Resection of the primary tumour versus no resection prior to systemic therapy in patients with colon cancer and synchronous unresectalbe metastases (UICC stage IV) - A randomised controlled multicentral trial
Final Report Abstract
Systemic chemotherapy improves survival of patients with stage UICC IV colorectal cancer and unresectable metastases. Data from two randomized controlled trials in renal cancer and nonrandomized data from breast and colorectal cancer have suggested the possibility that resection of the primary tumor prior to chemotherapy may further prolong survival. We investigated the prognostic value of primary tumor resection in patients with newly diagnosed stage IV colon cancer who were not amenable to curative treatment. SYNCHRONOUS was designed as a multicenter, randomized, controlled, superiority trial with two parallel groups. Patients with newly diagnosed histologically proven colon cancer and synchronous unresectable metastases were randomly assigned to undergo primary tumor resection (PTR group) or upfront chemotherapy (CTX group). The chemotherapy regimen was left to the discretion of the local team. Patients with prior treatment of the colorectal tumor disease, primary tumor related symptoms, inability to tolerate surgery and/or systemic chemotherapy and history of another primary cancer were excluded. The primary endpoint was overall survival (OS), secondary endpoints were shortand long-term safety, course of tumor markers and quality of life. A total of 295 patients were recruited at 82 sites in Germany and Austria between September 2011 and March 2017. 144 patients were randomized in the PTR and 151 in the CTX group. All demographics and baseline characteristics were similar in both groups with no significant differences (gender, age, BMI, ECOG and ASA status, tumor grade, metastatic site and stage of disease, medical history, laboratory values). With a median follow-up of 36.6, median overall survival (OS) in the intention-to-treat (ITT) population was 17.2 months (95% CI: 14.8-19.6) in the PTR group and 19.1 months (95% CI: 16.2-22.6) in the CTX group. There was no significant difference for OS in the primary analysis p=0.3302 (hazard ratio = 0.866, 95% CI: 0.649-1.156 based on a cox regression model (with shared frailty). Most frequent complications in the PTR group were anastomotic leak with 6.47% and renal failure with 4.17%; other complications like surgical site infection or wound dehiscence, postoperative ileus, abscess, bleeding or general complications as pneumonia, lung embolism, apoplex, myocardial infarction etc. were under 4%. The 30-day mortality was 3.5% in the PTR group. In the CTX group a total of 6 (4%) died within 30 days after randomization. A broad-spectrum chemotherapy regimen was applicated, most frequently FOLFIRI and FOLFOX with or without additional antibody treatment. 23.4% of the patients in the CTX group had at least one complication related to the primary tumor, major complication was am stenosis with 17.2%. In the CTX group more serious adverse events were observed compared to the PTR group (10.2% vs. 18.0%; p = 0.027) and these were primarily related to the gastrointestinal tract. Quality of life analysis showed only few statistically relevant differences between the treatment groups, whose frequency was as expected considering the number of executed tests. Also, these statistically relevant p-values showed no systematic relation over time or frequencies in any scale. Conclusion: Resection of the primary tumor before systemic chemotherapy does not prolong OS in patients with newly diagnosed stage IV colon cancer and synchronous unresectable metastases.
Publications
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Resection of the primary tumour versus no resection prior to systemic therapy in patients with colon cancer and synchronous unresectable metastases (UICC stage IV): SYNCHRONOUS - a randomised controlled multicentre trial (ISRCTN30964555). BMC Cancer, 12(1).
Rahbari, Nuh N; Lordick, Florian; Fink, Christine; Bork, Ulrich; Stange, Annika; Jäger, Dirk; Luntz, Steffen P; Englert, Stefan; Rossion, Inga; Koch, Moritz; Büchler, Markus W; Kieser, Meinhard & Weitz, Jürgen
