1. Medical Management of Colorectal Cancer
Dr. Patricia Tang MD FRPCP
Southern Alberta GI Tumor Group Leader
Medical Oncologist
Tom Baker Cancer Centre

2. Faculty/Presenter Disclosure
Dr. Patricia Tang
Relationships with commercial interests:
Speakers Bureau/Honoraria: Roche, Sanofi, Amgen, Celgene

3. Colorectal Cancer

4. Epidemiology
4th most commonly diagnosed cancer in Canadians (22,000 new cases per year)
2nd leading cause of cancer death after lung cancer
lifetime risk of developing CRC is 1 in 18

5. What are risk factors for developing colorectal cancer?

6. Risk Factors for Colorectal Cancer (CRC)
age (>50)
lifestyle: diet (high calorie and fat, low fibre), smoking, alcohol, obesity
genetics (family Hx of CRC, FAP, HNPCC, MUTYH associated polyposis)
personal Hx of CRC or adenomas (esp. villous)
ulcerative colitis, Crohn’s disease
Prior abdominal or pelvic radiation

7. Patient Case 1

8. Presentation Next steps?
68 year old man presents to his family doctor with fatigue:
hemoglobin 100 (Normal Range = )
MCV 75 (Normal Range = )
Past Medical History
Diabetes Mellitus Type 2 on metformin
Hypertension on ramipril
Dyslipidemia on atorvastatin
ASA 81 mg / day
Next steps?

9. Diagnosis Physical examination is performed
Digital rectal exam reveals a palpable mass in the rectum
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10. Work up
Baseline laboratory work: CBC CR LYTES LFTS CEA, (INR if on warfarin)
Refer for urgent endoscopy: in Calgary, page the gastroenterologist on call at the nearest hospital (ROCA)

11. Diagnosis A gastroenterologist performs an urgent colonoscopy
a mass consistent with cancer that was near obstructing noted at 10 cm from anal verge

12. Diagnosis: Rectal Cancer
A biopsy of the mass was taken and sent to a pathologist who confirms moderately differentiated adenocarcinoma (up to 1 week)

13. Staging
Gastroenterologist receives the pathology report and orders a CT scan of the chest, abdomen and pelvis
CT scan: Rectal mass, otherwise, completely normal

14. Which has the highest risk of local recurrence?
Colon Cancer
Rectal Cancer
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15. Staging
If emergent surgery is not needed, the surgeon would order a MRI pelvis
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16. Preoperative “Neoadjuvant” Treatment
Locally advanced rectal adenocarcinomas (T3/4 or node positive on MRI) would be referred to the cancer centre for neoadjuvant chemoradiation
Goal: reduce local recurrence & shrink the tumor
Then surgery to cut out the cancer
Then further adjuvant chemotherapy
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17. Treatment: Chemoradiotherapy
Referred to the cancer centre to see a radiation oncologist and medical oncologist
Capecitabine (pills) given concurrently with radiation for 5 weeks
The patient has mild diarrhea and hand-foot syndrome
6-8 week wait prior to OR
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18. Treatment: Surgery
Surgery: low anterior resection with diverting loop ileostomy
Loose ileostomy output: metamucil, imodium, codeine
Ileostomy sometimes
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19. Lower tumors, Abdominoperineal resection: Permanent colostomy

20. An ostomy is life changing

21. Pathologic Staging
Pathologist evaluates the specimen, the tumor is staged at T3N1 (3 out of 20 lymph nodes)M0 Stage III
Referred back to the cancer centre for adjuvant chemotherapy and the patient receives 4 months of capecitabine
Physical &
CT scan
Stage I-III
Curative Intent

22. How you can help while the patient is on treatment
Past Medical History
Diabetes Mellitus Type 2 on metformin: if a patient receives IV chemo, we often worsen diabetic control
Backup plan for hyperglycemia
Chemo can cause nausea/vomiting: back up plan for poor oral intake
Hypertension on ramipril
Some patients lose weight, which treats their hypertension
May need adjustments
Dyslipidemia on atorvastatin: ongoing prescriptions for continuitiy
ASA 81 mg / day: This is fine. However, A fib requiring anticoagulation often requires LMWH, Novel anticoagulants controversial

23. Surveillance: Family Medicine
Loop ileostomy is reversed. Bowel function takes awhile to improve
Surveillance:
CEA (blood test) q 3 mo x 3 yrs then q6 months x 2 yrs
physical exam q6 mo x 3 yrs then annually
CT Chest abdomen pelvis annually x 3 years
colonoscopy within 6-12 mos of surgery then q3-5 years
What are common places of metastases?
Ask Mr. Leaper what it was like
How is the venous drainage of the rectum different from the colon?

