A Pathologic Complete Response to

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.

PURPOSE: Preoperative chemoradiation reduces tumor size

and nodal metastasis in patients with rectal cancer. Tumor
downstaging has been associated with an increased probability of a sphincter-saving procedure and with improved
local control. However, pathologic complete response to
chemoradiation has not been correlated with local control
and patient survival. We studied the prognostic value of
pathologic complete response to preoperative chemoradiation in rectal cancer patients. METHODS: We have prospectively followed up 168 consecutive patients with ultrasound
Stages II (46) and III (122) rectal cancer treated by preoperative chemoradiation followed by radical resection with
mesorectal excision; 161 had a curative resection. Recurrence and survival were compared with tumor characteristics and pathologic complete response. Average follow-up
was 37 months. RESULTS: Tumor downstaging occurred in
97 (58 percent) patients, including 21 (13 percent) patients
who had a pathologic complete response. None of the
clinical or pathologic variables was associated with pathologic complete response. The estimated 5-year rate of local
recurrence was 5 percent; of distant metastasis, 14 percent.
None of the patients with pathologic complete response
has developed disease recurrence. We found no difference
in survival among patients with pathologic Stages I, II, or III
tumors. CONCLUSIONS: A pathologic complete response to
preoperative chemoradiation is associated with improved
local control and patient survival. For patients without
pathologic complete response, the pathology stage does
not have prognostic significance. [Key words: Rectal cancer; Radiation therapy; Chemotherapy; Adjuvant therapy;
Chemoradiation; Pathologic complete response; Downstaging]

reoperative chemoradiation has been shown to

cause tumor regression, manifested by size reduction, downstaging, and even complete disappearance. Tumor downstaging has been associated with
an increased probability of tumor resectability,1,2 a
higher rate of sphincter-saving procedures,35 and increased local control and patient survival.69 However, the prognostic significance of a pathologic complete response in patients who undergo radical
proctectomy after chemoradiation is still unclear. We
reviewed our series of rectal cancer patients treated
with preoperative chemoradiation followed by radical
surgery. We compared local control and survival in
patients with and without a pathologic complete response to chemoradiation.

PATIENTS AND METHODS

We searched the University of Minnesota Colorectal
Cancer Database to identify patients with rectal cancer treated by preoperative chemoradiation followed
by radical surgery between January 1, 1987, and December 31, 1998. The study population includes 168
consecutive patients whose tumors were staged preoperatively by endorectal ultrasound (ERUS) using a
rotating probe (Bruel & Kjaer Medical Systems,
Naerum Denmark) with a 7-mHz or 10-mHz transduc-

Garca-Aguilar J, Hernandez de Anda E, Sirivongs P, Lee S-H,

Madoff RD, Rothenberger DA. A pathologic complete reRead at the meeting of the Association of Coloproctology of Great
Britain and Ireland, Manchester, United Kingdom, July 2 to 5, 2002.
No reprints are available.

298

Vol. 46, No. 3

COMPLETE RESPONSE AFTER CHEMORADIATION FOR RECTAL CANCER

er.10 The ERUS staging was assigned according to

Hildebrandts criteria.11 All patients underwent preoperative colonoscopy, biopsy of the specimen, abdominal and pelvic CT, and chest x-ray. Tumor size was
measured as the maximal tumor width per ultrasound
examination. In circumferential tumors, the length of
the lesion measured during the proctoscopic examination was considered the maximal diameter.
Of the 168 patients, 163 received the full scheduled
dose of radiation (range, 4,0006,500; mean, 4,787
cGy). The radiation was administered in divided fractions over a five-week period. 5-Fluorouracil (5-FU)
sensitizing chemotherapy was administered for five
consecutive days during weeks one and five of the
radiation. Of the 168 patients, 5 (3 percent) developed
neutropenia, thrombocytopenia, or diarrhea; so they
did not complete the chemoradiation (range, 2,520
3,240, mean, 3,080 cGy).
Operations were performed by a group of 12
Board-certified colorectal surgeons. The vascular
pedicle was usually ligated at the take-off of the left
colic vessels. For the proctectomy, sharp mesorectal
excision was performed using electrocautery. For tumors in the mid and distal rectum, the plane of dissection was continued distally to the level of the
pelvic floor. For tumors in the upper rectum, the
mesorectum was transected perpendicular to the rectum, 5 or more cm distal to the tumor. The operation
was considered curative if the resection margins were
free of macroscopic or microscopic residual tumor
and if no distant metastases were identified by preoperative workup or at laparotomy. After recovering
from surgery, some patients received additional adjuvant chemotherapy according to the criteria of their
medical oncologists. They typically received 4 cycles
of 5-FU (400 mg/m2/day) and Leucovorin (20 mg/m2/
day during) given during 5 consecutive days, every 28
days.
The resected specimens were staged according to
the TNM classification.12 Tumor size was determined
by the pathologists using the fixed specimen. Tumor
downstaging in response to chemoradiation was defined as a pathologic stage lower than the ultrasound
stage; pathologic complete response, as the absence of
gross and microscopic tumor in the surgical specimen.
Our database includes follow-up information from
periodic visits to our clinic as well as data from tumor
registries of hospitals that are part of the American
College of Surgeons National Cancer Database. Patients treated by low anterior resection (LAR) were
followed up according to a protocol in which ERUS is

