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Management of
Colorectal Cancer
Dr. Gayanga Kottegoda
June 2022
Objectives
• Epidemiology
• Anatomy
• Pathology
• Aetiology
• Clinical Features
• Workup
• Staging
• Management of Colon Cancer
• Management of Rectal Cancer
Epidemiology
• Sri Lanka
• 3rd Commonest cancer diagnosis when
both sexes considered
• 4th commonest in males and 4th
commonest in females
• 7% of total crude cancer incidence (2304
new cases)
• 2/3 colonoc, 1/3 rectal
• Global
• 3rd most common cancer worldwide
• 3rd most common cancer in men
• 2nd most common cancer in women
• There were more than 1.9 million new
cases of colorectal cancer in 2020
Frequency of
Colorectal
Cancer
1/3 Rectum
2/3 Colon
Men = Women
When is it Considered to be in the Rectum
• Within 15 cm from anal verge (rigid sigmoidoscopy is best at
measuring)
• MRI – plane of sigmoid take off
• Introperative - identification of the plane of fusion of the two
antemesenteric taenia into to an amorphous area.
• Importance
• Significant difference in management (eg – neoadjuvent RT)
• 3 parts of Rectum
• 0-6 cm lower rectum
• 7 – 11 cm mid rectum
• 12 -15 cm upper rectum
Tumour Pathology
•Morphology
4 types
• Annular
• Tubular
• Ulcer
• Cauliflower
WHO Histological Classification
• Majority are adenocarcinomas – 90 – 95%
• Mucinous adenocarcinoma
• Signet-ring cell carcinoma
• Squamous cell carcinoma
• Adenosquamous carcinoma
• Undifferentiated carcinoma
• Carcinoid tumours
• Non epithelial tumours
• Sarcoma
• Lymphoid neoplasm
• Hematopoietic neoplasm
Tumour Pathology - Spread
• Local/ Direct – longitudinally, transversely or radially to anatomicaly
adjesent structures
• Colonic
• retroperitoneal colonic cancer - the ureter, duodenum and muscles of the posterior abd wall
• Intraperitoneal tumour - small intestine, stomach, pelvic organs, the anterior abd wall
• Rectal – pelvic organs, side walls
• Lymphatic – usually upwards to nodes along the vascular pedicle
• Colonic - Paracolic  nodes along main vessels  Para-aortic nodes (30% may skip)
• Rectum – via mesorectal nodes
• tumours below the peritoneal reflection may also spread laterally and downward
• Vascular – Liver, Lung (10%), Ovary, Adrenal, Brain, Bone, Kidney
• 37% have occult liver mets at Sx, 50% develop overt mets at some stage
• Transcoelomic – Colonic to peritoneum (by subperitoneal lymphatics/ drop mets)
Tumour Pathology
• 20% present with metastetic disease
• 40% develop metastesis at some time
Aetiology
• Genetic susceptibility -20%
• Well defined familial syndromes
• HNPCC (Lynch syndrome)
• FAP/ Gardner’s syndrome
• Turcot syndrome
• Other rarer syndromes
• Without well defined familial syndromes
Aetiology
• Lifestyle related
• Diet
• Western diet
• Red meat, poultry
• Obesity
• Smoking and alcohol
• Micronutrients
• Low folate
• Low vitamin D ?
• Lack of physical activity
• DM treated with Insulin
Aetiology
• Inflammatory bowel diseases
• Ulcerative colitis
• Crohns disease
• Past Surgery/ procedure
• Pelvic cancer irradiation
• Cholecystectomy
• Gastrectomy
• ureterosigmoidostomy
Protective Factors
• Exercise
• Folic acid
• Calcium/ Vitamin D
• High fibre diet
• Aspirin (but given only when
cardiac risk is high)
• COX -2 Inhibitors (Celecoxib)
• Over expression of COX-2 seen in
tumour cells
Familial Adenomatous Polyposis
• Presence of more than 100 colorectal adenomas - Diagnostic
• Positive family history – 80%, Remainder new mutations
• APC gene on the short arm of chromosome 5, autosomal dominant,
Men = Female
• Lifetime risk of colorectal cancer is 100%
• Associated with benign mesodermal tumours such as desmoid
tumours and osteomas.
• Epidermoid cysts in Gardner’s syndrome
• Congenital hypertrophy of the retinal pigment epithelium – screening
• Polyps at 15 y, almost all at 30 y
• Carcinoma after 10 -20y of polyps
Familial Adenomatous Polyposis - Management
• Surgery deffered till 17y as malignancy unusual till 20y
• Family tree maintained, Genetic screening refferals
• Target of treatment – Prevent development of colorectal cancer
• Options
• Colectomy with ileorectal anastomosis – IRA
• Less morbidity and mortality
• Invasive malignancy at 30y up to 10%
• Restorative proctocolectomy with an ileal pouch – anal
anastomosis - RPC
• Temporary stoma
• Pouch failure 10%
• Cancer in residual cuff of tumour - annual pouch surveillance with biopsy
• Total proctectomy and end ileostomy – Safest but with permanent
stoma
Hereditary non-polyposis colorectal cancer
• HNPCC/ Lynch syndrome – most common (2-4%)
• Increased risk of colorectal cancer and also cancers of the
endometrium, ovary, stomach and small intestine
• Autosomal dominant, DNA mismatch repair gene mutation (MLH1,
MSH2, MSH6, PMS2)
• Lifetime risk of colorectal cancer is 80%, mean age at diagnosis is 45 y
• Proximal colon common
• 30 – 50 % lifetime risk of developing endometrial cancer.
• Diagnosis – Genetic testing or Amsterdam II criteria
• Management
• Regular endoscopic surveilance of LGI tract
Screening
Importance of Adenoma Carcinoma Sequence
• Average age of adenoma patients is about 5 years younger than that
of the average age of carcinoma patients
• The distribution of adenomas in the colon is the same as that of
cancers (70% left sided)
• Adenomas often accompany carcinoma
• Unusual to find carcinoma without contiguous adenomatous tissues
• Sporadic adenomas are histologically identical to adenomas of FAP
which is unequivocally premalignant
• Large adenomas are more likely to display cellular atypia and genetic
abnormalities than small lesions
Screening
• Good candidate for a screening program
• Prognosis much better in early stage compared to late stage when treated
• Adenoma-carcinoma sequence provides ability to treat pre-malignant lesions
• Stool occult blood - guaiac-based test  detects the peroxidase-like
activity of haematin in faeces. Sensitivity 50-70%
• False negative – intermittent nature of bleeding (3 samples taken)
• False positive – animal haemoglobin, vegetable peroxidases
• Faecal immunoglobulin test minimises these
• Colonoscopy in stool occult blood positive patients
• Once only flexible sigmoidoscopy between 55-64 years – 70% coverage
Endoscopically Detected Polyp Variety
Mangement of a Endoscopically Detected Polyp
• Risk of malignancy increases with polyp size
• 1cm – 10%
• >3cm – 30%
• Colon Adenomas >5mm  Excised
• Snare polypectomy
• Large sessile – Endoscopic mucosal resection
• Rectal polyp – all polyps needs to be excised
• <2cm - EMR
• Lager
• Low lying - Transanal resection
• High – Transanal endoscopic microsurgery (Laparoscopic technique)
• Extensive villous lesion – argon beam ablation (Symptomatic but frail)
Management of Screening Detected Early Disease
• Risk catogorisation and plan management
• Endocopically detected malignant polyp  ? Need of completion
colectomy driven by
• Haggit stage
• Histological grade
• Staging CT findings
• Angiolymphatic invasion
• Positive margin
• within 1-2mm
Difficulties in Deciding on
a Completion Colectomy
• Identifying the site of innitial
polypectomy – Tattooing at
initial procedure
Colorectal Cancer
Pesentation of Colorectal Cancer
• RS colon – Anaemia, obstruction uncommon
• Liquid nature of faeces
• Wider diameter of colon
• Descending or Sigmoid colon - change of bowel habit, colicky
abdominal pain and blood in the stool
• Rectum - bleeding is predominant, mucus discharge
• large tumour - tenesmus
• Mass
• Incontinence, Anal pain
• Symptoms related to metastasis – pneumaturia, recurrent UTI, severe
diarrhoea, faecal vomiting
Targets of Evaluation
• Disease and differentials
• Complications
• Due to blood loss
• Due to spread – Local, Metastatic
• Obstructive symptoms
• Perforation
• Aetiology including famaily history
• need of family screening
• Fitness for surgery
• Fitness for chemo/radiotherapy
• Dissability
• Plan treatment and followup
Evaluation
• Clinical
• History
• Examination
• Diagnosis - Sigmoidoscopy/ Colonoscopy and biopsy
• Radiological
• USS, Endorectal USS
• CT Colonogram
• Barium studies – out of practice
• CECT – staging in colorectal ca
• Pelvic MRI – staging in rectal
• PET-CT – limited role
• Blood – CEA, FBC, RFT, LFT
For Diagnosis Colonoscopy is Prefered
• Gold standard for Diagnosis
• 1:1000 risk of perforation
• Evaluate synchronous cancer in 3-4%, Polyps in 30%
• 2 or more coeisting tumours at diagnosis or within 6 months, seperated by 5 cm, not
submucosally connected or a satellite lesion
• Flat adenomas are difficult to detect without special techniques
• Indigo-carmine dye
• Narrow band imaging
CT Colonogram
• 90% sensitive for >6mm lesions
• Adequate alternative where colonoscopy is
unfavourable
• Advantages
• No need sedation
• Non invasive
• Can do CECT at the same go with IV contrast
• Disadvantages
• Can not take biopsy
• Need similar bowel preperation
Preoperative Staging
• Colonic
• CECT (IV and Oral contrast) Chest Abdomen and Pelvis
• When IV contrast contraindicated – NCCT chest + MRI abdomen pelvis with
contrast
• USS abdomen and Chest X ray as an alternative in resource poor setting
• Rectal in addition
• MRI Pelvis
• Assesment of circumferential resection margin (CRM)
• Accurate for Nodal stage
• EUS
• Accuracy better for T staging
• Poor accuracy for N staging
• In cases where CT/ MRI studies are inconclusive - PET/CT
Staging
• Staging is similar in colon and rectal cancer
• Preoperative – Clinical and Radiological  To plan manangement
• TNM – T componenet most important
• Postoperative – Pathological staging  To plan adjuvent treatment
and followup
• T1/ T2 distinction is
difficult in MRI
• Possible in TRUSS
• CRM evaluation
better in MRI
• Poorer in TRUSS
TNM Prognostic Groups
• Stage 0 – Tis, N0, M0
• Stage I - T1/2, N0, M0
• Stage II - T3/4 N0, M0
• IIa - T3 N0
• IIb - T4a N0
• IIc - T4b N0
• Stage III – Any T with nodes, M0
• IIIa - Stage 1 with N1
• IIIb - Stage II with N1
• IIIc - Stage II with N2
• Stage IV – Any T Any N with Metastasis
Management of Colorectal Cancer
• Surgical excision is the mainstay of treatment
• Surgical options - Elective
• Colon cancer – Complete Mesocolonic Excision (CME)
• Right hemicolectomy
• Extended right hemicolectomy
• Left hemicolectomy
• Sigmoid colectomy
• (sub) Total colectomy
• Rectal cancer – Mesorectal excision (TME)
• Anterior resection
• Abdomino-perineal excision  Permenant colostomy
• But evolving area – Neoadjuvant and Adjuvant treatment
options
Surgical Options
Pathological Staging
• Accurate, detailed and consistent pathology reporting for colorectal
cancer is important for
• Prognostication
• Plan adjuvant treatment
• Macroscopic description
• Size of the tumour (greatest dimension).
