Editing Colon cancer (section)

= '''Management''' =

== Approach ==

*** '''Resectable non-metastatic cancers'''
**** Where the primary tumour can be resected with adequate free margins, en bloc with locoregional lymphadenectomy
*** '''Potentially resectable metastatic cancers'''
**** Neoadjuvant therapy followed by restaging and surgery
**** Consider up-front resection of everything
**** See separate topic under 'liver'
*** '''Unresectable metastatic cancers'''
**** Palliative chemotherapy vs best supportive care

== '''Neoadjuvant therapy''' ==

** Indications
*** Locally advanced disease with compromised surgical margins/clinical T4b
*** Medically inoperable cancer
*** Consider with bulky nodal disease
** Benefits
*** Reduce micro-metastatic disease
*** Improve operability of the primary tumour
*** Improved compliance compared to adjuvant therapy

== '''Surgery''' ==

** Principles
*** Gentle surgery, avoiding manipulation of the tumour
*** At least 12 nodes required, but generally around 20 are resected
*** Aim for a free margin of 5cm to minimise risk of recurrent cancer and capture perivisceral lymph nodes; however, if is more complex than that if we follow guidelines from JSCCR
**** If there is a clear main vessel, resect 5cm past it, or 10cm past the tumour in the opposite direction
**** If the tumour is between two main vessels, then 5cm past each main vessel is necessary
***
*** Tension-free anastomosis
*** Avoid injury to vascular supply of the colon, including marginal artery
*** Central venous ligation should be performed
*** Aim for D3 resection - there is a survival benefit, although it is small, and only relevant for more advanced disease. However, it is almost impossible to accurately stage these cancers pre-op, so best to perform D3 resection by default.
***
** Open vs laparoscopic
*** Favourable recovery with minimally invasive
*** Oncologic outcomes non-inferior, with similar disease-free survival and local recurrence rate
*** No clear advantages to robotics yet
** Right-sided cancers
*** Right hemicolectomy
*** Excise the lymphatic tissue around SMV en bloc for a complete lymphadenectomy
***
** Transverse colon cancers
*** Mostly extended right hemicolectomy - need to also divide middle colic vessels at the origin
***
** Splenic flexure cancers
*** Controversial - extended right hemicolectomy or left hemicolectomy (segmental) or extended left hemicolectomy or subtotal colectomy
**** '''Extended RHC''' would take both branches of middle colic and go round as far as upper descending colon, but is really only an option when you think lymphatic drainage will definitely be to the middle colic pedicle
**** '''Segmental left hemicolectomy''' would involve IMV ligation, left colic artery division at origin, sometimes the left branch of middle colic, and anastomosis between transverse colon and descending colon. Still usually gets enough nodes to stage.
**** '''Extended left hemicolectomy''' ligates left branch of middle colic with IMA at origin, then joins distal transverse to sigmoid. Not thought to be a good operation by some colorectal surgeons as it is non-anatomical.
**** '''Subtotal colectomy''' - perhaps the best oncological operation, given total resection of middle colic and IMA pedicles, but worst functional outcome
*** In one study, 96% of normal splenic flexure lymphatic drainage was to left colic/IMA pedicle, so argument for middle colic lymphadenectomy is probably not warranted
*** Key factors:
**** Younger patients can handle the longer operation and functional impairment of subtotal colectomy better
**** Older patients may opt for a segmental left hemicolectomy to preserve function
***
** Left-sided cancers
*** Left hemicolectomy - high ligation of IMA, IMV ligation, splenic flexure mobilisation, and anastomosis between left colon and proximal rectum with circular stapler
***


== '''Adjuvant CTX''' ==

** Candidates:
*** Node-positive (stage III)
*** Node-negative (stage II) but high-risk
**** Consider adjuvant (poorly-differentiated, lymphovascular invasion, inadequate margins, T4 lesion, inadequate number of lymph nodes harvested, perforated or obstructed, MSI microsatellite instability)
**** However even in this group, the benefits are minimal
** Regimen:

*** Most commonly FOLFOX (folinic acid, 5-FU and oxaliplatin) for 6 months
*** Fluoropyrimidine alone can be used for more frail patients
*** Sometimes FOLFIRI is also used (folinic acid, 5-FU and irinotecan
*** Trials ongoing 3 months vs 6 months

'''Other systemic options'''

** EGFR inhibitors

*** Cetuximab or panitumumab
*** Indicated with metastatic disease and wild-type KRAS/NRAS and BRAF wild-type
*** If BRAF is mutated, EGFR inhibitors can be combined with a BRAF inhibitor (encorafenib)

** Immune checkpoint inhibitors

*** Given for patients with stage IV CRC and dMMR (MSI-H)
*** Nivolumab plus ipilimumab usually given instead of traditional chemotherapy for those patients

** HER2-targeted therapy

*** Used as second-line therapy for patients with HER2 overexpression

** VEGF inhibitors

*** Bevacizumab (Avastin)
*** Small benefit when added to cytotoxic chemotherapy in some situations
*** Risk of perforation

