Implications of para-aortic lymph node metastasis in patients with endometrial cancer without pelvic lymph node metastasis

Yukiharu Todo; Sho Takeshita; Kazuhira Okamoto; Katsushige Yamashiro; Hidenori Kato

doi:10.3802/jgo.2017.28.e59

Journal List > J Gynecol Oncol > v.28(5) > 1093845

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Todo, Takeshita, Okamoto, Yamashiro, and Kato: Implications of para-aortic lymph node metastasis in patients with endometrial cancer without pelvic lymph node metastasis

Original Article

J Gynecol Oncol 2017;28(5):e59.

Published online: 4 September 2017

DOI: https://doi.org/10.3802/jgo.2017.28.e59

Implications of para-aortic lymph node metastasis in patients with endometrial cancer without pelvic lymph node metastasis

Yukiharu Todo^1,, Sho Takeshita¹, Kazuhira Okamoto¹, Katsushige Yamashiro², Hidenori Kato¹

¹Division of Gynecologic Oncology, National Hospital Organization, Hokkaido Cancer Center, Sapporo, Japan

²Division of Pathology, National Hospital Organization, Hokkaido Cancer Center, Sapporo, Japan

Correspondence to Yukiharu Todo Division of Gynecologic Oncology, National Hospital Organization, Hokkaido Cancer Center, 4-2 Kikusui, Shiroishi-ku, Sapporo 003-0804, Japan. E-mail: yukiharu@sap-cc.go.jp

Received 31 March 2017 Revised 21 April 2017 Accepted 4 May 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

The aim of this study was to confirm the incidence and implications of a lymphatic spread pattern involving para-aortic lymph node (PAN) metastasis in the absence of pelvic lymph node (PLN) metastasis in patients with endometrial cancer.

Methods

We carried out a retrospective chart review of 380 patients with endometrial cancer treated by surgery including PLN dissection and PAN dissection at Hokkaido Cancer Center between 2003 and 2016. We determined the probability of PAN metastasis in patients without PLN metastasis and investigated survival outcomes of PLN−PAN+ patients.

Results

The median numbers of PLN and PAN removed at surgery were 41 (range: 11–107) and 16 (range: 1–65), respectively. Sixty-four patients (16.8%) had lymph node metastasis, including 39 (10.3%) with PAN metastasis. The most frequent lymphatic spread pattern was PLN+PAN+ (7.9%), followed by PLN+PAN− (6.6%), and PLN−PAN+ (2.4%). The probability of PAN metastasis in patients without PLN metastasis was 2.8% (9/325). The 5-year overall survival rates were 96.5% in PLN−PAN−, 77.6% in PLN+PAN−, 63.4% in PLN+PAN+, and 53.6% in PLN−PAN+ patients.

Conclusion

The likelihood of PAN metastasis in endometrial cancer patients without PLN metastasis is not negligible, and the prognosis of PLN−PAN+ is likely to be poor. The implications of a PLN−PAN+ lymphatic spread pattern should thus be taken into consideration when determining patient management strategies.

Keywords: Endometrial Neoplasms, Lymphatic Metastasis, Lymph nodes, Prognosis

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Fig. 1.

Lymphatic spread pattern in 60 patients who underwent PAND up to the renal vein and were diagnosed with LNM. LNM, lymph node metastasis; PAN, para-aortic lymph node; PAND, para-aortic lymph node dissection; PLN, pelvic lymph node.

Fig. 2.

Kaplan-Meier OS curves according to lymphatic spread pattern. OS, overall survival; PAN, para-aortic lymph node; PLN, pelvic lymph node.

Table 1.

Characteristics of 754 patients with endometrial cancer who underwent surgical treatment

Characteristic	LND (−) (n=199)	PLND alone (n=175)	PLND+PAND (n=380)	p-value
Age (yr)	59.0 (20–93)	60.0 (33–83)	58.5 (28–76)
≥70	65 (32.7)	40 (22.9)	25 (6.6)	<0.001
≥75	40 (20.1)	19 (10.9)	1 (0.3)	<0.001
BMI (kg/m²)	23.6 (15.5–51.8)	23.1 (15.5–46.6)	23.8 (13.4–44.9)
>30	41 (20.6)	30 (17.1)	47 (12.4)	0.029
>35	17 (8.5)	9 (5.1)	14 (3.7)	0.046
Final pathology				<0.001
Endometrioid grade 1	129 (64.8)	120 (68.6)	164 (43.2)
Endometrioid grade 2	28 (14.1)	30 (17.1)	91 (23.9)
Endometrioid grade 3	16 (8.0)	8 (4.6)	65 (17.1)
Other	26 (13.1)	17 (9.7)	60 (15.8)
Postoperative stage				<0.001
IA	132 (66.3)	121 (69.1)	188 (49.5)
IB	34 (17.1)	27 (15.4)	79 (20.8)
II	9 (4.5)	7 (4.0)	21 (5.5)
III	7 (3.5)	11 (6.3)	82 (21.6)
IV	17 (8.5)	9 (5.1)	10 (2.6)

Values are presented as median (range) or number (%). BMI, body mass index; LND, lymph node dissection; PAND, para-aortic lymph node dissection; PLND, pelvic lymph node dissection.

Table 2.

