Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Raltitrexed

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Enzyme Inhibitors

Folinic Acid

Folate

Vitamin B9

Treatment including preoperative chemoradiotherapy (preoperative radiation with concurrent chemotherapy) with Raltitrexed followed by surgery. Radiotherapy will be delivered to a planning target volume with a dose of 45-50.4Gy (1.8-2.0Gy daily) using with Intensity-Modulated Radiotherapy or Volumetric-Modulated Arc Therapy technique. During the radiation treatment, concurrent chemotherapy will be delivered (Raltitrexed, intravenous infusion, 3 mg/m2, on d1 and d22). Pelvic surgery is planned 6 weeks after completion of CRT based on the decision of MDT.

Preoperative radiation

Pelvic surgery

Jing Jin, MD

The aim of this multicenter phase II study is to evaluate the response rate, local control, disease-free survival and treatment-related toxicity of preoperative chemoradiation for intermediate or locally advanced rectal cancer in the fit elderly.

The concurrent chemoradiotherapy has become the standard treatment for patients with intermediate or locally advanced rectal cancer. However, the data from prospective trial for elderly patients is still lacking.

The aim of this multicenter phase II study is to evaluate the response rate, local control, disease-free survival and treatment-related toxicity of preoperative chemoradiation with Raltitrexed for intermediate or locally advanced rectal cancer in the fit elderly aged 70 years above.

And all the participants have to be evaluated by comprehensive geriatric assessment (CGA). Clinical stage was evaluated by chest and abdominal computed tomography, endorectal ultrasound, and/or pelvic magnetic resonance imaging.

5 weeks after the preCRT, the multi-disciplinary team decided the following treatment of patients based on imaging evaluation. Surgical resection would be done with a minimum interval of 6 weeks after the last radiation. Acute toxicity was evaluated during and within 2 weeks after CRT. Toxicities were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.

Sample size consideration.It has been calculated that 68 patients will need to be included, according to the following assumptions:

Recruitment period of 24 months. Minimum follow-up period of 24 months. We estimated that 51 patients were required to test the hypothesis that the 2-year DFS was equal to or greater than 78% with 80% power and to reject the hypothesis that the 2-year DFS rate was less than 63% at a significance level of 5% (one sided).Taking into account that a 5% percentage of losses, 20% of patients will refuse surgery, 68 patients are expected to be included in the study.

The interim analysis design. An interim safety evaluation will be carried out when 39 patients have finished their preoperative CRT. As the tolerance of elderly patients for nonhematological toxicities (such as diarrhoea) was often more poor than hematological toxicities, we estimated that 39 patients were required to test the hypothesis that the nonhematological G3 or higher acute toxicities rate was equal to or less than 21% ( safety result of patients aged 70 years or older from ACCOR12/PRODIGE 2 phase III trial) with 80% power and to reject the hypothesis that the rate was more than 36% at a significance level of 10% (one sided). If nonhematological G3 or higher acute toxicites is observed in12 or more patients, the H0 hypothesis will be rejected, and the protocal should be re-evaluated.

Biospecimen Retention. Blood, plasma, feces and tissue (optional). Feces were collected before any treatment. Peripheral blood samples of 10-20mL were collected from the patients for CTCs analysis, exploration analysis for frailty and tumor marker before and after preCRT, before and after surgery, and then on each follow up visit, according to our study protocal.

Preoperative Chemoradiotherapy With Raltitrexed for Intermediate or Locally Advanced Rectal Cancer in the Fit Elderly

Multicenter, Phase II Study of Preoperative Chemoradiotherapy With Raltitrexed for Intermediate or Locally Advanced Rectal Cancer in the Fit Elderly

To investigate the biomarker from blood or feces (such as circulating tumor cells, circulating tumor DNA) for treatment response and prognosis predicting. To investigate the CGA elements, and willingness evaluation to surgery for predicting the adherence, tolerence and prognosis of patients.

The probability of staying free from recurrence at 2 year after surgery or clinical complete response of tumor validated on imaging or pathological examination.

The probability of staying alive at 5 year after surgery or end of CRT (for those who did not receive surgery).

The probability of staying free from death caused by cancer at 5 year after surgery or end of CRT (for those who did not receive surgery).

The ratio of patients occured pathological complete response of tumor.

The quality of life assessment score by EORTC QLQ-C30 and EORTC QLQ-CR29.

