ORIGINAL ARTICLE

Results of a Japanese Nationwide Multi-Institutional Study on

Lateral Pelvic Lymph Node Metastasis in Low Rectal Cancer
Is It Regional or Distant Disease?
Takashi Akiyoshi, MD,∗ Toshiaki Watanabe, MD,† Satoshi Miyata, PhD,‡ Kenjiro Kotake, MD,§
Tetsuichiro Muto, MD,∗ and Kenichi Sugihara, MD; on behalf of the Japanese Society for Cancer of the Colon
and Rectum

countries and Japan. In Western countries, lateral pelvic LN metas-

Objective: To evaluate whether lateral pelvic lymph nodes (LNs) in low rectal
tasis is generally considered a metastatic disease, and preoperative
cancer are metastatic disease or part of regional LNs that are amenable to
chemoradiotherapy combined with total mesorectal excision (TME)
curative resection.
is the standard treatment.1–3 In contrast, in Japan, surgeons generally
Background: It is highly controversial whether lateral pelvic LNs should
consider that lateral pelvic LN metastasis can be cured with removal,
be considered as regional or distant disease, although the American Joint
and TME with lateral pelvic LN dissection (LPLD) is the standard
Committee on Cancer (AJCC) defines internal iliac LNs as regional LNs of
operation for locally advanced low rectal cancer.4,5 It is highly contro-
rectal cancer.
versial whether lateral pelvic LNs should be considered a metastatic
Methods: Data of patients with stage I to III low rectal cancer who under-
disease or part of regional LNs that are amenable to curative resec-
went curative resection from 1978 to 1998 were extracted from the multi-
tion. However, the seventh edition of the American Joint Committee
institutional registry of large bowel cancer in Japan. Patients with only
on Cancer (AJCC) Cancer Staging Manual clearly defines internal
mesorectal LN metastasis were classified as the mesorectal-LN group. Pa-
iliac LNs as regional LNs of rectal cancer.6 On the contrary, LNs in
tients with lateral pelvic LN metastasis localized to or extending beyond the
the area of the obturator, external iliac, and common iliac that are re-
internal iliac area were classified as the internal lateral pelvic lymph nodes
moved by LPLD are not clearly defined as regional LNs,6 suggesting
(LPLN) group and external-LPLN group, respectively. Overall survival (OS)
that lateral pelvic LN metastasis extending beyond the internal iliac
and cancer-specific survival (CSS) were compared between the groups.
area should be considered as distant disease.
Results: Lateral pelvic LN dissection was performed in 5789 (50%) of 11,567
In the present study, we analyzed the prognosis of low rec-
patients. Overall, 3905 (34%), 411 (3.6%), and 244 (2.1%) patients were
tal cancer with lateral pelvic LN metastasis localized to or extend-
classified as the mesorectal-LN, internal-LPLN, and external-LPLN groups,
ing beyond the internal iliac area to clarify whether lateral pelvic
respectively. When the mesorectal LN group was subdivided as defined by the
LNs represent regional or distant disease. We used a large nation-
AJCC, both 5-year OS and CSS were not significantly different between the
wide multi-institutional database compiled in Japan over a 20-year
N2a and internal-LPLN groups (OS: 45% vs 45%, P = 0.9585; CSS: 51%
period.7–10
vs 49%, P = 0.5742), and the N2b and external-LPLN groups (OS: 32% vs
29%, P = 0.3342; CSS: 37% vs 34%, P = 0.4347). OS and CSS were signif-
icantly better in the external-LPLN group than in stage IV patients who un- METHODS
derwent curative resection (OS: 29% vs 24%, P = 0.0240; CSS: 34% vs 27%, Data Source
P = 0.0117).
We used data from the multi-institutional registry of large
Conclusions: Lateral pelvic LNs can be considered as regional LNs in low
bowel cancer in Japan from 1978 to 1998.7–10 This registry has been
rectal cancer, although metastasis extending beyond the internal iliac area is
compiled by the Japanese Society for Cancer of the Colon and Rec-
associated with poorer survival.
tum (JSCCR), which includes the departments of surgery, internal
(Ann Surg 2012;255:1129–1134) medicine, pathology, and radiation in hospitals throughout Japan.
In this registry system, each member institution is responsible for
T he management of lateral pelvic lymph nodes (LNs) associated
with low rectal cancer is considerably different between Western
the registry of their patients. All patients diagnosed with colorectal
cancer at each institution were registered with the follow-up data,
including survival, causes of death, and the follow-up period. Causes
of death and the last follow-up depended on the outpatient follow-up
data of each institution. There was no intentional inclusion or exclu-
From the ∗ Gastroenterological Center, Department of Gastroenterological Surgery, sion of samples to the registry that might have induced any bias to
Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo,
Japan; †Department of Surgical Oncology, The University of Tokyo, Tokyo, the results. The registry database includes detailed clinicopathologi-
Japan; ‡Genome Center, Bioinformatics group, Cancer Institute Hospital, cal data related to factors specified by the JSCCR.4 This nationwide
Japanese Foundation for Cancer Research, Tokyo, Japan; §Department of multi-institutional database covers approximately 10% of all patients
Surgery, Tochigi Cancer Center, Tochigi, Japan; and Department of Surgi- with colorectal cancer diagnosed in Japan during 1978 to 1998.10 The
cal Oncology, Tokyo Medical and Dental University, Tokyo, Japan.
Disclosure: The authors declare no conflicts of interest. This study was supported study was approved by the local ethics committee.
in part by a Grant-in-Aid for Cancer Research from the Ministry of Health,
Labour and Welfare of Japan and a Grant-in-Aid for Cancer Research from the
Ministry of Education, Culture, Sports, Science and Technology of Japan. Patient Selection and Data Extraction
Reprints: Toshiaki Watanabe, MD, Department of Surgical Oncology, The Uni- Data of patients with low rectal tumors (bulk of the tumor
versity of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655 Japan, E-mail: located below the peritoneal reflection) from 1978 to 1998 were ex-
toshwatanabe@yahoo.co.jp.
Copyright C 2012 by Lippincott Williams & Wilkins
tracted from the database along with their clinicopathological data, in-
ISSN: 0003-4932/12/25506-1129 cluding sex, age, date and method of resection (surgery or endoscopy),
DOI: 10.1097/SLA.0b013e3182565d9d depth of invasion, presence of lymphatic or venous invasion, site and

