Rectal cancer
ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
R. Glynne-Jones, L. Wyrwicz, E. Tiret, G. Brown, C. Rödel, A. Cervantes & D. Arnold,
on behalf of the ESMO Guidelines Committee
*For details of author affiliations, correspondence and versions, please see the full version at [Link]/Guidelines/Gastrointestinal-Cancers/Rectal-Cancer
Diagnosis and
pathology
Categorisation
Diagnosis is based on a DRE and endoscopy, with biopsy
for histopathological confirmation
There is a wide overlap of molecular genomic profiles of
left-sided / sigmoid with rectal cancer; so rectal cancer
cannot be seen as a molecularly defined different entity
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Staging and risk
assessment
Management should be by an MDT of
radiologists, surgeons, radiation oncologists,
medical oncologists and pathologists
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Parameter Method of choice
DRE/Palpation
Location (distance from anal verge)
Rigid sigmoidoscopy (flexible endoscopy)*
Staging and risk Morphological verification Biopsy
assessment cT stage
Early ERUS
MRI
Diagnostic work-up in primary rectal cancer Intermediate/advanced MRI (ERUS)*
Sphincter infiltration MRI (ERUS, palpation, EUA)*
cN stage MRI (CT, ERUS)*
CT, MRI (or US)* of the liver/abdomen
M stage CT of the thorax
PET-CT if extensive EMVI for other sites
*Methods within brackets are less optimal Evaluation for all patients MDT discussion
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TNM Clinical Classification TNM Clinical Classification
T – Primary Tumour N – Regional Lymph Nodes
TX Primary tumour cannot be assessed NX Regional lymph nodes cannot be assessed
T0 No evidence of primary tumour N0 No regional lymph node metastasis
Tis Carcinoma in situ: Invasion of lamina propria* N1 Metastasis in 1 to 3 regional lymph nodes
Staging and risk T1 Tumour invades submucosa N1a Metastasis in 1 regional lymph node
T2 Tumour invades muscularis propria N1b Metastasis in 2–3 regional lymph nodes
assessment Tumour invades subserosa or into non- Tumour deposit(s), i.e. satellites,║ in the subserosa,
T3
peritonealised pericolic or perirectal tissues N1c or in non-peritonealised pericolic or perirectal soft
Tumour directly invades other organs or tissue without regional lymph node metastasis
The UICC TNM staging T4
structures†,‡,§ and/or perforates visceral peritoneum N2 Metastasis in 4 or more regional lymph nodes
(8th edition) classification T4a Tumour perforates visceral peritoneum N2a Metastasis in 4–6 regional lymph nodes
for colon and rectal cancer
T4b Tumour directly invades other organs or structures N2b Metastasis in 7 or more regional lymph nodes
M – Distant Metastasis
M0 No distant metastasis
M1 Distant metastasis
*, †, ‡, §, ║
For details please see following slide Metastasis confined to one organ (liver, lung, ovary,
M1a non-regional lymph node(s)) without peritoneal
Brierley JD et al. TNM Classification of metastases
Malignant Tumours, 8th edition: John Wiley &
Sons, Inc., Oxford, 2016. Reprinted with M1b Metastasis in more than one organ
permission from John Wiley & Sons, Inc. Metastasis to the peritoneum with or without organ
M1c
involvement
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Stage T - Primary Tumour
Carcinoma in situ: *includes cancer cells confined within the mucosal lamina propria
Tis invasion of lamina (intramucosal) with no extension through the muscularis mucosae into the
propria* submucosa
†Invades through to visceral peritoneum to involve the surface
Staging and risk ‡Direct invasion in T4b includes invasion of other organs or segments of the
colorectum by way of the serosa, as confirmed on microscopic
Tumour directly invades
assessment other organs or
examination, or for tumours in a retroperitoneal or subperitoneal location,
direct invasion of other organs or structures by virtue of extension beyond
T4 structures†,‡,§ and/or
the muscularis propria
perforates visceral
§ Tumour that is adherent to other organs or structures, macroscopically, is
Notes to previous slide: peritoneum
The UICC TNM staging (8th edition) classified cT4b. However, if no tumour is present in the adhesion,
classification for colon and rectal microscopically, the classification should be pT1–3, depending on the
anatomical depth of wall invasion
cancer
║Tumour deposits (satellites) are discrete macroscopic or microscopic
nodules of cancer in the pericolorectal adipose tissue’s lymph
Tumour deposit(s), i.e. drainage area of a primary carcinoma that are discontinuous from the
satellites,║in the primary and without histological evidence of residual lymph node or
subserosa, or in non- identifiable vascular or neural structures. If a vessel wall is identifiable on
N1c peritonealised pericolic H&E, elastic or other stains, it should be classified as venous invasion
or perirectal soft tissue (V1/2) or lymphatic invasion (L1). Similarly, if neural structures are
Brierley JD et al. TNM Classification of Malignant without regional lymph identifiable, the lesion should be classified as perineural invasion (Pn1).
Tumours, 8th edition: John Wiley & Sons, Inc.,
node metastasis The presence of tumour deposits does not change the primary tumour T
Oxford, 2016. Reprinted with permission from
John Wiley & Sons, Inc. category, but changes the node status (N) to pN1c if all regional lymph
nodes are negative on pathological examination
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T3 Stage Depth of invasion beyond the muscularis propria, in mm
T3a* <1
T3b 1–5
Staging and risk T3c 6–15
assessment T3d > 15
Subclassification of T3 rectal cancer *This subclassification, based on pretreatment decision MRI evaluation, is
clinically valuable and can be used also in the histopathological classification,
although it is not validated nor incorporated in any of the TNM versions
Edge SB et al. AJCC Cancer Staging Handbook,
7th edition: Springer, New York, 2010. Reprinted
with permission.
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TNM Pathological Classification
The pT and pN categories correspond to the T and N categories
Historical examination of a regional lymphadenectomy specimen will ordinarily include 12 or more lymph nodes. If the
pN0
lymph nodes are negative, but the number ordinarily examined is not met, classify as pN0
Stage
Stage 0 Tis N0 M0
Stage I T1, T2 N0 M0
Staging and risk Stage II T3, T4 N0 M0
Stage IIA T3 N0 M0
assessment Stage IIB T4a N0 M0
Stage IIC T4b N0 M0
Stage grouping of colon and rectal cancer Stage III Any T N1, N2 M0
T1, T2 N1 M0
Stage IIIA
T1 N2a M0
T1, T2 N2b M0
Stage IIIB T2, T3 N2a M0
T3, T4a N1 M0
T3, T4a N2b M0
Stage IIIC T4a N2a M0
T4b N1, N2 M0
Brierley JD et al. TNM Classification of Malignant Stage IV Any T Any N M1
Tumours, 8th edition: John Wiley & Sons, Inc., Stage IVA Any T Any N M1a
Oxford, 2016. Reprinted with permission from
John Wiley & Sons, Inc. Stage IVB Any T Any N M1b
Stage IVC Any T Any N M1c
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Summary of recommendations
T1 tumours • According to Haggitt's sub-classification if the cancer is pedunculated
classification • According to Kudo/Kikuchi (sm)-system if in a sessile adenoma
Histopathology Resection
en bloc
Recommended for accurate assessment of invasion in the resection margin and the deepest area
According to Japanese guidelines, radical surgery and removal of lymph nodes is recommended
Radical surgery
for high-risk pathological features
Surrogate Involved CRM rate (i.e. < 1 mm) and TME quality are surrogates for good oncological outcomes
Lymph node
At least 12 regional lymph nodes should be examined and their margins documented
examination
Mesorectal Histopathological examination should include a photographic record of the surgical specimen and
resections assessment of TME quality
Evaluation ENE of nodal metastases, EMVI, PNI and tumour budding should be evaluated
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Objective grading of technical quality of TME surgery specimen
Histopathology Mesorectal plane (good plane of surgery
Intact mesorectum with only minor irregularities of a smooth mesorectal
surface; no defect deeper than 5 mm; no coning; and smooth circumferential
achieved)
resection margin on slicing
Moderate bulk to mesorectum, with irregularities of the mesorectal surface;
Intra-mesorectal plane (moderate plane of moderate distal coning; muscularis propria not visible with the exception of
surgery achieved) levator insertion; and moderate irregularities of circumferential resection
margin
Muscularis propria plane (poor plane of surgery Little bulk to mesorectum with defects down onto muscularis propria; very
achieved) irregular circumferential resection margin; or both
The specimen is examined as a whole (fresh) and as cross-sectional slices (fixed) to make an adequate interpretation
A TME specimen ideally should have a smooth surface, without incisions, defects or cracks, as an indication of
successful surgical excision of all mesorectal tissue. ‘Coning’ represents the tendency for the surgeon to cut inwards
towards the central tube of the rectum during distal dissection, rather than staying outside the visceral mesorectal
fascia. The specimen then shows a tapered, conical appearance representing suboptimal surgical quality
Quirke P et al. Lancet 2009;373:821–8.
Reprinted with permission.
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Treatment
recommendations
Very early, early and intermediate disease
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Treatment
recommendations
Locally advanced and advanced disease
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Summary of recommendations
Postoperative histopathological features with an impact on the risk of local recurrence, include:
Management of • pathological TNM stage
• T substage
local/locoregional • CRM status
disease •
•
the number/proportion of involved lymph nodes
extracapsular extension
• extranodal deposits
• tumour differentiation
Risk of recurrence according • lymphovascular invasion
to postoperative histology • extramural vascular invasion
• perineural invasion
The risk of local recurrence in patients with histologically involved nodes is reduced with good quality
mesorectal excision, ensuring removal of all mesorectal lymph nodes
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Summary of recommendations
The standards of care for preoperative treatment are SCPRT:
• 25 Gy total dose at 5 Gy/fraction during 1 week, then immediate surgery (< 10 days from the first radiation
fraction) and CRT with a recommended dose of 45–50 Gy in 25–28 fractions
• To be considered for preoperative RT, if CRM is threatened: boost of 5.4 Gy in 3 fractions
Management of • Postoperative RT: routinely with 5.4–9.0 Gy in 3–5 fractions according to CRM
local/locoregional CRT is recommended where CRM and/or R0 resection status are predicted by the MDT to be at risk
disease
Routine addition of oxaliplatin to fluoropyrimidine-based CRT is not recommended
Considerations for selection of the 5-FU IV infusion / oral capecitabine, are recommended in preference to bolus 5-FU during CRT and as adjuvant
most adequate (C)RT regimen systemic treatment
Preoperative RT or CRT reduces the rate of local recurrence for mid/low stage II/III rectal cancers, but is
associated with significantly worse postoperative intestinal and sexual functions
Upper rectal cancers above the peritoneal reflection should be treated as colon cancer
Patients with cT4 tumours falling back into the pelvis might benefit from neoadjuvant CRT or NACT alone
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Management of Preoperative chemotherapy
local/locoregional Fluoropyrimidine and oxaliplatin-based NACT, either alone or combined with targeted agents, instead
disease of preoperative CRT in cT3 tumours not threatening the CRM and cT4 tumours in the mid- and upper
rectum, is associated with pCR in 25% of early-stage cases
(NACT alone is not recommended for localised, non-metastatic disease outside clinical trials)
Preoperative (neoadjuvant)
chemotherapy
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Reassessment/response assessment after preoperative
Situation
(chemo)radiotherapy
Assessment of the
The standard methods of clinical reassessment are clinical examination using
Management of primary tumour
response
DRE, proctoscopy and MRI re-imaging
local/locoregional
Clinical complete
disease response and a
• An initially raised CEA level which returns to normal (< 5 ng/mL) after CRT
is associated with an increased likelihood of cCR and pCR
watch-and-wait
• Further validation of a watch-and-wait approach is required
approach
Preoperative (neoadjuvant)
chemotherapy • In LARC, the primary tumour/CRM should be re-evaluated with MRI after
CRT prior to resection
• mriTRG can predict survival outcomes but does not correlate well with
histopathological TRG
Patients planned for
• CT has relatively low value in assessing local response
surgery
• PET should not be routinely used as a response tool and surgery should
not be modified based on the findings
• Patients with persistent potential CRM involvement on imaging following
CRT should be referred to a MDT for tumour removal en bloc
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Reassessment/response assessment after preoperative
Situation
(chemo)radiotherapy
Management of Routine restaging of chest and abdomen after neoadjuvant CRT is not
recommended, but patients with cT4 cancers, threatened CRM and EMVI
local/locoregional Distant metastases should be re-staged within 3 months of original staging
NB: Applicable only for earlier stage tumours when clinical progression is
disease observed
• As a minimum, tumours should be graded as having either pCR, some
Preoperative (neoadjuvant) response or no response
chemotherapy • Other dynamic histopathological features, i.e. amount of necrosis,
regression of EMVI and downstaging of T and N stage, may also help to
Pathological define outcomes
assessment of
response • Interval to surgery
• For SCPRT in resectable cancers not requiring downstaging, immediate
surgery (within 7 days from the end of neoadjuvant treatment, and within
0–3 days if the patient is ≥ 75 years [< 10 days from the first radiation
fraction]) is recommended
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Summary of recommendations
Management of May be used selectively in patients with unexpected adverse
histopathological features after primary surgery, including
local/locoregional Postoperative