• Site of the tumour in relation to the resection margins.
• Any abnormalities of the background bowel.
Pathological Staging - Microscopic description
• Histological type.
• Differentiation of the tumour, based on the predominant grade within the
tumour
• Maximum extent of invasion into/through the bowel wall (submucosa,
muscularis propria, extramural).
• Serosal involvement by tumour
• A statement on the completeness of excision at the cut ends (including
the ‘doughnuts’ from stapling devices) and at any radial margin.
• The number of lymph nodes examined, the number containing metastases,
and whether or not the apical node is involved.
• Extramural vascular invasion if present
• Pathological staging of the tumour according to Dukes' classification.
Duke’s
Stages
• A - Tumour limited to the
wall
• B - Tumour in extra-rectal
tissues, but not LN
• C - Tumour in LNs
• C1 - Pararectal nodes
• C2 - Nodes along the
blood vessels
• D – Distant Spread
Colon Cancer
Colon Cancer
• Elective Surgery
• Surgery in emergencies
• Adjuvent therapy
Preoperative Checklist for Colon Cancer Surgery
• Preoperative optimisation
• Endoscopic biopsy and confirmation of histology
• Synchronous cancer detected/ excluded by colonoscopy/ CT
colonography
• Staging CECT chest abdomen and pelvis
• Preoperative CEA
• Mecahnical bowel preperation - ?
• VTE prophylaxis – Graduated compression stockings and SC Enoxa
• HB target – 7-8 in general, 8-9 in IHD,
• Antibiotic prophylaxis 30 – 60 mins prior to Sx
Mechanical Bowel Preperation
• No benefit in anastomotic leakage, re-operation or wound infection
and recommended avoidance of MBP in elective colectomy patients
• Recommended in high risk emergency where anastomotic leak risk is
high  creation of an upstream defunctioning stoma
• MBP is recommended in this setting to reduce faeces between the stoma and
anastomosis
Enhanced Recovery After Surgery
Principles of Colon Cancer Surgery
• Colectomy with enbloc removal of lymph nodes
• Complete Mesocolic Excision (CME)
• Dissection in the embryologically defined mesocolic plane.
• Central ligation of the vascular pedicle (CVL).
• Resection of an adequate length of apparently normal colon on either side of
the tumour.
Central Vascular
Ligation (CVL)
• Mortality benefit of D3
resection over D2 resection in
T3/ T4 disease
• removal of undetected
micrometastatic disease
within the mesentery
• resection of positive nodes
Longitudinal Resection Margin
Practical Guide to
Resection
• Right hemicolectomy
• Caecum
• Right colon
• Right transverse colon
• Transverse Colectomy
• Extent of longitudinal resection cannot be fulfilled
by either right hemicolectomy or segmental left
colectomy
• Segmental left colectomy
• Splenic flexure
• Left Hemicolectomy
• Left colon cancer
Open Surgery vs Laparoscopic vs Robotic
• Laparoscopic surgery
• Advantages
• Equivalent oncological outcome
• Equevalent LN harvesting ability
• Encouraging postoperative recovery – shorter hospital stay
• wound infection rates, blood loss and postoperative pain scores are lower
• Disadvantages
• Difficulty acquiring technical competence, long learning curve
• High cost of laparoscopic instruments/ consumables
• Increased operative times
• Robotic – again shortest stay, least blood loss, but longest operative
time and much increased cost
Minimally Invasive Techniques
• Only by experienced surgeons in minimally invasive colectomies
• Not utilized in
• Emergency
• Acutely obstructed
• Perforated
• Clearly locally advanced
• High risk prohibitive adhesions
Surgical Complications
• Anastomotic leak – Most devastating – 4 – 8%
• Wound infections - 10%
Surgical Complications - Anastomotic Leak
• Causes
• Technical problems – around 1-2 days
• Ischaemia – around day 5
• Diagnosis
• Poor progression
• Persistant tachycardia, pyrexia, arrhythmia
• Respiratory problems
• Abdominal pain or distension
• Sudden rise of CRP >200 (daily CRP)
Surgical Complications Anastomotic Leak
• Evaluation
• CECT – Chest abdomen pelvis without rectal contrast
• Subtle changes – bubbles adjacent to the anastomosis
• Also, to exclude other problems
• Followed by water soluble contrast enema
• Management
• Conservative in well patients – Not well established
• Antibiotics
• Operative when deteriorating
• Preserving anastomosis  Defunctioning stoma, Drain at site
• Anastomosis can not be preserved  Hartmann's procedure
Risk Factors for Anastomotic Leak
• Male sex
• Renal disease
• Comorbidities
• History of radiotherapy
• Tumour >3cm
• Advanced tumour stage
• Emergency surgery
• Metastatic disease
• Smoking
• Obesity
• Poor nutrition
• Alcohol intake in excess
• Immunosuppr
• essants
• Bevacizumab
• Blood loss/transfusion
• Duration of surgery (> 4 H)
Emergency Surgical Options for Colorectal Cancer
• Resuscitation
• Evaluation
• Main presentations requiring emergency surgery (20% in total)
• Obstruction (16% present like this)
• Perforation
• Significant haemorrhage
• Increased post op complications
• Increased mortality
• Principles of emergency surgical procedure
• Oncological clearance when appropraite
• Releive obstruction
• Remove contamination – control of sepsis
Obstruction
• Evaluation
• CT preffered over X ray
• Endoscopy/ contrast enema study to exclude psedo-obstruction
• Expedited management
• Evidence of sepsis
• Caecal region tenderness/ >12cm Caecal diameter
• Options
• Stenting (left colon lesion) – allows elective resection after stabilisation and evaluation
• Emergency Surgery – depending on the stability
• Resect and anastomose
• Resect and defunct – Hartmann’s procedure
• Defunct only (without resection)
• Systemic therapy with chemo
• In medically unfit or unresectable lesion
• Goal – Conversion to a resectable lesion or with palliative intent
Stenting for Left Colonic Lesions
• Relief of abstruction  Stabilisation 
Evaluation  Definitive Sx
• No evidence over definitive emergency
surgery without stenting
• Less stomas with this stratergy
• May be the definitive treatment in the pallitive
setup
• Problems
• Failure to releive obstruction
• Perforation
• Technical difficulty
Right Hemicolectomy Hartmann’s Procedure
Perforation
• At the site of the tumour
• At a distant site due to dilatation/ diverticuli
• Primary may be missed
• Management
• Resection
• Control of sepsis
• Reconstruction where appropriate
• Generally leads to a defunctioning stoma
Adjuvent Therapy – Resectable Colon Cancer
• Mainly as a postoperative adjuvant
• Not indicated
• T1/ T2 (Stage I)
• Some Stage II
• Indicated
• Some stage II
• T4
• benefit in node positive disease
• poorly differentiated/ undifferentiated tumours
• lymphovascular invasion
• perineural invasion
• Poor LN sampling
• Treatment
• Based on fluoropyrimidines (IV 5-fluorouracil Oral capcitabine)
• Combinations with oxaliplatin
• Radiotherapy has no role in primary disease in most cases
• Risk of radiation enetritis to adjacent small bowel
• Mobile nature of large bowel where directed therapy is difficult
• Limited role of radiotherapy for ablative radiotherapy for liver and
lung mets
• highly selected cases/ clinical trial.
