Management of colon cancer

1. MANAGEMENT OF COLON
CANCERS
E. E. Okon MD

2. Outline
 Management options
 Stage wise Management
 Follow up
 Treatment of Metastatic Colon Cancer

3. TREATMENT OPTIONS
SURGERY CHEMOTHERAPY RADIOTHERAPY TARGETED

4. Surgical management depends on
Tumor related
• Stage
• Location
Presentation
• elective
• emergency
Patient
related
• Age
• Performance
status
• Medical
comorbidities

5. Pre-operative Preparation
 Bowel Prep
 Antibiotics

6. SURGERY
Colectomy: Principal treatment of Ca colon
Intention
 Curative
 palliative
 Accurate disease staging
 Guides adjuvant treatment
Indication
 Stage 1 -3
 Resectable stage 4

7. Aim of surgery
R0 resection considered curative
wide resection of involved colon segment +lymphatic + mesocolon +enblock
resection of neighbouring organs with adequate margin before reconstituting bowel
continuity
 margin ~5 cm of normal bowel proximal and distal to tumor considered adequate
 Suspicious LNs outside field of resection removed or biopsied
Inspect abdomen viscera,peritoneum,non localized lymph nodes for metastasis

8. Laparoscopic vs. Open colectomy
Advantages:
• Improved visualization of visceral
structure
• Better abdominal exploration
• Increased no. of lymph node dissected
• Small incision
• Early return of bowel function
• Better recovery
• Less hospital stay
Disadvantages: Concern regarding
• inadequacy of resection margin
• Inadequacy in LN sampling
• seeding of port sites
• Cost

9. Laparoscopic-assisted colectomy
May be considered based upon the following criteria:
• experience surgeon performing laparoscopically assisted
colorectal operations.
• no locally advanced disease.
• not indicated for acute bowel obstruction or perforation.

10. Colonic resections
 Incision: Liberal Midline incision
 Inspection & Palpation

11. Extent of colectomy
Dictated by the size and location of lesions, vascular and
lymphatic supply.

12. Right Hemicolectomy

13. Ileotransverse Bypass Anastomosis

14. Ileocolic anastomosis

15. Colocolic Anastomosis

16. Left Hemicolectomy

17. Colorectal Anastomosis

18. Complicated Cases of Colon CA
 Left colon Ca with Obstruction
 An emergency temporary transverse colostomy
 3-stage operation: Colostomy with mucous fistula
+/- tumor resection; Colostomy closure
 Single stage resection
 Provided on-table irrigation and lavage

19. Perforation with peritonitis
 Option 1: Laparotomy with definitive resection and anastomosis, if
possible, is performed.
 Peritoneal lavage with warm saline.
 Protective colostomy to protect an uncertain anastomosis is
advisable.
 Option 2: The proximal or both ends of the resection are brought
out as colostomy.
 Antibiotics

20. Perforation with abscess
 Drainage + Hemicolectomy
 Antibiotics

21. Self Expanding Metal Stents
 Palliation in patients unfit for surgery or with
metastatic disease
 First stage procedure before resection
 Complication:Stent migration or re-obstruction
(10%).

22. TEN SUGGESTIONS OF SURGERY FOR CARCINOMA
COLON-OPEN SURGERY
 1. Should mark the ostomy site preoperatively in cases of emergency
colectomy.
 2. Should give an adequate incision.
 3. Should explore the peritoneal cavity for metastasis.
 4. Should remove the growth with adequate resetion margins, with all groups
of regional nodes, fat fascia and lymphatics called en block resection-R-0
resection.
 5. Should do the resection without touching or handling the tumour- follow no
touch technique of Turnbull.

23.  6. Should divide the vascular pedicle first and should ligate the
vessels as high at the origin-High tie.
 7. Should ensure the cut ends bleed well before anastomosis.
 8. Should ensure there is no tension at the suture line.
 9. Should do one stage procedure in all elective cases resection and
anastomosis.
 10. Should consider temporary ileostomy after resection anastomosis
in obstructed colon cancer.

24. Enhanced Recovery Strategies
 NGTube not required for elective colectomies unless in
obstructed cases
 Improved nutrition pre-op by increasing carbohydrate
intake
 Laparoscopic > traditional/open surgery
 Early mobilization, Early feeds, Early recovery and Early
removal of catheters.

