course and independent risk factors for metachronous peritoneal carcinomatosis of gastric origin—a longitudinal experience from a prospectively collected database of 1108 patients. BMC Cancer. 2015;15:73. https://doi.org/10.1186/s12885-015-1081-8.CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Glehen O, Gilly FN, Boutitie F, Bereder JM, Quenet F, Sideris L, et al. Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1,290 patients. Cancer. 2010;116(24):5608–18. https://doi.org/10.1002/cncr.25356.CrossRefPubMedGoogle Scholar
- 9.Glehen O, Gilly FN, Arvieux C, Cotte E, Boutitie F, Mansvelt B, et al. Peritoneal carcinomatosis from gastric cancer: a multi-institutional study of 159 patients treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy. Ann Surg Oncol. 2010;17(9):2370–7. https://doi.org/10.1245/s10434-010-1039-7.CrossRefPubMedGoogle Scholar
- 10.Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, et al. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008;26(9):1435–42. https://doi.org/10.1200/JCO.2007.13.9378.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki 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):687–97. https://doi.org/10.1016/S0140-6736(10)61121-X.CrossRefGoogle Scholar
- 12.Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016;17(12):1697–708. https://doi.org/10.1016/s1470-2045(16)30531-9.CrossRefGoogle Scholar
- 13.Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29(13):1715–21. https://doi.org/10.1200/jco.2010.33.0597.CrossRefGoogle Scholar
- 16.Imamoto H, Oba K, Sakamoto J, Iishi H, Narahara H, Yumiba T, et al. Assessing clinical benefit response in the treatment of gastric malignant ascites with non-measurable lesions: a multicenter phase II trial of paclitaxel for malignant ascites secondary to advanced/recurrent gastric cancer. Gastric Cancer. 2011;14(1):81–90. https://doi.org/10.1007/s10120-011-0016-6.CrossRefPubMedGoogle Scholar
- 18.Yonemura Y, Endou Y, Shinbo M, Sasaki T, Hirano M, Mizumoto A, et al. Safety and efficacy of bidirectional chemotherapy for treatment of patients with peritoneal dissemination from gastric cancer: selection for cytoreductive surgery. J Surg Oncol. 2009;100(4):311–6. https://doi.org/10.1002/jso.21324.CrossRefPubMedGoogle Scholar
- 19.Badgwell B, Blum M, Das P, Estrella J, Wang X, Ho L, et al. Phase II trial of laparoscopic hyperthermic intraperitoneal chemoperfusion for peritoneal carcinomatosis or positive peritoneal cytology in patients with gastric adenocarcinoma. Ann Surg Oncol. 2017;24(11):3338–44. https://doi.org/10.1245/s10434-017-6047-4.CrossRefPubMedGoogle Scholar
- 21.Nadiradze G, Giger-Pabst U, Zieren J, Strumberg D, Solass W, Reymond MA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with low-dose cisplatin and doxorubicin in gastric peritoneal metastasis. J Gastrointest Surg. 2016;20(2):367–73. https://doi.org/10.1007/s11605-015-2995-9.CrossRefPubMedGoogle Scholar
- 22.Canbay E, Mizumoto A, Ichinose M, Ishibashi H, Sako S, Hirano M, et al. Outcome data of patients with peritoneal carcinomatosis from gastric origin treated by a strategy of bidirectional chemotherapy prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a single specialized center in Japan. Ann Surg Oncol. 2014;21(4):1147–52. https://doi.org/10.1245/s10434-013-3443-2.CrossRefPubMedGoogle Scholar
- 24.Smyth EC, Fassan M, Cunningham D, Allum WH, Okines AF, Lampis A, et al. Effect of pathologic tumor response and nodal status on survival in the medical research council adjuvant gastric infusional chemotherapy trial. J Clin Oncol. 2016;34(23):2721–7. https://doi.org/10.1200/jco.2015.65.7692 (http://www.jco.org. Author contributions are found at the end of this article).
- 31.Al-Batran SE, Homann N, Pauligk C, Illerhaus G, Martens UM, Stoehlmacher J, et al. Effect of neoadjuvant chemotherapy followed by surgical resection on survival in patients with limited metastatic gastric or gastroesophageal junction cancer: the AIO-FLOT3 Trial. JAMA Oncol. 2017;3(9):1237–44. https://doi.org/10.1001/jamaoncol.2017.0515.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Ott K, Sendler A, Becker K, Dittler HJ, Helmberger H, Busch R, et al. Neoadjuvant chemotherapy with cisplatin, 5-FU, and leucovorin (PLF) in locally advanced gastric cancer: a prospective phase II study. Gastric Cancer. 2003;6(3):159–67. https://doi.org/10.1007/s10120-003-0245-4.CrossRefPubMedGoogle Scholar
- 33.Achilli P, De Martini P, Ceresoli M, Mari GM, Costanzi A, Maggioni D, et al. Tumor response evaluation after neoadjuvant chemotherapy in locally advanced gastric adenocarcinoma: a prospective, multi-center cohort study. J Gastrointest Oncol. 2017;8(6):1018–25. https://doi.org/10.21037/jgo.2017.08.13.CrossRefPubMedPubMedCentralGoogle Scholar
- 35.Yang XJ, Huang CQ, Suo T, Mei LJ, Yang GL, Cheng FL, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol. 2011;18(6):1575–81. https://doi.org/10.1245/s10434-011-1631-5.CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Sunakawa Y, Stremitzer S, Cao S, Zhang W, Yang D, Wakatsuki T, et al. Association of variants in genes encoding for macrophage-related functions with clinical outcome in patients with locoregional gastric cancer. Ann Oncol. 2015;26(2):332–9. https://doi.org/10.1093/annonc/mdu542.CrossRefPubMedGoogle Scholar