• should not be used in place of surgical resection
• highly conformal delivery required - 3-D conformal radiation therapy,
intensity-modulated radiation therapy (IMRT), or stereotactic body radiation
therapy (SBRT).
Adjuvent Therapy – Resectable Colon Cancer
Neoadjuvent Treatment Options –Colon Cancer
• Preoperative chemoradiation used selectively in
• T4 tumours penetrating to a fixed structure
• for patients with recurrent disease
• Locally unresectable tumours
• Neoadjuvant chemotherapy
• For bulky nodal disease or clinical T4b
Management of Locally Advanced Colon Cancer
• Target
• Where possible treatment with curative intent
• Or appropriate palliation
• Operative options
• Bypass surgery may be appropriate
• Multi-organ en bloc resection may be curative
• Neoadjuvant
• Intent of downgrading – improving resectability
• Palliative intent
Advanced Disease – Recurrence of Colon Cancer
• Local recurrence  Resection attempted, if not palliative bypass
Metastesis in Colon Cancer
• Usually metachronously after locoregional treatment (50– 60%)
• Synchronously 20 – 34% in liver (worse than metachronous)
• Operable
• Hepatic resection (No RCT, Generally for 1-3 mets in one lobe of liver,
preoperative chemo may have a role in improving operability, 30% 5 year
survival
• Don’t biopsy potentially resectable hepatic mets  risk of dissemination
• Pulmonary – rarely possible as only 10% pulmonary mets and only 10% of
them have disease confined to lung, 20% 5 year survival
• Peritoneal spread alone, or with easily operable liver metastases,
peritonectomy combined with heated intraperitoneal chemotherapy (HIPEC)
• Inoperable
• Chemotherapy containing fluoropyrimidines is the only established treatment
• Palliative surgery mainly to relieve obstruction – Stoma/ Stenting
Surveilance is Based on Prognostic Stage
• Stage I - Imaging is not routinely indicated and should only be based
on symptoms and clinical concern for recurrent/metastatic disease.
• Stage II & III - Chest, abdomen, and pelvic CT every 6 to 12 months for
a total of 5 years.
• PET/CT is not indicated.
• Stage IV –
• Chest, abdomen, and pelvic CT every 3 to 6 months 2 years
• then every 6 to 12 months for a total of 5 years
• PET/CT can be considered for assessment of response and liver recurrence
after image-guided liver-directed therapies (ie, ablation, radioembolization)
or serial CEA elevation during follow-up
Intensive
Follow Up
• History and physical examination in every 3 months for 2 years and then in
every 6 months for total of 5 years
• CEA in every 3 months for 2 years and then in every 6 months for total of 5
years
• Annual CECT of chest, abdomen and pelvis for 5 years
• Colonoscopy in 1, 3 and 5 years, (Then 5 yearly up to 80 years)
Rectal Cancer
Preoperative Checklist for Rectal Cancer
• Preoperative optimisation
• Endoscopic biopsy and confirmation of histology
• MMR/ MSI testing
• Synchronous cancer detected/ excluded by colonoscopy/ CT colonography
• Staging CECT chest abdomen and pelvis
• Pelvic MRI/ Endoscopic USS
• Preoperative CEA
• Mecahnical bowel preperation done for low anterior resection
• Siting of stoma and councelling preoperatively
• Fertility risk discussion/ counselling
• VTE prophylaxis – Graduated compression stockings and SC Enoxa
• HB target – 7-8 in general, 8-9 in IHD,
• Antibiotic prophylaxis 30 – 60 mins prior to Sx
Rectal cancer Surgery - Objectives
• Oncological cure
• Most cases  Radical excision of the rectum, together with the mesorectum
and associated lymph nodes (TME)
• High proximal ligation of the inferior mesenteric lymphovascular pedicle
• Margin distally minimum 1 cm, Proximally > 5cm
• Preserve function
• Restore GI continuity
• Preserve anal sphincter – lower margin of tumour >2cm from anaorectal
junction
• Stratergies in low rectal tumours -
• Stapled anastomosis
• Chemoradiotherapy down-staging
• Bladder function
• Sexual function
Management Options in Rectal Cancer
• Surgical
• Local excision - Difficult in higher lesions
• Trans anal excision
• Excision of the tumour by TEMS (transanal endoscopic microsurgery)
• Transabdominal resection + TME
• Higher - anterior resection
• Lower - abdominoperineal excision – smaller group
• Neoadjuvant
• LCCT
• SCRT
• Adjuvant
• CT/ RT/ CRT
Management Stratergies
• Localised Disease - <T2, N0, M0
• Upfront surgery
• Locoregional rectal cancer - >T2 or ≥ N1
• Neoadjuvant therapy
Circumferential Resection Margin
• CRM is the surface of the nonperitonealised part of the rectum that is
resected during surgery
• MRI is the most reliable imaging modality to determine potential CRM
• CRM is the shortest distance between the outermost part of the
rectal tumour and the MRF
• Positive < 1 mm
• Threatened - between 1 and 2 mm
• Not threatened - >2 mm
• CRM status is not applicable if the tumour is situated in a
peritonealised aspect of the rectal wall.
Circumferential Resection Margin
• Need to achieve a negative surgical margin as risk of local recurrence
is 40% if margins positive
• Reasons for this recurrence risk
• Close proximity of rectum to adjacent pelvic organs
• Absence of a serosa surrounding the rectum
• Technical difficulties obtaining a wide surgical margin at resection
• To achieve a negative margin, mesorectal fascia should be free of
tumour at the time of TME
• Radiotherapy enables an R0 resection by making the MRF free of tumour
• Radiotherapy is feasible to pelvis compared to abdomen where sensitive
small bowel is located
Neo-adjuvent for Rectal Cancer
• Neoadjuvant strategies – preoperative radiotherapy produces better
disease control and less morbidity than postoperative treatment
• Short course radiotherapy (SCRT)
• Long course chemoradiotherapy (LCRT)
• Total neoadjuvant therapy (TNT)
SCRT - Short Course Radiotherapy
• Indications
• T3 with uninvolved CRM in upper and mid rectal cancers
• T2 lower rectal cancer in which muscularis propria preserved < 1mm
• N1
• Modality - 25Gy over 5 days (Monday to Friday)
• Surgery in next week
• before acute mucosal side effects occur
• Surgery after 6 weeks if downstaging is needed
LCRT - Long Course Chemoradiotherapy
• CT given concurrently with RT to increase RT sensitization and enhances
tumoricidal effect
• Does not improve overall survival or disease free survival
• Indications - high risk features
• CRM threatened
• Presence of EMVI
• T4
• N2
• In lower rectal cancers T3 with >1mm from CRM
• Modality - 45-50.4Gy in 5 weeks RT + 5-FU in first 5 days and last 5 days
• Surgery is done in 12 weeks
• Recovery from CRT associated toxicities
• Time for pathological tumour response to occur
• before tumour starts repopulating
Primary Surgery without Neoadjuvant vs LCRT
vs SCRT
• Swedish trial, Dutch TME trial – local control is better compared to
surgery alone, but no improvement in overall survival
• Studies comparing LCRT and SCRT e.g. Polish trial
• No difference in LR, OS, R0 resection rates
• LCRT is associated with serious side effects
• SCRT patients would likely to have a permanent stoma
Assesment of Response to Neoadjuvant
• Clinically, repeat MRI and colonoscopy
• 50-60% are down sized
• 20% shows complete clinical response (normal 2 layered rectal
wall)
• Long term outcome of the patient directly correlates to response
to neoadjuvant - Mercury trial
Watch and Wait Stratergy
• Complete clinical response to long-course chemoradiotherapy (20%).
• Whitish fibrosis in previous site of tumour
• No residual cancer (clinical, biopsy or imaging  intense surveillance
• ? Cure
• No morbidity of resectional surgery.
• NCCN doesn’t recommend watch and wait, recommends to
perform resectional surgery to confirm complete response
pathologically
• 30% will recur  but can be salvaged by surgical resection.
Downstaging Rectal Cancer with Preoperative
Radiotherapy
• T3 above or mid rectal tumour – High risk local recurrence
• Surgery (TME with inact cover of fat and fascia)
• Lower T3 – by definition gone through bowel wall, may involve
sphincter complex
Complications of Preoperative Radiotherapy
for Rectal Cancer
• Perineal wound breakdown
• Diarrhoea
• Proctitis
• Urinary tract infection
• Small bowel obstruction
• Leukopenia
• Venous thrombosis
• Adverse effects on anal function
• Adverse effects on anastomosis
Trans Anal Excision/ TEMS
• TEMS has better oncological outcomes compared to trans anal
excision, same principles apply.