25. Surveillance: Family Medicine
Intensive surveillance in colorectal cancer has been shown to improve survival since isolated liver and/or lung metastases can be resected and patients can still be cured
5 year Overall Survival 40%

26. Approach to a Rising CEA
Repeat CEA, if still > 5, physical exam
CT chest abdomen pelvis
If resectable metastasis, send to appropriate surgeon (Thoracics or Hepatobiliary)
If normal, colonoscopy
Send back to medical oncology/Call the original medical oncologist
fax , May need a biopsy
Thoracic Oncology Program for lung/mediastinal LN

27. Metastatic Colorectal Cancer
Small pulmonary nodule seen in right lung on the CT scan suggestive of recurrent cancer (metastasis)
Thoracic surgeon
Resects the cancer
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28. Treatment of Resectable Metastatic CRC
Pathology from the lung surgery revealed a 1 cm focus of metastatic rectal adenocarcinoma
Started on “adjuvant” FOLFOX chemotherapy for 6 months
At 5 years the CT scan was clear and the patient’s intensive surveillance was discontinued
Ask Mr. Leaper what it was like

29. What are the current colorectal cancer screening guidelines?

30. Screening for CRC
beginning at age 50, all patients should have one of the following screening tests for CRC:
FOBT q1year
flexible sigmoidoscopy q5years
double-contrast barium enema q5years
colonoscopy q10years
any positive or abnormal test should be followed up with colonoscopy

31. Screening for CRC Lynch: Dr. W D Buie and Dr Bellutruti

32. Clinical Presentation of CRC
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33. Clinical Presentation
abdominal pain
bowel change (diarrhea, constipation, pencil stools, tenesmus)
hematochezia
weight loss
fatigue
iron-deficiency anemia
bowel obstruction
elevated liver enzymes (liver mets)

34. Diagnostic Approach CBC, lytes, BUN, Cr, liver enzymes & LFTs, CEA
CT chest/abdomen/pelvis
colonoscopy (tissue diagnosis)
liver lesions: may need extra imaging such as ultrasound and/or MRI
rectal lesions: endoscopic ultrasound and/or MRI

35. TNM Staging

36. Colon Cancer Treatment
Stage
Treatment
5 year Overall Survival
I: T1-2 N0
Surgery
93%
II: T3 N0
T4 N0
Adjuvant chemotherapy for high risk
72%
85%
IIIA: T1-2N0
IIIB: T3-4N1
IIIC: T1-4N2
64%
44%
IV: Distant Metastases
Chemotherapy if well enough
Select patients may be eligible for Metastatectomy
10%
40%

37. Treatment after surgery for Stage II Colorectal Cancer
surgical resection
adjuvant chemotherapy can be considered for patients with tumours exhibiting high-risk features: T4
poorly differentiated histology
lymphovascular or perineural invasion
inadequately sampled lymph nodes (<13)
clinical bowel perforation
clinical bowel obstruction

38. Treatment of Stage II Colon Cancer
adjuvant chemotherapy for resected stage II CRC is controversial since many studies have only shown trends towards a survival benefit
if a survival benefit exists it is likely 2% to 3% at 5 years and 5Y-OS in stage II CRC with surgery alone is 75%

39. Treatment of Stage III Colon Cancer
surgical resection
adjuvant chemotherapy recommended for all patients
5-fluorouracil (5-FU) + folinic acid x 6 months has been shown in a number of phase III trials to increase 5Y-OS by 5% to 15% in stage III CRC (5Y-OS with surgery alone 30% to 80%)