Chinese Academy of Medical Sciences

Vice Chair of Radiation Oncology

The rectum is mobilized and resected transanally (from bottom to up) according to TME principles, via transanal platform (either rigid or flexible platform).An ideal TaTME is defined as the extraperitoneal portion of the rectum being mobilized from below.

The traditional laparoscopic TME (LpTME) was performed via standard laparoscopic techniques, including multiple trocars and conventional laparoscopic instruments.

TaTME

Conventional Laparoscopic Total Mesorectal Excision

LpTME

Liang Kang, MD,PHD

Yi Xiao, MD, PhD

Weidong Tong, MD, PhD

Liang Kang, MD, PhD

Yanan Wang, MD.PhD

Qingwen Xu, MD

Ming Xie, MD

Yi Zhang, MD,PhD

Jun Ouyang, MD

Quan Wang, MD,PhD

Hong Zhang, MD

Yongchun Song, MD

Bo Feng, MD,PhD

Qing Xu, MD, PhD

Mingyang Ren, MD

Miao Wu, MD

Dan Ma, MD,Phd

Jianping Wang, MD,PHD

Laparoscopic surgery for rectal cancer has been successfully proven to be a non-inferior alternative regarding resection quality, and oncological outcomes of patients as compared to open surgery in mangy clinical trails. Moreover, laparoscopic surgery is advantageous over open surgery with regard to operative invasiveness, patient's recovery, and wound related complications. Thus, laparoscopic surgery has gained great popularity over the past decades. However, specifically for mid and low rectal cancer, laparoscopic surgery is technically demanding, which sometimes leads to high morbidity and unsatisfactory resection quality, especially in challenging cases such as bulky mesorectum, enlarged prostate, irradiated pelvis, etc. Under this circumstance, transanal total mesorectal excision (TaTME) , the so called "down-to-up" alternative, has emerged as a promising solution to these problems in recent years and more and more small studies have proven the feasibility and advantages of this technique, making it become a hot topic among both literature and conferences. However, TaTME is still at early birth, higher-level evidences, either multicentric, or comparative study with conventional surgery is strikingly lacking. Thus the investigators conduct this multicentre randomised clinical trial, comparing transanal TME versus laparoscopic TME for mid and low rectal cancer, aiming to prove the hypothesis that TaTME may achieve better resection quality and result in non-inferior oncological outcome, as well as short term operative morbidity and mortality.

Background:In recent years, transanal mesorectal excision (TaTME) has emerged as a promising surgical alternative for rectal cancer, especially for mid and low rectal cancer. Theoretically, TaTME holds the potential advantage of providing better access to mobilize the distal rectum, and thus could achieve better pathologic outcomes, such as lower involved circumferential margin (CRM) and incomplete resected mesorectum, which could translate into better oncological outcome for the patients in the long term. However, until now, the feasibility and the non-inferiority (compared with laparoscopic total mesorectal excision, LpTME) of this technique has only been validated in studies with limitations of small sample size, retrospective nature.

Study Objective:This study aims to evaluate the TaTME technique compared with conventional laparoscopic rectal surgery, focusing on resection quality, as well as long-term survival results.

Study design This study is a prospective, multi-center, randomized, open-label, parallel group trial. The randomisation ratio of TaTME over LpTME will be 1:1. A central electronic data capture (EDC) system will be utilized for randomization, electronic CRF and data collection. All comparative analyses will be conducted on an "intention to treat" basis.

Sample size: Sample-size calculation of this trial based on 3-year DFS and 5-year OS; but the sample size according to 5-year OS was larger than that based on 3-year DFS. The expected 5-year OS among clinical stage I-III rectal cancer patients treated with laTME was 77·4%. Allowing a difference of 10% as the non-inferiority margin, 910 patients would be required to sufficiently declare taTME noninferior to laTME in 5-year OS based on a log-rank test with an α error of 2·5% (in a two-sided test) and power of 80%. Assuming a dropout rate of 20%, a total of 1114 patients were planned to enroll for this trial.

Study Endpoints:The primary end point of this study is 3-year disease-free survival (DFS) rate and a 5-year overall survival (OS) rate. Secondary endpoints include: 1) resection quality, mainly including circumferential involvement rate, and completeness of mesorectum. Resected specimen was pathologically processed and assessed at each center by trained and qualified pathologists independently.2)short term operative results such as morbidity and mortality, etc.; 3) long term oncological outcome such as local recurrence, and overall survival. Besides, functional outcome and quality of life are also evaluated.