• Criteria
• T1, N0 cancers
• <3cm, well to moderately differentiated tumours
• within 8cm of the anal verge
• limited to <30% of the rectal circumference
• Procedure
• Full thickness excision of bowel wall in to perirectal fat should be done
• >3mm negative deep and mucosal margins should be achieved
• Tumour fragmentation should not happen
• Locally excised specimen should be oriented and pinned before fixation to be
sent to pathologist
Trans Anal Excision/ TEMS …
• If pathologic evaluation shows following
• Positive margins
• LVI
• Poor differentiation
• Invasion in to lower third of the submucosa
• → radical resection is needed
• Studies show CRT followed by TAE could be a safe alternative to
transabdominal resection for T2N0 lesions
• Good option for patients who refuse or are unfit for transabdominal surgery
Trans Anal Excision/ TEMS - Advantages
• Minimal morbidity (sphincter sparing)
• Minimal mortality
• Rapid post-operative recovery
• Limitations and disadvantages
• Pathologic staging of nodal involvement is not possible → probably
why patients have more local recurrences (LN micro metastases are
common in early rectal lesions and cannot be detected by endorectal
US)
• More local recurrences and less OS compared to radical resection
Transabdominal Surgery
• Options
• Anterior resection
• Abdominoperineal resection
• Options
• Open
• Laparoscopic
• Always with TME (Total mesorectal excision)
Total Mesorectal Excision (TME)
• En-bloc removal of the mesorectum including vascular and lymphatic
structures, fatty tissue and mesorectal fascia as a "tumor package"
• Through sharp dissection
• Autonomic nerves are spared
• Mesorectal excision should extend 4-5cm below the distal edge of the
tumour
• If CRM +ve → LR is 0%
• If CRM -ve → LR is 6-8%
• Unless other nodes are clinically suspicious, NCCN does not
recommend extension of nodal dissection beyond the TME (i.e. in to
iliac nodes etc.)
Anterior Resection (AR)
• Removal of part or the complete rectum for a rectal tumour
• can be performed if about 3cm is there from anorectal angle to the
tumour (limitation is application of the stapler to the pelvis)
• Procedure
• En bloc removal of rectosigmoid and surrounding mesentery
• Rectum with a 4-5cm distal clearance leaving a cuff of rectum for
upper and middle rectal cancer
• if lower rectal tumour 0.9mm pathological distal margin is enough
• TME
• followed by colorectal anastomosis
• Extended AR – Coloanal anaestomosis
Abdominoperineal Resection (APR)
• Indications
• Tumour directly involves anal sphincters
• Tumour directly involves levator muscles
• margin-negative resection of the tumour results in loss of sphincter function
• Procedure
• En bloc removal of Rectosigmoid and surrounding mesentery, rectum and
TME, anus and perianal soft tissue
• Creation of an end colostomy
• APR has worse local control and overall survival than AR
• Reasons unclear
• Due to surgical procedure?
• Tumour related factors as in APR offered for more malignant lesions?
IMA High Ligation or Low Ligation
• No evidence to say and difference in overall survival
• If patient is an elderly with possible atherosclerotic disease, high
ligation should not be done and instead low ligation of IMA should be
done to preserve blood supply to left colon
Diversion with Ileostomy
• Reduces but not prevent clinical anastomotic leak
• Mainly reduces clinical manifestation of a leak
• Considered in
• Anastomosis below the peritoneal reflection
• Leakage risk for overall colon is 4%, for below the peritoneal reflection is
17% (Approx. 4 times higher)
• Neoadjuvant RT (20% increased risk)
• Low nutritional status
• Anaemia
• Patients with atherosclerotic disease (likely to have poor blood supply)
• If spillage/perforation of the tumour/bowel wall occurs during surgery
Adjuvant Therapy
• Chemotherapy
• Sate II and III rectal cancer who received neoadjuvent CRT and surgery
• Chemoradiotherapy
• Sate I without neoadjuvant radiotherapy which are upstaged to II/III after
pathology
• Regimens
• FOLFOX = 5-FU, Folinic acid, oxaliplatin
• CapeOx = Capecitabine, Oxaliplatin
• FOLFIRI = 5-FU, Folinic acid, irinotecan
• Timing
• Should be started as soon as patient is medically able to withstand chemo
following surgery → if waited for longer times, results in reduction in overall
survival
• Should be given to complete 6 months of chemotherapy altogether (4 months
adjuvant if neoadjuvant CRT given)
Management of Locally Advanced Disease
• Target
• Where possible treatment with curative intent
• Or appropriate palliation
• Threatened circumferential resection margin/ spread to neighbouring
structures Neoadjuvant radiotherapy/ chemotherapy
• Long-course chemoradiotherapy is given as 5 fractions of radiotherapy
combined with chemotherapy over a 6-week period.  Aim is to downstage
• Resection margins are not threatened but the cancer is still at high
risk for local recurrence (e.g. peri-rectal lymph node involvement)
• Preoperative ‘short-course’ (5 days) radiotherapy
• Palliative radiotherapy with or without a defunctioning stoma
Management of Locally Advanced Disease
• Endoluminal Stenting
• Palliative intent
• Releive obstruction and plan curative procedure
• Colostomy – Intestinal obstruction
• Palliative intent
• Before downstaging treatment
• Extensive surgery
• Pelvic evisceration
• Pelvic exenteration (in younger, fitter patients)
• Perineal reconstruction
• Ileal conduit
• Palliative radiotherapy – Pain, obstruction, bleeding
Management of Metastetic Disease
• 50% will develop mets, 30% synchronously
• Prognosis worse with synchronous mets vs metachronous mets
• Resectable metastesis – Liver, Lung, Hilar nodes, Spleen, Adrenal
• Rationale – improves overall and disease free survival
• Unresectable mets – Coeliac axis, Paraaortic nodes, Peritoneal
carcinomatosis
• Assesment
• Possibility of R0 resection of primary
• R0 resection of mets should be possible (adequate residual organ etc)
• Healthy liver 20%, Unhealthy liver 40%
• No other unresectable mets
Management of Metastetic Disease
• Liver/ Lung resection in carefully selected patients offers the best
chance of cure for single or well-localised liver metastases
• Synchronous with primary surgery (Classical) or as a delayed procedure (Staged)
• Complete resection should be feasible
• Adequate hepatic/ lung function should be expected
• Re-resection in some very rare cases
• Unresectable
• Conformal external beam radiotherapy – highly selected cases to liver
• Chemotherapy  Conversion to resectable  Resection
• If not still resectable treatment with palliative intent
• Local chemotherapy – Hepatic arterial infusions, TACE, DEB-TACE
• Directed radiation – Arterial radioembolization, EBRT
• Tumour ablation – RFA, Microwave, Cryo, Perc ethanol, electrocoagulation
Management of Metastetic Disease
• Peritoneal Carcinomatosis
• 17% of metastatic colorectal cancer patients have this
• Only metastatic site in 2%
• Overall shorter survival Goal is palliative
• Primarily managed with systemic therapy
• Palliative surgery for primary or stenting if obstruction/impending
obstruction
• But if R0 resection is possible for the peritoneal met - experienced
centres can attempt to do surgical resection
• Complete cytoreductive surgery and HIPEC (hyperthermic
intraperitoneal chemotherapy)
Follow-up Depends on the Initial Findings
• Transanal local excision only
• Proctoscopy (with endoscopic ultrasound [EUS] or MRI with contrast) every
3–6 months for the first 2 y, then every 6 months for a total of 5 y
• Colonoscopy at 1 y after surgery
• If advanced adenoma, repeat in 1 y
• If no advanced adenoma, repeat in 3 y, then every 5 y
• Stage I with full surgical staging
• Colonoscopy at 1 y after surgery If advanced adenoma, repeat in 1 y
• If no advanced adenoma, repeat in 3 y, then every 5 y
• Stage II-IV
• Most intense surveillance
Follow Up
Stage II-IV
• History and physical examination in every 3 months for 2 years and then in
every 6 months for total of 5 years
• CEA in every 3 months for 2 years and then in every 6 months for total of 5
years
• Annual CECT of chest, abdomen and pelvis for 5 years
• Colonoscopy in 1, 3 and 5 years, (Then 5 yearly up to 80 years)
• PET CT not recommended
CEA – Carcinoembryonic Antigen
• An oncofoetal antigen
• Produced by foetal gut tissue and epithelial tumours, especially those of
the large bowel
• Normal value
• <2.5 ng/ml
• Smokers up to 5 ng/ml
• Low sensitivity and specificity
• Mucin-producing and poorly differentiated adenocarcinomas which do not
often present with a raised CEA
• Importance
• prognostic value - good prognosis is associated with lower levels
• tumour burden
• for follow up - levels raised 2-6mon before recurrent lesion becomes visible
CEA – Carcinoembryonic Antigen
• Other conditions with elevated CEA
• Malignant
• Pancreatic adenocarcinoma
• Medullary thyroid cancer
• Benign
• Smoking
• COPD
• IBD
• Pancreatitis
• liver disease
• OJ
CEA – Carcinoembryonic Antigen
In favour of CEA
• CEA rises 1.5 - 6 months prior to
macroscopic recurrence
• Helps in finding early liver mets -
helps in resecting liver mets
completely - long term relapse free
survival is possible up to 40% of
patients
• Even if the mets are unresectable -
still good overall survival can be
achieved with chemo (irinotecan,
oxaliplatin and 5-FU based chemo)
compared to only supportive care
for metastatic CRC
Argument against CEA
• 30-40% of patients with CRC
recurrence, CEA wouldn't rise
• Not a cost effective method (but
this is controversial, as some
studies have shown it's the best
cost effective test for detecting
potentially curable disease)
• There are no data showing that it
was CEA that improves survival or
quality of life
Management of Advanced Disease -
Recurrence in Rectal Cancer
• Local Recurrance
• Disease of pelvis, site of anastomosis of perineum
• Mostly incurable
• Debilitating symptoms - pelvic pain, ureteric obstruction, intestinal and urinary
tract fistulation, and poor bowel and urinary function
• Mainly due to failure in complete excision of tumour in primary surgery
• Risk Factors
• Size of the primary
• Involvement of CRM
• Distal tumour/ near the verge
• Extramural vascular invasion
• Poor differentiation of tumour
• Nodal status
• Extent of extramural spread
• Peritoneal involvement
Specific Management of Rectal Cancer Recurrence
Considered Unresectable/ Inoperable if
• Distant metastasis
• Sacral invasion above S2-S3
• Extensive pelvic side wall involvement resulting in bilateral
hydronephrosis
• Encasement of external iliac vessels (>180 degrees)
• Invasion to anterior pubic bone
• Extension through sciatic notch
Prognosis
Disease Stage 5 Year
Survival
Early Stages (Localised Stage I/ II) – Colon 91%
Early Stages (Localised Stage I/ II) – Rectal 88%
Regional disease (Stage III) – Colon/ Rectal 70%
Metastetic Disease (Stage IV) < 12%
Thank
You

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Management of Colorectal Cancer for the Trainee Surgeon

  • 1. Management of Colorectal Cancer Dr. Gayanga Kottegoda June 2022
  • 2. Objectives • Epidemiology • Anatomy • Pathology • Aetiology • Clinical Features • Workup • Staging • Management of Colon Cancer • Management of Rectal Cancer
  • 3. Epidemiology • Sri Lanka • 3rd Commonest cancer diagnosis when both sexes considered • 4th commonest in males and 4th commonest in females • 7% of total crude cancer incidence (2304 new cases) • 2/3 colonoc, 1/3 rectal • Global • 3rd most common cancer worldwide • 3rd most common cancer in men • 2nd most common cancer in women • There were more than 1.9 million new cases of colorectal cancer in 2020
  • 5. When is it Considered to be in the Rectum • Within 15 cm from anal verge (rigid sigmoidoscopy is best at measuring) • MRI – plane of sigmoid take off • Introperative - identification of the plane of fusion of the two antemesenteric taenia into to an amorphous area. • Importance • Significant difference in management (eg – neoadjuvent RT) • 3 parts of Rectum • 0-6 cm lower rectum • 7 – 11 cm mid rectum • 12 -15 cm upper rectum
  • 6.
