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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 – – – – 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 Copyright unknown 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 Copyright unknown Staging • If emergent surgery is not needed, the surgeon would order a MRI pelvis Copyright unknown 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 Copyright unknown 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 Copyright unknown Treatment: Surgery • Surgery: low anterior resection with diverting loop ileostomy • Loose ileostomy output: metamucil, imodium, codeine Ileostomy sometimes Copyright unknown 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 Copyright unknown 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 Copyright unknown 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 • • • • • • • • • 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