Clinical Significance of Lymph Node Sampling in Endometrial Carcinoma

Concept

Three methods of lymph node treatment have been suggested^[6], among which lymph node biopsy can be used for extirpation of the visible or palpable tumescent lymph nodes. However this method has limitations in it that fails to reflect the whole condition of the retroperitoneal lymph nodes, especially of the non-tumescent lymph nodes resulting in missed diagnosis or a missed microscopic micrometastasis. It was reported that only 30% of the metastasized lymph nodes could be detected by palpation. The examination failed to determine if there was a lymph node metastasis, since 50% of the positive lymph nodes were less than 1 cm^[3,7]. So lymph node palpation is an inadequate method for surgical pathological staging.

A second method, lymph node sampling, involves a vascular-orientated dissection of the lymph node chains with potential metastasis of the endometrial cancer involving the fatty tissue around the lymph nodes, such as the tissue of the external and common iliac zone, and the abdominal paraaortal lymph node zone, etc. In general, at least 4 subgroups are needed for sampling. However, the number of sampling sites are less compared to systemic lymphatic dissection, and the length and integrity of the sampling lymph node chain are usually less than that of the systemic dissection^[8]. The third method, lymph node dissection, involves pelvic and abdominal paraaortal lymph node dissection. Pelvic lymphadenectomy means a systemic removal of the lymph nodes in the bilateral common iliac zone, external and internal iliac zone, and the groin involving to the obturator foramen. The lymph nodes in the group of presacral tissue sometimes are included in the excision. Clearance of the abdominal paraaortal lymph nodes includes the bilateral abdominal aortal lymphatic fatty tissue, with its upper edge to the level of the renal vein or inferior mesenteric artery and the lower margin to the vascular crotch of the left and right common iliac zone.

Advantage of lymph node sampling

The results of lymph node sampling can indicate the state of lymph node metastasis. The lymph node metastatic rate of the endometrial cancers ranged from 3.9% to 18.2%^[9,10]. In our study, lymph node sampling was adopted in 114 cases, and lymph node dissection was employed in 83. Comparison of the two operative techniques showed that the median of the lymph nodes dissected in each case in the sampling group was 15, while the median in the lymphadenectomy subgroups was 5. In the dissection group, the median of the dissected lymph nodes in each case was 27, and the median of the subgroups ranged from 8 to 11 (including the subgroup of the bilateral common, external and internal iliac zone, the obturator foramen and groin, and of the abdominal paraaortal lymph node, etc.). Lymph node metastasis was found in 8 cases of the sampling group (7.0%) and 6 of the dissection group (7.2%). It follows that though the lymph node sampling may be imperfect, it can correctly determine the state of lymph node metastasis. As far as the surgical pathological staging is concerned, sampling can be used in place of lymph node dissection. Moreover, the procedure of lymph node sampling has a narrower scope compared to dissection, and complications during the operation or the adjuvant radiotherapy after operation can be minimized. It is worth noting that dissection of only several nodes may result in a missed diagnosis^[11,12].

Lymph node sampling is suitable for surgical pathological staging

Based on the regularity of lymph node metastasis, an implementation of multi-regional lymph node sampling may reveal the lymph node state better, thus providing a correct pathological staging. Based on reports from the literature,^[13-15] the lymph node group of the external iliac zone was the site most commonly involved, accounting for 61 to 78%. In our study, invasion of the external iliac zone was found in 9 of the 14 cases with lymph node metastasis (64.3%). And the invasion was also seen in the lymph nodes of the external and common iliac zone and obturator foramen. It was shown that the rate of abdominal paraaortal lymph node metastasis in these endometrial cancers was 1.8~14%,^[16-18] and a straight metastasis might occur there without passing through the pelvic lymph nodes. A total of 607 cases with endometrial cancer have been reported by McMeckin et al.^[12] among which 47 were in Stage-IIIc. Pelvic lymph node metastasis occurred in 20 of the 47 cases (43%), pelvic plus abdominal paraaortal lymph node metastasis in 19 (40%), and a simple abdominal paraaortal lymph node metastasis, without pelvic lymph node metastasis, in 8 (17%)^[11].

The metastatic rate was higher than that reported by the No. 33 document of the gynecologic oncology group (GOG). This finding is because, based on the GOG document, endometrial serous papillary carcinoma and clear-cell carcinoma were ruled out, and usually lymph node metastasis in these patients was very high. Moreover, simple dissection of the right abdominal paraaortal lymph nodes was conducted based on GOG regulations. However, a bilateral excision was performed by McMeckin et al.^[12] and they thought that the lymph node metastases were commonly seen. Therefore they suggested that a bilateral abdominal paraaortal lymph node sampling could enhance the positive detection rate. In our study, abdominal paraaortal lymph node metastasis was found in 1 case, without complicating the pelvic lymph node metastasis. According to suggestions from the GOG, the information considered should be within the scope of abdominal paraaortal lymph nodes sampling, including the positive pelvic lymph node and metastasis of the annex, as well as the depth of the myometrial infiltration of over than 1/3.

Lymph node sampling as the important basis for selecting the methods of postoperative treatment

Lymph node metastasis is an important prognostic factor. It was found in this study that the invasive depth of the myometrium was less than 1/3 in Stage-G2 cancer cases, with lymph node metastasis of 2.6%. A postoperative adjuvant treatment of the patients was reasonable. It was noted that lymph node metastasis might also occur in Stage-G1 cases. Ben-Shachar et al.^[9] reported that surgical pathological staging was conducted in 181 patients with Stage-G1 endometrial cancer, finding a lymphatic metastasis rate of 3.9%. Incorrect postoperative treatment might result if these patients failed to receive lymph node dissection.

It also has been reported that the lymph node sampling had some merits, e.g., it could reduce the complications such as vascular and ureteral injury, etc., and it might minimize a pelvic relapse, etc.^[3]

Correlation factor of lymph node metastasis

Based on analysis of our data, the rate of lymph node metastasis was very high when the cancer was pooly-differentiated and there was deep invasion of the myometrium and of the cervical canals. The lymph node metastasis rate was higher in cancers of various pathological types, such as clear-cell carcinoma, serous papilary adenocarcinoma and adenosquamous carcinoma, compared to endometrioid adenocarcinoma. These findings suggest that these patients should undergo either lymph node dissection, or lymph node sampling. Postoperative irradiation can be performed if there are lymph node metastases.

Effect of lymph node dissection on survival

The 197 cases with endometrial cancer were followed-up for 2 to 90 months, with a follow-up rate of 93.4%. Seven patients died in the sampling group, and 2 survived with a cancerous recurrence. The overall 5-year survival rate was 90.2%, reaching a satisfactory therapeutic effect. Four patients died in the dissection group and the 5-year survival rate was 90.9%.

With regard to the effect of lymph node sampling on the survival rate, Chuang et al.^[3] suggested that lymph node sampling could improve the survival rate. Gao et al.^[2] reported that Stage-I endometrial cancers related neither to the survivals and the mode of surgical operation, nor to the clearance of lymph nodes. It was reported by Trimble et al.^[19] that in 10,066 cases of Stage-I and II endometrial cancer, lymph node sampling increased the survival rate of the patients with stage-I G3. However, it failed to enhance the survival rate of the patients in Stage-I G1 and G2, which might have a low correlation with the number of lymph node specimens (with a median of 7 samples). Based on some reports of successful simple surgical treatment, the number of the dissected lymph nodes would at least amount to 20^{[20, 21]}.

In summary, whether or not the lymph node sampling can replace lymph node dissection during a surgical operation for endometrial cancer, still depends on prospective observation of a large number of cases.