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

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.

Keywords: T4 colon cancer; chemoradiotherapy; chemotherapy; locally advanced colon cancer; neoadjuvant therapy; radiotherapy.

Figure 1

Article selection.

Figure 2

Heatmap graphic showing the distribution of primary outcomes in the current literature on neoadjuvant therapy for T4 colon cancer. Each box in the grid represents the number of studies (color coded per the legend) that use the primary outcome listed on the y-axis to evaluate the neoadjuvant therapy listed on the x-axis. NAT, neoadjuvant therapy; R0, microscopically negative margins; DFS, disease-free survival; OS, overall survival.

Figure 3

Neoadjuvant therapies in the current literature. (Categories are not mutually exclusive. Some trials evaluated more than one neoadjuvant therapy). DTS, direct-to-surgery; CRT, chemoradiotherapy; FOLFOX, folinic acid + 5-fluorouracil + oxaliplatin; FOLFOXIRI, FOLFOX + irinotecan; mFOLFIRI: 5-fluorouracil + irinotecan; XELOX, capecitabine + oxaliplatin; XELOXIRI, XELOX + irinotecan; XELIRI, capecitabine + irinotecan; NAC, neoadjuvant chemotherapy; NAR, neoadjuvant radiotherapy.

Figure 4

Heatmap graphics showing the rationale (A) and eligibility criteria (B) for neoadjuvant therapy for T4 colon cancer. Each box in the grid represents the number of studies (color coded per the legend) that use the rationale (A) or eligibility criteria (B) listed on the y-axis, corresponding to the neoadjuvant therapy listed on the x-axis. (Categories are not mutually exclusive). NAT, neoadjuvant therapy; CRC, colorectal cancer; R0, microscopically negative margins; AC, adjuvant chemotherapy; CT, computed tomography.