  • 7. Tumour Pathology •Morphology 4 types • Annular • Tubular • Ulcer • Cauliflower
  • 8. WHO Histological Classification • Majority are adenocarcinomas – 90 – 95% • Mucinous adenocarcinoma • Signet-ring cell carcinoma • Squamous cell carcinoma • Adenosquamous carcinoma • Undifferentiated carcinoma • Carcinoid tumours • Non epithelial tumours • Sarcoma • Lymphoid neoplasm • Hematopoietic neoplasm
  • 9. Tumour Pathology - Spread • Local/ Direct – longitudinally, transversely or radially to anatomicaly adjesent structures • Colonic • retroperitoneal colonic cancer - the ureter, duodenum and muscles of the posterior abd wall • Intraperitoneal tumour - small intestine, stomach, pelvic organs, the anterior abd wall • Rectal – pelvic organs, side walls • Lymphatic – usually upwards to nodes along the vascular pedicle • Colonic - Paracolic  nodes along main vessels  Para-aortic nodes (30% may skip) • Rectum – via mesorectal nodes • tumours below the peritoneal reflection may also spread laterally and downward • Vascular – Liver, Lung (10%), Ovary, Adrenal, Brain, Bone, Kidney • 37% have occult liver mets at Sx, 50% develop overt mets at some stage • Transcoelomic – Colonic to peritoneum (by subperitoneal lymphatics/ drop mets)
  • 10. Tumour Pathology • 20% present with metastetic disease • 40% develop metastesis at some time
  • 11. Aetiology • Genetic susceptibility -20% • Well defined familial syndromes • HNPCC (Lynch syndrome) • FAP/ Gardner’s syndrome • Turcot syndrome • Other rarer syndromes • Without well defined familial syndromes
  • 12. Aetiology • Lifestyle related • Diet • Western diet • Red meat, poultry • Obesity • Smoking and alcohol • Micronutrients • Low folate • Low vitamin D ? • Lack of physical activity • DM treated with Insulin
  • 13. Aetiology • Inflammatory bowel diseases • Ulcerative colitis • Crohns disease • Past Surgery/ procedure • Pelvic cancer irradiation • Cholecystectomy • Gastrectomy • ureterosigmoidostomy
  • 14. Protective Factors • Exercise • Folic acid • Calcium/ Vitamin D • High fibre diet • Aspirin (but given only when cardiac risk is high) • COX -2 Inhibitors (Celecoxib) • Over expression of COX-2 seen in tumour cells
  • 15. Familial Adenomatous Polyposis • Presence of more than 100 colorectal adenomas - Diagnostic • Positive family history – 80%, Remainder new mutations • APC gene on the short arm of chromosome 5, autosomal dominant, Men = Female • Lifetime risk of colorectal cancer is 100% • Associated with benign mesodermal tumours such as desmoid tumours and osteomas. • Epidermoid cysts in Gardner’s syndrome • Congenital hypertrophy of the retinal pigment epithelium – screening • Polyps at 15 y, almost all at 30 y • Carcinoma after 10 -20y of polyps
  • 16. Familial Adenomatous Polyposis - Management • Surgery deffered till 17y as malignancy unusual till 20y • Family tree maintained, Genetic screening refferals • Target of treatment – Prevent development of colorectal cancer • Options • Colectomy with ileorectal anastomosis – IRA • Less morbidity and mortality • Invasive malignancy at 30y up to 10% • Restorative proctocolectomy with an ileal pouch – anal anastomosis - RPC • Temporary stoma • Pouch failure 10% • Cancer in residual cuff of tumour - annual pouch surveillance with biopsy • Total proctectomy and end ileostomy – Safest but with permanent stoma
  • 17. Hereditary non-polyposis colorectal cancer • HNPCC/ Lynch syndrome – most common (2-4%) • Increased risk of colorectal cancer and also cancers of the endometrium, ovary, stomach and small intestine • Autosomal dominant, DNA mismatch repair gene mutation (MLH1, MSH2, MSH6, PMS2) • Lifetime risk of colorectal cancer is 80%, mean age at diagnosis is 45 y • Proximal colon common • 30 – 50 % lifetime risk of developing endometrial cancer. • Diagnosis – Genetic testing or Amsterdam II criteria • Management • Regular endoscopic surveilance of LGI tract
  • 19. Importance of Adenoma Carcinoma Sequence • Average age of adenoma patients is about 5 years younger than that of the average age of carcinoma patients • The distribution of adenomas in the colon is the same as that of cancers (70% left sided) • Adenomas often accompany carcinoma • Unusual to find carcinoma without contiguous adenomatous tissues • Sporadic adenomas are histologically identical to adenomas of FAP which is unequivocally premalignant • Large adenomas are more likely to display cellular atypia and genetic abnormalities than small lesions
  • 20.
  • 21. Screening • Good candidate for a screening program • Prognosis much better in early stage compared to late stage when treated • Adenoma-carcinoma sequence provides ability to treat pre-malignant lesions • Stool occult blood - guaiac-based test  detects the peroxidase-like activity of haematin in faeces. Sensitivity 50-70% • False negative – intermittent nature of bleeding (3 samples taken) • False positive – animal haemoglobin, vegetable peroxidases • Faecal immunoglobulin test minimises these • Colonoscopy in stool occult blood positive patients • Once only flexible sigmoidoscopy between 55-64 years – 70% coverage
  • 23. Mangement of a Endoscopically Detected Polyp • Risk of malignancy increases with polyp size • 1cm – 10% • >3cm – 30% • Colon Adenomas >5mm  Excised • Snare polypectomy • Large sessile – Endoscopic mucosal resection • Rectal polyp – all polyps needs to be excised • <2cm - EMR • Lager • Low lying - Transanal resection • High – Transanal endoscopic microsurgery (Laparoscopic technique) • Extensive villous lesion – argon beam ablation (Symptomatic but frail)
  • 24.
  • 25.
  • 26. Management of Screening Detected Early Disease • Risk catogorisation and plan management • Endocopically detected malignant polyp  ? Need of completion colectomy driven by • Haggit stage • Histological grade • Staging CT findings • Angiolymphatic invasion • Positive margin • within 1-2mm
  • 27. Difficulties in Deciding on a Completion Colectomy • Identifying the site of innitial polypectomy – Tattooing at initial procedure
  • 29. Pesentation of Colorectal Cancer • RS colon – Anaemia, obstruction uncommon • Liquid nature of faeces • Wider diameter of colon • Descending or Sigmoid colon - change of bowel habit, colicky abdominal pain and blood in the stool • Rectum - bleeding is predominant, mucus discharge • large tumour - tenesmus • Mass • Incontinence, Anal pain • Symptoms related to metastasis – pneumaturia, recurrent UTI, severe diarrhoea, faecal vomiting
  • 30. Targets of Evaluation • Disease and differentials • Complications • Due to blood loss • Due to spread – Local, Metastatic • Obstructive symptoms • Perforation • Aetiology including famaily history • need of family screening • Fitness for surgery • Fitness for chemo/radiotherapy • Dissability • Plan treatment and followup
  • 31. Evaluation • Clinical • History • Examination • Diagnosis - Sigmoidoscopy/ Colonoscopy and biopsy • Radiological • USS, Endorectal USS • CT Colonogram • Barium studies – out of practice • CECT – staging in colorectal ca • Pelvic MRI – staging in rectal • PET-CT – limited role • Blood – CEA, FBC, RFT, LFT
  • 32. For Diagnosis Colonoscopy is Prefered • Gold standard for Diagnosis • 1:1000 risk of perforation • Evaluate synchronous cancer in 3-4%, Polyps in 30% • 2 or more coeisting tumours at diagnosis or within 6 months, seperated by 5 cm, not submucosally connected or a satellite lesion • Flat adenomas are difficult to detect without special techniques • Indigo-carmine dye • Narrow band imaging
  • 33. CT Colonogram • 90% sensitive for >6mm lesions • Adequate alternative where colonoscopy is unfavourable • Advantages • No need sedation • Non invasive • Can do CECT at the same go with IV contrast • Disadvantages • Can not take biopsy • Need similar bowel preperation
  • 34. Preoperative Staging • Colonic • CECT (IV and Oral contrast) Chest Abdomen and Pelvis • When IV contrast contraindicated – NCCT chest + MRI abdomen pelvis with contrast • USS abdomen and Chest X ray as an alternative in resource poor setting • Rectal in addition • MRI Pelvis • Assesment of circumferential resection margin (CRM) • Accurate for Nodal stage • EUS • Accuracy better for T staging • Poor accuracy for N staging • In cases where CT/ MRI studies are inconclusive - PET/CT
  • 35. Staging • Staging is similar in colon and rectal cancer • Preoperative – Clinical and Radiological  To plan manangement • TNM – T componenet most important • Postoperative – Pathological staging  To plan adjuvent treatment and followup
  • 36.