Transanal or Laparoscopic Total Mesorectal Excision treat rectal cancer

Transanal Versus Laparoscopic Total Mesorectal Excision For Rectal Cancer

Transanal Versus Laparoscopic Total Mesorectal Excision For Mid And Low Rectal Cancer (TaLaR): A Multicentre Randomised Clinical Trial

The quality of the mesorectum or TME specimen (complete;nearly complete; incomplete)

To evaluate defecating function with Wexner score

To evaluate sexual function with IIEF(International Index of Erectile Function) questionnaire

To evaluate quality of life with EORTC QLQ-30 questionnaire

Peking Union Medical College Hospital

The First Hospital of Jilin University

RenJi Hospital

Shengjing Hospital

The Second People's Hospital of Yibin

Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

Nanchong Central Hospital

Zunyi Medical College

The First Affiliated Hospital of University of South China

Xinqiao Hospital

Nanfang Hospital, Southern Medical University

First Affiliated Hospital Xi'an Jiaotong University

Ruijin Hospital

Affiliated Hospital of Guangdong Medical University

The Third Xiangya Hospital of Central South University

Sun Yat-sen University

Carcinoma

Oxaliplatin

Capecitabine

Patients will receive 4 cycles of neoadjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks). In case of partial response or stable disease (based on pelvic MRI) patients proceed to surgery within 2 weeks. In case of disease progression patients receive 50 Gy pelvic chemoradiotherapy with capecitabine 825 mg/m2 bid per os on radiation days and then surgery following 8-10 weeks. After surgery patients receive 4 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks).

Patients will receive 5x5 Gy radiotherapy and then surgery following 6-8 weeks. After surgery patients receive 8 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks).

2000 mg/m2, bid, per os, days 1-14, 4 cycles

825 mg/m2, bid, per os, only on days of radiation (Monday through Friday)

Pelvic radiotherapy dose: 44 Gy on regional nodes, 50 Gy on primary tumor

Radiotherapy

Laparoscopic or open total mesorectal excision

Rectal cancer surgery

Pelvic radiotherapy dose: 25 Gy in 5 Gy fractions

Zaman Z Mamedli, PhD

The purpose of this study is to determine whether 3 months of neoadjuvant CapOx is non-inferior to neoadjuvant radiotherapy in patients with moderate risk CRM"-" mid rectal cancer.

This trial aims to investigate the efficacy of neoadjuvant chemotherapy compared to 5x5 Gy neoadjuvant radiotherapy in moderate risk CRM-negative rectal cancer patients. This is a prospective multicenter open-label non-inferiority randomized phase III clinical trial. Patients will be randomized using an online randomization system to receive either 4 cycles of neoadjuvant CapOx (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 per os bid days 1-14) chemotherapy, surgery and 4 cycles of adjuvant CapOx chemotherapy or 5x5 Gy radiotherapy, surgery and 8 cycles of adjuvant CapOx chemotherapy. A stratification will be performed based on сN stage and clinical center. Patients with сT3c-T3dN0-1M0, cT1-T3dN2M0 cancer in the middle rectum are included. Chemoradiotherapy (50 Gy with concomitant capecitabine 825 mg/m2 per os bid on radiation days) will be performed for patients with tumor progression after neoadjuvant chemotherapy. The main hypothesis is that the 2-year local recurrence rate is non-inferior after neoadjuvant chemotherapy and neoadjuvant radiotherapy in moderate risk mid rectal cancer patients. The target accrual is 158 patients in each treatment arm (including 10% potential data loss) based on non-recurrence rate of 98% in investigated and 96% in the control group with a non-inferiority margin of 3%, α=0,05, power 80%. An interim analysis is planned after 50% of the patients will reach a 2-year followup. Pelvic Magnetic Resonance Imaging (MRI) is performed in all patients for staging before and after neoadjuvant chemotherapy and before surgery. Pelvic MRI is subject to central review. Conduction of this study and data collection are controlled by a local institutional board.