Surgical results of 380 patients who underwent PLND and PAND

Characteristic	Value (n=380)
Type of PAND
Low PAN alone (below the IMA)	5
Low PAN and high PAN	375
No. of lymph nodes removed
PLN	41 (11–107)
PAN	16 (1–65)
Total	56.5 (18–131)
Lymphatic spread pattern
PLN−PAN−	316 (83.1)
PLN−PAN+	9 (2.4)
PLN+PAN−	25 (6.6)
PLN+PAN+	30 (7.9)

Values are presented as median (range) or number (%). IMA, inferior mesenteric artery; PAN, para-aortic lymph node; PAND, para-aortic lymph node dissection; PLN, pelvic lymph node; PLND, pelvic lymph node dissection.

Table 3.

Profile of the 9 patients with PLN−PAN+

Age (yr)	Peritoneal disease	Final histological type	Myometrial invasion	Cervical involvement	LVSI m	Adnexal metastasis	Peritoneal washing	Preoperative histological type	Myometrial invasion (MRI)	Radiological signs of extrauterine disease	Outcome	OS (M)
46	+	G2	<1/2	+	+	+	+	G2	>1/2	−	NED	75
70	+	S	>1/2	+	+	−	+	S	>1/2	+	DOD	8
63	+	G2	>1/2	−	+	+	+	G1	>1/2	+	NED	7
67	−	G2	>1/2	+	+	+	+	G1	>1/2	+	DOD	15
70	−	Mixed	<1/2	−	+	+	+	S	>1/2	−	NED	9
40	−	G2	>1/2	−	+	−	+	G1	>1/2	−	DOD	43
55	−	G1	>1/2	−	+	−	−	G1	>1/2	−	NED	63
63	−	G1	>1/2	+	+	−	−	G1	>1/2	−	NED	61
61	−	G1	>1/2	−	+	−	−	G2	>1/2	−	NED	22

DOD, died of disease; G1, grade 1 endometrioid adenocarcinoma; G2, grade 2 endometrioid adenocarcinoma; LVSI, lympho-vascular space invasion; M, month; Mixed, mixed epithelial carcinoma; MRI, magnetic resonance imaging; NED, no evidence of disease; OS, overall survival; PAN, para-aortic lymph node; PLN, pelvic lymph node; S, serous adenocarcinoma.

Table 4.

Results of pooled analysis: lymphatic spread pattern in endometrial cancer according to number of PANs removed

Author	Year	No.	FIGO stage III/IV (%)	NE histology (%)	No. of PLNs removed^*	No. of PANs removed^*	A	B	C	D	B/A+B (%)
Author	Year	No.	FIGO stage III/IV (%)	NE histology (%)	No. of PLNs removed^*	No. of PANs removed^*	PLN−/PAN−	PLN−/PAN+	PLN+/PAN−	PLN+/PAN+	B/A+B (%)
No. of PAN removed: <10
Larson et al. [6]	1993	50	28	0	13	5	50	0	2	8	0.0
Fanning et al. [7]	1996	60	8	0	21	7	55	0	5	0	0.0
Yokoyama et al. [8]	1997	63	13	3	14	6	45	4	6	8	8.2
Lee et al. [9]	2009	349	NA	0	(22.8)	(9.5)	277	7	26	39	2.5
Abu-Rustum et al. [10]	2009	847	NA	NA	16	5	722	12	52	61	1.6
Chiang et al. [11]	2011	171	22	6	17	5	154	2	12	3	1.3
Solmaz et al. [12]	2015	516	NA	0	22	8.5	449	4	37	26	0.9
Subtotal		2,056					1,752	29	140	145	1.6
No. of PAN removed: not available
Chen and Lee [13]	1983	74	NA	11	NA	NA	63	3	3	5	4.5
Creasman et al. [14]	1987	621	22	4	NA	NA	551	12	36	22	3.9
Ayhan et al. [15]	1995	209	NA	NA	NA	NA	173	6	17	13	3.4
Hirahatake et al. [16]	1997	200	42	4	NA	NA	158	2	24	16	1.3
Milam et al. [17]	2012	582	11	0	NA	NA	520	12	31	19	2.3
Sueoka et al. [18]	2015	502	17	18	NA	NA	422	15	27	38	3.4
Mahdi et al. [19]	2015	91	NA	NA	NA	NA	56	6	18	11	9.7
Subtotal		2,279					1,943	56	156	124	2.8
No. of PAN removed: >10
Onda et al. [20]	1997	173	24%	1	(37.9)	(28.7)	143	2	10	18	1.4
Matsumoto et al. [21]	2002	106	NA	5	(36.8)	(30.5)	79	2	7	18	2.5
Mariani et al. [22]	2008	281	NA	NA	35	17	218	10	24	29	4.4
Fujimoto et al. [23]	2009	355	25	0	42	19	306	7	20	22	2.2
Dogan et al. [24]	2012	161	21	21	(49.5)	(19.0)	143	2	11	5	1.4
Odagiri et al. [25]	2014	266	NA	17	62.5	20	224	7	16	19	3.0
Altay et al. [26]	2015	173	NA	27	26	12	135	7	12	19	4.9
Tomisato et al. [27]	2014	260	46	17	50	22	169	9	34	48	5.1
Fotopoulou et al. [28]	2015	128	15	24	29	21.5	101	4	8	15	3.9
Sautua et al. [29]	2015	90	NA	NA	(11.9)	(10.7)	77	6	3	4	7.2
Alay et al. [30]	2015	204	26	23	(44.1)	(24.9)	160	8	17	19	4.8
Subtotal		2,197					1,755	64	162	216	3.5
Total		6,532					5,450	149	458	485	2.7

FIGO, International Federation of Gynecology and Obstetrics; NA, not available; NE, non-endometrioid; PAN, para-aortic lymph node; PLN, pelvic lymph node.* Values are presented as median (mean).

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