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Korean Journal of Clinical Oncology 2015;11:114-119
http://dx.doi.org/10.14216/kjco.15019
pISSN 1738-8082 ∙ eISSN 2288-4084
Original
Article
대장암의 위치에 따른 생존율 분석: 단일 술자 경험
이인화1, 백승현1, 김현성2, 조홍재2, 오남건2, 고상화1
부산대학교병원 외과, 2부산대학교 의과전문대학원 외과학교실
1
Survival analysis for colon subsite and rectal cancers: Experience from a
single surgeon
Inhwa Lee1, Seung-Hyun Baek1, Hyunsung Kim2, Hong-Jae Jo2, Nahm-Gun Oh2, Sanghwa Ko1
1
Department of Surgery, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan;
Department of Surgery, Biomedical Research Institute, Pusan National University School of Medicine, Busan, Korea
2
Purpose: The survival rates of patients with colorectal cancers have been well documented in many studies. Some studies have shown that
proximal colon cancers have inferior survival rates when compared with distal colon cancers. However, the prognostic significance of tumor
location with respect to survival remains controversial. By using data from a single physician, we analysed patient survival rates based on colon cancer subsite location, including rectal cancers.
Methods: We retrospectively analysed 881 patients with colorectal cancers between 1987 and 2008. Colon subsite locations were defined as
cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. Subsite-specific survival analyses were performed
using Kaplan-Meier analysis and Cox proportional hazards ratios. The median follow-up time was 93 months.
Results: A total of 689 colorectal cancer cases were included in our analysis, of which 14 were cecum (2.0%), 95 were ascending colon
(13.8%), 21 were transverse colon (3.0%), 25 were descending colon (3.6%), 129 were sigmoid colon (18.7%), and 405 were rectum (58.8%)
cancers. The 5-year overall survival rates were 77.8% for all colorectal cancers, which consisted of 92.9% for cecal cancer, 69.5% for ascending colon cancer, 76.2% for transverse colon cancer, 84.0% for descending colon cancer, 82.2% for sigmoid colon cancer, and 77.5% for rectal cancer.
Conclusion: Ascending colon cancer was associated with the poorest survival outcome, whereas descending colon cancer was associated
with the best survival outcome except cecal cancer. Moreover, the survival rate associated with left colon cancer was better than the survival
for right colon and rectal cancer.
Keywords: Colorectal neoplasms, Survival rate, Treatment outcome
INTRODUCTION
Colorectal cancer (CRC) is the third most common cancer in South
Received: Aug 1, 2015 Accepted: Oct 20, 2015
Correspondence to: Sanghwa Ko
Department of Surgery, Biomedical Research Institute, Pusan National
University Hospital, Pusan National University School of Medicine,
305 Gudeok-ro, Seo-gu, Busan 49241, Korea
Tel: +82-51-240-7238, Fax: +82-51-247-1365
E-mail: [email protected]
Copyright © Korean Society of Surgical Oncology
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which
permits unrestricted non-commercial use, distribution, and reproduction in any medium,
provided the original work is properly cited.
Korean Journal of Surgical Oncology
114 Korea [1]. Survival rates associated with CRCs have been well documented in many studies. The proximal and distal colon and the rectum have different characteristics, including different embryologic
origins, anatomical appearance and physiological functions. Additionally, colon and rectal cancers show differences in their biological features, treatment susceptibility profiles, and prognoses. Several studies have reported inconsistent results regarding the survival
rates of colon cancer patients based on the location of the primary
tumor. Some reports have shown superior survival in patients with
left colon cancers after treatment than in patients with right colon
cancers [2-5], whereas other studies reported no difference in the
survival between these two patient cohorts [6,7]. Furthermore, survival comparisons between colon and rectal cancer patients have
Inhwa Lee et al. • Survival for subsite of colorectal cancer
been inconsistent. Therefore, in this study, we compared the survival rates of patients with colon cancers at different subsites, including rectal cancers, using data accrued by a single surgeon.
METHODS
Study population
From January 1987 to December 2008, we retrospectively analysed
689 among 881 patients diagnosed with CRC and treated by a single surgeon. Patients who underwent palliative surgery, underwent
surgery at another hospital, died within 30 days of surgery, or experienced hereditary colon cancers, such as familial adenomatous
polyposis and hereditary nonpolyposis CRC, were excluded from this
study. Variables for clinical characteristics included age, gender, anatomic tumor location, preoperative serum carcinoembryonic antigen (CEA) levels, tumor node and metastasis (TNM) stage, and
lymph node ratio (LNR). Written informed consent was obtained
from all patients before the operation. After Institutional Review
Board approval of our hospital, all records and medical charts of
patients were reviewed.
Classification of location
Subsite location of the tumors was defined as follows: cecum, ascending colon (includes ascending colon and hepatic flexure),
transverse colon, descending colon (includes splenic flexure and descending colon), sigmoid colon (includes sigmoid colon and rectosigmoid junction), and rectum. Moreover, right or proximal colon
included cancers of the cecum, ascending colon, hepatic flexure,
and transverse colon. The left or distal colon included cancers of
the splenic flexure, descending colon, sigmoid colon, and the rectosigmoid junction.
Statistical analysis
The chi-square test was used for comparing risk factor distributions
between subsite groups. Overall survival rates were analysed using
the Kaplan–Meier method, and statistical significance of the survival
rates was evaluated using the log-rank test. Multivariate analysis
was used to assess all of the clinicopathological factors associated
with overall survival using Cox proportional hazards regression (i.e.,
age, sex, CRC subsite location, TNM stage, LNR, and preoperative serum CEA levels). A P-value of < 0.05 was considered statistically significant. Statistical analysis was performed using MedCalc Statistical
Software ver. 14.10.2 (MedCalc Software bvba, Ostend, Belgium).
RESULTS
Clinicopathological characteristics of CRC patients
A total of 689 CRC patients were included in the analysis with a
Table 1. Baseline characteristics of the patients with colorectal cancer
Characteristic
No.
Age (yr)
< 65
≥ 65
Sex
Male
Female
TNM
I
II
III
IV
CEA
< 5 ng/mL
≥ 5 ng/mL
LNR
0
< 0.125
< 0.25
≥ 0.25
Cecum
Ascending
Transverse
Descending
Sigmoid
Rectum
14
95
21
25
129
405
9
5
49
46
13
8
11
14
82
47
252
153
9
5
46
49
11
10
9
16
58
71
173
232
0
7
5
2
3
44
25
23
2
12
4
3
0
13
10
2
10
54
52
13
32
196
141
36
9
5
49
46
10
11
13
12
68
61
251
154
P-value
0.083
0.122
0.019
0.062
0.850
7
4
1
2
48
25
7
15
14
3
2
2
15
6
3
1
66
31
15
17
234
77
46
48
TNM, tumor node and metastasis; CEA, carcinoembryonic antigen; LNR, lymph node ratio.
www.kjco.org 115
Table 2. Five years survival rate according to colonic subsite and rectal cancer with prognostic factors
Factor
5-YSR
Age (yr)
< 65
≥ 65
Sex
Male
Female
TNM
I
II
III
IV
CEA
< 5 ng/dL
≥ 5 ng/dL
LNR
0
< 0.125
< 0.25
≥ 0.25
Cecum
Ascending
Transverse
Descending
Sigmoid
Rectum
P-value
92.9
69.5
76.2
84.0
82.2
77.5
0.012
88.9
100
79.6
58.7
92.3
50.0
72.7
92.9
81.7
83.0
81.3
71.9
0.66
< 0.001
88.9
100
73.9
65.3
81.8
70.0
88.9
81.3
79.3
84.5
79.2
76.3
< 0.001
0.46
100
100
50
100
88.6
76.0
21.7
100
83.3
75.0
33.3
92.3
88.9
33.3
100
92.3
90.0
15.4
93.8
88.8
72.3
22.2
0.953
0.586
0.030
0.393
88.9
100
83.7
54.3
90.0
63.6
92.3
75.0
94.1
68.9
84.1
66.9
0.356
0.026
100
75.0
100
100
89.6
72.0
14.3
26.7
85.7
100
0
50.0
80.0
83.3
100
100
90.9
87.1
86.7
35.3
87.2
81.8
60.9
39.6
0.729
0.650
< 0.001
0.041
5-YSR, 5-year survival rate; TNM, tumor node and metastasis; CEA, carcinoembryonic antigen; LNR, Lymph node ratio.
100
Cecum
Ascending
Transverse
Descending
Sigmoid
Rectum
Survival probability (%)
95
90
85
80
75
70
65
0 1224364860
Month
Fig. 1. Five years survival rates according to the subsite of colorectal cancer.
median follow-up of 93 months (range, 1–193 months). Of these
patient tumors, 14 tumors were located in the cecum, 95 in the ascending colon, 21 in the transverse colon, 25 in the descending colon, 129 in sigmoid colon, and 405 in the rectum. The TNM stage of
the study population was I in 47 patients, II in 326 patients, III in
236 patients, and IV in 79 patients. The number of patients with
tumors located at each subsite is listed in Table 1 according to paKorean Journal of Surgical Oncology
116 tient sex, age, and TNM stage.
Overall survival of CRC patients
Overall survival rates according to cancer subsite location are
shown in Table 2, and the overall survival curves according to tumor subsite location are presented in Fig. 1. The 5-year survival rate
was 92.9% for patients with cancer of the cecum, 69.5% for patients with cancer of the ascending colon, 76.2% for patients with
cancer of the transverse colon, 84.0% for patients with cancer of
the descending colon, 82.2% for patients with cancer of the sigmoid colon, 77.5% for patients with cancer of the rectum, and
77.8% for all cancer patients combined. The overall survival curves
after grouping the subsites according to right and left colon cancers are presented in Fig. 2. Right colon cancers were associated
with a poorer survival rate (70.7%) than left colon cancers (82.5%)
(P < 0.05). There was no statistically significant difference in the
5-year survival rates between patients with colon cancer and rectal
cancer (77.4% and 77.5%, respectively) (Table 3).
Survival analysis of stage I and II cancers showed no difference
based on tumor location. However, stage III tumors showed statistically significant differences based on the location of the malignancy (P< 0.05). Furthermore, stage III descending colon cancers were
associated with a better survival rate than stage III tumors at any
other location except cecum due to its rarity, whereas stage III rec-
Inhwa Lee et al. • Survival for subsite of colorectal cancer
Right colon
Left colon
Rectum
100
Survival probability (%)
95
Factor
90
85
80
75
70
0 1224364860
Month
Fig. 2. Five years survival rates after right and left grouping colon
and rectal cancer.
Table 3. Five years survival rate after right and left grouping colon
and rectal cancer
Factor
5-YSR
Age (yr)
< 65
≥ 65
Sex
Male
Female
TNM
I
II
III
IV
CEA
< 5 ng/dL
≥ 5 ng/dL
LNR
0
< 0.125
< 0.25
≥ 0.25
Table 4. Factors associated with survival
Right colon
Left colon
Rectum
P-value
73.1
82.5
77.5
0.02
83.1
61.0
80.6
85.2
81.3
71.9
0.859
0.002
77.3
68.8
80.6
83.9
79.2
76.3
0.011
0.582
100
88.9
79.4
25.0
100
91.0
87.1
13.3
93.8
88.8
72.3
22.2
0.621
0.557
0.040
0.766
85.3
59.7
93.8
69.9
84.1
66.9
0.100
0.065
89.90
75.0
20.0
36.8
88.9
86.5
88.9
38.9
87.2
81.8
60.9
39.6
0.869
0.302
< 0.001
0.228
5-YSR, 5-year survival rate; TNM, tumor node and metastasis; CEA, carcinoembryonic
antigen; LNR, lymph node ratio.
tal cancers were associated with the worst overall survival rate of
all stage III tumor locations. In patients with stage IV tumors, no
differences in the survival rates for any tumor location were observed. Additionally, right colon tumors were associated with worse
survival when compared with left colon tumors (hazard ratio [HR],
Age
< 65
≥ 65
Sex
Male
Female
TNM stage
I
II
III
IV
CEA
< 5 ng/dL
≥ 5 ng/dL
LNR
0
< 0.125
< 0.25
≥ 0.25
Location
Cecum
Ascending
Transverse
Descending
Sigmoid
Rectum
Hazard ratio on
Hazard ratio on
univariable
P-value
multivariable
P-value
analysis (95% CI)
analysis (95% CI)
< 0.001
1.00
1.72 (1.28–2.32)
< 0.001
1.00
1.93 (1.43–2.60)
0.299
-
1.00
1.17 (0.87–1.56)
< 0.001
1.00
3.53 (2.01–6.20)
7.73 (4.32–13.83)
40.20 (18.09–89.35)
1.00
2.78 (2.06–3.74)
1.00
1.62 (1.13–2.32)
3.47 (2.09–5.78)
7.01 (4.09–11.99)
1.00
8.84 (1.81–43.16)
0.002
30.67 (6.50–144.73) < 0.001
< 0.001
< 0.001
1.00
1.77 (1.29–2.43)
< 0.001
1.00
11.55 (1.44–92.59) < 0.001
0.012
1.00
6.94 (2.48–19.39)
6.28 (1.79–22.09)
3.13 (0.94–10.41)
3.23 (1.19–8.76)
4.27 (1.63–11.14)
1.00
0.49 (0.29–0.82)
-
0.006
0.020
Right colon 1.00
Left colon 0.53 (0.34–0.84)
Rectum
0.71 (0.48–1.05)
1.00
0.60 (0.41–0.88)
-
0.032
-
CI, confidence interval; TNM, tumor node and metastasis; CEA, carcinoembryonic antigen; LNR, lymph node ratio.
0.31; 95% confidence interval [CI], 0.13–0.72) and rectal tumors
(HR, 0.75; 95% CI, 0.35–1.61) (P < 0.05) when analysing stage III
tumors, but not when analysing stage I, II or IV tumors (Table 3).
The variables associated with survival rate included serum CEA level, LNR, age over 65 years and CRC location. In the multivariate
analysis, age, advanced CRC stage, serum CEA level, lymph node ratio and presence of sigmoid colon cancer or left colon cancer were
associated with statistically significant survival differences (Table 4).
DISCUSSION
Due to their similar characteristics, colon and rectal cancers are ofwww.kjco.org 117
ten defined together as CRCs. Well-known prognostic factors for
CRCs include age, sex, T stage, N stage, preoperative serum CEA
level, tumor differentiation, lympho-vascular invasion, and perineural invasion [8]. Treatments for CRCs include surgical resection,
chemotherapy and radiotherapy, of which adequate surgical resection is considered a cornerstone of CRC treatment. However, differences in CRC patient survival rates have been reported based on the
accuracy of resection, the response of the tumor to chemotherapy,
and the presence/absence of radiotherapy among other factors.
Moreover, many studies have shown that colon cancers are different from rectal cancers in terms of their embryologic, environmental, genetic and biomolecular characteristics. In addition, right-sided colon cancers are associated with a different prognosis than
left-sided colon and rectal cancers. We assumed that based on the
tumor location, different CRCs may be treated differently in terms
of surgery and chemoradiotherapy. Therefore, to reduce interpatient
variability in treatment, our study was designed based on the data
obtained from a single surgeon.
