Clinical trial NCT06652672: Sentinel Node and Organ-sparing Surgery in Stage I Colon Carcinoma
Official title: Sentinel Node and Organ-sparing Surgery in Stage I Colon Carcinoma (SENTRY Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colon Cancer
Colon Adenocarcinoma
Sentinel Lymph Node
Sentinel Lymph Node Biopsy
Colon Neoplasms
Colon Neoplasm
Fluorescence
Fluorescence Guided Surgery
Fluorescence Laparoscopy
Fluorescence-guided Resection
Colon Surgery
Indocyanine Green (ICG)
Keywords: Colon cancer
Fluorescence
Sentinel lymph node
Indocyanine green (ICG)
Organ sparing surgery
Organ preserving surgery
Local resection
Lead sponsor: Meander Medical Center
Sponsor class: OTHER
First posted: 2024-10-22
Enrollment: 325
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center, prospective, non-inferior, partially randomized patient-preference trial
Primary purpose: TREATMENT

Brief summary: The aim of this study is to reduce the need for segmental colonic resection and its associated morbidity and mortality in patients with high-risk pT1 and low-risk pT2 colon cancer following endoscopic resection, by performing an endoscopic-assisted laparoscopic/robotic wedge resection of the residual tumor or scar, along with sentinel node biopsy using indocyanine green (ICG). This intervention will be compared to the standard-of-care segmental resection using a partially randomized patient preference design. The primary outcome is the 3-year recurrence rate.

Detailed description: Colorectal cancer is the third most common type of cancer in the Netherlands and the second leading cause of cancer-related deaths. An increased incidence of T1-T2 tumors has been observed following the introduction of population screening programs, leading to more frequent endoscopic excisions. The risk of lymph node metastasis in high-risk T1 and low-risk T2 colon cancers is relatively low. However, the diagnostic accuracy of abdominal CT scans for detecting lymph node metastasis is limited, necessitating a formal segmental colonic resection to allow definitive nodal staging through pathological examination of the draining lymph nodes. Nevertheless, segmental resections following endoscopic excision of early-stage colon cancer will overtreat 85-95% of patients, depending on the histological risk profile, as the majority do not have lymph node metastases.

Segmental colonic resections are associated with substantial morbidity. Based on large population-based data, 33% of patients experience at least one complication including anastomotic leakage, with a postoperative mortality rate of 1.5-3.1%. Morbidity is known to substantially impact quality of life and contribute to a high economic burden. Additionally, major symptoms of low anterior resection syndrome (LARS) is present in 21% of patients after segmental resection, with reported effects on quality of life comparable to those experienced by patients who undergo rectal cancer resection and develop LARS.

To reduce the number of segmental resections in early colon cancer, risk stratification is applied based on histopathological examination of locally excised lesions. In low-risk T1 cancer, segmental resections are already omitted. The risk of lymph node metastasis varies between 5-15%, depending on the presence of one or more risk factors. For low-risk T2 tumors, the risk of lymph node metastasis ranges from 10.5-14%. As a result, the vast majority of patients still undergo surgery with potential harm but no benefit.

The investigators hypothesize that in patients who have undergone R0/R1/Rx endoscopic excision of high-risk T1 or low-risk T2 colon cancer, sentinel lymph node (SLN) biopsy combined with wedge resection of the residual tumor or scar can safely spare the majority of patients with negative SLNs from undergoing segmental resection. For reliable identification of high-risk features, endoscopic resection with pathological examination of a complete specimen is required; therefore, only patients who have had endoscopic resection will be included in this study. In our systematic review and meta-analysis, the investigators found a pooled accuracy of 98% and a sensitivity of 80% for SLN detection in T1-2 colon cancer. The investigatorsuse endoscopic submucosal injection of indocyanine green (ICG) at the tumor site, which carries a low risk of intra-abdominal spillage that could hinder SLN identification.

The SLN biopsy will be combined with an endoscopy-assisted wedge resection of the residual tumor or scar following endoscopic resection. During the endoscopy-assisted wedge resection, the surgeon first identifies and mobilizes the colon to facilitate the wedge resection. A gastroenterologist then performs a colonoscopy to visualize the scar from the previously resected tumor. With intraluminal endoscopic visualization, the surgeon places a suture, which allows for traction to position the linear stapler. The gastroenterologist confirms complete inclusion of the scar and ensures lumen patency before the stapler is fired. Endoscopy-assisted limited wedge resection is associated with low complication rates and is performed at a lower cost compared to laparoscopic segmental resection. Since no anastomosis is created, the risk of anastomotic leakage is eliminated. This approach could reduce morbidity, mortality, hospital stay, and stoma rates. Although staple line failure and leakage are theoretical risks, such complications have not been reported in previous cases.

Patients with a positive SLN (macro- or micrometastasis) are offered segmental resection with adjuvant chemotherapy. SLN-negative patients do not undergo further surgery and are managed with an intensive follow-up strategy. A conservative estimate of 80% sensitivity and an average of 10% lymph node metastases results in a 2% risk of retained positive nodes after SLN biopsy. Additionally, tumor deposits (TDs) could potentially be missed when patients are treated with the SLN biopsy and wedge resection. However, only 0.45% of patients with stage I disease are TD-positive. The investigators consider the absolute risks of missed lymph node metastases and TDs acceptable, given the reduced perioperative morbidity and mortality associated with segmental colectomy.

