Interventions and Outcomes for Neoadjuvant Treatment of T4 Colon Cancer: A Scoping Review.

Flora Jung,Marina Englesakis,Grace Zhao,Sami Chadi,Grainne O’Kane,Fayez Quereshy,Sachin Doshi,Kimberley Lam-Tin-Cheung,Michael Lee,Jelena Lukovic,Tyler Chesney,Keegan Guidolin

doi:10.3390/curroncol28030191

Abstract

While adjuvant treatment of colon cancers that penetrate the serosa (T4) have been well-established, neoadjuvant strategies have yet to be formally evaluated. Our objective was to perform a scoping review of eligibility criteria, treatment regimens, and primary outcomes for neoadjuvant approaches to T4 colon cancer. A librarian-led, systematic search of MEDLINE, Embase, Cochrane Library, Web of Science, and CINAHL up to 11 February 2020 was performed. Primary research evaluating neoadjuvant treatment in T4 colon cancer were included. Screening and data abstraction were performed in duplicate; analyses were descriptive or thematic. A total of twenty studies were included, most of which were single-arm, single-center, and retrospective. The primary objectives of the literature to date has been to evaluate treatment feasibility, tumor response, disease-free survival, and overall survival in healthy patients. Conventional XELOX and FOLFOX chemotherapy were the most commonly administered interventions. Rationale for selecting a specific regimen and for treatment eligibility criteria were poorly documented across studies. The current literature on neoadjuvant strategies for T4 colon cancer is overrepresented by single-center, retrospective studies that evaluate treatment feasibility and efficacy in healthy patients. Future studies should prioritize evaluating clear selection criteria and rationale for specific neoadjuvant strategies. Validation of outcomes in multi-center, randomized trials for XELOX and FOLFOX have the most to contribute to the growing evidence for this poorly managed disease.

Highlights

While 10 to 15% of patients with colon cancer are diagnosed with disease that penetrates the colonic serosa (T4), the outcomes for T4 colon cancer remain poor [1,2]
Neoadjuvant FOLFOX is reportedly associated with tumor downstaging, pathologic complete response, near-complete tumor regression, negative margin resection, and reduced perioperative morbidity
Our review protocol was developed a priori and submitted to Open Science Framework (OSF) on 16 August 2021 using methods recommended by the Joanna Briggs Institute (JBI) [18] and the PRISMA-ScR extension [19]

Summary

Introduction

While 10 to 15% of patients with colon cancer are diagnosed with disease that penetrates the colonic serosa (T4), the outcomes for T4 colon cancer remain poor [1,2]. The 2012 FOxTROT (fluoropyrimidine, oxaliplatin, and targeted receptor pre-operative therapy) study is the only randomized, controlled trial to date to evaluate neoadjuvant approaches to T4 colon cancer [15] It compared neoadjuvant FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin) chemotherapy to the conventional direct-to-surgery approach in 150 patients and reported significant improvement in negative margin resection with no negative effects on postoperative morbidity [15]. Based largely on this data, the National Comprehensive Cancer Network added neoadjuvant chemotherapy as a treatment option for T4b disease in 2016; long-term outcome data supporting this recommendation are sparse [16]. Neoadjuvant FOLFOX is reportedly associated with tumor downstaging, pathologic complete response, near-complete tumor regression, negative margin resection, and reduced perioperative morbidity

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