Transcript Colorectal Cancer

Medical Management of
Colorectal Cancer
Dr. Patricia Tang MD FRPCP
Southern Alberta GI Tumor Group Leader
Medical Oncologist
Tom Baker Cancer Centre
Faculty/Presenter Disclosure
Dr. Patricia Tang
Relationships with commercial interests:
Speakers Bureau/Honoraria: Roche, Sanofi, Amgen,
Celgene
Colorectal Cancer
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
What are risk factors for
developing colorectal cancer?
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
Patient Case 1
Presentation
• 68 year old man presents to his family doctor with
fatigue:
– hemoglobin 100 (Normal Range = 137-180)
– MCV 75 (Normal Range = 82-100)
• Past Medical History
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Diabetes Mellitus Type 2 on metformin
Hypertension on ramipril
Dyslipidemia on atorvastatin
ASA 81 mg / day
• Next steps?
Diagnosis
• Physical examination is performed
• Digital rectal exam reveals a palpable mass in
the rectum
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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)
Diagnosis
• A gastroenterologist performs an urgent
colonoscopy
http://www.cancercare.ns.ca/en/home/preventionscreening/coloncancerprevention/faq.aspx
Diagnosis: Rectal Cancer
• A biopsy of the mass was taken and sent to a
pathologist who confirms moderately
differentiated adenocarcinoma (up to 1 week)
http://www.proteinatlas.org/dictionary/cancer/colorectal+cancer/detail+1
Staging
• Gastroenterologist receives the pathology
report and orders a CT scan of the chest,
abdomen and pelvis
• CT scan: Rectal mass, otherwise, completely
normal
http://www.radiologyinfo.org/en/photocat/gallery3.cfm?image=abdo-ct-ped.jpg&pg=abdominct
Which has the highest risk of local recurrence?
Colon Cancer
Rectal Cancer
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Staging
• If emergent surgery is not needed, the
surgeon would order a MRI pelvis
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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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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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Treatment: Surgery
• Surgery: low anterior resection with diverting
loop ileostomy
• Loose ileostomy output: metamucil, imodium,
codeine
Ileostomy sometimes
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Lower tumors, Abdominoperineal
resection: Permanent colostomy
An ostomy is life changing
Pathologic Staging
• Pathologist evaluates the specimen, the tumor is staged
at T3N1 (3 out of 20 lymph nodes)M0 Stage III
Stage I-III
Curative Intent
Physical &
CT scan
• Referred back to the cancer centre for adjuvant
chemotherapy and the patient receives 4 months of
capecitabine
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
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?
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%
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 403-521-3245, May need a biopsy
• Thoracic Oncology Program for lung/mediastinal LN
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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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
What are the current colorectal
cancer screening guidelines?
Screening for CRC
http://www.screeningforlife.ca/
• 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
http://www.topalbertadoctors.org/download/301/colorectal_summary.pdf?_20150805182214
Screening for CRC
Lynch: Dr. W D Buie and Dr Bellutruti
http://www.topalbertadoctors.org/download/301/colorectal_summary.pdf?_20150805182214
Clinical Presentation of CRC
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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)
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
Colon Cancer Treatment
Stage
Treatment
5 year Overall Survival
I: T1-2 N0
Surgery
93%
II: T3 N0
T4 N0
Surgery
72%
Adjuvant chemotherapy for 85%
high risk
IIIA: T1-2N0
IIIB: T3-4N1
IIIC: T1-4N2
Surgery
72%
Adjuvant chemotherapy for 64%
high risk
44%
IV: Distant Metastases
Chemotherapy if well
enough
10%
Select patients may be
eligible for Metastatectomy
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
Patient Case 2
• 55 year old post-menopausal woman presents
with fatigue, 20 lb un-intentional weight loss,
and progressively narrow stool caliber
Approach
• History
• Physical Exam
• Labwork
Results
• Hb 75, MCV 72
• ALT is 1.5 x upper limit of normal (it was
normal last year)
Results
• U/S Abdomen shows innumerable liver
metastases
• Next step
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
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
Treatment of Metastatic CRC
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Median Survival (Months)
Best Supportive Care
5-fluorouracil (60’s) + leucovorin (80’s)
IFL (irinotecan/5-FU/LV) (2000)
FOLFIRI (irinotecan/5-FU/LV) (2000)
FOLFOX (oxaliplatin/5-FU/LV) (2000)
FOLFIRI  FOLFOX (2004)
IFL + bevacizumab (2007)
FOLFIRI + cetuximab (2009)
FOLFIRI or FOLFOX + bevacizumab
or cetuximab (2014)
6
8 - 12
15
17
20
21
20
24
29
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
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
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%
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:
a. Refer to the cancer centre
b. Refer to surgeon
c. Refer for colonoscopy
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:
a. Refer to the cancer centre because the CT is suggestive
of cancer
b. Refer to surgery because the patient is obstructed
Rectal Cancer Clinical Pathway – Standards of Care
Proposed Rectal Cancer Pathway
No neoadjuvant therapy for colon
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
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
Questions???
• http://whatnow.atlargecommunications.com/
• Above website will be eventually migrated to
Cancerwhatnow.com
• http://www.colorectal-cancer.ca/en/ostomy/
[email protected]
•
http://www.albertahealthservices.ca/info/cancerguidelines.aspx
http://www.bccancer.bc.ca/health-professionals/professionalresources/cancer-management-guidelines