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Akiyoshi et al Annals of Surgery r Volume 255, Number 6, June 2012

number of LN metastasis, presence and site of distant metastasis,
date of the most recent follow-up, and cancer-specific prognosis. We
excluded patients with in situ or metastatic disease, patients with ma-
lignancies other than adenocarcinoma, patients who did not undergo
a curative (R0) tumor resection, and patients in whom the region or
number of LN metastasis was unknown. The total number of patients
after all exclusions was 11,567.
Division of the Lateral Pelvic Area
The lateral pelvic area was classified into 6 regions according
to the JSCCR classification5 : internal iliac, obturator, external iliac,
common iliac, aortic bifurcation, and median sacral regions (Fig. 1).
The registry database included the number of dissected and metastatic
LNs in each of the 6 regions, and patients with 1 or more dissected
LNs in the lateral pelvic area were classified as having undertaken
LPLD.
Patients were divided into 4 groups according to the extent
of their LN metastasis. Patients without LN metastasis were clas-
sified as the N0 group, whereas those with mesenteric metastatic
LNs (mesorectal nodes or nodes adjacent to the inferior mesenteric
artery) without metastatic lateral pelvic LNs were classified as the
mesorectal-LN group. Patients who had metastatic internal iliac LNs
without metastatic LNs in the other 5 lateral pelvic regions were
classified as the internal-lateral pelvic lymph nodes (LPLN) group,
whereas those with metastatic lateral pelvic LNs in the 5 lateral
pelvic regions (obturator, external iliac, common iliac, aortic bifurca-
tion, and median sacral), with or without the internal iliac area, were
classified as the external-LPLN group.
proportional hazards model with the backward stepwise elimination
method (significance level to stay = 0.05) was used to multivariately
assess predictors of outcome. Covariates considered in this analysis
were sex, age, histological type, depth of tumor, lymphatic invasion,
venous invasion, LPLD, number of LNs removed, perioperative radia-
tion, adjuvant chemotherapy, and status of LN metastasis. The results
of Cox model analysis are reported using hazard ratios (HRs) and
95% confidence intervals (CIs).
RESULTS
Table 1 summarizes the characteristics of the 11,567 patients
with low rectal cancer who underwent curative resection from 1978
to 1998. Male prevalence was higher and the median age was 61 years
(IQR [interquartile range], 53–69 years). Sixty-two percent of the pa-
tients had T3 or T4 tumors in depth. LPLD was performed in almost
50% of the patients. Mesenteric LN metastasis without lateral pelvic
LN metastasis (mesorectal-LN) was present in 33.7% of the patients.
Lateral pelvic LN metastasis (internal- and external-LPLN) was iden-
tified in 5.7% (655/11,567) of the total patients, in 7.8% (558/7123)
of the patients who had T3 or T4 tumors, in 11.3% (655/5789) of the
patients who underwent LPLD, and in 14.6% (558/3832) of the pa-
tients with T3 or T4 tumors who underwent LPLD. Of the 655 patients
with lateral pelvic LN metastasis, metastasis in the lateral pelvic area
TABLE 1. Characteristics of Patients with Low Rectal
Cancer Who Underwent Curative Resection