Neoadjuvant Chemotherapy in Patients With Moderate Risk Mid Rectal Cancer

A Multicenter Prospective Phase III Clinical Trial of Neoadjuvant CapOx in Patients With Intermediate Risk CRM-negative Middle Rectal Cancer

Proportion of patients who receive a complete course of adjuvant chemotherapy

Toxicity measured according to NCI-CTCAE v.5.0

Morbidity measured according to Clavien-Dindo classification

Proportion of patients with disease progression during neoadjuvant chemotherapy

The rate of tumor-associated complications (bowel obastruction, bleeding etc) during neoadjuvant chemotherapy

Blokhin's Russian Cancer Research Center

Principal Investigator, Consultant surgeon

Patients receive 2 cycles of induction CapOx (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 per os bid days 1-14) chemotherapy, followed by chemoradiotherapy (54 Gy in 2 Gy fractions with concomitant capecitabine 825 mg/m2 per os bid on radiation days), then 2 cycles of consolidation CapOx chemotherapy, surgery (10-12 weeks following chemoradiotherapy) and 2 cycles of adjuvant CapOx chemotherapy

Patients receive 54 Gy pelvic chemoradiotherapy in 2 Gy fractions with capecitabine 825 mg/m2 bid per os on radiation days and then surgery following 10-12 weeks. After surgery patients receive 6 cycles of adjuvant CapOx chemotherapy.

Pelvic radiotherapy dose: 44 Gy on regional nodes, 54 Gy on primary tumor in 2 Gy fractions

Laparoscopic or open total mesorectal excision or extralevator abdominoperineal resection

The purpose of this study is to determine whether the addition of 2 cycles of induction CapOx chemotherapy and 2 cycles of consolidation CapOx chemotherapy to standard chemoradiation improves 3-year disease-free survival in patients with locally advanced CRM"+" mid and low rectal cancer.

This trial aims to investigate the efficacy of adding neoadjuvant induction and consolidation chemotherapy compared to standard chemoradiotherapy in locally advanced rectal cancer patients with circumferential resection margin involvement. This is a prospective multicenter open-label randomized phase III clinical trial. Patients will be randomized using an online randomization system to receive either 2 cycles of induction CapOx (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 per os bid days 1-14) chemotherapy, followed by chemoradiotherapy (54 Gy in 2 Gy fractions with concomitant capecitabine 825 mg/m2 per os bid on radiation days), then 2 cycles of consolidation CapOx chemotherapy, surgery (10-12 weeks following chemoradiotherapy) and 2 cycles of adjuvant CapOx chemotherapy OR chemoradiotherapy (54 Gy in 2 Gy fractions with concomitant capecitabine 825 mg/m2 per os bid on radiation days), surgery (10-12 weeks following chemoradiotherapy) and 6 cycles of adjuvant CapOx chemotherapy. A stratification will be performed based on N stage, tumor location in the middle or low rectum and clinical center. Patients with middle or low rectal cancer without distant metastases, with involved circumferential resection margin (based on pretreatment MRI) will be included.

The target accrual is 270 patients in each treatment arm (including 10% potential data loss) based on potential benefit of 12% 3-yr disease-free survival (60% vs 72%), α=0,05, power 80% in the experimental arm. An interim analysis is planned after 50% of the patients will reach a 3-year followup. Pelvic Magnetic Resonance Imaging (MRI) is performed in all patients for staging before and after neoadjuvant chemotherapy and before surgery. Pelvic MRI is subject to central review. Conduction of this study and data collection are controlled by a local institutional board.

Induction and Consolidation Chemotherapy in Patients With Locally Advanced CRM-positive Rectal Cancer

Induction and Consolidation Chemotherapy in Locally Advanced Rectal Cancer Patients With Circumferential Resection Margin Involvement: a Multicenter Prospective Randomized Phase III Clinical Trial

The rate of tumor-associated complications (bowel obstruction, bleeding etc) during neoadjuvant chemotherapy

Patients of the control group who are to receive the traditional approach-- total mesorectal excision approach to transect the distal rectum are assigned into this arm.

Patients of the experimental group who are to receive the novel approach-- transanterior obturator nerve gateway approach to transect the distal rectum are assigned into this arm.

