Gastric Cancer Sentinel Lymph Node Sampling: Refining Patient Selection for Organ Sparing Resection of Early Gastric Cancer in a North American Context

Gastric cancer incidence in North America is 7.4/100,000 population, with 24,590 new cases diagnosed annually in the United States1. Of these, approximately 15% are detected at the early gastric cancer stage with no spread to regional lymph nodes2. Recent advances in gastric cancer detection, such as endoscopic use of narrow band imaging and magnification endoscopy, can help improve the detection rate of early lesions3-5. Gastric cancers detected at an early stage have an excellent prognosis, with reported long term overall survival rates of 71-92%6-9 due to the low rate of peritoneal and distant metastatic spread which frequently occur in patients with more advanced lesions. However, the mainstay of treatment even for early gastric cancers (EGC) remains anatomical resection with regional lymphadenectomy. While oncologically sound, anatomical resection is often associated with complications and unpleasant short and long-term side effects, including post-operative weight loss, dumping syndrome, vitamin deficiencies, anastomotic complications, delayed gastric emptying, and bile reflux, among others. Given the long life expectancy of patients after resection of EGC, curative resection with organ preservation to improve post-operative quality of life should be a treatment goal.

Recently, organ-sparing techniques have emerged which allow select early gastric cancers to be treated without anatomical resection. These techniques, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), allow for curative resection of highly-selected lesions with complete organ preservation. The shortcoming of all organ sparing resection techniques presently is that lymphadenectomy is not performed, leading some patients to perhaps be under-staged and therefore under-treated.

According to the Japanese Gastric Cancer Treatment Guidelines10, early lesions are deemed appropriate for organ-sparing endoscopic resection if they meet the following criteria: confined to the mucosa (T1a), tumour size <2cm, no ulceration, and well-differentiated tumour grade. Together, tumours with these features have a very low risk of lymph node metastases (<1%). Long-term outcomes of ESD are highly favorable, with local recurrence and overall survival rates comparable to anatomical resection7,8. For tumours that do not meet the above criteria however, risk of lymph node involvement is drastically increased, with submucosal invasion, ulceration, tumour size >3cm, poorly differentiated tumour type, and lymphovascular invasion conferring a risk of lymphatic metastases of 4-26%11. For this reason, current best practices recommend EGCs with high risk features continue to undergo anatomical resection with regional lymphadenectomy. However 75-95% of such patients will ultimately have no regional metastases on final pathological analysis, suggesting they could have been spared anatomical resection if only their lymph node basins had been definitively staged prior to surgery.

Presently, several imaging modalities are available to characterize lymph node stage for gastric cancer, including endoscopic ultrasound (EUS), computed tomography (CT) and positron emission tomography (PET). Unfortunately, the sensitivity of these modalities is woefully inadequate to accurately predict microscopic lymph node metastases, and therefore they cannot be reliably used to differentiate high risk EGCs that require anatomical resection and lymphadenectomy from those amenable to organ-sparing resection12-15.

To address this gap in the ability to accurately detect nodal metastases in early gastric cancer, sentinel lymph node (SNL) sampling was pioneered in Asia and has undergone refinement and study there since the early 2000s. A recent multi-institutional study of 397 patients conducted across 12 centres in Japan reported rates of SLN detection of 97.5% and accuracy of SLN stage when compared to post-resection stage of 99%16. These numbers rival those reported for SLN biopsy of breast and melanoma cancers in large randomized controlled trials17,18. Indeed, for these tumour types, SLN biopsy is now the standard of care globally for staging clinically node-negative patients due to its diagnostic superiority over other staging modalities. Following the success of SLN sampling in gastric cancer, select Asian institutions are now applying this technique to diverting sentinel node-negative (SLN -ve) T1 and T2 gastric cancer patients away from anatomical resection with extensive lymphadenectomy and towards organ-sparing endoscopic or wedge resection.