Statistical Analysis Variables n (%)

Statistical analysis was performed using JMP software V 8.0.2 Sex
(SAS Institute, Cary, NC). The relationships between each of the Male 7229 (62.5)
variables and LPLD were analyzed using the χ 2 test or Fisher ex- Female 4338 (37.5)
act test. Survival analysis was performed using the Kaplan-Meier Age
<60 5258 (45.5)
method with log-rank analysis. Patients who died from other causes
≥60 6297 (54.5)
or were alive at the most recent follow-up were treated as censored Histological type
in the analysis of cancer-specific survival (CSS). Logistic regression Well/moderate 10828 (93.8)
analysis was used to determine independent risk factors for lateral Other 710 (6.2)
pelvic LN metastasis among patients who underwent LPLD. The Cox Depth of tumor
T1/T2 4388 (38.1)
T3/T4 7123 (61.9)
Lymphatic invasion
Yes 6917 (62.9)
No 4080 (37.1)
Venous invasion
Yes 5089 (46.9)
No 5769 (53.1)
LPLD
Yes 5789 (50.0)
No 5778 (50.0)
Number of LNs removed
1–11 3849 (33.2)
≥12 7718 (66.8)
Perioperative radiation
Yes 729 (6.4)
No 10695 (93.6)
Adjuvant chemotherapy
Yes 6726 (58.9)
No 4698 (41.1)
Status of LN metastasis
FIGURE 1. Schematic figure of the 6 lateral pelvic areas: in- N0 7007 (60.6)
ternal iliac (A), obturator (B), external iliac (C), common il- Mesorectal-LN 3905 (33.7)
iac (D), aortic bifurcation (E), and median sacral (F). Patients Internal-LPLN 411 (3.6)
with metastasis limited to A were classified as the internal-LPLN External-LPLN 244 (2.1)
group, whereas those with metastasis in the other regions (B-F) All unknown cases were excluded.
were classified as the external-LPLN group.

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Annals of Surgery r Volume 255, Number 6, June 2012 Lateral Lymph Node in Low Rectal Cancer

