Usefulness of histological superstudy of sentinel node detected with radioisotope in colon cancer

Abstract

Introduction: Adjuvant chemotherapy (CT) significally reduces the rate of relapse in +pN (stage III) colon cancer and in some pN0 (stage II) with risk factors such as pT4, vascular invasion V1, perineural invasion Pn1, and complicated tumors. However, unexpectedly, 20-30% of pN0 present a relapse in the follow-up, which may suggest that the lymph node involvement was not discovered in the conventional histological study (CS), and its finding with a superstudy (SS) could increase the number of patients who would benefit from neoadjuvant CT. It is not possible to perform this SS in every lymph node (LN) from the specimen, but it is possible in a small group of LN which are representative of the N status (definition of sentinel node SN). The aim of our work is to state the representativeness of the SN and to analyze de number of patients who are suprastaged after the SS of the SN.

Material and methods: Prospective study of a series of patients who have undergone curative surgery for colon cancer, to whom we perform selective biopsy of sentinel node. Identification of SN was carried out with in vivo injection of the radiotracer, with ex vivo isolation of SN. Once the specimen is out, we take pictures of the surgical bed to rule out the presence of aberrant drainage routes, out of the routine oncological resection area. We performed the histological CS (hematoxilin-eosin stain in conventional sections) in the rest of the LN from the mesocolon. In the SN we performed the CS and a SS with hematoxilin-eosin in serial sections, immunohistochemistry (IHC) and molecular study with One Step Nucleic Acid Amplification (OSNA®). Diagnostic validity study od selective biopsy of sentinel node was carried out, defining the false negative (FN) as the negativity of the SN while other LN are positive (N+), as well as a valuation of the suprastaging due to the SS of the SN.

Results: We performed lymphatic map in 72 patients, finding the SN in 62 of them (87.3%). The 9 identification failures happened in the first 17 cases. We have not found aberrant drainage routes. A total of 1.164 LN were studied in the 62 patients (18.8 LN/ patient), from which 145 are SN (2,34 SN/ patient), having found 103 positive LN with the CS and 112 positive with the SS of SN (9 +LN more in 8 patients than detected with the CS). Positivity after CS in the SN group is 17.24% (25/145), while it is 8.53% in the rest (87/1.019) (p<.001). With the CS, 50% of the patients (31/62) were pN+ (4 are N+ exclusively in the SN), and after the SS of the SN, only 1 of the 31 pN0 patients (3.2%) becomes pN1a, with a definitive 51.6% of N+ in the whole series (32 N+ in the 62 patients) (5 are N+ exclusively in the SN). Exclusively with the SS of the SN, FN rate ("-SN, +others", meaning patients who are N+ having -SN) is 54.8% (17/31). With the SS of the SN, 8 of the 62 patients (12.9%) increase their total number of +LN: apart from the patient who turns from pN0 to pN1a, suprastaging from IIA to IIIB (and therefore increasing the total number of pN+ to 32), 5 of the 17 FN in the CS turns into positive (2 change the pN subindex and one is suprastaged from IIIB to IIIC), decreasing FN to 37.5% (12/32 cases). Besides, 2 patients whose SN is already positive in the CS increase the number of +SN after the SS of the SN, therefore both changing their pN subindex and one of them suprastaging from IIIB to IIIC. In summary, 8 patients increase the total number of positive SN after the SS (8/62, 12.9%), 5 of them changing the pN subindex (5/62, 12.9%), even if only 3 of them get suprastaged (3/62, 4.8%), among them the one who turns from pN0 to pN1a.

Conclusion: Technique is valid and reproducible, with a high detection rate even with a high learning curve. It globally increases the number of affected LN in 12.9% of patients, having prognostic implications in 4.8% (suprastaging rate). Only 3.2% of pN0 patients in the CS turn to be +pN after the SS of the SN, with its therapeutic implications (prescription of adjuvant CT), which could be relevant when extrapolated to a big number of patients. The high FN rate (37.5%) prevents us from accepting the representativeness of SN as the global N status, but it is not clinically relevant in colon cancer, as its aim is not to avoid lymphadenectomy, which remains mandatory (opposite to breast cancer or melanoma in which SN detection decides upon whether to perform or not the lymphadenectomy), but to decide which patients would benefit from adjuvant CT.

Keywords: Colon cancer; Cáncer de colon; Ganglio centinela; Localización radioguiada; Mix technique; Radioguided localization; Sentinel node; Supraestadificación; Suprastaging; Técnica mixta.