Globally, the incidence of colorectal cancer is about 1.36 million causing about 693, 933 deaths last published in 2012. Nodal metastases remain pivotal in decision making for adjuvant chemotherapy. Much research is being done looking at the biology of the primary tumor to prognosticate the tumor. At this time, patients with stage III disease (node positive) are treated with systemic chemotherapy across the globe. However, in patients with node negative disease, stage II patients, the role of adjuvant chemotherapy is somewhat controversial. Some of the biologic markers ie, microsatellite instability, BRAF or K-Ras mutations have been considered for chemotherapeutic decision making. None of these are being investigated routinely across the globe. As 15-20% of the so-called node-negative patients still developed metastatic disease within 5 years, many of these patients have been considered for chemotherapy somewhat empirically. In 1980s and 1990s multiple studies were done to identify various methods to increase the sensitivity of diagnosis of nodal metastases, i.e., increased number of nodes detected, ultrastaging of the nodes with multilevel sections, inmmunohistochemistry, and lately RT-PCR or OSHNA.
More recently, multiple authors have shown the negative prognostic effect of the presence of micrometastases if they remain undiagnosed and untreated. In 2011, Saad et al showed in a meta-analysis of the prognostic impact of micrometastases papers that presence of these micrometastases reduces the 5-year survival from 82% to 64% and increases the recurrence from 17% to 31%. However, to diagnose micrometastases in the lymph nodes, all the lymph nodes have to be ultrastaged. This is highly time-consuming and cost prohibitive. Precisely this reason, sentinel lymph node (SLN) mapping was used in colon cancer as in melanoma and the breast almost 18 years ago. SLN’s are diagnosed by simple dye injection at the tumor site and doing a resection of the segment of the colon with regional lymphadenectomy along with resection of 1 to 3 SLNs. The few SLN’s only were then examined by ultra-staging with multilevel sections and IHC. This resulted in diagnoses of micrometastases in 25% of the node positive patients. An international data collection was done from major global centers over 3 continents (Table 1).
In this analysis, over 4497 patients were included with average number of lymph nodes per patient was 17.8 and overall success rate of SLNM was 93.7%. Accuracy, sensitivity and negative predictive value were 90%, 77.3% and 83.5% respectively. Overall nodal positivity was 45%; off these in 36% of the patients, the sentinel lymph node was the only site of metastases and micrometastases were detected in 30% of the patient’s. Even though skip metastases were found in 22.7% of the patient’s, all patients with true positive sentinel lymph node and false-negative sentinel lymph node (non-sentinel lymph node positive, sentinel lymph node negative) were diagnosed as node positive (stage III) and were treated with systemic therapy. So unlike in breast cancer and melanoma, patients with skip metastases in colon cancer are neither understaged nor undertreated. In addition, our data of SLNM in colon cancer showed, it identified aberrant SLN in 20% of the patient’s which changed the extent of the operation compared to conventional surgery. This identified 9.8% of the patient’s with the aberrant SLN as the only site of the positive lymph nodes. These nodes could have been left behind without SLN mapping.
In conclusion, by doing SLN mapping in early stage colon cancer, we can identify 1 to 3 SLN’s in >93% of patients, which then can be ultrastaged by IHC. This will allow about 25% of the patients to be diagnosed with micrometastases. These patients can then be either treated with systemic therapy or entered into clinical trial with the placebo control arm versus 5-FU/ Leucovorin with or without oxaliplatin.