299

performed every four months for the first three years,

then every six months for the next two years. In
addition, females treated by abdominoperineal resection (APR) were followed up by endovaginal ultrasound at the same intervals.
The endpoints of our study were pathologic complete response and tumor downstaging after chemoradiation, local and distant tumor recurrence, and
overall patient survival. Tumor relapse in the pelvis
was considered local recurrence; a recurrence outside
the pelvis was considered a distant metastasis. Response to radiation, tumor recurrence, and patient
survival were compared by the chi-squared test or
Fishers exact test. Stepwise proportional hazards regression models were used to determine the association of clinical variables with time to confirmed recurrence and with length of survival. Survival curves
were estimated by the Kaplan-Meier method and
compared by the log-rank test.

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.

5-year distant recurrence rate of 14 (SE, 5.5) percent.

The mean time between surgery and local recurrence
was 31 (range, 958) months; between surgery and
distant recurrence, 21 (range, 341) months. The
number of patients with local or distant recurrence
was too small for a separate regression analysis of
factors associated with each type of failure, so we
analyzed the factors associated with overall recurrence together. The association of the clinical and
pathologic characteristics with tumor recurrence is
presented in Table 3. Female gender was the only
factor associated with tumor recurrence by univariate
and multivariate analysis. Other clinical and pathologic characteristics such as patient age, ERUS stage,
tumor differentiation, surgical procedure, and the
presence of metastatic lymph nodes in the resected
specimen were not associated with overall recurrence
(Table 3). The estimated 5-year overall survival rate
for the 161 curative-resection patients was 68 (SE, 5)
percent.
Of the 21 patients with a pathologic complete re-

Dis Colon Rectum, March 2003

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.

sponse, 1 died as a consequence of a myocardial

infarction 5 months after surgery, without evidence of
disease at autopsy. The remaining 20 patients were
alive and free of disease at a mean of 37 (range,
8111) months after surgery. Disease-free survival
was 95.2 (SE, 4.6) percent for patients with a pathologic complete response vs. 55.4 (SE, 6.2) percent for
patients without a pathologic complete response (P
0.03). We found that, in patients without a pathologic
complete response, survival was identical for different
pathologic stages (Fig. 1).

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-

Vol. 46, No. 3

COMPLETE RESPONSE AFTER CHEMORADIATION FOR RECTAL CANCER

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.

radiation produces changes in the tumor that may

alter the original pathologic stage. Such changes are
minor in rectal cancer patients who undergo a short
course of adjuvant radiation, but are more noticeable
in patients treated by high-dose, small-fraction, multiple-port radiotherapy associated with chemotherapy. According to the American Joint Committee on
Cancer/International Union Against Cancer TNM staging system, cases in which the classification is performed following multimodality therapy which might
affect the original pathology categories should be
defined by a y prefix.12 However, few studies of
rectal cancer patients who underwent multimodality

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

therapy take into consideration any altered pathology

when reporting their results.
Tumor response to radiation has been associated
not only with an increase in the proportion of sphincter-saving procedures,35 but also with an improvement in local control and patient survival.68,9 However, the assessment of response to chemoradiation
is, for the most part, based on subjective clinical
evaluation, such as reduced tumor size, improved
tumor mobility, or histopathologic criteria. ERUS is
widely accepted as the most accurate technique for
the preoperative staging of rectal cancer. Downstaging (documented by a decrease in the pathologic

302

GARCIA-AGUILAR ET AL

Figure 1. Overall survival by pathologic stage of rectal

cancer patients treated by preoperative chemoradiation
therapy and radical surgery.

