A Simpliﬁed Tumor Regression Grade Correlates
with Survival in Locally Advanced Rectal Carcinoma Treated
with Neoadjuvant Chemoradiotherapy
D. Beddy, FRCS, J. M. P. Hyland, FRCSI, D. C. Winter, FRCSI, C. Lim, MB,
A. White, M. Moriarty, MRCPI, J. Armstrong, MRCPI, D. Fennelly, MRCPI,
D. Gibbons, MRCPI, and K. Sheahan, MRCPI
Centre for Colorectal Disease, St Vincent’s University Hospital, Dublin 4, Ireland
Background: Locally advanced rectal cancer is frequently treated with neoadjuvant che-
moradiotherapy to reduce local recurrence and possibly improve survival. The tumor response
to chemoradiotherapy is variable and may inﬂuence the prognosis after surgery. This study
assessed tumor regression and its inﬂuence on survival in patients with rectal cancer treated
with chemoradiotherapy followed by curative surgery.
Methods: One hundred twenty-six patients with locally advanced rectal cancer (T3/T4 or
N1/N2) were treated with chemoradiotherapy followed by total mesorectal excision. Patients
received long-course radiotherapy (50 Gy in 25 fractions) in combination with 5-ﬂourouracil
over 5 weeks. By means of a standardized approach, tumor regression was graded in the
resection specimen using a 3-point system related to tumor regression grade (TRG): complete
or near-complete response (TRG1), partial response (TRG2), or no response (TRG3).
Results: The 5-year disease-free survival was 72% (median follow-up 37 months), and 7%
of patients had local recurrence. Chemoradiotherapy produced downstaging in 60% of pa-
tients; 21% of patients experienced TRG1. TRG1 correlated with a pathological T0/1 or N0
status. Five-year disease-free survival after chemoradiotherapy and surgery was signiﬁcantly
better in TRG1 patients (100%) compared with TRG2 (71%) and TRG3 (66%) (P = .01).
Conclusion: Tumor regression grade measured on a 3-point system predicts outcome after
chemoradiotherapy and surgery for locally advanced rectal cancer.
Rectal carcinoma is an important cause of mor-
bidity and mortality in Western populations. In the
United States, there were 42,000 cases of rectal cancer
diagnosed in 2002, resulting in 8500 deaths.
risk of developing local recurrence after surgery for
rectal cancer is high (4% to 27%).
total mesorectal excision has reduced this risk; how-
ever, recurrence after resection of locally advanced
disease remains a problem.
In an effort to reduce
local recurrence and improve survival, preoperative
neoadjuvant chemoradiotherapy has been introduced
as an adjunct to total mesorectal excision. A number
of trials have reported reduced local recurrence rates
and a potential survival advantage associated with
A potential advantage of preoperative chemora-
diotherapy is that it can lead to complete clinical and
pathological regression of the tumor. Complete
pathological response rates are described in 10% to
30% of patients with rectal cancer.
It has been
reported that patients who undergo complete patho-
logical response to chemoradiotherapy have an im-
proved overall survival with lower local recurrence
Published online October 10, 2008.
Address correspondence and reprint requests to: J. M. P. Hyland,
FRCSI; E-mail: firstname.lastname@example.org
Published by Springer Science+Business Media, LLC Ó 2008 The Society of
Surgical Oncology, Inc.
Annals of Surgical Oncology 15(12):3471–3477