Principles of Adjuvant and Neoadjuvant Therapy for Locally Advanced Rectal Cancer

  • Sepehr Khorasani
  • Arun Nagarajan
  • Timothy Nguyen
  • Sami A. ChadiEmail author


More than half the patients with rectal cancer present with locally advanced rectal disease at diagnosis with a high risk of recurrence. Preoperative chemoradiotherapy and standardized radical surgery with total mesorectal excision have been established as the ‘gold standard’ for treating these patients. Pathological staging using the ypTNM classification system to decide on adjuvant chemotherapy (ACT) is widely used in clinical practice, but the delivery of ACT is still controversial, as many discrepancies persist in the conclusions of different trials, due to heterogeneity of the inclusion criteria between studies, lack of statistical power, and variations in preoperative and adjuvant regimens. In 2014, a meta-analysis of four randomized phase-III trials (EORTC 22921, I-CNR-RT, PROCTOR-SCRIPT, CHRONICLE) failed to demonstrate any statistical efficacy of fluorouracil (5FU)-based ACT. Three recent randomized trials aimed to compare 5FU with 5FU plus oxaliplatin-based chemotherapy. Two of them (ADORE, CAO/ARO/AIO-04) appeared to find a disease-free survival benefit for patients treated with the combination therapy. Thus, while awaiting new data, it can be said that, as of 2015, patients with yp stage I tumors or histological complete response derived no benefit from adjuvant therapy. On the other hand, the FOLFOX chemotherapy regimen should be proposed for yp stage III patients, and may be considered for yp stage II tumors in fit patients with high-risk factors. Nevertheless, well-designed and sufficiently powered clinical trials dedicated to adjuvant treatments for rectal cancer.


Adjuvant therapy Neoadjuvant therapy Locally advanced rectal cancer Chemoradiotherapy Recurrence Total mesorectal excision Pathological staging Randomized trials Tumor staging 


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  • Sepehr Khorasani
    • 1
  • Arun Nagarajan
    • 2
  • Timothy Nguyen
    • 3
  • Sami A. Chadi
    • 1
    Email author
  1. 1.Department of SurgeryUniversity Health Network, University of TorontoTorontoCanada
  2. 2.Department of Radiation OncologyCleveland Clinic FloridaWestonUSA
  3. 3.Department of Hematology/OncologyCleveland Clinic FloridaWestonUSA

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