25. Complications
 Leak (fecal fistula)
 Bleeding
 Infection like intraperitoneal/pelvic abscess,
 Respiratory problems
 DVT
 Wound infection
 Burst abdomen

26. Pathologic report
Following parameters should be reported:
 Depth
 Number of LN evaluated
 Number of LN positive
 Status of margin: proximal, distal, and radial
 Grade
 LymphoVascular Invasion
 Perineural Invasion
 Extranodal tumor deposits

27. ADJUV
ANT THERAPY
BASIS
• Despite curative surgery many patients suffer tumor
recurrence leading to cancer related death
• Therefore there is a need of adjuvant therapy.
• Adjuvant therapy is indicated in T3-T4 & N+ disease (stage
II & III)

28. Stage I
• No adjuvant treatment
Stage II
• Role of adjuvant chemotherapy unclear
for stage II
 STAGE IIA:T3N0M0
 STAGE IIB:T4aN0MO
 STAGE IIC T4b N0M0
• Risk estimation

29. Who Needs Adjuvant Therapy in stage
II?
Indicated
pT4
Grade 3-4
LVI +
<12 L.N examined
indeterminate, close or +
margin
obstruction, perforation

30. Stage II
High Risk IIA& Stage IIB,IIC
• FOLFOX
• Cape-Ox
• flox
• Capecitabine
• 5FU + leucovorin.
Low Risk IIA
• Observation
• clinical trial.
• Capecitabine
• 5FU + leucovorin.

31. Stage III
Role of adjuvant chemotherapy established
Preferred
• FOLFOX
• CapeOx
Other option
• Flox
• Capecitabine
• 5FU plus leucovorin.

32. Adjuvant Chemotherapy
In Resected Colon Cancer

34. 1990 1993 1995 2005 2006 2007 2009 2011 2012
Pooled
analysis High
dose bolus
5FU/LV vs.
obs.
Bolus
5FU+Levamisole
vs. observation
Bolus 5FU+LV vs
MOF
Xeloda-ACT
similar OS/DFS less toxicity to Mayo regimen
Tegafur
Irinotecan with 5FU/LV:
No significant benefit.
Cetuximab with
FOLFOX
Bevacizumab with
FOLFOX
Cape-OX vs
FU/LV
1. Mayo Clinic: monthly bolus 5FU D1-D5
+LDLV
2. Roswell: weekly bolus 5FU+ HDLV
3. 5- FU/levamisole,
4. 5-FU/LV/ levamisole.
Overall survival similar, toxicity different Dec
neutropenia & mucositis, Increased diarrhoea
with weekly regimen
infusion 5FU/LV vs
bolus (Mayo)
Bolus 5FU/LV vs.
FLOX
Improve DFS
Oxalipl.with infusion
5FU/LV
improved DFS & OS

35. Conclusion:
Adjuvant therapy in stage III
colon cancer

36.  Indicated in stage III & High risk stage II
 FOLFOX or CapeOx are preferred regimen in stage III colon cancer
 Addition of oxaliplatin increased benefit :
i. FOLFOX is superior to5FU/LV therapy in stage III increased DFS & OS
ii. benefit for the addition of oxaliplatin to 5-FU/leucovorin in patients ≥ 70 not been
proven
iii. survival benefit has not been demonstrated in stage II colon cancer.
 Capecitabine/oxaliplatin is superior to bolus 5-FU/ leucovorin for stage III colon
cancer.
 Capecitabine equally effective to bolus 5-FU/LV

37. Among the various 5FU/LV regimen
• Schedule of 5-FU/LV administration does not affect efficacy, but
toxicities may be different
i. Mayo Clinic monthly regimen - more commonly associated with
leucopenia and stomatitis
ii. Roswell Park weekly regimen - more commonly associated with
diarrhea
iii. Infusional 5-FU/LV may have less toxicity vs. bolus
• Irinotecan no benefit the adjuvant setting
• No targeted agents are approved for use in the adjuvant setting

38. Adjuvant Radiation therapy in colon
cancer
Aim:
• tumor bed irradiation to decrease local failure.
• should be delivered in a highly conformal manner.

39. Rationale
 Local failure in colon cancer depends on stage & location
• anatomic constraints on radial resection margins,
• tumors adherent/ invading adjacent structures increases risk of LF
 LF high in ascending/descending colon :
• anatomically immobile,” limits wide surgical resection
 LF less in mid-sigmoid and mid-transverse colon:
• relatively “mobile,” with a wide mesentery, wide margins
 LF rates for caecal, hepatic/splenic flexure, proximal/distal sigmoid tumors are
variable,
• depending on amount of mesentery present, tumor extension, and adequacy of radial
margins.

