Medical Management of Medical Management of Colorectal CancerColorectal Cancer

Dr. Patricia Tang MD FRPCPSouthern Alberta GI Tumor Group Leader

Medical OncologistTom Baker Cancer Centre

Faculty/Presenter Disclosure

Dr. Patricia Tang

Relationships with commercial interests:

Speakers Bureau/Honoraria: Roche, Sanofi, Amgen, Celgene

Colorectal CancerColorectal 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 1Patient 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– 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

• A biopsy of the mass was taken and sent to a pathologist who confirms moderately differentiated adenocarcinoma (up to 1 week)

Diagnosis: Rectal Cancer

http://www.proteinatlas.org/dictionary/cancer/colorectal+cancer/detail+1

• Gastroenterologist receives the pathology report and orders a CT scan of the chest, abdomen and pelvis

• CT scan: Rectal mass, otherwise, completely normal

Staging

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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• 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

Treatment: Chemoradiotherapy

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• Surgery: low anterior resection with diverting loop ileostomy

• Loose ileostomy output: metamucil, imodium, codeine

Treatment: Surgery

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Lower tumors, Abdominoperineal resection: Permanent colostomy

An ostomy is life changing

• 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

Pathologic Staging

Stage I-IIICurative Intent

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

• 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

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

• Small pulmonary nodule seen in right lung on the CT scan suggestive of recurrent cancer (metastasis)

Thoracic surgeonResects the cancer

Metastatic Colorectal Cancer

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• 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

Treatment of Resectable Metastatic CRC

What are the current colorectal cancer screening guidelines?

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

http://www.topalbertadoctors.org/download/301/colorectal_summary.pdf?_20150805182214

http://www.screeningforlife.ca/

Screening for CRC

http://www.topalbertadoctors.org/download/301/colorectal_summary.pdf?_20150805182214

Lynch: Dr. W D Buie and Dr Bellutruti

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

SurgeryAdjuvant chemotherapy for high risk

72%85%

IIIA: T1-2N0IIIB: T3-4N1IIIC: T1-4N2

SurgeryAdjuvant chemotherapy for high risk

72%64%44%

IV: Distant Metastases Chemotherapy if well enough

Select patients may be eligible for Metastatectomy

10%

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

ASCO Colorectal Slide Deck 2008

• 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

Treatment of Metastatic CRC

• Best Supportive Care 6• 5-fluorouracil (60’s) + leucovorin (80’s) 8 - 12• 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)

Median Survival (Months)

• 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: 5-fluorouracil

• 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

Chemotherapy: Oxaliplatin

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 centreb. Refer to surgeonc. 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 cancerb. Refer to surgery because the patient is obstructed

Proposed Rectal Cancer PathwayRectal Cancer Clinical Pathway – Standards of Care

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/

•

patricia.tang@albertahealthservices.ca

http://www.albertahealthservices.ca/info/cancerguidelines.aspxhttp://www.bccancer.bc.ca/health-professionals/professional-

resources/cancer-management-guidelines