  • 37. • T1/ T2 distinction is difficult in MRI • Possible in TRUSS • CRM evaluation better in MRI • Poorer in TRUSS
  • 38.
  • 39. TNM Prognostic Groups • Stage 0 – Tis, N0, M0 • Stage I - T1/2, N0, M0 • Stage II - T3/4 N0, M0 • IIa - T3 N0 • IIb - T4a N0 • IIc - T4b N0 • Stage III – Any T with nodes, M0 • IIIa - Stage 1 with N1 • IIIb - Stage II with N1 • IIIc - Stage II with N2 • Stage IV – Any T Any N with Metastasis
  • 40. Management of Colorectal Cancer • Surgical excision is the mainstay of treatment • Surgical options - Elective • Colon cancer – Complete Mesocolonic Excision (CME) • Right hemicolectomy • Extended right hemicolectomy • Left hemicolectomy • Sigmoid colectomy • (sub) Total colectomy • Rectal cancer – Mesorectal excision (TME) • Anterior resection • Abdomino-perineal excision  Permenant colostomy • But evolving area – Neoadjuvant and Adjuvant treatment options
  • 42. Pathological Staging • Accurate, detailed and consistent pathology reporting for colorectal cancer is important for • Prognostication • Plan adjuvant treatment • Macroscopic description • Size of the tumour (greatest dimension). • Site of the tumour in relation to the resection margins. • Any abnormalities of the background bowel.
  • 43. Pathological Staging - Microscopic description • Histological type. • Differentiation of the tumour, based on the predominant grade within the tumour • Maximum extent of invasion into/through the bowel wall (submucosa, muscularis propria, extramural). • Serosal involvement by tumour • A statement on the completeness of excision at the cut ends (including the ‘doughnuts’ from stapling devices) and at any radial margin. • The number of lymph nodes examined, the number containing metastases, and whether or not the apical node is involved. • Extramural vascular invasion if present • Pathological staging of the tumour according to Dukes' classification.
  • 44. Duke’s Stages • A - Tumour limited to the wall • B - Tumour in extra-rectal tissues, but not LN • C - Tumour in LNs • C1 - Pararectal nodes • C2 - Nodes along the blood vessels • D – Distant Spread
  • 46. Colon Cancer • Elective Surgery • Surgery in emergencies • Adjuvent therapy
  • 47. Preoperative Checklist for Colon Cancer Surgery • Preoperative optimisation • Endoscopic biopsy and confirmation of histology • Synchronous cancer detected/ excluded by colonoscopy/ CT colonography • Staging CECT chest abdomen and pelvis • Preoperative CEA • Mecahnical bowel preperation - ? • VTE prophylaxis – Graduated compression stockings and SC Enoxa • HB target – 7-8 in general, 8-9 in IHD, • Antibiotic prophylaxis 30 – 60 mins prior to Sx
  • 48. Mechanical Bowel Preperation • No benefit in anastomotic leakage, re-operation or wound infection and recommended avoidance of MBP in elective colectomy patients • Recommended in high risk emergency where anastomotic leak risk is high  creation of an upstream defunctioning stoma • MBP is recommended in this setting to reduce faeces between the stoma and anastomosis
  • 50. Principles of Colon Cancer Surgery • Colectomy with enbloc removal of lymph nodes • Complete Mesocolic Excision (CME) • Dissection in the embryologically defined mesocolic plane. • Central ligation of the vascular pedicle (CVL). • Resection of an adequate length of apparently normal colon on either side of the tumour.
  • 51. Central Vascular Ligation (CVL) • Mortality benefit of D3 resection over D2 resection in T3/ T4 disease • removal of undetected micrometastatic disease within the mesentery • resection of positive nodes
  • 53. Practical Guide to Resection • Right hemicolectomy • Caecum • Right colon • Right transverse colon • Transverse Colectomy • Extent of longitudinal resection cannot be fulfilled by either right hemicolectomy or segmental left colectomy • Segmental left colectomy • Splenic flexure • Left Hemicolectomy • Left colon cancer
  • 54. Open Surgery vs Laparoscopic vs Robotic • Laparoscopic surgery • Advantages • Equivalent oncological outcome • Equevalent LN harvesting ability • Encouraging postoperative recovery – shorter hospital stay • wound infection rates, blood loss and postoperative pain scores are lower • Disadvantages • Difficulty acquiring technical competence, long learning curve • High cost of laparoscopic instruments/ consumables • Increased operative times • Robotic – again shortest stay, least blood loss, but longest operative time and much increased cost
  • 55. Minimally Invasive Techniques • Only by experienced surgeons in minimally invasive colectomies • Not utilized in • Emergency • Acutely obstructed • Perforated • Clearly locally advanced • High risk prohibitive adhesions
  • 56. Surgical Complications • Anastomotic leak – Most devastating – 4 – 8% • Wound infections - 10%
  • 57. Surgical Complications - Anastomotic Leak • Causes • Technical problems – around 1-2 days • Ischaemia – around day 5 • Diagnosis • Poor progression • Persistant tachycardia, pyrexia, arrhythmia • Respiratory problems • Abdominal pain or distension • Sudden rise of CRP >200 (daily CRP)
  • 58. Surgical Complications Anastomotic Leak • Evaluation • CECT – Chest abdomen pelvis without rectal contrast • Subtle changes – bubbles adjacent to the anastomosis • Also, to exclude other problems • Followed by water soluble contrast enema • Management • Conservative in well patients – Not well established • Antibiotics • Operative when deteriorating • Preserving anastomosis  Defunctioning stoma, Drain at site • Anastomosis can not be preserved  Hartmann's procedure
  • 59. Risk Factors for Anastomotic Leak • Male sex • Renal disease • Comorbidities • History of radiotherapy • Tumour >3cm • Advanced tumour stage • Emergency surgery • Metastatic disease • Smoking • Obesity • Poor nutrition • Alcohol intake in excess • Immunosuppr • essants • Bevacizumab • Blood loss/transfusion • Duration of surgery (> 4 H)
  • 60. Emergency Surgical Options for Colorectal Cancer • Resuscitation • Evaluation • Main presentations requiring emergency surgery (20% in total) • Obstruction (16% present like this) • Perforation • Significant haemorrhage • Increased post op complications • Increased mortality • Principles of emergency surgical procedure • Oncological clearance when appropraite • Releive obstruction • Remove contamination – control of sepsis
  • 61. Obstruction • Evaluation • CT preffered over X ray • Endoscopy/ contrast enema study to exclude psedo-obstruction • Expedited management • Evidence of sepsis • Caecal region tenderness/ >12cm Caecal diameter • Options • Stenting (left colon lesion) – allows elective resection after stabilisation and evaluation • Emergency Surgery – depending on the stability • Resect and anastomose • Resect and defunct – Hartmann’s procedure • Defunct only (without resection) • Systemic therapy with chemo • In medically unfit or unresectable lesion • Goal – Conversion to a resectable lesion or with palliative intent
  • 62. Stenting for Left Colonic Lesions • Relief of abstruction  Stabilisation  Evaluation  Definitive Sx • No evidence over definitive emergency surgery without stenting • Less stomas with this stratergy • May be the definitive treatment in the pallitive setup • Problems • Failure to releive obstruction • Perforation • Technical difficulty
  • 64. Perforation • At the site of the tumour • At a distant site due to dilatation/ diverticuli • Primary may be missed • Management • Resection • Control of sepsis • Reconstruction where appropriate • Generally leads to a defunctioning stoma
  • 65. Adjuvent Therapy – Resectable Colon Cancer • Mainly as a postoperative adjuvant • Not indicated • T1/ T2 (Stage I) • Some Stage II • Indicated • Some stage II • T4 • benefit in node positive disease • poorly differentiated/ undifferentiated tumours • lymphovascular invasion • perineural invasion • Poor LN sampling • Treatment • Based on fluoropyrimidines (IV 5-fluorouracil Oral capcitabine) • Combinations with oxaliplatin
  • 66. • Radiotherapy has no role in primary disease in most cases • Risk of radiation enetritis to adjacent small bowel • Mobile nature of large bowel where directed therapy is difficult • Limited role of radiotherapy for ablative radiotherapy for liver and lung mets • highly selected cases/ clinical trial. • should not be used in place of surgical resection • highly conformal delivery required - 3-D conformal radiation therapy, intensity-modulated radiation therapy (IMRT), or stereotactic body radiation therapy (SBRT). Adjuvent Therapy – Resectable Colon Cancer
  • 67. Neoadjuvent Treatment Options –Colon Cancer • Preoperative chemoradiation used selectively in • T4 tumours penetrating to a fixed structure • for patients with recurrent disease • Locally unresectable tumours • Neoadjuvant chemotherapy • For bulky nodal disease or clinical T4b
  • 68. Management of Locally Advanced Colon Cancer • Target • Where possible treatment with curative intent • Or appropriate palliation • Operative options • Bypass surgery may be appropriate • Multi-organ en bloc resection may be curative • Neoadjuvant • Intent of downgrading – improving resectability • Palliative intent
  • 69. Advanced Disease – Recurrence of Colon Cancer • Local recurrence  Resection attempted, if not palliative bypass
  • 70. Metastesis in Colon Cancer • Usually metachronously after locoregional treatment (50– 60%) • Synchronously 20 – 34% in liver (worse than metachronous) • Operable • Hepatic resection (No RCT, Generally for 1-3 mets in one lobe of liver, preoperative chemo may have a role in improving operability, 30% 5 year survival • Don’t biopsy potentially resectable hepatic mets  risk of dissemination • Pulmonary – rarely possible as only 10% pulmonary mets and only 10% of them have disease confined to lung, 20% 5 year survival • Peritoneal spread alone, or with easily operable liver metastases, peritonectomy combined with heated intraperitoneal chemotherapy (HIPEC) • Inoperable • Chemotherapy containing fluoropyrimidines is the only established treatment • Palliative surgery mainly to relieve obstruction – Stoma/ Stenting
  • 71. Surveilance is Based on Prognostic Stage • Stage I - Imaging is not routinely indicated and should only be based on symptoms and clinical concern for recurrent/metastatic disease. • Stage II & III - Chest, abdomen, and pelvic CT every 6 to 12 months for a total of 5 years. • PET/CT is not indicated. • Stage IV – • Chest, abdomen, and pelvic CT every 3 to 6 months 2 years • then every 6 to 12 months for a total of 5 years • PET/CT can be considered for assessment of response and liver recurrence after image-guided liver-directed therapies (ie, ablation, radioembolization) or serial CEA elevation during follow-up
  • 72. Intensive Follow Up • History and physical examination in every 3 months for 2 years and then in every 6 months for total of 5 years • CEA in every 3 months for 2 years and then in every 6 months for total of 5 years • Annual CECT of chest, abdomen and pelvis for 5 years • Colonoscopy in 1, 3 and 5 years, (Then 5 yearly up to 80 years)
  • 74. Preoperative Checklist for Rectal Cancer • Preoperative optimisation • Endoscopic biopsy and confirmation of histology • MMR/ MSI testing • Synchronous cancer detected/ excluded by colonoscopy/ CT colonography • Staging CECT chest abdomen and pelvis • Pelvic MRI/ Endoscopic USS • Preoperative CEA • Mecahnical bowel preperation done for low anterior resection • Siting of stoma and councelling preoperatively • Fertility risk discussion/ counselling • VTE prophylaxis – Graduated compression stockings and SC Enoxa • HB target – 7-8 in general, 8-9 in IHD, • Antibiotic prophylaxis 30 – 60 mins prior to Sx
  • 75. Rectal cancer Surgery - Objectives • Oncological cure • Most cases  Radical excision of the rectum, together with the mesorectum and associated lymph nodes (TME) • High proximal ligation of the inferior mesenteric lymphovascular pedicle • Margin distally minimum 1 cm, Proximally > 5cm • Preserve function • Restore GI continuity • Preserve anal sphincter – lower margin of tumour >2cm from anaorectal junction • Stratergies in low rectal tumours - • Stapled anastomosis • Chemoradiotherapy down-staging • Bladder function • Sexual function
  • 76. Management Options in Rectal Cancer • Surgical • Local excision - Difficult in higher lesions • Trans anal excision • Excision of the tumour by TEMS (transanal endoscopic microsurgery) • Transabdominal resection + TME • Higher - anterior resection • Lower - abdominoperineal excision – smaller group • Neoadjuvant • LCCT • SCRT • Adjuvant • CT/ RT/ CRT
  • 77. Management Stratergies • Localised Disease - <T2, N0, M0 • Upfront surgery • Locoregional rectal cancer - >T2 or ≥ N1 • Neoadjuvant therapy
  • 78. Circumferential Resection Margin • CRM is the surface of the nonperitonealised part of the rectum that is resected during surgery • MRI is the most reliable imaging modality to determine potential CRM • CRM is the shortest distance between the outermost part of the rectal tumour and the MRF • Positive < 1 mm • Threatened - between 1 and 2 mm • Not threatened - >2 mm • CRM status is not applicable if the tumour is situated in a peritonealised aspect of the rectal wall.
  • 79.
  • 80.
  • 81. Circumferential Resection Margin • Need to achieve a negative surgical margin as risk of local recurrence is 40% if margins positive • Reasons for this recurrence risk • Close proximity of rectum to adjacent pelvic organs • Absence of a serosa surrounding the rectum • Technical difficulties obtaining a wide surgical margin at resection • To achieve a negative margin, mesorectal fascia should be free of tumour at the time of TME • Radiotherapy enables an R0 resection by making the MRF free of tumour • Radiotherapy is feasible to pelvis compared to abdomen where sensitive small bowel is located
  • 82. Neo-adjuvent for Rectal Cancer • Neoadjuvant strategies – preoperative radiotherapy produces better disease control and less morbidity than postoperative treatment • Short course radiotherapy (SCRT) • Long course chemoradiotherapy (LCRT) • Total neoadjuvant therapy (TNT)
  • 83. SCRT - Short Course Radiotherapy • Indications • T3 with uninvolved CRM in upper and mid rectal cancers • T2 lower rectal cancer in which muscularis propria preserved < 1mm • N1 • Modality - 25Gy over 5 days (Monday to Friday) • Surgery in next week • before acute mucosal side effects occur • Surgery after 6 weeks if downstaging is needed
  • 84. LCRT - Long Course Chemoradiotherapy • CT given concurrently with RT to increase RT sensitization and enhances tumoricidal effect • Does not improve overall survival or disease free survival • Indications - high risk features • CRM threatened • Presence of EMVI • T4 • N2 • In lower rectal cancers T3 with >1mm from CRM • Modality - 45-50.4Gy in 5 weeks RT + 5-FU in first 5 days and last 5 days • Surgery is done in 12 weeks • Recovery from CRT associated toxicities • Time for pathological tumour response to occur • before tumour starts repopulating
  • 85. Primary Surgery without Neoadjuvant vs LCRT vs SCRT • Swedish trial, Dutch TME trial – local control is better compared to surgery alone, but no improvement in overall survival • Studies comparing LCRT and SCRT e.g. Polish trial • No difference in LR, OS, R0 resection rates • LCRT is associated with serious side effects • SCRT patients would likely to have a permanent stoma
  • 86. Assesment of Response to Neoadjuvant • Clinically, repeat MRI and colonoscopy • 50-60% are down sized • 20% shows complete clinical response (normal 2 layered rectal wall) • Long term outcome of the patient directly correlates to response to neoadjuvant - Mercury trial
  • 87. Watch and Wait Stratergy • Complete clinical response to long-course chemoradiotherapy (20%). • Whitish fibrosis in previous site of tumour • No residual cancer (clinical, biopsy or imaging  intense surveillance • ? Cure • No morbidity of resectional surgery. • NCCN doesn’t recommend watch and wait, recommends to perform resectional surgery to confirm complete response pathologically • 30% will recur  but can be salvaged by surgical resection.
  • 88. Downstaging Rectal Cancer with Preoperative Radiotherapy • T3 above or mid rectal tumour – High risk local recurrence • Surgery (TME with inact cover of fat and fascia) • Lower T3 – by definition gone through bowel wall, may involve sphincter complex
  • 89. Complications of Preoperative Radiotherapy for Rectal Cancer • Perineal wound breakdown • Diarrhoea • Proctitis • Urinary tract infection • Small bowel obstruction • Leukopenia • Venous thrombosis • Adverse effects on anal function • Adverse effects on anastomosis
  • 90. Trans Anal Excision/ TEMS • TEMS has better oncological outcomes compared to trans anal excision, same principles apply. • Criteria • T1, N0 cancers • <3cm, well to moderately differentiated tumours • within 8cm of the anal verge • limited to <30% of the rectal circumference • Procedure • Full thickness excision of bowel wall in to perirectal fat should be done • >3mm negative deep and mucosal margins should be achieved • Tumour fragmentation should not happen • Locally excised specimen should be oriented and pinned before fixation to be sent to pathologist
  • 91. Trans Anal Excision/ TEMS … • If pathologic evaluation shows following • Positive margins • LVI • Poor differentiation • Invasion in to lower third of the submucosa • → radical resection is needed • Studies show CRT followed by TAE could be a safe alternative to transabdominal resection for T2N0 lesions • Good option for patients who refuse or are unfit for transabdominal surgery
  • 92. Trans Anal Excision/ TEMS - Advantages • Minimal morbidity (sphincter sparing) • Minimal mortality • Rapid post-operative recovery • Limitations and disadvantages • Pathologic staging of nodal involvement is not possible → probably why patients have more local recurrences (LN micro metastases are common in early rectal lesions and cannot be detected by endorectal US) • More local recurrences and less OS compared to radical resection
  • 93. Transabdominal Surgery • Options • Anterior resection • Abdominoperineal resection • Options • Open • Laparoscopic • Always with TME (Total mesorectal excision)
  • 94. Total Mesorectal Excision (TME) • En-bloc removal of the mesorectum including vascular and lymphatic structures, fatty tissue and mesorectal fascia as a "tumor package" • Through sharp dissection • Autonomic nerves are spared • Mesorectal excision should extend 4-5cm below the distal edge of the tumour • If CRM +ve → LR is 0% • If CRM -ve → LR is 6-8% • Unless other nodes are clinically suspicious, NCCN does not recommend extension of nodal dissection beyond the TME (i.e. in to iliac nodes etc.)