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

Dis Colon Rectum, March 2003

patients. Therefore, a longer follow-up is required

before we can definitively conclude that a pathologic
complete response carries a favorable prognosis.
More patients in the pathologic complete response
group received postoperative chemotherapy, compared with patients with residual tumor, but the differences were not statistically significant. Consequently, the favorable outcome in patients with
pathologic complete response compared with patients with residual tumor cannot be solely explained
by differences in postoperative chemotherapy.
In addition, our study suggests that, if patients with
a pathologic complete response are excluded, the
pathologic stage determined after initial chemoradiation does not hold its prognostic significance. Other
authors have also reported a lack of association between pathologic stage and tumor recurrence in rectal
cancer patients treated by preoperative radiation or
chemoradiation.22,23 Still other studies have reported
a prognostic value of the postoperative pathologic
stage despite significant tumor downstaging as a consequence of preoperative chemoradiation.7,18,24
These conflicting results probably reflect variations in
radiation dosage and fractionation,18 in the proportion of patients receiving sensitizing chemotherapy,7,18 and in the criteria used to define tumor response to radiation.18
In our study, pathologic complete response was
not related to specific clinical characteristics, such as
patient age and gender, or tumor size, stage, grade,
and proximity to the anal verge. In the Janjan and
colleagues study,23 tumor size was the only clinical
characteristic associated with tumor downstaging (by
logistic regression analysis). As in the study of Berger
et al.,18 we found that tumor downstaging was more
common among well or moderately differentiated tumors (vs. poorly differentiated or undifferentiated tumors), but the differences were not statistically significant. Several studies have already suggested that
certain molecular biomarkerse.g., the PCNA-labeling index, p21 expression, and p53 immunostainingin the preradiation biopsy specimen may predict
tumor response to chemoradiation.2527 However, the
preliminary results of those relatively small retrospective studies require corroboration in a prospective
trial.
In light of our findings, this question follows: Could
tumors with a pathologic complete response considered be cured by preoperative chemoradiation alone?
In 1935 Gordon-Watson provided evidence that some
rectal cancers can be cured by radium.28 Since then,

Vol. 46, No. 3

COMPLETE RESPONSE AFTER CHEMORADIATION FOR RECTAL CANCER

several studies have reported cures of rectal cancer

with radiationendocavitary,29 external beam,30 or a
combination of both.31 Given this type of evidence,
some authors have raised the possibility of using
chemoradiation alone in rectal cancer patients with
complete clinical response.32 The potential benefits to
patients in terms of reduced mortality and morbidity,
improvement in quality of life, and savings in medical
expenses are appealing. However, the information
about pathologic complete response is very limited;
the rate of pathologic complete response varies between studies,1,8,20,23,33 the timing to assess pathologic complete response is unknown, and the prognosis of patients with a pathologic complete response
has not been assessed prospectively. In addition, clinical complete response is a poor predictor of pathologic complete response,33 and the diagnostic imaging modalities used for the staging of rectal cancer are
unable to distinguish between residual tumor and
radiation fibrosis.3440 Consequently, rectal cancer response to chemoradiation requires further investigation.
In summary, our study suggests that complete
pathologic response to preoperative chemoradiation
is associated with improved tumor control and patient
survival. For patients without complete pathologic
response, the pathologic tumor stage does not have
prognostic significance. The role of chemoradiation
alone for rectal cancer patients with a complete
pathologic response remains to be determined.

ACKNOWLEDGMENTS
The authors thank Deb Caldwell and Claudia Genung for data collection and management and Robin
Bliss for statistical analysis.

REFERENCES
1. Chen ET, Mohiuddin M, Brodovsky H, Fishbein G,
Marks G. Downstaging of advanced rectal cancer following combined preoperative chemotherapy and high
dose radiation. Int J Radiat Oncol Biol Phys 1994;30:
169 75.
2. Minsky BD, Cohen AM, Kemeny N, et al. Enhancement
of radiation-induced downstaging of rectal cancer by
fluorouracil and high-dose leucovorin chemotherapy.
J Clin Oncol 1992;10:79 84.
3. Rouanet P, Fabre JM, Dubois JB, et al. Conservative
surgery for low rectal carcinoma after high-dose radiation. Functional and oncologic results. Ann Surg 1995;
221:6773.
4. Minsky BD, Cohen AM, Enker WE, Paty P. Sphincter

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

303

preservation with preoperative radiation therapy and

coloanal anastomosis. Int J Radiat Oncol Biol Phys 1995;
31:5539.
Janjan NA, Khoo VS, Abbruzzese J, et al. Tumor downstaging and sphincter preservation with preoperative
chemoradiation in locally advanced rectal cancer: the
M. D. Anderson Cancer Center experience. Int J Radiat
Oncol Biol Phys 1999;44:102738.
Minsky BD, Cohen AM, Enker WE, et al. Preoperative
5-FU, low-dose leucovorin, and radiation therapy for
locally advanced and unresectable rectal cancer. Int J
Radiat Oncol Biol Phys 1997;37:289 95.
Kaminsky-Forrett MC, Conroy T, Luporsi E, et al. Prognostic implications of downstaging following preoperative radiation therapy for operable T3-T4 rectal cancer.
Int J Radiat Oncol Biolo Phys 1998;42:935 41.
Chan AK, Wong AO, Langevin J, et al. Preoperative
chemotherapy and pelvic radiation for tethered or fixed
rectal cancer: a phase II dose escalation study. Int J
Radiat Oncol Biol Phys 2000;48:84356.
Theodoropoulos G, Wise WE, Padmanabhan A, et al.
T-level downstaging and complete pathologic response
after preoperative chemoradiation for advanced rectal
cancer result in decreased recurrence and improved
disease-free survival. Dis Colon Rectum 2002;45:
895903.
Orrom WJ, Wong WD, Rothenberger DA, Jensen LL,
Goldberg SM. Endorectal ultrasound in the preoperative staging of rectal tumors. A learning experience. Dis
Colon Rectum 1990;33:654 9.
Hildebrandt U, Feifel G. Preoperative staging of rectal
cancer by intrarectal ultrasound. Dis Colon Rectum
1985;28:42 6.
Fleming ID, Cooper JS, Henson DE, et al. AJCC Cancer
Staging Handbook. Philadelphia: Lippincott-Raven,
1998:10.
Garcia-Aguilar J, Pollack J, Lee S-H, et al. Accuracy of
endorectal ultrasonography in preoperative staging of
rectal tumors. Dis Colon Rectum 2002;45:10 5.
Holdsworth PJ, Johnston D, Chalmers AG, et al. Endoluminal ultrasound and computed tomography in the
staging of rectal cancer. Br J Surg 1988;75:1019 22.
Katsura Y, Yamada K, Ishizawa T, Yoshinaka H,
Shimazu H. Endorectal ultrasonography for the assessment of wall invasion and lymph node metastasis in
rectal cancer. Dis Colon Rectum 1992;35:362 8.
Adams DR, Blatchford GJ, Lin KM, Ternent CA, Thorson
AG, Christensen MA. Use of preoperative ultrasound
staging for treatment of rectal cancer. Dis Colon Rectum
1999;42:159 66.
Chari RS, Tyler DS, Anscher MS, et al. Preoperative
radiation and chemotherapy in the treatment of adenocarcinoma of the rectum. Ann Surgery 1995;221:778 7.
Berger C, De Muret A, Garaud P, et al. Preoperative
radiotherapy (RT) for rectal cancer: predictive factors of

