Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group
Dave E. W. van der Kruijssen, Sjoerd G. Elias, Peter M. van de Ven, Karlijn L. van Rooijen, Jorine ‘t Lam-Boer, Linda Mol, Cornelis J.A. Punt, Dirkje W. Sommeijer, Pieter J. Tanis, Jørn Dalsgaard Nielsen, M.K. Yilmaz, J.M.G.H. van Riel, D.K. Wasowiz-Kemps, O. J. L. Loosveld, George P. van der Schelling, J.W.B. de Groot, Henderik L. van Westreenen, Henrik Jakobsen, A.L. Fromm, Paul Hamberg, M. Verseveld, Claudia Jaensch, Gábor Liposits, Peter van Duijvendijk, Jamal Oulad Hadj, Joost A.B. van der Hoeven, Marija Trajkovic, Johannes H.W. de Wilt, M. Koopman, Jeroen Vincent, Johannes A. Wegdam, Brigitte C.M. Haberkorn, Erwin van der Harst, Mathijs P. Hendriks, Wilhelmina H. Schreurs, Huib A. Cense, Ron C. Rietbroek, Marie-José de Gier, Edwin A. van Breugel, Aad I. de Vos, Rebecca P. M. Brosens, Pascal G. Doornebosch, Felix E. de Jongh, Wouter J. Vles, Marien O. den Boer, Jeroen W. A. Leijtens, A. J. Gelderblom, Koen Peeters, Bart C. Kuenen, Bareld B. Pultrum, Joyce M. van Dodewaard-de Jong, Esther C. J. Consten, A.J. Yes van de Wouw, Joop Konsten, Ronald Hoekstra, Martijn F. Lutke Holzik, Allert H. Vos, M.J. van Hoogstraten, Nis H. Schlesinger, Geert-Jan Creemers, Ignace H. J. T. de Hingh, Monica L Kjaer, Lone N. Petersen, Michael Seiersen, Rahim Altaf, Hester van Cruijsen, Daniël A. Hess, Lobke L. van Leeuwen-Snoeks, Apollo Pronk, Coen I.M. Baeten, Wendy M. van der Deure, Koop Bosscha, Heidi Schut, Wouter K. G. Leclercq, Lieke H. J. Simkens, Koen Reijnders, Kees van Arkel, W.M.U. Helma van Grevenstein, Anthony W. H. van de Ven, Ronald J.C.L.M. Vuylsteke, Philomeen Kuijer, Sandra D. Bakker, Hauwy Goei, Helgi H. Helgason, Gijs J.D. van Acker, Mehmet Temizkan, Marc W. A. van Tilburg, Michael F. Gerhards, Emile D. Kerver, Elske C. Gootjes, Peter Nieboer, Wim Bleeker, Gitta Bleeker
Abstract
BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSIONS: Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.