The SENTRY trial will be the first to offer organ-sparing surgery combined with a SLN biopsy for patients with early-stage colon cancer following endoscopic resection. This organ-sparing approach is anticipated to improve postoperative mortality, morbidity, hospital stay, quality of life, and costs compared to standard segmental resection, without compromising oncological outcomes. This multicenter, partially randomized patient preference trial will compare the organ-sparing approach to the standard of care segmental resection to assess oncologic safety.

Eligibility criteria: Inclusion Criteria:

* Oral and written informed consent
* Aged 18 years and older
* Fit for both organ-sparing surgery and colectomy
* Pathologically confirmed high-risk T1 or low-risk T2 adenocarcinoma of the colon after R0/R1/Rx endoscopic resection
* The resection scar after local excision is expected to be clearly recognized during endoscopy, either by a tattoo or by detecting a scar in the colonic segment where no other polypectomies were performed

High-risk features for T1-T2 colorectal carcinoma are:

* Poor differentiation grade or undifferentiated (WHO classification of tumors: exhibits glandular structures in \&amp;lt;50%)
* Positive tumour budding (tumour budding grade 2-3)
* Presence of lymphovascular invasion (The presence of cancer cells within endothelial-lined channels)

Exclusion Criteria:

* Lesion located \&amp;lt;25cm from the anus based on endoscopic measurement
* Distant metastasis
* Mucinous carcinoma
* Signet ring cell carcinoma
* Lynch syndrome
* Other primary malignancy treated within 5 years prior to diagnosis of colon cancer, except for curatively treated prostate, breast, skin and cervical cancer
* Tumours that comprised \&amp;gt;50% of the colon circumference before endoscopic resection
* Tumours involving the ileocaecal valve
* Pregnancy, lactation or a planned pregnancy during the course of the study
* Known allergy to any of the compounds used for SLN identification (ICG, Iodine or Sodium iodide)
* Previous colonic surgery (excluding appendectomy).
* Contraindication for laparoscopic or robotic surgery
* Severe kidney- or liver failure
* Hyperthyroidism or an autonomously functioning thyroid adenoma

Primary outcomes:
measure: 3-year recurrence rate
timeFrame: 3 years postoperatively
measure: Successful sentinel lymph node biopsy
timeFrame: Intraoperative
Secondary outcomes:
measure: 5-year recurrence rate
timeFrame: 5 years postoperatively
measure: 3-year overall survival
timeFrame: 3 years postoperatively
measure: 5-year overall survival
timeFrame: 5 years after postoperatively
measure: 90-days complication rate
timeFrame: 90 days postoperatively
measure: 90-days postoperative mortality
timeFrame: 90 days postoperatively
measure: Proportion of patients with preference for standard and experimental treatment, and without preference
timeFrame: 1 day postoperatively
measure: Procedure time of organ-sparing surgery and segmental resection
timeFrame: Directly after surgery, on the same day
measure: Successful wedge resections
timeFrame: Intraoperative
measure: Intraoperative complications
timeFrame: Intraoperative
measure: Upstaging of sentinel lymph nodes due to ultrastaging
timeFrame: During postoperative pathological examination, conducted within two weeks after surgery.
measure: Quality of life - EQ5D-5L
timeFrame: From enrollment to the end of study. Questionnaires will be sent preoperatively and 6, 12, 18, 24, 36, 48, and 60 months postoperatively
measure: Quality of life - QLQ-CR29
timeFrame: From enrollment to the end of study. Questionnaires will be sent preoperatively and 6, 12, 18, 24 months postoperatively.
measure: Quality of life - QLQ-C30
timeFrame: From enrollment to the end of study. Questionnaires will be sent preoperatively and 6, 12, 18, 24 months postoperatively.
measure: Quality of life - Surv100
timeFrame: From enrollment to the end of study. Questionnaires will be sent 36, 48, and 60 months postoperatively
measure: Quality of life - LARS
timeFrame: From enrollment to the end of study. Questionnaires will be sent preoperatively and 6, 12, 18, 24, 36, 48, and 60 months postoperatively
measure: Quality of life - WAI
timeFrame: From enrollment to the end of study. Questionnaires will be sent preoperatively and 6, 12, 18, 24, 36, 48, and 60 months postoperatively
measure: Quality of life - iMCQ
timeFrame: From enrollment to the end of study. Questionnaires will be sent 6, 12, 18, and 24 months postoperatively
measure: Costs associated with wedge resection and sentinel lymph node biopsy.
timeFrame: 5 years postoperatively
measure: Costs standard of care segmental resection
timeFrame: 5 years postoperatively
Other outcomes:
Locations:
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
Study officials:
affiliation: Meander Medical Center
name: Frank J Voskens
role: PRINCIPAL_INVESTIGATOR
References: