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These Clinical Practice Guidelines are endorsed by the Japanese Society of Medical Oncology (JSMO)
Approved by the ESMO Guidelines Working Group: August 2002, last update May
2013. This publication supersedes the previously published versionAnn Oncol 2010;
21 (Suppl. 5): v82v86.
The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: journals.permissions@oup.com.
clinical practice
guidelines
Annals of Oncology
Table 2. TNM classication (version 7, 2010) with sub-classications
Parameter
Method of choice
TNM
Extension to
Palpation
Rigid sigmoidoscopy (exible
endoscopy)
Biopsy
Tis
Morphological verication
T stage
Early
Intermediate/advanced
ERUS
MRI
MRI (ERUS)
Sphincter inltration
N stage
M stage
Evaluation
MDT conference
management of local/locoregional
disease
overall strategy
An important aim is to treat so that the risk of residual disease
in the pelvis, frequently causing a disabling local recurrence, is
very low. This risk should preferably be less than about 5% in
the population in whom curative treatment is intended, and, at
the same time, as little acute and late morbidity as possible
should be targeted. This should be possible in all but the few
(10%) cases presenting with a xed tumour growing into a
non-readily resectable organ (some cT4b).
Another aim is to treat such that a good sphincter function is
preserved.
From a practical point of view, rectal cancers could be divided
into four groups:
a) very early (some cT1),
b) early (cT1-2, some cT3),
c) intermediate (cT3- some cT4a)
d) locally advanced (cT3crm +, some cT4a, all cT4b).
vi | Glimelius et al.
T1
T2
T3
T4
N1
N1a
N1b
N1c
N2
N2a
N2b
M1
M1a
M1b
a
IIIC
IVA
IVB
T1-2, N0, M0
T3, N0, M0
T4a, N0, M0
T4b, N0, M0
T1-2, N1/N1c, M0
T1, N2a, M0
T3-T4a, N1/N1c, M0
T2-T3, N2a, M0
T1-2, N2b, M0
T4a, N2a, M0
T3-4a, N2b, M0
T4b, N1-2, M0
T1-4, N1-2, M1a
T1-4, N1-2, M1b
Edge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging
Manual. 7th ed. New York, NY.: Springer, 2010. Used with the
permission of the American Joint Committee on Cancer
(AJCC), Chicago, Illinois. The original source for this material
is the AJCC Cancer Staging Manual, Seventh Edition (2010)
published by Springer Science and Business Media LLC, www.
springer.com.
Annals of Oncology
Table 4. Haggitts subclassication of polypoid T1 cancers
based upon the extent of invasion of the stalk
Level
0
1
2
3
4
risk-adapted treatment
Upper third
Middle third
Lower third
doi:10.1093/annonc/mdt240 | vi
Edge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging
Manual. 7th ed. New York, NY.: Springer, 2010. Used with the
permission of the American Joint Committee on Cancer
(AJCC), Chicago, Illinois. The original source for this material
is the AJCC Cancer Staging Manual, Seventh Edition (2010)
published by Springer Science and Business Media LLC, www.
springer.com.
Therapeutic options
Very early
Early (good)
Intermediate
(bad)
Advanced
(ugly)
The preoperative staging should be of such high quality so that this is rarely seen.
Other factors than T and N stages are also relevant, such as distance from the
anus and sphincters, direction, size of mesorectum and patient characteristics.
TEM, transanal endoscopic microsurgery; TME, total mesorectal excision;
CRT, chemoradiotherapy; RT, radiotherapy; cCR, clinical complete remission;
CT, chemotherapy; EMVI, extramural vascular invasion; V1, vascular invasion.
vi | Glimelius et al.
rates), but also more acute toxic effect. Early results of several
comparative randomised trials have not been favourable (e.g.
[26]), and these combinations are still experimental.
The choice of treatment according to risk category for
primary rectal cancer without distant metastases is shown in
Table 6.
organ preservation?
Besides the earliest tumours that can be treated with a local
procedure or local radiation therapy as described above, it has
become increasingly popular to rst give CRT, wait and then
restage the tumour clinically or with multiple biopsies/excision
biopsy of the previous tumour area. If no tumour can be
detected and/or no viable tumour cells are found, i.e. a clinical
or a pathological complete response (cCR or pCR) is achieved,
no further therapy is provided (organ preservation) and the
patient is monitored closely for at least 5 years [29, 30]. It is then
assumed that potential lymph node metastases have been
eradicated in conjunction with the excellent response of the
tumour. Although this undoubtedly may occur in some
patients, this strategy has not been subject to properly
controlled prospective studies [IV, D].
Risk group
Annals of Oncology
Annals of Oncology
postoperative therapy
Postoperative chemoradiotherapy (e.g. about 50 Gy, 1.82.0 Gy/
fraction) with concomitant uoropyramidine-based
chemotherapy is no longer recommended but could be used in
patients with positive crm, perforation in the tumour area,
defects in the mesorectum, or in other cases with high risk of
local recurrence if preoperative radiotherapy has not been given
[8] [I, A]. Traditionally, postoperative CRT was recommended
for all patients with pT3-4 or N+ tumours, but the routine use
of this has been questioned for all pT3N0 tumours [8].
As in colon cancer stage III (and high-risk stage II), adjuvant
chemotherapy can be given, even if the level of scientic
evidence for sufcient benet is much lower than in colon
cancer [33, 34, 35] [II, B].
In Japan, postoperative adjuvant chemotherapy with uraciltegafur is considered standard therapy since this treatment
improved relapse-free and overall survival [36].
doi:10.1093/annonc/mdt240 | vi
vi | Glimelius et al.
personalised medicine
There are no molecular or other markers which can evaluate
whether a patient is in need of preoperative treatment of a rectal
cancer indicating that surgery will not be radical. MRI gives
accurate information provided it is done appropriately.
Similarly, there are no known markers that can predict response
to radiotherapy or chemoradiotherapy.
In metastatic disease, KRAS mutant status predicts nonresponse to EGFR inhibition [II, A].
Annals of Oncology
Annals of Oncology
Table 7. Summary of key recommendations in primary rectal cancer
CRT,
note
A summary of key recommendations is given in Table 7. Levels
of evidence and grades of recommendation have been applied
using the system shown in Table 8. Statements without grading
were considered justied standard clinical practice by the
experts and the ESMO faculty.
conict of interest
Prof. Arnold has reported research grants from Roche and
Sano. The other authors have reported no potential conicts of
interest.
Levels of evidence
I
Evidence from at least one large randomised, controlled trial of good
methodological quality (low potential for bias) or meta-analyses of
well-conducted randomised trials without heterogeneity
II Small randomised trials or large randomised trials with a suspicion
of bias (lower methodological quality) or meta-analyses of such trials
or of trials with demonstrated heterogeneity
III Prospective cohort studies
IV Retrospective cohort studies or casecontrol studies
V Studies without control group, case reports, experts opinions
Grades of recommendation
A Strong evidence for efcacy with a substantial clinical benet,
strongly recommended
B Strong or moderate evidence for efcacy but with a limited clinical
benet, generally recommended
C Insufcient evidence for efcacy or benet does not outweigh the
risk or the disadvantages (adverse events, costs, ), optional
D Moderate evidence against efcacy or for adverse outcome, generally
not recommended
E Strong evidence against efcacy or for adverse outcome, never
recommended
a
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Annals of Oncology