Cancers 2023, 15, 5451. https://doi.org/10.3390/cancers15225451 www.mdpi.com/journal/cancers Article Primary Tumor Resection in Synchronous Metastatic Colorectal Cancer Patients Treated with Upfront Chemotherapy plus Bevacizumab: A Pooled Analysis of TRIBE and TRIBE2 Studies Valentina Fano(o 1,† , Daniele Rossini 2,3,† , Mariaelena Casagrande 1 , Francesca Bergamo 4 , Andrea Spagnole(i 5 , Daniele Santini 6 , Carlo(a Antonio(i 2,3 , Samanta Cupini 7 , Francesca Daniel 4 , Vincenzo Nasca 5 , Guglielmo Vetere 2,3 , Alberto Zaniboni 8 , Beatrice Borelli 2,3 , Martina Carullo 2,3 , Veronica Conca 2,3 , Alessandro Passardi 9 , Emiliano Tamburini 10 , Gianluca Masi 2,3 , Nicole(a Pella 1 and Chiara Cremolini 2,3, * 1 Department of Oncology, Academic Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy; valentina.fano/o@asufc.sanita.fvg.it (V.F.); mariaelena.casagrande@asufc.sanita.fvg.it (M.C.); nicole/a.pella@asufc.sanita.fvg.it (N.P.) 2 Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; daniele.rossini@unifi.it (D.R.); carlo/a.antonio/i@unipi.it (C.A.); g.vetere1@studenti.unipi.it (G.V.); beatrice.borelli@phd.unipi.it (B.B.); m.carullo@studenti.unipi.it (M.C.); veronica.conca@phd.unipi.it (V.C.); gianluca.masi@unipi.it (G.M.) 3 UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy 4 Medical Oncology 1, Veneto Institute of Oncology IOV—IRCCS, 35128 Padua, Italy; francesca.bergamo@iov.veneto.it (F.B.); francesca.daniel@iov.veneto.it (F.D.) 5 Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, 20133 Milan, Italy; andrea.spagnole/i@unimi.it (A.S.); vincenzo.nasca@unimi.it (V.N.) 6 Medical Oncology Unit A, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy; daniele.santini@uniroma1.it 7 Department of Oncology, Division of Medical Oncology, Azienda USL Toscana Nord Ovest, 57124 Livorno, Italy; samanta.cupini@uslnordovest.toscana.it 8 Oncology Department, Istituto Ospedaliero Fondazione Poliambulanza, 25124 Brescia, Italy; alberto.zaniboni@poliambulanza.it 9 Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy; alessandro.passardi@irst.emr.it 10 Oncology Department and Palliative Care, Cardinale Panico Tricase City Hospital, 73039 Tricase, Italy; Etamburini@piafondazionepanico.it * Correspondence: chiara.cremolini@unipi.it † These authors have contributed equally to this work. Simple Summary: The management of primary tumors in metastatic colorectal cancer patients is still a broad and controversial scenario. While in the case of symptomatic primary tumors, the indication for surgery is a need rather than a choice, in the case of asymptomatic patients, literature data are conflicting about the benefit of primary tumor resection in terms of survival. This pooled analysis of patients enrolled in TRIBE and TRIBE2 studies revealed that primary tumor resection at baseline was independently associated with good prognosis and with lower incidence of serious gastrointestinal and surgical adverse events during upfront chemotherapy plus bevacizumab. Moreover, we observed that the benefit and toxicity profile of FOLFOXIRI plus bevacizumab was independent of the primary tumor resection. In the absence of strong evidence from randomized trials and considering the failure of many studies in this field, our results support the choice of primary tumor resection in selected asymptomatic patients. Abstract: Background: The decision to resect or not the primary tumor in asymptomatic patients with synchronous metastatic colorectal cancer (mCRC) is a complex and challenging issue for oncologists, especially when an antiangiogenic-based therapy is planned. Methods: Patients enrolled in the phase III TRIBE and TRIBE2 studies that compared upfront FOLFOXIRI + bevacizumab to FOLFIRI or FOLFOX + bevacizumab, respectively, were included. We assessed the association of primary tumor resection (PTR) with progression-free survival (PFS), overall survival Citation: Fano/o, V.; Rossini, D.; Casagrande, M.; Bergamo, F.; Spagnole/i, A.; Santini, D.; Antonio/i, C.; Cupini, S.; Daniel, F.; Nasca, V.; et al. Primary Tumor Resection in Synchronous Metastatic Colorectal Cancer Patients Treated with Upfront Chemotherapy plus Bevacizumab: A Pooled Analysis of TRIBE and TRIBE2 Studies. Cancers 2023, 15, 5451. h/ps://doi.org/ 10.3390/cancers15225451 Academic Editor: David Wong Received: 7 October 2023 Revised: 8 November 2023 Accepted: 11 November 2023 Published: 16 November 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, SwiNerland. This article is an open access article distributed under the terms and conditions of the Creative Commons A/ribution (CC BY) license (h/ps://creativecommons.org/license s/by/4.0/).