Distal rectal transection of cases in the experimental group will be performed using transanterior obturator nerve gateway approach

Transanterior obturator nerve gateway approach

Distal rectal transection of cases in the control group will be performed using total mesorectal excision approach

Total mesorectal excision approach

Jianqiang Tang, MD

The wide application of ISR and DST has greatly improved the anal preservation rate for low rectal cancers, but the technical difficulty has also been obviously increased because of the limited pelvic space. Although many scholars have tried to solve this problem, all the methods have failed to fundamentally solve the problem of "the oblique dissection" of the distal rectum. To solve the problem above, the director of this clinical trial has explored a new distal rectal resection method-- transanterior obturator nerve gateway approach. The purpose of this clinical trial is to prospectively collect and compare data on the patients' perioperative variables and postoperative functional and oncological outcomes of this novel approach with the traditional approach to confirm the safety and feasibility of this novel approach and its advantages over the traditional approach.

Objective To confirm the safety, feasibility and advantages by comparing the perioperative variables, postoperative functional and oncological outcomes of patients with ultralow rectal cancer treated by laparoscopic traditional distal rectal dissection vs. by transanterior obturator nerve gateway approach.

Patients Patients with ultralow (≤5cm from the anal verge) rectal cancer who are to undergo laparoscopic radical resection (ISR- DST) without any contraindications of general anesthesia, surgery or chemotherapy. (See details in Eligibility part) Sample size Two groups are designed, patients who are to receive the traditional approach to transect the distal rectum are assigned to the control group, patients who are to receive the transanterior obturator nerve gateway approach to transect the distal rectum are assigned to the experimental group. 100 cases are to be enrolled for the experimental group and not less than 100 cases are to be enrolled for the controlled group.

Treatment If the participant match with the requirements for this study and agree to take part in it, once hospitalized, the participant will complete the established preoperative tests including blood routine, the comprehensive metabolic panel, blood coagulation function, tumor markers, blood type, infectious disease screening tests, chest, abdominal and pelvic CT (Computed Tomography) scan and MRI (Magnetic Resonance Imaging), colonoscopy, echocardiogram, pulmonary function, venous duplex ultrasound of legs. All male patients will be routinely asked to fill in the IIEF-5 (International Index of Erectile Function-5) sexual function scoring questionnaire preoperatively.

The following comprehensive treatment will be depended on the examination results:

Neoadjuvant therapy The treatment plan will be made in accordance with the NCCN (National Comprehensive Cancer Network) Guidelines for Diagnosis and Treatment of Colorectal Cancer (Version 1.2021).

Neoadjuvant chemoradiotherapy: Pelvis radiotherapy with a total dose of 50 Gy with 25 courses in 5 weeks. Neoadjuvant chemotherapy include single drug therapy: capecitabine (CAP, 1250 mg/m2, BID) or double drug therapy: oxaliplatin combined with capecitabine (CapeOX, oxaliplatin 130 mg/m2, day 1, capecitabine 1000mg/ m2, day 1 \~ 14, then rest for 7 days, repeated every 3 weeks) or three-drug therapy (mFOLFOX6, oxaliplatin 85 mg/ m2 intravenous infusion for 2 hours, leucovorin calcium 400 mg/m2 intravenous infusion for 2 hours, 5-FU (fluorouracil) 400 mg/m2 intravenous infusion for 1 day, Then 1200 mg/ m2/d×2 days of continuous intravenous infusion with a total of 2400mg/m2 for 46 \~ 48 hours, repeated every 2 weeks.

Abdominal and pelvic MRI and contrast enhanced CT will be routinely performed 6 to 8 weeks after neoadjuvant therapy to confirm the extent of tumor regression without new-found distant metastasis. Those whose clinical stage after neoadjuvant therapy changes from T4 to T3 will be seen as eligible in this study.

Surgical treatment Preoperative preparation

1) Patients older than 60 years old or having a smoking history for over 10 years will receive lung ventilation training and atomization treatment for 3 days. 2) Intestinal preparation will be done with oral cathartic medications 12-24 hours before surgery. 3) Prophylactic antibiotics will be given once anesthesia is begun, the second antibiotics will be given if the operation lasts for over 3 hours. 4）Urethral catheterization will be routinely done preoperatively. 5）If the patient refuses to accept the novel approach before surgery, they will be directly enrolled in the traditional group. If both approaches are acceptable to the patient, the decision whether to use the novel approach will be made according to the intraoperative conditions (see operating procedures below).

Operating procedures General anesthesia; Modified lithotomy position; Establishment of pneumoperitoneum: Place a trocar 1cm above the umbilicus through which to establish pneumoperitoneum and keep the abdominal pressure as 12mmHg (millimeters of mercury).

