Is neoadjuvant therapy an alternative strategy to immediate surgery in locally perforated colon cancer?

BACKGROUND: Perforations are a rare but serious complication of colorectal cancer. The current standard of treatment is emergent surgery followed by adjuvant chemotherapy. The concern with this approach is not only the uncertainty of achieving a R0 resection but also potential injury to adjacent vessels, nerves and ureters due to inflamed tissue planes. A subset of this patient population with a contained perforation who are clinically stable may have superior oncological outcomes with local sepsis control, neoadjuvant therapy followed by radical resection. The aim of this study is to report on the pre-operative safety profile for neoadjuvant therapy in the setting of an abscess from colon cancer perforation and the short-term oncological surgical quality outcomes. METHODS: In this retrospective observational study, all consecutive perforated colon cancer receiving neoadjuvant therapy from Jan 2010 to Dec 2019 were included. RESULTS: There were 21 patients that met the inclusion criteria. The most common symptom at presentation was abdominal pain (71.4%) and most common site of perforation was sigmoid colon (61.9%). Local sepsis control was achieved with a combination of radiological or surgical drainage, diverting ostomy and/or intravenous antibiotics. Thirteen patients had long-course chemoradiation and eight patients had neoadjuvant chemotherapy. Of these, 13 (61.9%) had tumour regression, with one patient having a pathological complete response. All patients achieved a R0 resection. CONCLUSIONS: In a small subset of patients with colon cancer perforation, this study has demonstrated the potential safe usage of neoadjuvant therapy first before radical surgery to achieve a clear resection margin.

Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review and meta-analysis.

BACKGROUND: There is increasing evidence to support the use of neoadjuvant chemotherapy (NAC) in locally advanced colon cancer (LACC). However, its safety, efficacy and side effect profile is yet to be completely elucidated. This review aims to assess NAC regimens, duration, compare completion rates, intra-operative and post-operative complication profiles and oncological outcomes, in order to provide guidance for clinical practice and further research. METHODS: PubMed, EMBASE and MEDLINE were searched for a systematic review of the literature from 2000 to 2020. Eight eligible studies were included, with a total of 1213 patients, 752 (62%) of whom received NAC. Of the eight studies analysed, two were randomised controlled trials comparing neoadjuvant chemotherapy followed by oncological resection to upfront surgery and adjuvant chemotherapy, three were prospective single-arm phase II trials analysing neoadjuvant chemotherapy followed by surgery only, one was a retrospective study comparing neoadjuvant chemotherapy followed by surgery versus surgery first followed by adjuvant chemotherapy and the remaining two were single-arm retrospective studies of neoadjuvant chemotherapy followed by surgery. RESULTS: All cases of LACC were determined and staged by computed tomography; majority of the studies defined LACC as T3 with extramural depth of 5 mm or more, T4 and/or nodal positivity. NAC administered was either folinic acid, fluorouracil and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (XELOX) with the exception of one study which utilised 5-fluorouracil and mitomycin. Most studies had NAC completion rates of above 83% with two notable exceptions being Zhou et al. and The Colorectal Cancer Chemotherapy Study Group of Japan who both recorded a completion rate of 52%. Time to surgery from completion of NAC ranged on average from 16 to 31 days. The anastomotic leak rate in the NAC group ranged from 0 to 4.5%, with no cases of postoperative mortality. The R0 resection rate in the NAC group was 96.1%. Meta-analysis of both RCTs included in this study showed that neoadjuvant chemotherapy increased the likelihood of a negative resection margin T3/4 advanced colon cancer (pooled relative risk of 0.47 with a 95% confidence interval) with no increase in adverse consequence of anastomotic leak, wound infection or return to theatre. CONCLUSIONS: Our systematic review and meta-analysis show that NAC is safe with an acceptable side effect profile in the management of LACC. The current data supports an oncological benefit for tumour downstaging and increased in R0 resection rate.