• positive CRM
• perforation in the tumour area
disease chemoradiotherapy
• incomplete mesorectal resection
or in other cases with high risk of local recurrence if preoperative RT has not
been given
Postoperative therapy
• Adjuvant ChT after preoperative CRT/RT with postoperative histology
(ypTNM) stage III (and ‘high-risk’ yp stage II) can be considered (level of
Postoperative evidence is lower than in colon cancer)
chemotherapy • The decision to use postoperative ChT (fluoropyrimidine alone or
combined with oxaliplatin) should take into account the predicted toxicity
and the risk of relapse
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Sufficient and necessary Insufficient and unnecessary
CRM ≤ 1 mm pT1/pT2
pT4b pT3
pN2 extracapsular spread close to MRF CRM > 2 mm
Management of Extranodal deposits (N1c) pT4a above peritoneal reflection
local/locoregional pN2 if poor mesorectal quality/defects
pN1
If good quality smooth intact mesorectum
disease Sufficient
pN2 low tumours within 4 cm of anal verge (risk
of involved LPLN)
Potential indications for postoperative CRT
if preoperative CRT not given Extensive extramural vascular
invasion/perineural invasion close to MRF
Borderline sufficient
pN2 in mid/upper rectum if good mesorectal
quality
CRM 1–2 mm
Circumferential obstructing tumours
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Summary of recommendations
Management of Surgical salvage should be carried out by specialist team
local recurrence
If RT has not already been administered, patients should be considered for standard dose
preoperative CRT (45–50 Gy in 5–6 weeks), or SCPRT followed by a fluoropyrimidine and
oxaliplatin-based ChT, prior to attempted resection
In patients previously irradiated, re-irradiation to lower doses (with concomitant ChT) is safe and can
be used to facilitate a curative resection or to palliate symptoms
Systemic palliative ChT to downstage a tumour and enable salvage surgery may be considered
Palliative surgical diversion procedures and brachytherapy are effective palliative options
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Management of
local recurrence
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Summary of recommendations
Metastatic rectal cancer management should reflect tumour-, disease-, patient- and treatment-related
factors
Management of
ChT alone may be insufficient where the primary tumour remains in situ and untreated and local RT
advanced/ palliation of rectal symptoms may be required
metastatic disease
SCPRT is preferable to CRT
Rapid local control with effective systemic ChT and appropriate sequence/timing of metastasectomy is the
aim of treatment where cure is a possibility
SPCRT with capecitabine/oxaliplatin/bevacizumab can be used to facilitate resection borderline resectable
liver metastases and primary tumour
The MDT should be responsible for critical treatment decisions in patients with potentially curable
metastatic disease
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Management of
advanced/
metastatic disease
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Summary of recommendations
Personalised
medicine There are no molecular markers to guide treatment approaches or to predict response to RT or CRT
Rectal cancers with distant metastases should be studied for RAS and BRAF mutational status and the
other requirements addressed in the ESMO consensus guidelines on metastatic colorectal cancer
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Follow-up, long-term
implications and
survivorship
Surveillance and follow-up
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Disclaimer and how to obtain more information
This slide set provides you with the most important content of the full ESMO Clinical Practice Guidelines (CPGs) on the management
of rectal cancer. Key content includes diagnostic criteria, staging of disease, treatment plans and follow-up.
The ESMO CPGs are intended to provide you with a set of recommendations for the best standards of care, using evidence-based
medicine. Implementation of ESMO CPGs facilitates knowledge uptake and helps you to deliver an appropriate quality of focused
care to your patients.
This slide set contains information obtained from authentic and highly regarded sources ([Link]). Although every effort has
been made to ensure that treatment and other information are presented accurately in this publication, the ultimate responsibility
rests with the prescribing physician. Neither the publisher nor the ESMO Guidelines Committee can be held responsible for errors or
for any consequences arising from the use of information contained herein. For detailed prescribing information on the use of any
product or procedure discussed herein, please consult the prescribing information or instructional material issued by the
manufacturer.
The slide set can be used as a quick reference guide to access key content on evidence-based management and individual slides
may be used for personal presentation in their present version and without any alterations. All rights reserved.
© 2018 European Society for Medical Oncology
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