Trocar placement: above the umbilicus (trocar C, 10 mm), upper right and left quadrants (trocars B and D, 5 mm), lower right quadrant (trocar A, 12 mm), lower left quadrant (trocar E, 5 mm), the midpoint between the pubic symphysis and umbilicus (trocar F, 5 mm).

Abdominal exploration: Explore the abdominal cavity in accordance with the principle of non-contact, from far to near step by step, explore the tumor finally.

The mesosigmoid and mesorectum are dissected from the right lateral rectum towards the root of the inferior mesenteric artery (IMA). The IMA is transected and ligated, so is the inferior mesenteric vein. Posterior space of the descending colon is dissected following opening the peritoneum beside the left rectum. The rectum in the pelvis is been mobilized from posterior rectal space, anterior rectal space to bilateral rectal space successively. The lower edge of the tumor is marked by a clamp. The linear stapler is placed in the pelvis to clamp the distal rectum below the tumor to see if the transection can be done more than 1cm from the lower edge of the tumor. If yes, the distal rectum will be transected by the traditional approach (that means the patient will be assigned to the traditional group). The proximal bowel is transected through a small midline incision. Then the coloanal anastomosis will be done intracorporeally. A surgical drain is placed in the pelvis and a terminal ileostomy is routinely performed. All incisions are closed.

If the distal rectal transection cannot be done more than 1cm from the lower edge of the tumor, the anterior obturator nerve gateway approach will be used (that means the patient will be assigned to the experimental group). The steps are as follows: The peritoneum covering the ureter and external iliac artery is opened more than 2 cm across the vas deferens (male) or round ligament (female). The Retzius space and vesicohypogastric fascia are exposed. The obturator vessels and obturator nerve are properly identified. Care should be taken to avoid any injury when using energy devices near the obturator nerve. The gateway is then opened through the TME (total mesorectal excision) compartment and the lateral compartment. If necessary, an "endoloop" can be placed through the gateway, and the bundled S2-4 nerves, ureter and bladder vessels are gently retracted toward the cranial direction to widen the gap. The linear stapler is placed in the gateway to vertically transect the distal rectum. The following procedures are the same with the traditional group as described above.

During the operation, the following variables will be recorded: the angle between the linear stapler and the rectum, distance from the lower edge to the resecting margin, whether the operation converted to transanal approach, operative time, bleeding volume, anastomotic height from anal verge and the length of the stapling line.

Postoperative management：

The following information will be recorded:

1）Vital signs (body temperature, pulse rate, respiration rate, blood pressure) are routinely monitored, gross volume of fluid input and output will be recorded every 24h, blood routine, the comprehensive metabolic panel and coagulation function tests will be performed every 3 days. 2）The time of catheter removal (days after operation), residual urine volume in the bladder will be measured by ultrasound examination. Whether there is a request to be re-catheterized or take oral medication to relive the dysuria. All patients will be asked to fulfil the IPSS (International prostate symptom score) questionnaire to assess urinary function. 3）The time of pelvic drain removal (days after operation). 4）Whether complicated with anastomotic leakage, ileus and long-lasting (more than 5 days) pulmonary or abdominal infection. 5）All information of the pathologic report. 6）Postoperative hospital stay (days) Postoperative chemoradiotherapy Radiotherapy program is the same with the neoadjuvant therapy. Chemotherapy will be advised for patients with stage II cancer accompanied with the following high-risk factors: histologically poorly differentiated with normal mismatched repair or stable microsatellite (MSS), pT4 (pathological stage T 4), vascular/nerve invasion, preoperative intestinal obstruction or perforation, ≤ 12 lymph nodes retrieved and R1 resection. The chemotherapy program is the same with neoadjuvant chemotherapy. If mismatch repair defect (dMMR) or high-level microsatellite instability (MSI-H) is confirmed by pathology, chemotherapy will not be advised. Patients with stage III cancer will routinely receive chemotherapy.