304

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

GARCIA-AGUILAR ET AL
tumor downstaging and residual tumor cell density
(RTCD): prognostic implications. Int J Radiation Oncology Biol Phys 1997;37:619 7.
Burke SJ, Percarpio BA, Knight DC, Kwasnik EM. Combined preoperative radiation and mitomycin/5fluorouracil treatment for locally advanced rectal adenocarcinoma. J Am Coll Surg 1998;187:164 70.
Bosset JF, Magnin V, Maingon P, et al. Preoperative
radiochemotherapy in rectal cancer: long-term results
of a phase II trial. Int J Radiat Oncol Biol Phys 2000;46:
3237.
Ahmad NR, Nagle D. Long-term results of preoperative
radiation therapy alone for stage T3 and T4 rectal cancer. Br J Surg 1997;84:1445 8.
Kodner IJ, Shemesh EI, Fry RD, et al. Preoperative
irradiation for rectal cancer: improved local control and
long-term survival. Ann Surg 1989;209:194 9.
Janjan NA, Abbruzzese J, Pazdur R, et al. Prognostic
implications of response to preoperative infusional chemoradiation in locally advanced rectal cancer. Radiother Oncol 1999;51:153 60.
Rich TA, Skibber JM, Ajani JA, et al. Preoperative infusional chemoradiation therapy for stage T3 rectal cancer. Int J Radiat Oncol Biol Phys 1995;32:10259.
Fu C-G, Tominaga O, Nagawa H, et al. Role of p53 and
p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients. Dis Colon
Rectum 1998;41:68 74.
Palazzo JP, Kafka NJ, Grasso L, et al. The role of p53,
p21 WAF1/CIP1, and bcl-2 in radioresistant colorectal
carcinoma. Hum Pathol 1997;28:1189 95.
Qiu H, Sirivongs P, Rothenberger M, Rothenberger DA,
Garcia-Aguilar J. Molecular prognostic factors in rectal
cancer treated by radiation and surgery. Dis Colon Rectum 2000;43:4519.
Gordon-Watson C. Discussion on the radium treatment
of malignant disease of the rectum and anus. Proc R Soc
Med 1935;28:1251 63.
Papillon J, Berard P. Endocavitary irradiation in the
conservative treatment of adenocarcinoma of the low
rectum. World J Surg 1992;16:4517.
Brierley JD, Cummings BJ, Wong CS, et al. Adenocarcinoma of the rectum treated by radical external radiation therapy. Int J Radiat Oncol Biol Phys 1995;31:
2559.

Dis Colon Rectum, March 2003

31. Kodner IJ, Gilley MT, Shemesh EI, Fleshman JW, Fry
RD, Myerson RJ. Radiation therapy as definitive treatment for selected invasive rectal cancer. Surgery 1993;
114:850 7.
32. Habr-Gama A, de Souza PM, Ribeiro U Jr., et al. Low
rectal cancer: impact of radiation and chemotherapy on
surgical treatment. Dis Colon Rectum 1998;41:108796.
33. Hiotis SP, Weber SM, Cohen AM, et al. Assessing the
predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488
patients. J Am Coll Surg 2002;194:131 6.
34. Williamson PR, Hellinger MD, Larach SW, Ferrara A.
Endorectal ultrasound of T3 and T4 rectal cancers after
preoperative chemoradiation. Dis Colon Rectum 1996;
39:459.
35. Bernini A, Deen KI, Madoff RD, Wong WD. Preoperative adjuvant radiation with chemotherapy for rectal
cancer: its impact on stage of disease and the role of
endorectal ultrasound. Ann Surg Oncol 1996;3:1315.
36. Kahn H, Alexander A, Rakinic J, Nagle D, Fry R. Preoperative staging of irradiated rectal cancers using digital
rectal examination, computed tomography, endorectal
ultrasound, and magnetic resonance imaging does not
accurately predict T0, N0 pathology. Dis Colon Rectum
1997;40:140 4.
37. Rau B, Hunerbein M, Barth C, et al. Accuracy of endorectal ultrasound after preoperative radiochemotherapy
in locally advanced rectal cancer. Surg Endosc 1999;13:
980 4.
38. Barbaro B, Schulsinger A, Valentini V, Marano P, Rotman M. The accuracy of transrectal ultrasound in predicting the pathological stage of low-lying rectal cancer
after preoperative chemoradiation therapy. Int J Radiat
Oncol Biol Phys 1999;43:10437.
39. Gavioli M, Bagni A, Piccagli I, Fundaro S, Natalini G.
Usefulness of endorectal ultrasound after preoperative
radiotherapy in rectal cancer: comparison between
sonographic and histopathologic changes. Dis Colon
Rectum 2000;43:1075 83.
40. Guillem JG, Puig-La Calle J Jr., Akhurst T, et al. Prospective assessment of primary rectal cancer response to
preoperative radiation and chemotherapy using 18fluorodeoxyglucose positron emission tomography. Dis
Colon Rectum 2000;43:18 24.

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.