Multimodal treatment strategies have significantly improved the long-term results in the treatment of non-metastatic EGAC. Up to date, there is an ongoing debate about the best treatment option for EGAC with oligometastatic disease. Synchronous metastatic disease is seen in up to 14% of cases [13, 14]. Up to date, guidelines across Europe do not recommend multimodal treatment including surgery for patients with distant metastases, but rather recommend palliative chemotherapy [6, 15, 16]. The value of surgery for metastases, especially for liver metastases originating from colorectal cancer, has evolved over the last few years as it has been shown to improve long-term and disease-free survival, with 5 year survival rates of 25% − 40% [17, 18]. Thus, the option of surgery as a potential curative treatment is standardly offered to patients with hepatic metastatic colorectal disease. Furthermore, even though the addition of treatment modalities like cytoreductive surgery and HIPEC have been shown to prolong survival in selected patients with gastrointestinal and gynecological tumors there is in an ongoing debate about the best management of patients with metastatic disease [19–21]. Although some retrospective studies suggest an improved survival of patients with surgical resection of metastases for EGAC [22, 23], there is a lack of prospective, randomized evidence. There is currently an ongoing RCT comparing surgical intervention for oligometastatic disease to the effectiveness of palliative chemotherapy .
Comparing our survival data with the existing literature, certain consistencies can be identified. The median survival of all patients included in this study was 15 months, the data in the literature ranges from 13–31 months [9, 10, 13]. Most definitions of oligometastatic disease, however, do not include peritoneal carcinomatosis. A difference in 5-year survival is shown between lymphatic and hepatic metastases (43% and 40%) compared to peritoneal carcinomatosis of 11%, suggesting that results might differ according to which definition of oligometastases was used. Patients with peritoneal carcinomatosis are often only treated with best supportive care or palliative chemotherapy, with a median survival of 4 and 7 months, respectively . Our data suggests median survival rates of 13 months for patients with peritoneal carcinomatosis and perioperative chemotherapy followed by surgery, with 15 patients receiving additional HIPEC. The median survival correlates with data found in the literature regarding HIPEC and gastric cancers quoting median survival of between 10 and 21 months [25–27]. Although some authors suggest an improved overall survival for patients with limited peritoneal metastatic disease and HIPEC, it is not introduced in national and international treatment guidelines for patients with EGAC [25, 26, 28–30].
Different studies suggest a significantly improved overall survival of patients with surgical resection of the primary EGAC and metastases [8–10, 13, 14, 31], although results from RCTs are still anticipated. Patients without any detectable metastases after perioperative chemotherapy and surgical resection (ypM0) had a similar overall survival to patients without any metastatic disease at primary diagnosis (48% and 52% at 5 years, respectively), demonstrating the effectiveness of good response to neoadjuvant chemotherapy. Similar survival benefits could not be established with chemotherapy alone. Median survival for patients with ypM0 of 47 months compares to median survival quoted in the literature for patients after FLOT therapy for locally advanced tumors of 50 months . The phase 2 AIO-FLOT3 trial suggests better overall survival after resection compared to chemotherapy alone, quoting almost double the median survival (31.3 months vs 15.9 months) . Patients selected for surgery of metastases had to show a chance of R0 resection of the primary and metastatic lesion at restaging, assuming a good response to preoperative chemotherapy. Metastases found intraoperatively suggest either progress of disease or lack of sensitivity of staging diagnostics.
Although results in the literature suggest a favorable outcome for patients with perioperative FLOT chemotherapy and surgery of the primary and metastases, we could not directly reproduce these results in our analysis. Similar to our results, a large retrospective analysis of 5185 patients did not show a survival benefit of simultaneous resection of metastases compared to resection of the primary alone . Prognostic factors were pT- staging, regression grading and type of recurrence. Although some studies suggest significant influence of age, gender, sex, tumor location and nodal stage [2, 8, 13, 33] a significance could not be reproduced for patients with oligometastatic disease from EGAC.
Limitations of this study included foremost the sample size of 48 heterogenous patients and the retrospective, non-randomized nature of this study. The patients analyzed in this manuscript are a highly selected collective of patients with metastasized EGAC, who underwent surgical resection. The majority of patients with metastatic disease received palliative chemotherapy only. Secondly, all types of metastases were included in our study, with some patients receiving additional HIPEC. In single cases a misdiagnosis of preoperative cM1 status in patients with postoperative ypM0 status is possible and may thus create a bias. Furthermore, a multidisciplinary tumor board only selected patients with a good response to chemotherapy to proceed to surgery, for a potential cure of malignant disease.