  • 95. Anterior Resection (AR) • Removal of part or the complete rectum for a rectal tumour • can be performed if about 3cm is there from anorectal angle to the tumour (limitation is application of the stapler to the pelvis) • Procedure • En bloc removal of rectosigmoid and surrounding mesentery • Rectum with a 4-5cm distal clearance leaving a cuff of rectum for upper and middle rectal cancer • if lower rectal tumour 0.9mm pathological distal margin is enough • TME • followed by colorectal anastomosis • Extended AR – Coloanal anaestomosis
  • 96. Abdominoperineal Resection (APR) • Indications • Tumour directly involves anal sphincters • Tumour directly involves levator muscles • margin-negative resection of the tumour results in loss of sphincter function • Procedure • En bloc removal of Rectosigmoid and surrounding mesentery, rectum and TME, anus and perianal soft tissue • Creation of an end colostomy • APR has worse local control and overall survival than AR • Reasons unclear • Due to surgical procedure? • Tumour related factors as in APR offered for more malignant lesions?
  • 97. IMA High Ligation or Low Ligation • No evidence to say and difference in overall survival • If patient is an elderly with possible atherosclerotic disease, high ligation should not be done and instead low ligation of IMA should be done to preserve blood supply to left colon
  • 98. Diversion with Ileostomy • Reduces but not prevent clinical anastomotic leak • Mainly reduces clinical manifestation of a leak • Considered in • Anastomosis below the peritoneal reflection • Leakage risk for overall colon is 4%, for below the peritoneal reflection is 17% (Approx. 4 times higher) • Neoadjuvant RT (20% increased risk) • Low nutritional status • Anaemia • Patients with atherosclerotic disease (likely to have poor blood supply) • If spillage/perforation of the tumour/bowel wall occurs during surgery
  • 99. Adjuvant Therapy • Chemotherapy • Sate II and III rectal cancer who received neoadjuvent CRT and surgery • Chemoradiotherapy • Sate I without neoadjuvant radiotherapy which are upstaged to II/III after pathology • Regimens • FOLFOX = 5-FU, Folinic acid, oxaliplatin • CapeOx = Capecitabine, Oxaliplatin • FOLFIRI = 5-FU, Folinic acid, irinotecan • Timing • Should be started as soon as patient is medically able to withstand chemo following surgery → if waited for longer times, results in reduction in overall survival • Should be given to complete 6 months of chemotherapy altogether (4 months adjuvant if neoadjuvant CRT given)
  • 100. Management of Locally Advanced Disease • Target • Where possible treatment with curative intent • Or appropriate palliation • Threatened circumferential resection margin/ spread to neighbouring structures Neoadjuvant radiotherapy/ chemotherapy • Long-course chemoradiotherapy is given as 5 fractions of radiotherapy combined with chemotherapy over a 6-week period.  Aim is to downstage • Resection margins are not threatened but the cancer is still at high risk for local recurrence (e.g. peri-rectal lymph node involvement) • Preoperative ‘short-course’ (5 days) radiotherapy • Palliative radiotherapy with or without a defunctioning stoma
  • 101. Management of Locally Advanced Disease • Endoluminal Stenting • Palliative intent • Releive obstruction and plan curative procedure • Colostomy – Intestinal obstruction • Palliative intent • Before downstaging treatment • Extensive surgery • Pelvic evisceration • Pelvic exenteration (in younger, fitter patients) • Perineal reconstruction • Ileal conduit • Palliative radiotherapy – Pain, obstruction, bleeding
  • 102. Management of Metastetic Disease • 50% will develop mets, 30% synchronously • Prognosis worse with synchronous mets vs metachronous mets • Resectable metastesis – Liver, Lung, Hilar nodes, Spleen, Adrenal • Rationale – improves overall and disease free survival • Unresectable mets – Coeliac axis, Paraaortic nodes, Peritoneal carcinomatosis • Assesment • Possibility of R0 resection of primary • R0 resection of mets should be possible (adequate residual organ etc) • Healthy liver 20%, Unhealthy liver 40% • No other unresectable mets
  • 103. Management of Metastetic Disease • Liver/ Lung resection in carefully selected patients offers the best chance of cure for single or well-localised liver metastases • Synchronous with primary surgery (Classical) or as a delayed procedure (Staged) • Complete resection should be feasible • Adequate hepatic/ lung function should be expected • Re-resection in some very rare cases • Unresectable • Conformal external beam radiotherapy – highly selected cases to liver • Chemotherapy  Conversion to resectable  Resection • If not still resectable treatment with palliative intent • Local chemotherapy – Hepatic arterial infusions, TACE, DEB-TACE • Directed radiation – Arterial radioembolization, EBRT • Tumour ablation – RFA, Microwave, Cryo, Perc ethanol, electrocoagulation
  • 104. Management of Metastetic Disease • Peritoneal Carcinomatosis • 17% of metastatic colorectal cancer patients have this • Only metastatic site in 2% • Overall shorter survival Goal is palliative • Primarily managed with systemic therapy • Palliative surgery for primary or stenting if obstruction/impending obstruction • But if R0 resection is possible for the peritoneal met - experienced centres can attempt to do surgical resection • Complete cytoreductive surgery and HIPEC (hyperthermic intraperitoneal chemotherapy)
  • 105. Follow-up Depends on the Initial Findings • Transanal local excision only • Proctoscopy (with endoscopic ultrasound [EUS] or MRI with contrast) every 3–6 months for the first 2 y, then every 6 months for a total of 5 y • Colonoscopy at 1 y after surgery • If advanced adenoma, repeat in 1 y • If no advanced adenoma, repeat in 3 y, then every 5 y • Stage I with full surgical staging • Colonoscopy at 1 y after surgery If advanced adenoma, repeat in 1 y • If no advanced adenoma, repeat in 3 y, then every 5 y • Stage II-IV • Most intense surveillance
  • 106. Follow Up Stage II-IV • History and physical examination in every 3 months for 2 years and then in every 6 months for total of 5 years • CEA in every 3 months for 2 years and then in every 6 months for total of 5 years • Annual CECT of chest, abdomen and pelvis for 5 years • Colonoscopy in 1, 3 and 5 years, (Then 5 yearly up to 80 years) • PET CT not recommended
  • 107. CEA – Carcinoembryonic Antigen • An oncofoetal antigen • Produced by foetal gut tissue and epithelial tumours, especially those of the large bowel • Normal value • <2.5 ng/ml • Smokers up to 5 ng/ml • Low sensitivity and specificity • Mucin-producing and poorly differentiated adenocarcinomas which do not often present with a raised CEA • Importance • prognostic value - good prognosis is associated with lower levels • tumour burden • for follow up - levels raised 2-6mon before recurrent lesion becomes visible
  • 108. CEA – Carcinoembryonic Antigen • Other conditions with elevated CEA • Malignant • Pancreatic adenocarcinoma • Medullary thyroid cancer • Benign • Smoking • COPD • IBD • Pancreatitis • liver disease • OJ
  • 109. CEA – Carcinoembryonic Antigen In favour of CEA • CEA rises 1.5 - 6 months prior to macroscopic recurrence • Helps in finding early liver mets - helps in resecting liver mets completely - long term relapse free survival is possible up to 40% of patients • Even if the mets are unresectable - still good overall survival can be achieved with chemo (irinotecan, oxaliplatin and 5-FU based chemo) compared to only supportive care for metastatic CRC Argument against CEA • 30-40% of patients with CRC recurrence, CEA wouldn't rise • Not a cost effective method (but this is controversial, as some studies have shown it's the best cost effective test for detecting potentially curable disease) • There are no data showing that it was CEA that improves survival or quality of life
  • 110. Management of Advanced Disease - Recurrence in Rectal Cancer • Local Recurrance • Disease of pelvis, site of anastomosis of perineum • Mostly incurable • Debilitating symptoms - pelvic pain, ureteric obstruction, intestinal and urinary tract fistulation, and poor bowel and urinary function • Mainly due to failure in complete excision of tumour in primary surgery • Risk Factors • Size of the primary • Involvement of CRM • Distal tumour/ near the verge • Extramural vascular invasion • Poor differentiation of tumour • Nodal status • Extent of extramural spread • Peritoneal involvement
  • 111. Specific Management of Rectal Cancer Recurrence
  • 112. Considered Unresectable/ Inoperable if • Distant metastasis • Sacral invasion above S2-S3 • Extensive pelvic side wall involvement resulting in bilateral hydronephrosis • Encasement of external iliac vessels (>180 degrees) • Invasion to anterior pubic bone • Extension through sciatic notch
  • 113. Prognosis Disease Stage 5 Year Survival Early Stages (Localised Stage I/ II) – Colon 91% Early Stages (Localised Stage I/ II) – Rectal 88% Regional disease (Stage III) – Colon/ Rectal 70% Metastetic Disease (Stage IV) < 12%