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Preoperative Chemoradiation Is
Associated With Lower Local
Recurrence and Improved Survival in
Rectal Cancer Patients Treated by
Mesorectal Excision
Julio Garca-Aguilar, M.D., Ph.D., Enrique Hernandez de Anda, M.D.,
Prayuth Sirivongs, M.D., Suk-Hwan Lee, M.D., Robert D. Madoff, M.D.,
David A. Rothenberger, M.D.
From the Division of Colon and Rectal Surgery, Department of Surgery, University of Minnesota Medical
School and the University of Minnesota Cancer Center, Minneapolis, Minnesota
sponse to preoperative chemoradiation is associated with
lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis Colon Rectum 2003;46:298-304.
298
299
RESULTS
Patient and tumor characteristics are provided in
Table 1. In all, 163 patients underwent curative resection; 5 underwent palliative resection because of
gross residual disease (2 patients) or microscopic positive margins (3 patients). The 2 patients with gross
residual disease died of cancer at 13 and 19 months
after surgery. Of the 3 patients with microscopic positive margins, 1 died of cancer 15 months after surgery; however, 2 were alive without evidence of disease at 7 and 54 months after surgery. Of the 163
curative-resection patients, 2 were lost for follow-up;
they were included in our tumor response analysis,
but excluded from our survival analysis.
The average tumor diameter measured by ERUS
before chemoradiation was 4.4 1.4 cm; it was 2.3
1.2 cm in the resected specimen (P 0.001, paired
sample t-test). Tumor downstaging occurred in 97 (58
percent) of the 168 patients, including 21 (13 percent)
with pathologic complete response. The pathologic
stage was identical to the ERUS stage in 62 patients
(37 percent) and more advanced than the ERUS stage in
9 (5 percent). None of the factors analyzed were associated with pathologic complete response (Table 2).
The tumor recurred in 30 (19 percent) of the 161
curative-resection patients. Local recurrence, either
alone or with distant metastasis, occurred in 8 patients, for an estimated 5-year local recurrence rate of
5 (standard error (SE), 3.4) percent. An additional 22
patients had distant recurrence alone, for an estimated
300
GARCIA-AGUILAR ET AL
Table 1.
Patient and Tumor Characteristics of the 168 Patients
with Rectal Cancer Treated by Preoperative
Chemoradiation and Radical Surgery
N (%)
Gender
Male
Female
Age (yr)
Distance from anal verge (cm)
Tumor size (cm)
ERUS stage
II
III
Grade
Not stated
1 or 2
3 or 4
Procedure
LAR
APR*
Number of nodes examined
94 (56)
74 (44)
60 12
(range, 26 83)
6.4 2.7
(range, 0 13)
4.4 1.4
46 (27)
122 (73)
5 (3)
121 (72)
42 (25)
96 (57)
72 (43)
8.8 9
(range, 0 89)
6 2.3
Chemoradiation-to-surgery
interval (wk)
Postoperative chemotherapy
76 (45)
Follow-up (mo)
37.5 23.2
ERUS endorectal ultrasound; LAR low anterior
resection; APR abdominoperineal resection.
* Included three cases of pelvic exenteration and one
case of total proctocolectomy.
Table 2.
Patient and Tumor Characteristics of Patients With and
Without Complete Pathologic Response
to Chemoradiation
Pathologic Complete
Response
Yes
P Value
No
N
21 (13)
140 (87)
Age (yr)
57 12.8
60 12.2
0.38
Gender
Male
15 (17)
73 (83)
0.18
Female
6 (8)
67 (92)
ERUS Tumor
4.4 1.9
4.4 1.3
0.9
size (cm)
ERUS Stage
II
3 (7)
43 (93)
0.32
III
18 (16)
97 (84)
Grade
1 or 2
16 (14)
102 (86)
0.16
3 or 4
2 (5)
36 (95)
Radiation dose
50 Gy
14 (15)
79 (85)
0.22
50 Gy
7 (10)
61 (90)
Chemoradiation5.7 2.1
5.9 2.3
0.8
to-surgery
interval (wk)
Procedure
LAR
15 (16)
77 (84)
0.16
APR
6 (9)
63 (91)
Postoperative
chemotherapy
Yes
12 (16)
64 (84)
0.23
No
8 (9)
77 (91)
ERUS endorectal ultrasound; LAR low anterior
resection; APR abdominoperineal resection.