was limited to the internal iliac area in 411 patients (62.7%, internal- = 0.0004), histology other than well/moderately differentiated ade-
LPLN). nocarcinoma (P < 0.0001), T3/T4 tumor in depth (P < 0.0001),
Table 2 summarizes the characteristics of patients with and of presence of lymphatic invasion (P = 0.0069), presence of venous
those without LPLD. LPLD was significantly associated with a higher invasion (P = 0.0263), and presence of mesenteric LN metastasis
percentage of age less than 60 years (P < 0.0001), histology other (P < 0.0001) were independently associated with lateral pelvic LN
than well/moderately differentiated adenocarcinoma (P = 0.0364), metastasis.
T3/T4 tumor in depth (P < 0.0001), presence of lymphatic (P < Follow-up data were available in 8933 patients who were reg-
0.0001) or venous (P < 0.0001) invasion, number of LNs removed istered from 1978 to 1994. The overall median follow-up time was 67
12 or more (P < 0.0001), and performing perioperative radiation (P months (IQR, 32–82 months). Both overall survival (OS) and CSS
< 0.0001) or adjuvant chemotherapy (P < 0.0001). Table 3 summa- were significantly different according to the status of LN metastasis
rizes the risk factors for lateral pelvic LN metastasis in 5789 patients (Fig. 2). Five-year OSs of the N0, mesorectal-LN, internal-LPLN, and
with LPLD. Logistic regression analysis showed that female sex (P external-LPLN groups were 80% (95% CI, 79%–81%), 55% (53%–
56%), 45% (39%–50%), and 29% (23%–37%), respectively. Five-
year CSSs of the N0, mesorectal-LN, internal-LPLN, and external-
LPLN groups were 88% (95% CI, 87%–89%), 61% (59%–62%),
TABLE 2. Characteristics of Patients With and Without 49% (43%–55%), and 34% (27%–42%), respectively.
Lateral Pelvic Lymph Node Dissection To determine which variables had an independent effect on
LPLD No LPLD postoperative survival, a multivariate Cox regression analysis with the
Variables n (%) n (%) P backward stepwise elimination technique was performed using the 11
variables shown in Table 1. The results are summarized in Table 4.
Sex Independent prognostic factors associated with both OS and CSS were
Male 3659 (63.2) 3570 (61.8) 0.1153
age, histological type, depth of tumor, lymphatic invasion, LPLD,
Female 2130 (36.8) 2208 (38.2)
Age number of LNs removed, and status of LN metastasis. Gender was
<60 2792 (48.3) 2466 (42.7) <0.0001 independently associated with OS, and venous invasion and adjuvant
≥60 2993 (51.7) 3304 (57.3) chemotherapy were independently associated with CSS.
Histological type
Well/moderate 5396 (93.4) 5432 (94.3) 0.0364
Other 383 (6.6) 327 (5.7)
A 1
Depth of tumor
0.9 80%
T1/T2 1927 (33.5) 2461 (42.8) <0.0001
Probability of survival

0.8 N0
T3/T4 3832 (66.5) 3291 (57.2)
0.7
Lymphatic invasion 55%
0.6
Yes 3708 (66.6) 3209 (59.1) <0.0001 45% Mesorect al-LN
0.5
No 1863 (33.4) 2217 (40.9)
Venous invasion 0.4 29% Internal -LPLN
Yes 2877 (52.3) 2212 (41.3) <0.0001 0.3
External-LPLN
No 2619 (47.7) 3150 (58.7) 0.2 P < .0001
Number of LNs removed 0.1
1–11 762 (13.2) 3087 (53.4) <0.0001 0
0 1 2 3 4 5 6 7
≥12 5027 (86.8) 2691 (46.6) Years from surgery
Perioperative radiation No. at risk
Yes 458 (8.0) 271 (4.7) <0.0001
N0 5391 5005 4623 4296 3968 3575 2710 1388
No 5249 (92.0) 5446 (95.3)
Mesorect al-LN 3053 2760 2316 1922 1631 1373 1016 517
Adjuvant chemotherapy Internal -LPLN 316 291 232 172 140 117 100 67
Yes 3613 (63.3) 3113 (54.5) <0.0001 External -LPLN 173 149 105 79 55 46 29 13
No 2094 (36.7) 2604 (45.5)
Status of LN metastasis
N0 3335 (57.6) 3672 (63.6) <0.0001
Mesorectal-LN 1799 (31.1) 2106 (36.4) B 1 88%
Internal-LPLN 411 (7.1) 0 0.9 N0
Probability of survival

External-LPLN 243 (4.2) 0 0.8

0.7 61%
All unknown cases were excluded.
0.6 Mesorectal-LN
49%
0.5
34% Internal-LPLN
0.4
0.3 External-LPLN
TABLE 3. Results of Logistic Regression Analysis of 0.2 P < .0001
the Risk Factors for Lateral Pelvic Lymph Node 0.1
Metastasis 0
0 1 2 3 4 5 6 7
Variables OR (95% CI) P Years from surgery
No. at risk
Sex (female) 1.39 (1.16–1.66) 0.0004 N0 5391 5005 4623 4296 3968 3575 2710 1388
Histological type (other) 2.01 (1.52–2.64) <0.0001 Mesorect al-LN 3053 2760 2316 1922 1631 1373 1016 517

Depth of tumor (T3/4) 2.19 (1.71–2.84) <0.0001 Internal -LPLN 316 291 232 172 140 117 100 67
External -LPLN 173 149 105 79 55 46 29 13
Lymphatic invasion (yes) 1.39 (1.10–1.76) 0.0069
Venous invasion (yes) 1.24 (1.03–1.51) 0.0263
FIGURE 2. Overall survival (A) and cancer-specific survival (B)
Mesenteric LN metastasis (yes) 4.64 (3.77–5.74) <0.0001
for 8933 patients.


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Akiyoshi et al
TABLE 4. Results of Stepwise Cox Multivariate Regression Analysis
OS
Variables HR (95% CI)
Sex (male) 1.16 (1.07–1.26)
Age (≥60) 1.55 (1.43–1.67)
Histological type (other) 1.46 (1.27–1.66)
Depth of tumor (T3/4) 2.30 (2.09–2.54)
Lymphatic invasion (yes) 1.24 (1.13–1.35)
Venous invasion (yes) — —
LPLD (yes) 0.85 (0.78–0.93)
Number of LNs removed (≥12) 0.77 (0.71–0.85)
Peri-operative radiation (yes) — —
Adjuvant chemotherapy (yes) — —
Status of LN metastasis
N0 1.00
Mesorectal-LN 2.05 (1.88–2.23)
Internal-LPLN 2.96 (2.49–3.50)
External-LPLN 4.68 (3.80–5.71)
Finally, we tried to determine whether lateral pelvic LN metas-
tasis is regional or distant disease. We subdivided the mesorectal-LN
group into 4 categories on the basis of the AJCC Cancer Staging
Manual (N1a: 1 regional LN metastasis; N1b: 2–3 metastases; N2a:
4–6 metastases; N2b: ≥7 metastases). Five-year OSs of the N1a,
N1b, N2a, and N2b groups were 68% (95% CI, 65%–70%), 54%
(51%–57%), 45% (41%–49%), and 32% (28%–37%), respectively.
Five-year CSSs of the N1a, N1b, N2a, and N2b groups were 74%
(95% CI, 72%–77%), 60% (56%–63%), 51% (46%–55%), and 37%
(32%–42%), respectively. Both OS and CSS were not significantly
different between the internal-LPLN and N2a groups (P = 0.9585
for OS and 0.5742 for CSS), or between the external-LPLN and N2b
groups (P = 0.3342 for OS and 0.4347 for CSS) (Fig. 3). In ad-
dition, the survival of 260 patients with stage IV low rectal cancer
who underwent R0 resection from 1978 to 1994 was also analyzed.
Five-year OSs and CSSs of the stage IV group were 24% (95% CI,
19%–29%) and 27% (21%–33%), respectively. Both OS and CSS of
the external-LPLN group were significantly better than those of the
stage IV group (P = 0.0240 for OS and 0.0117 for CSS) (Fig. 3).
DISCUSSION
The effectiveness of LPLD is controversial because lateral
pelvic LN metastasis may represent systemic disease not amenable to
surgical cure.1,3 In an analysis of 11,567 patients with low rectal can-
cer registered in a nationwide multi-institutional database in Japan,
we showed that lateral pelvic LN metastasis could be considered as
regional disease. We also showed that LPLD conferred a significant
cancer-specific advantage when analyzed using the multivariate Cox
proportional hazards model. To date, the present study is the largest
study to analyze the prognosis of lateral pelvic LN metastasis in low
rectal cancer.1–3,11–20
The survival of patients with lateral pelvic LN metastasis was
significantly poorer than that of those with LN metastasis limited to
the mesenteric area, suggesting that lateral pelvic LN metastasis is a
poor prognostic indicator. However, among the patients with lateral
pelvic LN metastasis, the survival of patients with LN metastasis
limited to the internal iliac area was comparable with that of N2a and
better than that of N2b. This result indicates that internal iliac LNs in
low rectal cancer represent regional LNs that can be cured by LPLD,
and it supports the AJCC definition in which internal iliac LNs are
classified as regional LNs in rectal cancer. On the contrary, survival
of patients with lateral pelvic LN metastasis extending beyond the
internal iliac area was poorer than that of those with metastasis limited
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Annals of Surgery r Volume 255, Number 6, June 2012
CSS
P HR (95% CI) P
0.0002 — —
<0.0001 1.20 (1.10–1.32) <0.0001
<0.0001 1.57 (1.35–1.82) <0.0001
<0.0001 2.73 (2.40–3.12) <0.0001
<0.0001 1.34 (1.19–1.51) <0.0001
1.10 (1.00–1.22) 0.0447
0.0003 0.88 (0.79–0.98) 0.0162
<0.0001 0.77 (0.69–0.86) <0.0001
— —
1.13 (1.02–1.25) 0.0192
<0.0001 <0.0001
1.00
2.88 (2.59–3.20)
4.20 (3.45–5.07)
6.88 (5.44–8.61)
to the internal iliac area, but it was comparable with that of N2b and
better than that of stage IV patients who underwent curative resection.
Our findings suggest that lateral pelvic LNs other than internal iliac
LNs can also be treated by LPLD as regional LNs in low rectal
cancer.
With regard to the effectiveness of LPLD for rectal cancer,
Georgiou and colleagues1 demonstrated by meta-analysis that LPLD
did not confer a significant overall cancer-specific advantage. How-
ever, there are potential limitations to this previous study by Geor-
giou and colleagues1 that might have led to misleading conclusions.21
First, there was a significant selection bias between the LPLD and
non-LPLD groups. LPLD is generally indicated for advanced (T3 and
T4) rectal cancer that extends below the peritoneal reflection in Japan,
based on the fact that the rectum below the peritoneal reflection has
lymphatic channels that extend laterally.3 However, the final indica-
tion is at the surgeon’s discretion, and consequently there is variability
in the LPLD indications among institutions. A recent large multicen-
ter study reported by Kobayashi and colleagues11 analyzed 1272 pa-
tients with low rectal cancer and showed that LPLD was more likely
to be performed in high-risk patients for lateral pelvic LN metastasis,
that is, larger tumors, a higher stage, and more aggressive pathology.
Up until the current study, Kobayashi and colleagues11 had performed
the largest comparative study examining LPLD versus non-LPLD for
low rectal cancer, and it was included in the meta-analysis reported
by Georgiou and colleagues.1 Therefore, considering that more ad-
vanced tumors are prevalent in LPLD patients compared with those
who do not have LPLD, the finding of a similar survival and local
recurrence rate between the 2 groups of patients suggests that LPLD
is beneficial. Second, the time period of the meta-analysis was very
long (1984 to 2007). Recently, Japanese surgeons have become more
selective with regard to the indications for LPLD because of previous
analyses of large studies and using modern imaging techniques12,22 ;
therefore, the effectiveness of LPLD has not been the same over time.
Given that the prognosis of patients with lateral pelvic LN metastasis
who underwent LPLD was similar to N2, we can conclude that se-
lected patients with lateral pelvic LN metastasis would benefit from
LPLD. In contrast, it is uncertain whether LPLD can confer a survival
benefit for patients without obvious lateral pelvic LN metastasis. In
an attempt to determine this issue, the Japanese Clinical Oncology
Group has started a phase 3 randomized controlled trial comparing
TME with LPLD and that without LPLD for stage II-III low rec-
tal cancer without clinical imaging diagnosis of lateral pelvic LN
metastasis.

C 2012 Lippincott Williams & Wilkins
Annals of Surgery r Volume 255, Number 6, June 2012 Lateral Lymph Node in Low Rectal Cancer

A 1 therapy, instead of LPLD for patients with low rectal cancer without
0.9 lateral pelvic LN metastasis.
Probability of survival

0.8
0.7
68% In contrast, it is unknown whether neoadjuvant chemoradio-
0.6 54%
N1a therapy without LPLD is an adequate therapy for lateral pelvic LN
0.5 45% N1b metastasis. Liang25 demonstrated that the rate of lateral pelvic LN
45% N2a
0.4
32% Internal -LPLN
P = 0.9585 metastasis was 71.1% in 45 LPLDs when imaging showed persis-
0.3 29% N2b
P = 0.3342 tent lateral pelvic LNs after neoadjuvant chemoradiotherapy. Kim
0.2 External -LPLN
0.1
24%
StageI V P = 0.0240 and colleagues26 demonstrated that lateral pelvic recurrence is the
0 most common pattern of local recurrence after neoadjuvant chemora-
0 1 2 3 4 5 6 7 diotherapy plus TME alone, and that it is strongly associated with
Years from surgery
No. at risk the preoperative radiologic size of lateral pelvic LN. These results
N1a 1129 1043 927 806 719 629 473 248 suggest that patients with preoperative evidence of lateral pelvic
N1b 974 887 750 634 519 428 311 153 lymphadenopathy could benefit from LPLD, even after neoadjuvant
N2a 563 508 402 310 256 211 154 77
N2b 387 326 239 175 140 109 79 39
chemoradiotherapy.
Internal-LPLN 316 291 232 172 140 117 100 67 There are several potential limitations of this study. The first
External-LPLN 173 149 105 79 55 46 29 13 potential limitation involves the accuracy of the data, because there
Stage IV 260 198 122 85 65 54 36 16
may have been coding errors. However, the validity of the JSCCR
database, including the records of various clinicopathological vari-
B 1 ables and outcomes, has been well established.7–10 The second poten-
0.9 tial limitation is that data on the morbidity associated with LPLD and
Probability of survival

0.8 74% the recurrence pattern were not available in the JSCCR database. The
0.7 N1a
60% third potential limitation is that our data included only the Japanese
0.6
0.5
51% N1b population, and it is not clear whether the frequency of lateral pelvic
49% N2a
0.4 37% Internal -LPLN
P = 0.5742 LN metastasis is similar between Western countries and Japan. There
0.3 34% N2b
P = 0.4347 are some previous studies reporting the results of rectal cancer treat-
External -LPLN
0.2 27%
StageI V P = 0.0117 ment by radical resection and LPLD from Western countries, but the
0.1 lateral pelvic LN metastatic status was not reported.19,20 Despite these
0
0 1 2 3 4 5 6 7 potential limitations, we believe that the results of this study could
No. at risk
Years from surgery serve as a basis for management of lateral pelvic LN metastasis in
N1a 1129 1043 927 806 719 629 473 248
low rectal cancer.
N1b 974 887 750 634 519 428 311 153 In conclusion, internal iliac LNs are considered to be regional
N2a 563 508 402 310 256 211 154 77 LNs in low rectal cancer, as defined by the AJCC. Patients with
N2b 387 326 239 175 140 109 79 39
Internal-LPLN 316 291 232 172 140 117 100 67
metastasis to the lateral pelvic LNs other than the internal iliac LN
External-LPLN 173 149 105 79 55 46 29 13 have a poorer prognosis, but the prognosis is similar to that of N2b,
Stage IV 260 198 122 85 65 54 36 16
and better than that of stage IV. In light of the findings that lateral
FIGURE 3. Overall survival (A) and cancer-specific survival (B) pelvic LN metastasis can be regarded as regional disease in a large
for 3542 patients with lymph node metastasis and 260 patients nationwide multi-institutional study, selected patients with low rectal
with stage IV who underwent curative resection. cancer could benefit from LPLD.

ACKNOWLEDGMENTS
The authors thank all members and staff in the JSCCR mem-
In Western countries, neoadjuvant chemoradiotherapy is ber institutions for collecting data for Japanese colorectal cancer
widely used as an adjunct to TME for advanced low rectal cancer. registration.
There have only been a few studies comparing the efficacy of LPLD
and radiotherapy. Recently, Kim and colleagues18 demonstrated that
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