Sentinel Node and Organ-sparing Surgery in Stage I Colon Carcinoma (SENTRY Trial)
Sentinel Node and Organ-sparing Surgery in Stage I Colon Carcinoma (SENTRY Trial)
The aim of this study is to reduce the need for colectomy and its' associated morbidity and mortality in patients with pT1-2 colon carcinoma after endoscopic resection and an estimated lymph node metastasis (LNM) risk of >15%, or with macroscopically suspected T1 tumors, by performing an endoscopic-assisted laparoscopic/robotic wedge resection of the tumor or scar, along with sentinel node (SLN) 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.
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 T1-2 tumors has been observed following the introduction of population screening programs, leading to more frequent endoscopic excisions. The risk of LNM in T1-2 colon cancers is relatively low. However, local excision does not allow assessment of lymph node status. Moreover, the diagnostic accuracy of computed tomography (CT) and other preoperative imaging modalities for detecting LNM remains limited.
Segmental colonic resections are associated with substantial morbidity. Based on large population-based datasets, 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) are 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 minimize unnecessary completion surgery, histopathological risk stratification is applied. In the Netherlands, histopathological risk factors for the presence of LNM in pT1-2 colon cancer are poor (high-grade) differentiation, lymphovascular invasion, high-grade tumor budding (Bd 2-3), and Haggitt level 4. The risk of LNM varies depending on the number of risk factors, pT stage, polyp morphology, and margin status. Completion segmental resection is omitted for pT1-2 tumors with a predicted LNM risk below 15%. Management is guided by risk stratification: for a 5-15% risk, active follow-up is preferred; for a 15-25% risk, active follow-up may be considered as an alternative to completion segmental resection through shared decision-making; and for a >25% risk, segmental resection is the preferred treatment. However, the vast majority of patients with a >15% risk of LNM who undergo surgery experience potential harm but no benefit, as they ultimately do not have LNM. Additionally, suspected T1 tumors are sometimes difficult or impossible to resect endoscopically. In such cases, wedge resection or segmental resection is the standard of care. Depending on T stage and other histopathological risk factors identified after wedge resection, a subsequent segmental resection may still be required. By adding SLN biopsy to the procedure, we aim to avoid the need for segmental resection after wedge resection.
The investigators hypothesize that, in patients who have undergone R0/R1/Rx endoscopic resection of T1-2 colon cancer and have a >15% risk of LNM, or in those with macroscopically suspected T1 tumors, an 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. In our systematic review and meta-analysis, we found a pooled accuracy of 98% and a sensitivity of 80% for SLN detection in T1-2 colon cancer. The investigators use endoscopic submucosal injection of 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 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 to provide traction and 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 lower cost compared to laparoscopic segmental resection. Because 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) or T3-4 tumors are offered segmental resection. Node-positive patients are recommended to undergo adjuvant chemotherapy if performance status allows. SLN-negative patients do not undergo further surgery and are managed with an intensive follow-up strategy. Assuming 80% sensitivity and a 20% prevalence of lymph node metastasis, the risk of retained positive nodes after SLN biopsy is approximately 4%. Additionally, tumor deposits (TDs) could potentially be missed when patients are treated with 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 resection.
The SENTRY trial will be the first to offer organ-sparing surgery combined with an SLN biopsy for patients with selected early-stage colon cancer. 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 oncologic outcomes. This multicenter, partially randomized, patient-preference trial will compare the organ-sparing approach with standard-of-care segmental resection to assess oncologic safety.
Inclusion Criteria:
Exclusion Criteria:
bct.vande.laar@meandermc.nl+31338507137