1. Aakash H. Gajjar, MD, FACS Assistant Professor of Surgery Colon & Rectal Surgery University of Texas Medical Branch Galveston, Texas February 10 th, 2014 The ‘Ins & OUTS’ of ColoRECTAL Cancer

2. Homer ’ s Odyssey Homer.mov

3. ANATOMY

4. WHAT IS CANCER? Cells that become abnormal and divide without control -> growth -> tumor Colon and Recal Cancer (CRC) is the 3 rd most common cancer Prostate and lung in men; breast and lung in women WHO IS AT RISK? Age Personal history of polyps or cancer Family history Inflammatory Bowel Disease (IBD) Diet (red and processed meats & low fruits, grains and vegetables), Smoking, Lack of Exercise

5. Adenoma–Carcinoma Sequence

7. COLON & RECTAL CANCER INCIDENCE UNITED STATES in 2010 New cases: 102,900 (colon); 39,670 (rectal) (Total: 142,570) Deaths: 51,370 (colon and rectal combined) 2004-2008: average age of diagnosis : 70 years (SEER database) 0.1% under 20 1.1% ages 20-34 3.9% ages 35-44 12.8% ages 45-54 19.6% ages 55-64 1% ages 65-74 26.2% ages 75-84 12.2% ages 85+

8. COLON & RECTAL CANCER MORTALITY UNITED STATES in 2010 New cases: 102,900 (colon); 39,670 (rectal) (Total: 142,570) Deaths: 51,370 (colon and rectal combined) 2003-2007: average age at death : 75 years (SEER database) 0.0% under 20 0.6% ages 20-34 2.4% ages 35-44 8.1% ages 45-54 15.6% ages 55-64 22.2% ages 65-74 30.4% ages 75-84 20.6% ages 85+

9. COLORECTAL CANCER TREND IN UNITED STATES

10. SCREENING OPTIONS Digital Rectal Exam (DRE) Fecal Occult Blood Test (FOBT) Sigmoidoscopy Colonoscopy Virtual colonoscopy (computerized tomographic colonography) Double Contrast Barium Enema (DCBE) ABNORMAL COLONOSCOPY? -> REFERRAL TO SURGEON Staging work-up Carcinoembryonic antigen (CEA)

11. STAGING SYSTEM - TNM T = Tumor (penetration of tumor in wall)T1, T2, N0, M0 = Stage I N = Node Status (any spread to lymph nodes)T3, T4, N0, M0 = Stage II M = Metastasis (spread to any other organ)Any N, M0 = Stage III Any M = Stage IV

12. COLON CANCER

13. COLON CANCER STAGING VS. SURVIVAL

14. HOW ARE COLON AND RECTAL CANCER TREATED? DIFFERENTLY, BUT….SIMILARLY…How can that be? 2 FLAVORS Colon Cancer – staging (CT) Surgery (open vs. laparoscopic) Adjuvant chemotherapy (after surgery) based on stage (III and IV) Stage II – remains controversial - American Society of Clinical Oncology does not recommend adjuvanct chemotherapy, however, may recommend if inadequate node sampling, T4 lesions, perforation, or poorly differentiated.

15. SURGICAL OPTIONS

16. HOW ARE COLON AND RECTAL CANCER TREATED? Rectal Cancer – staging (US, MRI, CT) +/- Neoadjuvant chemo/radiation (before surgery) based on stage (Stage II, III) Improves local control, disease-free survival, and overall survival Swedish Rectal Cancer Trial – pre-op XRT or no XRT? showed pre-op XRT had improvement in local control (89% vs. 73%) and overall survival (58% vs. 48%) European Trial – Preop XRT or Preop chemo/XRT? Combined had lower recurrence rate (8.1% vs 16.5%) Similar 5-year overall survival German Rectal Cancer Trial – pre-op chemo/XRT or post-op chemo/XRT? - T3/T4, or +N Pre-op chemo/XRT had lower local recurrence (6% vs 13%) Same 5-year disease-free and overall survival rates

