Risk-Adapted Neoadjuvant Chemoradiotherapy in Rectal Cancer?

Megan Brooks

June 27, 2023


Patients with localized rectal cancer classified as low risk can skip neoadjuvant chemoradiotherapy (nCRT) with an acceptably low risk of local relapse, new research suggests. 


  • A prospective study of patients with stage cT2-4 rectal cancer classified into high- and low-risk groups based on a mix of factors, which dictated treatment.

  • Overall, 530 low-risk patients (tumor-free mesorectal fascia) underwent upfront total mesorectal excision (TME) and 354 high-risk patients received nCRT followed by TME.

  • The primary endpoint was 5-year locoregional recurrence; 5-year distant metastases was a secondary outcome.

  • A subgroup analysis divided 570 patients with tumors in the lower and middle rectal third, classified as clinical stages II and III, into low- and high-risk groups.


  • The overall 5-year locoregional recurrence was 4.1% for protocol-treated patients, 2.9% for low-risk patients who had upfront TME, and 5.7% for high-risk patients who had nCRT followed by TME.

  • The 5-year rates of distant metastases were 15.9% for low-risk patients and 30.5% for high-risk patients.

  • In the subgroup, low-risk patients had slightly higher rates of 5-year locoregional recurrence (3.8%) and distant metastases (16.8%).

  • In the subgroup, high-risk patients with involved mesorectal facia and/or cT4 tumors who received nCRT then TME exhibited the highest risk of metastases (34.5%).


"These data support de-escalation of nCRT in low-risk patients and escalation of neoadjuvant therapy in high-risk patients to improve long-term outcomes," the authors write.


The study, led by Reinhard Ruppert, MD, with Municipal Hospital of Munich-Neuperlach, Munich, Germany, was published June 19 in the Journal of Clinical Oncology


This study was nonrandomized and lacked a true comparator group. There was a high percentage of protocol deviation.


The study had no commercial funding. Ruppert reported no relevant disclosures. Some authors disclosed relationships with Intuitive Surgical, Johnson & Johnson/Janssen, Serag-Wiessner, Merck Serono, and AbbVie.


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