== '''Adjuvant RTX''' ==

** Unlike rectal cancer, rarely used for colon cancer

== '''Complications''' ==

** Obstructing cancers
*** '''Approach'''
**** Surgery
**** Stent (see below for left-sided cancers)
***** Bridge to surgery only
***** Reduces stoma rates from 69% to 45%
*** '''Timing of intervention'''
**** Expedited if caecal tenderness, signs of sepsis or caecal diameter >12cm
**** Otherwise prefer using experienced staff during daylight hours
*** '''Principles of surgery'''
**** Colonic decompression
***** Often done at start of case - use either a 19G needle on suction or a Foley
***** If no caecal injury, may allow left-sided segmental resection
**** Anastomosis?
***** If proximal bowel viable, segmental resection with primary anastomosis (unless there is a contraindication, in which case do Hartmann procedure)
***** Leak rates 2-8% (similar to elective surgery)
***** Consider diverting ileostomy, but does not decrease leak rates, just leaks requiring operation
***** Companion series suggests defunctioning in most cases
***** If unwell, just do a Hartmann's; and if seriously compromised physiology is present, just defunction
*** '''Choice of operation'''
**** '''Right-sided, up to and including splenic flexure'''
***** Oncological segmental resection - right hemicolectomy
***** Most cases can have primary anastomosis, but consider diversion for those at risk of failure
**** '''Left-sided'''
***** Options
****** '''Resect''' (Hartmann's (wouldn't survive a leak, or too high risk for leak), or primary anastomosis +/- proximal diversion)
******* Resectable tumour, curative intent
******* Resectable tumour, not much metastatic disease and prospect of survival
****** '''Divert'''
******* Unresectable primary tumour
******* Obstructing rectal cancer
******* Widespread metastatic disease
******* Major comorbidities precluding resection
****** '''Stent'''
******* May permit higher rates of primary anastomosis, decreased wound infections and a lower rate of conversion. Mainly in high-risk or unwell patients. Contraindicated in suspected ischaemic or perforated bowel. See separate topic.
** Perforation
*** Usually occurs in the caecum (Laplace), but can also be at the tumour or in a segment of diverticulitis proximal to the tumour
*** Contained perf: drain percutaneously followed by semi-elective surgery
*** Free perf: surgical emergency. Resection with proximal colostomy or ileostomy (Hartmann's). Can possibly MAYBE do primary anastomosis with covering loop ileostomy.


== '''Prognosis''' ==

** Majority of recurrences occur within two years
** Stage IV
*** Chemotherapy median survival - 2 years
*** Best supportive care median survival - 6 months


== '''Surveillance''' ==

** Normal CEA does not negate utility of tracking CEA later to detect recurrences
** Goals:
*** Identify recurrence a stage potentially resectable
*** Identify metachronous tumours
*** Identify mets (especially liver)
*** Reassures patient
** T1/T2 or patient doesn't want further treatment
*** ?Less than below, need local guidelines on specifics
*** In the engaged, well patient who would like surveillance, it is reasonable to offer the same protocol as for stage II/III disease
** T3 or greater:
*** 2 years of 3-monthly hx, exam, CEA. Then 3 years of 6-monthly hx, exam, CEA - then depending on risk
**** If concerns, colonoscopy and CT
*** Minimum annual CT CAP regardless though (needs to be 5mm slices, contrast-enhanced) for first three years, then depending on risk
** Colonoscopy at 1 year, then 4 or 5 years, then every 5 years until 75 or 80
*** Do the colonoscopy within 6 months if it could not be done pre-operatively (e.g. because of obstructing cancer)
*** If further adenomas found, keep doing yearly colonoscopy (i.e. at year 2, year 3, etc) until colon is clear (Sabiston)

== '''Screening''' ==

** NBSCP
*** FOBT 2-yearly between 45 and 74
**** Two samples each time
**** iFOBT (now used for NBCSP): immunochemical test which identifies only human haemoglobin
**** gFOBT: The samples placed in a hydrogen peroxide solution. If haem is in the stool sample, there will be pseudoperoxidase activity, and oxygen will be released from the hydrogen peroxide in the ensuing reaction. A card containing guiac resin is placed in the solution, and if oxygen is present, the guiac will be oxidised to a different colour. Thus, the guiac changes colour if haem is present. False positives can occur with dietary red meat, vitamin C and anti-inflammatories for three days prior.
**** Can also be ok to use as screening tool in 50-74 year olds with abdo pain/weight loss/fe-defic anaemia
*** For pre-cancerous adenoma detection: 90.6% sp / 33.9% se
*** For early CRC: 89.8% sp / 84.6% se
*** Positive FOBT:
**** 58% normal colonoscopy
**** 39% polyp
**** 10% advanced adenoma >1cm
**** 3% CRC
*** Benefits:
**** 9% disease-specific mortality vs 24%
**** 2300-3200 deaths prevented each year in Australia
** If positive - should proceed to colonoscopy within 120 days


[[Category:Colorectal]]
[[Category:Intern education]]