40. INDICATIONS OF RT
Adjuvant tumor bed irradiation with concurrent 5-
FU–based chemotherapy should be considered for
patients with tumors
• invading adjoining structures: T4
• where incomplete resection is performed
• Complicated by perforation or fistula
Perez & Brady's Principles and Practice of
Radiation Oncology

41. Technique:
• Bowel preparation
• Positioning:
 Supine:
 Prone:
 lateral decubitus:
• Immobilization:
• Contrast: oral& iv
 Oral contrast aids in delineating small-bowel, may be useful to compare films in decubitus &
supine
positions to determine bowel shift
• Simulation- Conventional/CT
• CT based planning preferred:facilitate defining the tumor bed, beam orientation, and estimating the
volume of small bowel,kidney included within treatment fields

42. Target volume delineation
• TUMOR BED/TARGET
• Involved segment of colon and, when present, the adjacent structures to which it was
adherent or invading
• If adherent to partially resected organ→ whole organ has to be treated if within tolerance
• If adherent to structure (pelvic side wall, psoas, diaphragm) → 3-5 cm margins beyond
area of adherence
• Surgical clips aid in the identification of high-risk areas (i.e., positive margins) to assist in
target delineation
• The nodal basins in the mesentery beyond surgical margins are usually not treated
.However the final inclusion of local & regional nodal group is based on operative &
pathologic findings.

43. • MARGINS:
 Tumor bed covered with a 4- to 5-cm margin proximally and distally and
with a 3- to 4-cm margin
 Medially and laterally to cover areas of potential residual disease

44. FIELD ARRANGEMENT
• Field arrangement will vary, depending on the site of the
primary disease, as well as on areas judged to be at high risk for
local recurrence
• Parallel opposed or other multifield techniques are used to treat
target & spare OAR: small bowel, kidney, liver, S.C

45. PostoperativeAP-PAIrradiation Fields Of Extra pelvic
Colon Cancer (Tumor BedAnd Nodal Regions).
Para-aortic nodes may be at risk, due to
tumor adherence to posterior
abdominal wall with descending colon
External and common iliac nodes
may be at risk, from a proximal
ceacal/ascending colon cancer

46. Dose prescription
• total dose depends on the amount of suspected residual disease and
tolerance constraints of surrounding normal tissue.
• initial dose of 45 Gy/25 # at 1.8/# delivered through larger fields to
primary tumor and at-risk tissues followed by reduced boost fields.
• For patients with T4 tumors, the general goal is to treat the tumor bed to
a total dose of 50.4-54Gy
• Any treatment beyond 50 Gy generally mandates exclusion of all small
bowel from the field

47. Critical normal (dose limiting)
tissues
• Small intestine: 45-50 Gy
• Liver : 2/3rd of liver should get <30 Gy
• Kidneys: 2/3rd of one kidney should get
<20 Gy
• Spinal cord: max dose to spinal cord<
50 Gy

48. Surveillance for colon cancer
 History, physical examination & Serum CEA:
every 3–6 month for 2 y, then every 6 month for a total of 5 yrs.
Colonoscopy:
In 1st yr:
Abnormal repeat in one yr.
Normal: repeat in 3rd yr then every 5 yrs
If it was not done before: 3-6 months post surgery.
CT scan chest & abdomen:
Annually for pts. with high risk for recurrence(eg. LVI/PNI ,poorly
differentiated tumors

49. Treatment Options for Metastatic Colon Cancer (Stage IV)
with synchronous liver only or lung only metastases
1. For resectable lesions
 Colectomy with synchronous resection of liver or lung metastases followed by
adjuvant chemotherapy with FOLFOX or CapeOx
 Neoadjuvant CT to increase curative resection rates
1. For unresectable lesions
 Treated with chemotherapy and evaluated every 2 months to assess resectability of
liver and/or lung metastases,colon resection if risk of obstruction or significant
bleeding.
 Combination chemotherapy for 2-3 months followed by chemo-radiation with 5-FU
or capecitabine and then resection of metastases and primary

50. 3. For patients that are able to undergo resection of metastatic disease
 6 months of adjuvant therapy with an active regimen for advanced disease,
observation, or shortened course of palliative chemotherapy

51. Pts. with unresectable mCRC treated with BSC have poor prognosis( median
OS= 5 months). In contrast, pts. who receive CT have been shown to have a
median OS of ≈ 2 yrs.
Metastatic colon cancer: impact of chemotherapy

52. Targeted agents

53. • All patients with mCRC should have tumor tissue genotyped for RAS mutations
performed only in certified laboratories
• The testing can be performed on the primary colorectal cancers and/or the
metastasis
Cetuximab
• Cetuximab is monoclonal antibody against the epidermal growth factor receptor
(EGFR).
• Indicated in KRAS wild type ,EGFR expressing colon cancer
• can be added to either FOLFIRI or FOLFOX as first-line treatment of metastatic
colorectal cancer

54.  Panitumumab
• Indicated in wild type KRAS metastatic colorectal cancer
• The U.S. Food and DrugAdministration approved panitumumab for use in
patients with metastatic colorectal cancer refractory to FOLFIRI
chemotherapy
 Patients with any known KRAS mutation should not be treated with either
cetuximab or panitumumab

55. Bevacizumab
• monoclonal antibody that binds to vascular endothelial growth factor.
• can be added to either FOLFIRI or FOLFOX as first-line & second
line treatment of metastatic colorectal cancer
Aflibercept
• Aflibercept is anti-VEGF molecule
• evaluated as a component of second-line therapy in patients with
metastatic colorectal cancer
• use of FOLFIRI plus aflibercept is an acceptable second-line regimen
for patients previously treated with FOLFOX-based chemotherapy

56. Regorafenib
• Regorafenib is an inhibitor of multiple tyrosine kinase pathways
including VEGF, PDGF, FGFR, B-Raf, RET, KIT
• Indicated in metastatic colon cancer progressed to 5FU,oxaliplatin,
irinotecan & bevacizumab, aflibercept, cetuximab & panitumumab
based chemotherapy
• In September 2012, the FDA granted approval for the use of
regorafenib in patients who had progressed on prior therapy.

57. FOLLOW UP
 CEA every 3 month x 1st 3 yrs, than 6 monthly up to 5 yrs (CEA
detects 80% recurrence) and
 Complete physical examination on each Follow Up
• CECT whole abdomen yearly x 1st 3 yrs
• Colonoscopy every 3 to 5 yrs
• FDG-PET- rising CEA in two consecutive tests in absence of
imageable disease by CT
• Liquid Biopsy – CTCs, ctDNA, miRNAs, lncRNAs

58. RISING CEA
COLONOSCOPY
FDG-PET
NORMAL
CXR CECT

59. TAKE HOME MESSAGE
 SCREENING! SCREENING!! SCREENING!!!
 Screening saves lives
 ALL RECTAL BLEEDS MUST BE INVESTIGATED!
 NOT ALL RECTAL BLEEDS ARE HEMORRHOIDS
 Most people get screened because their doctor told them
to
 Advances in treatment have led to improved survival
 Advances in molecular profiling of cancers has led to
personalized treatments

60. References
 Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst 2001; 93:583.
 prospective random assignment trial conducted by Clinical Outcomes of Surgical Therapy (COST) Study Group A comparison of laparoscopically
assisted and open colectomy for colon cancer. N Engl J Med2004;350(20):2050–2059.
 Fleshman J, et al. Laparoscopic colectomy for cancer is not inferior to open surgery based on 5-year data from the COST Study Group trial. Ann
Surg2007;246(4):655–662; discussion 662–664.
 Bonjer HJ, et al. Laparoscopically assisted vs open colectomy for colon cancer: a meta-analysis. Arch Surg 2007;142(3):298–303.
 Jackson TD, et al. Laparoscopic versus open resection for colorectal cancer: a metaanalysis of oncologic outcomes. J Am Coll Surg 2007;204(3):439–446
 College ofAmerican Pathologists Consensus Statement NCCN 2015
 Atkin, G., Chopada, A. & Mitchell, I. Colorectal cancer metastasis: in the surgeon's hands?. Int Semin Surg Oncol 2, 5 (2005).
https://doi.org/10.1186/1477-7800-2-5
 Principles and Practice of Surgery by BADOE
 Manipal Manual of Surgery
 Schwartz Principles of surgery
 Agnew JL, Abbadessa B, Leitman IM. Strategies to evaluate synchronous carcinomas of the colon and rectum in patients that
present for emergent surgery. Int J Surg Oncol. 2013;2013:309439. doi: 10.1155/2013/309439. Epub 2013 Feb 6. PMID: 23476758;
PMCID: PMC3580935.


61. THANK YOU