17. HOW ARE COLON AND RECTAL CANCER TREATED? Surgery (open vs. laparoscopic) – LOCATION, LOCATION, LOCATION… TAE (TransAnal Excision) – T1 lesions LAR (Low Anterior Resection) APR (Abdominal Perineal Resection) Adjuvant chemo/radiation (after surgery) based on final pathology

18. DRUGS APPROVED FOR COLON CANCER Adrucil (Fluorouracil) Avastin (Bevacizumab) Bevacizumab Camptosar (Irinotecan Hydrochloride) Capecitabine Cetuximab Efudex (Fluorouracil) Eloxatin (Oxaliplatin) Erbitux (Cetuximab) Fluoroplex (Fluorouracil) Fluorouracil FOLFIRI FOLFOX Irinotecan Hydrochloride Leucovorin Calcium Oxaliplatin Panitumumab Vectibix (Panitumumab) Wellcovorin (Leucovorin Calcium) Xeloda (Capecitabine) Adrucil (Fluorouracil) Avastin (Bevacizumab) Bevacizumab Camptosar (Irinotecan Hydrochloride) Capecitabine Cetuximab Efudex (Fluorouracil) Eloxatin (Oxaliplatin) Erbitux (Cetuximab) Fluoroplex (Fluorouracil) Fluorouracil FOLFIRI FOLFOX Irinotecan Hydrochloride Leucovorin Calcium Oxaliplatin Panitumumab Vectibix (Panitumumab) Wellcovorin (Leucovorin Calcium) Xeloda (Capecitabine)

19. DRUGS APPROVED FOR RECTAL CANCER Adrucil (Fluorouracil) Avastin (Bevacizumab) Bevacizumab Camptosar (Irinotecan Hydrochloride) Cetuximab Efudex (Fluorouracil) Erbitux (Cetuximab) Fluoroplex (Fluorouracil) Fluorouracil FOLFIRI FOLFOX Irinotecan Hydrochloride Panitumumab Vectibix (Panitumumab) Adrucil (Fluorouracil) Avastin (Bevacizumab) Bevacizumab Camptosar (Irinotecan Hydrochloride) Cetuximab Efudex (Fluorouracil) Erbitux (Cetuximab) Fluoroplex (Fluorouracil) Fluorouracil FOLFIRI FOLFOX Irinotecan Hydrochloride Panitumumab Vectibix (Panitumumab)

20. COMMON CHEMOTHERAPEUTIC REGIMENS 5-FU w/ Levamisole (gold standard until 1996) – Stage III/IV  recurrence 41%,  death 31% 5-FU w/ Leucovorin (increased overall survival 78% to 83%) Oxaliplatin (FOLFOX, XELOX) (MOSAIC Trial – compared to 5-FU/Leucovorin) – 1 st line Irinotecan (FOLFIRI, IFL, IROX) (FOLFOX > FOLFIRI) – 2 nd line Bevacizumab (AVASTIN®) – Stage IV- 1 st biologic- blocks angiogenesis Cetuximab (ERBITUX®) – Stage IV NOT WITHOUT THEIR OWN COMPLICATIONS!!!! DECISION IS BASED ON AN INDIVIDUAL BASIS based on overall health. RISKS vs. BENEFITS (diarrhea, nausea, emesis, alopecia, neutropenia, neuropathy) – 50% will not complete treatment

21. SUMMARY Based on rates from 2005-2007, ~5% of men & women born today will be diagnosed with CRC sometime during their lifetime. (1 in 20 individuals in this room) Screening is extremely important for prevention of colon or rectal cancer Colon Cancer is Detectable, Treatable, and Beatable Be proactive regarding your health – you only have one life

22. ADDITIONAL INFORMATION http://www.cancer.gov/cancertopics/types/colon-and-rectal http://seer.cancer.gov/