Studies have suggested that the anatomical site of the tumor is
an important factor in the management of CRCs. However,
site-specific CRC survival data remain controversial. Many studies
have classified colon cancers as right or left, of which right colon
cancers are associated with poorer prognosis [2-5,9-11]. For example, Elsaleh et al. [3] reported the 10-year survival rates to be 27%
and 37% for right and left CRCs, respectively. Meguid et al. [2]
demonstrated a 5% decrease in the survival rate for patients with
right colon cancer when compared with patients with left colon
cancers. In terms of disease-free survival, Park et al. [8] reported
that the right colon cancer patients performed better than the leftside colon cancer patients. Moreover, Sjo et al. [12] showed improved survival in the patients with right colon cancer than in those
with left colon cancers. Other studies involving rectal cancers
showed that transverse colon cancers were associated with the
worst outcome (HR, 1.25) [13]. Moreover, in another study, colon
cancer patients showed superior survival than rectal cancer patients [14,15]. However, patients with advanced stage rectal cancer
experienced better survival rates than advanced stage colon cancer
patients [16].
In our study, proximal colon cancer patients experienced poorer
survival rates than distal colon cancer patients. Ascending colon
cancer was associated with the worst survival of all locations analysed. Moreover, descending colon cancer was associated with the
best survival rate out of all cancer analysed except cecal cancer,
which was excluded due to the small sample size. Nawa et al. [17]
reported that right-sided cancers are more likely to be detected at
an advanced stage. In our study, more patients with stage III tumors
experienced left colon cancer, whereas more patients with stage IV
Korean Journal of Surgical Oncology
118 tumors experienced right colon cancer (P< 0.05). These results suggest that right-sided cancers tend to be less symptomatic in the
earlier stages. Furthermore, surgical strategies in patients with left
colon and rectal colon cancers include high ligation of the inferior
mesenteric artery or the inferior mesenteric vein for access to the
high-yield lymph nodes and inferior reach. In contrast, the strategy
for lymph node harvest remains constant in patients with right-side
colon cancers and consists of ligation of the mesocolic vessels near
the superior mesenteric vessel. Moreover, complete mesocolic excision was not conducted in patients with advanced stage disease.
Complete mesocolic excision is associated with improved outcomes
for patients with colon cancers [18]. Additionally, the worst survival
rate associated with ascending colon cancer patients is consistent
with other studies [2,10] for reasons that remain unclear. Our results showing that the best survival rate was associated with descending colon cancers differs from other reports, which have
shown that sigmoid colon cancers are associated with the best survival in our multivariate analysis and other study [2]. One possibility
is that other studies misclassified some rectal cancers as rectosigmoid junction cancers to meet the conditions of national insurance
coverage for adjuvant chemotherapy. This could result in a decrease
in the survival rate of sigmoid colon cancer patients in our study.
We observed no significant differences in the survival rates of colon
cancer and rectal cancer patients, even in stage III patients. In addition, cecal cancers were associated with the best survival rates in
our study; however, the sample size was too small for analysis. Majek et al. [19] previously reported survival results for cecal cancer
patients and showed no survival advantage for patients with this
type of tumor. The cecum is an independent colonic subsite that
should be classified as a separate site; however, our study is insufficient to define a significant survival advantage in cecum cancer
patients. We anticipate that a larger study of cecal cancer patients
is necessary to show more accurate and reliable results.
Several limitations are associated with this study. Some cancer
locations, including the cecum, the transverse colon and the descending colon, were represented by very few patients. Moreover,
accurate grouping of junctional cancers, such as hepatic, splenic
flexure and rectosigmoid cancers, could have influenced our results.
Finally, biomolecular analysis of the tumors for the mutational and
expression level statuses of genes such as KRAS, BRAF, p53, and
microsatellite instability could not be obtained because a large proportion of the data were obtained too long before the analysis.
Among all CRCs, patients with ascending colon cancer showed
the poorest survival outcome. Descending colon cancer was associated with the best overall survival in CRC patients to the exclusion
of cecal cancer. Moreover, left colon cancers were associated with
better survival than right colon cancers and rectal cancers. There-
Inhwa Lee et al. • Survival for subsite of colorectal cancer
fore, our results suggest that more careful approaches are needed
for CRC treatment depending on the localization of the tumor.
CONFLICT OF INTEREST
No potential conflict of interest relevant to this article was reported.
ACKNOWLEDGMENTS
This study was supported by a clinical research grant from the Pusan National University Hospital in 2014.
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