Total Neoadjuvant Therapy in Rectal Cancer

Abstract

Background: The addition of induction chemotherapy to concomitant neoadjuvant chemoradiation in locally advanced rectal cancer could increase pathological downstaging and act on occult micrometastatic disease, leading ultimately to a better outcome. A systematic review was carried out of the existing literature on the treatment outcomes of total neoadjuvant therapy (TNT) on locally advanced rectal cancer. TNT was defined as chemotherapy using cycles of induction and/or consolidation in conjunction with standard chemoradiotherapy prior to surgery. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was performed according to the PRISMA statement up until January 2019. The primary endpoints were complete pathologic response (pCR), disease-free survival, and overall survival rates. Results: A total of 28 studies (3 retrospective and 25 prospective for a total of 3579 patients) were included in the final analysis (n = 2688 treated with TNT and n = 891 with neoadjuvant chemoradiotherapy therapy). The pooled pCR rate was 22.4% (95% CI 19.4%–25.7%) in all patients treated with TNT (n = 27 studies with data available). In n = 10 comparative studies with data available, TNT was found to increase the odds of pCR by 39% (1.40, 95% CI 1.08–1.81, P = 0.01). Conclusions: The addition of induction or consolidation chemotherapy to standard neoadjuvant chemoradiotherapy results in a higher pCR rate. Given that the comparative analysis was derived from few randomized publications, large confirmatory trials should be carried out before a strong recommendation is made in favor of TNT.

Impact of Total Neoadjuvant Therapy vs. Standard Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis of Randomized Trials

“…In summary, and to the best of our knowledge, our study is the largest meta-analysis on RCTs comparing TNT with standard neoadjuvant treatment in LARC and the first to demonstrate a significant impact on survival based on controlled data. A previous meta-analysis [26] included 28 studies, but the majority were retrospective and non-controlled trials. Only five were RCTs and just two reported survival outcomes.…”

Management strategies for patients with advanced rectal cancer and liver metastases using modified Delphi methodology: results from the PelvEx Collaborative

“…There was consensus that induction chemotherapy should be offered to patients, and this reflects recent literature [22][23][24]. In the setting of symptomatic diseases such as obstruction or fistulation due to local invasion, the majority recommended a diverting stoma before commencing chemotherapy on the basis that this might downstage nonresectable or borderline resectable tumours and increase R0 resection margin rates [25,26].…”

Prognostic Value of Interval Between the Initiation of Neoadjuvant Treatment to Surgery for Patients With Locally Advanced Rectal Cancer Following Neoadjuvant Chemotherapy, Radiotherapy and Definitive Surgery

“…An example of adding cytotoxic drugs was the CAO/ARO/AIO-04 multicenter study, which involved patients with LARC who received neoadjuvant chemoradiotherapy, surgery, and ACT with or without oxaliplatin, and demonstrated 3-year DFS rates of 75.9 and 71.2%, respectively (21). TNT has been evaluated in a meta-analysis which involved 28 studies and demonstrated 3-year DFS and OS rates of 67 and 78.9%, respectively, in patients receiving TNT for LARC (22). Our FORWARC study, which also used an intensified NCT regimen in the preoperative setting, showed that 3-year DFS rates for fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 alone, were 72.9, 77.2, and 73.5%, respectively (23).…”