Follow-up

1) Information on general medical history and physical examination will be collected every 3 months for 3 years. 2) Blood tumor markers of CEA (carcinoembryonic antigen) and CA19-9 (carbohydrate antigen 19-9) will be tested every 3 months for 3 years. 3) Abdominal and pelvic ultrasound and chest X-ray examinations will be carried out every 3 months for 3 years. 4) Abdominal and pelvic MRI or contrast enhanced CT scan will be done every year for 3 years. 5) Colonoscopy will be performed within 1 year after surgery. If there is any abnormity, reexamination will be required within half a year. If no abnormality is found, once a year for 3 years. All new-found adenomas by the colonoscopy during follow-up are recommended to be resected. 6) Sexual function score is assessed by filling in the questionnaire (IIEF-5) both preoperatively and 1 year later since operation. 7) 3-year tumor-free survival (month): The time from operation to confirmation of tumor's local recurrence or distant metastasis. The end point of the patient lost to follow-up is the date of loss. 30 days is defined as one month. 8) 3-year overall survival (month): The time from operation to death. The end point of the patient lost to follow-up is the date of loss. 30 days is defined as one month. 9) Stoma closure time (months since operation). Anal function is assessed by Wexner scale 3 months and 12 months after stoma closure, respectively.

(As to possible risks and benefits of participating in this trial, see details in the informed consent document.) Study start date (actual) 2020-12-01 Study completion date (anticipated) 2025-12-01 (All outcomes of the last patient are recorded 3 years postoperatively, death or loss to follow-up of the last patient.) Statistics IBM SPSS (Statistical Package for the Social Sciences) Statistics 25 (IBM, Inc., Armonk, NY) will be used to perform statistical analyses. The t test and Mann-Whitney U test were used for quantitative data between groups. Qualitative data were compared by Chi-square test or Fisher's exact test and survival distributions were analyzed by log-rank test.

A Study on the Efficacy of a Novel Approach to Achieving Laparoscopic Distal Rectal Transection for Rectal Cancers

A Prospective Non-randomized Controlled Multi-center Study of Laparoscopic Intracorporeal Distal Rectal Transection by Using the Traditional Approach vs. Using Transanterior Obturator Nerve Gateway Approach for Ultralow Rectal Cancers

There is not a plan to make IPD available.

The degree of angle between the linear stapler and the longitudinal axis of the rectum when transecting the distal rectum.

The degree of angle between the simulated stapling line with the total mesorectal excision approach and the real stapling line with the transanterior obturator nerve gateway approach (this outcome is measured only in patients of the experimental group).

The shortest distance between the distal border of the tumor and the edge of the distal resection.

The gross conversion rate (No. of cases undergoing conversion/total No. of cases enrolled \*100%) will be calculated immediately after the last patient's surgery.

The gross anastomotic leakage rate (No. of cases diagnosed with anastomotic leakage/total No. of cases enrolled \*100%) will be calculated 6 months after the last patient's surgery. Anastomotic leakage will be diagnosed if the patient has clinically apparent leakage signs (such as the emission of gas, pus, or feces from the pelvic drain, or peritonitis) or extravasation of endoluminally administered watersoluble contrast medium according to CT.

The time between the first incision and final closure of the operation.

The gross volume of blood loss during the operation.

Distance between the coloanal anastomosis and the anal verge.

The length of the lower stapling margin of the specimen.

Days from operation to discharge from hospital.

Urinary retention is defined as requiring a second urinary catheterization or postvoid residual urine volume ≥ 50ml by ultrasound examination after first removal of the urinary catheter.

See IPSS scale in study protocol. Total score: 0-35 points, higher scores mean worse outcome.

See Wexner score in study protocol. Total score: 0-20 points, higher scores mean worse outcome.

See IIEF-5 scale in study protocol. Total score: 5-25 points, higher scores mean better outcome.

The percentage of people who are alive after 3 years from operation.

The percentage of patients who are alive without cancer relapse or metastasis after 3 years from operation.

Shengli Oilfield Hospital

The Second Affiliated Hospital of Baotou Medical College

Peking University First Hospital

Patients will receive 4 cycles of neoadjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks). In case of partial response or stable disease (based on pelvic MRI) patients proceed to surgery. In case of disease progression patients receive 50 Gy pelvic chemoradiotherapy with capecitabine 825 mg/m2 bid per os on radiation days and then surgery. The decision to proceed with adjuvant chemotherapy postoperatively will be based on pTNM stage

Patients will receive standard surgery for rectal cancer with partial or total mesorectal excision (based on exact tumor location and surgeons discretion). The decision to proceed with adjuvant chemotherapy postoperatively will be based on pTNM stage

Laparoscopic or open partial or total mesorectal excision (based on exact tumor location and surgeons discretion)

The purpose of this study is to determine whether 4 cycles of neoadjuvant CapOx chemotherapy is more effective than the upfront surgery in patients with intermediate risk CRM"-" mid and upper rectal cancer.

