Total neoadjuvant treatment for MRI-stratified high-risk rectal cancer: a single-center, single-arm, prospective Phase II trial (PKUCH-R02)

Peng-Ju Chen; Lin Wang; Ting-Ting Sun; Yun-Feng Yao; Yi-Fan Peng; Jun Zhao; Tian-Cheng Zhan; Jia-Hua Leng; Yong Cai; Yong-Heng Li; Xiao-Yan Zhang; Ying-Shi Sun; Zhong-Wu Li; Wei-Hu Wang; Ai-Wen Wu

doi:10.1093/gastro/goad017

Total neoadjuvant treatment for MRI-stratified high-risk rectal cancer: a single-center, single-arm, prospective Phase II trial (PKUCH-R02)

Gastroenterol Rep (Oxf). 2023 Apr 18:11:goad017. doi: 10.1093/gastro/goad017. eCollection 2023.

Authors

Affiliations

¹ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Cancer Unit III, Peking University Cancer Hospital & Institute, Beijing, P. R. China.
² Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, P. R. China.
³ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiology, Peking University Cancer Hospital & Institute, Beijing, P. R. China.
⁴ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, P. R. China.

Abstract

Background: Induction chemotherapy combined with neoadjuvant chemoradiotherapy has been recommended for patients with high-risk, locally advanced rectal cancer. However, the benefit of more intensive total neoadjuvant treatment (TNT) is unknown. This study aimed to assess the safety and efficacy of induction chemotherapy combined with chemoradiotherapy and consolidation chemotherapy for magnetic resonance imaging-stratified high-risk rectal cancer.

Methods: This was a single-center, single-arm, prospective Phase II trial in Peking University Cancer Hospital (Beijing, China). Patients received three cycles of induction oxaliplatin and capecitabine (CapeOX) followed by chemoradiotherapy and two cycles of consolidation CapeOX. The primary end point was adverse event rate and the second primary end points were 3-year disease-free survival rate, completion of TNT, and pathological downstaging rate.

Results: Between August 2017 and August 2018, 68 rectal cancer patients with at least one high risk factor (cT3c/3d/T4a/T4b, cN2, mesorectal fascia involvement, or extramural venous invasion involvement) were enrolled. The overall compliance of receiving the entire treatment was 88.2% (60/68). All 68 patients received induction chemotherapy, 65 received chemoradiotherapy, and 61 received consolidation chemotherapy. The Grade 3-4 adverse event rate was 30.8% (21/68). Nine patients achieved clinical complete response and then watch and wait. Five patients (7.4%) developed distant metastasis during TNT and received palliative chemotherapy. Fifty patients underwent surgical resection. The complete response rate was 27.9%. After a median follow-up of 49.2 months, the overall 3-year disease-free survival rate was 69.7%.

Conclusions: For patients with high-risk rectal cancer, this TNT regimen can achieve favorable survival and complete response rates but with high toxicity. However, it is necessary to pay attention to the possibility of distant metastasis during the long treatment period.

Keywords: MRI; neoadjuvant chemoradiotherapy; pathological complete response; prognosis; rectal cancer.