Total Mesorectal Excision(TME) With Lateral Lymph Node Dissection Versus TME After Neoadjuvant Chemo-radiotherapy

Official title

Total Mesorectal Excision(TME) With Lateral Lymph Node Dissection Versus TME After Neoadjuvant Chemo-radiotherapy of Lower Rectal Cancer With Suspected Local Lymph Node Metastasis

Overview

Treatment for Low rectal cancer, especially in patients with regional lymph node metastasis are quite different between Japanese guideline (JSCCR) and western countries' guideline (NCCN, ESMO). While Japanese scholars advocate total mesorectal excision (TME) plus lateral lymph node dissection (LLND), European and American scholars advocate TME alone after Neoadjuvant Chemo-radiotherapy (nCRT), without the need of LLND. Accordingly, this clinical trial is designed to directly compare the efficacy and safety of these two treatment strategies for low rectal cancer with regional lymph node metastasis. It will provide high-level clinical evidence for the treatment of low rectal cancer with suspected local lymph node metastasis

Detailed description

There are significant differences between Japanese guidelines (JSCCR) and Western guidelines (NCCN, ESMO) in the treatment of low rectal cancer, especially in patients with regional lymph node metastasis. Japanese scholars advocated total meso rectal resection (TME) + Lateral lymph node dissection (LLND), However, European and American scholars advocate that only TME is used after new adjuvant chemo-radiation (nCRT), without LLND. Therefore, the purpose of this clinical trial was to directly compare the efficacy and safety of these two treatment strategies for low rectal cancer with regional lymph node metastasis. This will provide a high level of clinical evidence for the treatment of low rectal cancer with suspected local lymph node metastasis

Interventions

• Procedure TME+LLND
  patients in TME+LLND group receive Lateral Lymph Node Dissection (LLND) after Total Mesorectal Excision(TME)
• Procedure TME+nCRT
  patients in TME+nCRT group receive Neoadjuvant Chemo-radiotherapy (nCRT) before Total Mesorectal Excision(TME)

Primary outcome measures

• 3-year disease-free survival [Time frame: From date of operation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years]

Secondary outcome measures (10)

• Operative time [Time frame: Operation day]
• Blood loss [Time frame: Operation day]
• Incidence of sexual dysfunction [Time frame: 3 years]
• Incidence of urinary dysfunction [Time frame: 3 years]
• Incidence of defecation dysfunction [Time frame: 3 years]
• incidence of Postoperative complications [Time frame: 3 months]
• overall survival [Time frame: From the date of operation until the date of death,assessed up to 5 years]
• 3-year local recurrence rate [Time frame: From date of operation until the date of local-recurrence (up to 3 years)]
• 5-year disease-free survival [Time frame: From date of operation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years]
• the score of quality of life [Time frame: 3 months after operation]

Eligibility criteria

Inclusion criteria

• Histologically confirmed adenocarcinoma(below the peritoneal reflection) Clinical stage Ⅲ
• Tumor is capable of performing radical recession
• No past history of chemotherapy, pelvic radiation of other cancers.
• Written informed consent
• Lower tumor margin is confirmed below the peritoneal reflection
• Clinical state T(1-3)N(1-2)M0 is confirmed by the multiple disciplines team(MDT) including surgeons,diagnostic radiologist,radiation oncologist and medical oncologists base on MRI and endorectal ultrasound -

Exclusion criteria

• Past history of other cancers
• Multiple Primary Colorectal Cancers or Familial adenomatous polyposis(FAP)
• Combine with inflammatory bowl disease(IBD)
• Recurrence tumor or invade other organs
• Combine with obstruction,perforation or bleeding which need emergency surgery.
• Local tumor invade the external sphincter, levator ani muscle or adjacent organs
• Participant join other clinical trials in 4 weeks.
• American Society of Anesthesiologists(ASA) ≥Ⅳ and/or Eastern Cooperative Oncology Group(ECOG) ≤2
• Pregnant or lactating patients
• Severity infection before operation
• Psychological disorder
• Severe dysfunction of organs or other contraindications
• Cardiac infarction within six months
• Severe pulmonary emphysema and pulmonary fibrosis
• Doctor's decision for exclusion
• Operative findings:

Tumor invade other organs Lower tumor margin is above the peritoneal reflection

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Sixth Affiliate Hospital of Sun Yat-Sen University — Guangzhou

Publications

• Ito M, Kobayashi A, Fujita S, Mizusawa J, Kanemitsu Y, Kinugasa Y, Komori K, Ohue M, Ota M, Akazai Y, Shiozawa M, Yamaguchi T, Akasu T, Moriya Y; Colorectal Cancer Study Group of Japan Clinical Oncology Group. Urinary dysfunction after rectal cancer surgery: Results from a randomized trial comparing mesorectal excision with and without lateral lymph node dissection for clinical stage II or III low PMID 29428473
• Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. Modified FOLFOX6 With or Without Radiation Versus Fluorouracil and Leucovorin With Radiation in Neoadjuvant Treatment of Locally Advanced Rectal Cancer: Initial Results of the Chinese FOWAR PMID 27480145
• Qin Q, Ma T, Deng Y, Zheng J, Zhou Z, Wang H, Wang L, Wang J. Impact of Preoperative Radiotherapy on Anastomotic Leakage and Stenosis After Rectal Cancer Resection: Post Hoc Analysis of a Randomized Controlled Trial. Dis Colon Rectum. 2016 Oct;59(10):934-42. doi: 10.1097/DCR.0000000000000665. PMID 27602924
• Huang M, Lin J, Yu X, Chen S, Kang L, Deng Y, Zheng J, Luo Y, Wang L, Lan P, Wang J. Erectile and urinary function in men with rectal cancer treated by neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy alone: a randomized trial report. Int J Colorectal Dis. 2016 Jul;31(7):1349-57. doi: 10.1007/s00384-016-2605-7. Epub 2016 Jun 6. PMID 27270480
• Shinagawa T, Tanaka T, Nozawa H, Emoto S, Murono K, Kaneko M, Sasaki K, Otani K, Nishikawa T, Hata K, Kawai K, Watanabe T. Comparison of the guidelines for colorectal cancer in Japan, the USA and Europe. Ann Gastroenterol Surg. 2017 Dec 19;2(1):6-12. doi: 10.1002/ags3.12047. eCollection 2018 Jan. PMID 29863118
• Fujita S, Akasu T, Mizusawa J, Saito N, Kinugasa Y, Kanemitsu Y, Ohue M, Fujii S, Shiozawa M, Yamaguchi T, Moriya Y; Colorectal Cancer Study Group of Japan Clinical Oncology Group. Postoperative morbidity and mortality after mesorectal excision with and without lateral lymph node dissection for clinical stage II or stage III lower rectal cancer (JCOG0212): results from a multicentre, randomised co PMID 22591948
• Fujita S, Mizusawa J, Kanemitsu Y, Ito M, Kinugasa Y, Komori K, Ohue M, Ota M, Akazai Y, Shiozawa M, Yamaguchi T, Bandou H, Katsumata K, Murata K, Akagi Y, Takiguchi N, Saida Y, Nakamura K, Fukuda H, Akasu T, Moriya Y; Colorectal Cancer Study Group of Japan Clinical Oncology Group. Mesorectal Excision With or Without Lateral Lymph Node Dissection for Clinical Stage II/III Lower Rectal Cancer (JCOG PMID 28288057
• Nagawa H, Muto T, Sunouchi K, Higuchi Y, Tsurita G, Watanabe T, Sawada T. Randomized, controlled trial of lateral node dissection vs. nerve-preserving resection in patients with rectal cancer after preoperative radiotherapy. Dis Colon Rectum. 2001 Sep;44(9):1274-80. doi: 10.1007/BF02234784. PMID 11584199

Identifiers

NCT: NCT03587480 · Luo-20180624

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