This trial aims to investigate the efficacy of neoadjuvant chemotherapy compared to upfront surgery in intermediate risk rectal cancer patients. This is a prospective multicenter open-label randomized phase III clinical trial. Patients will be randomized using an online randomization system to receive either 4 cycles of neoadjuvant CapOx (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 per os bid days 1-14) chemotherapy and surgery or surgery alone. A stratification will be performed based on N stage, tumor location in the middle or upper rectum and clinical center. Patients with cT3-4aN1-2M0, T4aN0M0 cancer in the upper rectum and сТ2-Т3bN1M0 (based on preoperative MRI) cancer in the middle rectum are included. All patients are potential candidates for adjuvant chemotherapy, according to preoperative staging. Chemoradiotherapy (50 Gy with concomitant capecitabine 825 mg/m2 per os bid on radiation days) will be performed for patients with tumor progression after neoadjuvant chemotherapy. The decision to proceed with adjuvant chemotherapy postoperatively will be based on pTNM stage in both treatment arms, according to actual treatment guidelines. The target accrual is 280 patients in each treatment arm (including 10% potential data loss) based on potential benefit of 10% 3-yr disease-free survival (75% vs 85%), α=0,05, power 80% in the experimental arm. An interim analysis is planned after 50% of the patients will reach a 3-year followup. Pelvic Magnetic Resonance Imaging (MRI) is performed in all patients for staging before and after neoadjuvant chemotherapy and before surgery. Pelvic MRI isbject to central review. Conduction of this study and data collection are controlled by a local institutional board.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Preoperative Chemoradiotherapy With Raltitrexed for Intermediate or Locally Advanced Rectal Cancer in the Fit Elderly	NCT02992886	Rectal Neoplasm...	Preoperative ra... Raltitrexed Pelvic surgery	71 Years -	ChineseAMS
Transanal Versus Laparoscopic Total Mesorectal Excision For Rectal Cancer	NCT02966483	Rectal Neoplasm... Surgery	TaTME LpTME	18 Years - 75 Years	Sun Yat-sen University
Transanal Versus Laparoscopic Total Mesorectal Excision For Rectal Cancer	NCT02966483	Rectal Neoplasm... Surgery	TaTME LpTME	18 Years - 75 Years	Sun Yat-sen University
Preoperative Chemoradiotherapy With Raltitrexed for Intermediate or Locally Advanced Rectal Cancer in the Fit Elderly	NCT02992886	Rectal Neoplasm...	Preoperative ra... Raltitrexed Pelvic surgery	71 Years -	ChineseAMS
Neoadjuvant Chemotherapy in Patients With Moderate Risk Mid Rectal Cancer	NCT04134897	Rectal Neoplasm... Rectum Carcinom... Rectal Cancer	Capecitabine Oxaliplatin Capecitabine Radiotherapy Rectal cancer s... Radiotherapy	18 Years - 75 Years	Blokhin's Russian Cancer Research Center
Induction and Consolidation Chemotherapy in Patients With Locally Advanced CRM-positive Rectal Cancer	NCT04135313	Rectal Neoplasm... Rectum Carcinom... Rectal Cancer	Capecitabine Oxaliplatin Capecitabine Radiotherapy Rectal cancer s...	18 Years - 75 Years	Blokhin's Russian Cancer Research Center
A Study on the Efficacy of a Novel Approach to Achieving Laparoscopic Distal Rectal Transection for Rectal Cancers	NCT05067413	Rectal Neoplasm...	Transanterior o... Total mesorecta...	18 Years - 80 Years	Peking University First Hospital
A Study on the Efficacy of a Novel Approach to Achieving Laparoscopic Distal Rectal Transection for Rectal Cancers	NCT05067413	Rectal Neoplasm...	Transanterior o... Total mesorecta...	18 Years - 80 Years	Peking University First Hospital
Neoadjuvant Chemotherapy in Patients With Intermediate Risk Upper and Mid Rectal Cancer	NCT04103697	Rectal Neoplasm... Rectum Carcinom... Rectal Cancer	Capecitabine Oxaliplatin Capecitabine Radiotherapy Rectal cancer s...	18 Years - 70 Years	Blokhin's Russian Cancer Research Center

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