Figures in parentheses are percentages.
DISCUSSION
In the absence of distant metastasis, rectal wall
invasion and spread to the regional lymph nodes are
the main criteria to estimate prognosis and report end
results in rectal cancer patients. Preoperative chemo-
301
Table 3.
Patients and Tumors Characteristics of Patients With and Without Tumor Recurrence
Recurrence (n 161)
No
Number
131 (81)
30 (19)
Gender
Male
77 (88)
11 (12)
Female
54 (74)
19 (26)
Age (yr)
59.9 12
58 13.3
Distance from anal verge (cm)
6.6 2.7
5.7 2.7
ERUS Stage (uTNM)
II
39 (85)
7 (15)
III
92 (80)
23 (20)
Ultrasound tumor size (cm)
4.4 1.4
4.2 1.5
Grade
1 or 2
97 (82)
21 (18)
3 or 4
30 (79)
8 (21)
Radiation dose
50 Gy
74 (80)
18 (20)
50 Gy
57 (83)
12 (17)
Procedure
LAR
81 (84)
15 (16)
APR
50 (77)
15 (23)
Pathologic stage (yTNM)
0
21 (100)
I
41 (84)
8 (16)
II
34 (79)
9 (21)
III
35 (73)
13 (27)
Lymph nodes
No
96 (85)
17 (15)
Yes
35 (93)
13 (27)
Downstage
No
50 (75)
17 (25)
Yes
81 (86)
13 (14)
Chemoradiation-to-surgery interval (wk)
5.8 2.3
6.2 2.1
Postoperative chemotherapy
No
70 (82)
15 (18)
Yes
61 (80)
15 (20)
ERUS endorectal ultrasound; LAR low anterior resection; APR abdominoperineal resection.
Figures in parentheses are percentages.
P Value
Yes
0.03
0.45
0.09
0.54
0.36
0.65
0.73
0.23
0.06
0.07
0.06
0.41
0.6
302
GARCIA-AGUILAR ET AL
stage vs. the preoperative ERUS stage) has been considered a precise way to measure tumor response to
chemoradiation. However, the accuracy of ERUS for
assessing rectal wall invasion ranges from 69 to 92
percent; for lymph node metastasis; 61 to 83 percent.13 Tumor up-staging after pathologic analysis is
more common than downstaging;1316 consequently,
assessment of response to radiation comparing the
preoperative ERUS stage with the pathology stage
probably overestimates the rate of tumor downstaging.6,1719 In this article we have selected pathologic
complete response as a clearly definable outcome,
compared with the more nebulous results of clinical
tumor downstaging.
Our study suggests that a pathologic complete response to chemoradiation is a favorable prognostic
factor in patients with locally advanced rectal cancer.
Other studies have also reported no local recurrence
and no cancer-specific mortality in patients with a
pathologic complete response to preoperative chemoradiation.7,18,20 However, those studies were relatively small; the number of patients with a pathologic
complete response was too small to reach statistical
significance.
Local recurrences tend to present later in patients
receiving preoperative radiation, and it is possible
that some of these patients diagnosed with a pathologic complete response may ultimately develop a
recurrence from a small nest of viable tumor cells. In
our own study, the average time to local recurrence
was 31 months, with no recurrences diagnosed before
9 months and some recurrences diagnosed as late as
7 years after surgery. These findings are in agreement
with the results of Ahmad and Nagle,21 who found
median times to local and distant recurrence of 34 and
22 months, respectively, in irradiated rectal cancer
ACKNOWLEDGMENTS
The authors thank Deb Caldwell and Claudia Genung for data collection and management and Robin
Bliss for statistical analysis.
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