40. Treatment after surgery for Stage III Colorectal Cancer
FOLFOX is the standard of care for adjuvant treatment of stage III CRC and improves 5 year survival by 10% to 20% compared to no further chemotherapy
Can cause chronic peripheral neuropathy
Painful neuropathy can be helped with Duloxetine
capecitabine has been shown to be equivalent to 5-FU/LV and is routinely used for patients who cannot tolerate oxaliplatin (FOLFOX) or those who prefer oral chemotherapy

41. Patient Case 2
55 year old post-menopausal woman presents with fatigue, 20 lb un-intentional weight loss, and progressively narrow stool caliber

42. Approach
History
Physical Exam
Labwork

43. Results
Hb 75, MCV 72
ALT is 1.5 x upper limit of normal (it was normal last year)

44. Results
U/S Abdomen shows innumerable liver metastases
Next step

45. Patient Case
CT chest abd pelvis: innumerable liver and lung metastases
Refer to GI for urgent scope
Non-obstructing mass in the sigmoid colon
Pathology: adenocarcinoma
GP refers to cancer centre for further management

46. Stage IV CRC
cancer has spread outside of colon or rectum to other areas of body
stage IV cancer is usually treated with chemotherapy alone
surgery to remove the primary tumor may be done
additional surgery to remove metastases may also be done in carefully selected patients
ASCO Colorectal Slide Deck 2008

47. Treatment of Metastatic CRC
Median Survival (Months)
Best Supportive Care 6
5-fluorouracil (60’s) + leucovorin (80’s)
IFL (irinotecan/5-FU/LV) (2000) 15
FOLFIRI (irinotecan/5-FU/LV) (2000) 17
FOLFOX (oxaliplatin/5-FU/LV) (2000) 20
FOLFIRI  FOLFOX (2004) 21
IFL + bevacizumab (2007) 20
FOLFIRI + cetuximab (2009) 24
FOLFIRI or FOLFOX + bevacizumab 29
or cetuximab (2014)

48. Chemotherapy: 5-fluorouracil
Benefits: can shrink the cancer, delay time to progression and improve survival time
Potential Toxicities:
myelosuppression  febrile neutropenia
rash, photosensitivity
diarrhea
fatigue
coronary vasospasm/chest pain (rare)
* low rates of nausea and vomiting
* rare hair loss

49. Chemotherapy: Oxaliplatin
Benefits: can shrink the cancer, delay time to progression and improve survival time
Potential Toxicities:
Myelosuppression  febrile neutropenia
cold-induced dysesthesia
peripheral neuropathy
infusion reaction
* moderate rates of nausea and vomiting
* can have hair thinning

50. Metastatic CRC May Be Curable
selected patients with oligometastatic disease isolated to liver and/or lung
refer to hepatobiliary surgeon or thoracic surgeon for opinion regarding metastectomy
refer to medical oncologist for perioperative chemotherapy
in case series where patients had liver metastasis resection:
5Y-OS = 40%, 10Y-OS = 20%

51. Scenario 1 You are a family doctor
You order a FIT test on your 51 year old female patient as part of routine screening
It comes back POSITIVE
Next step:
Refer to the cancer centre
Refer to surgeon
Refer for colonoscopy

52. Scenario 2 You are an Emergency Room doctor
A patient presents with a bowel obstruction, CT shows a mass suggestive of cancer in the colon that is obstructing, one mass in the liver suggestive of a metastasis
Next step:
Refer to the cancer centre because the CT is suggestive of cancer
Refer to surgery because the patient is obstructed

53. Proposed Rectal Cancer Pathway
Rectal Cancer Clinical Pathway – Standards of Care
Proposed Rectal Cancer Pathway
No neoadjuvant therapy for colon

54. In Summary colorectal cancer (CRC) is a common disease
screen for CRC in general population age ≥50
surgical resection for cure in stage I-III CRC
adjuvant chemotherapy (5-FU, capecitabine, FOLFOX) increases overall survival in stage III CRC and possibly in high-risk stage II

55. In Summary
oligometastatic CRC isolated to the liver and/or lungs can be resected for chance at cure in selected patients
modern chemotherapy and biologic therapy are effective and generally well-tolerated palliative treatments for metastatic CRC
median survival for patients with metastatic CRC with treatment is now >2 years

56. Questions??? http://whatnow.atlargecommunications.com/
Above website will be eventually migrated to Cancerwhatnow.com