UPDATE IN THE MANAGEMENT AND TREATMENT OF

Edwin A. Empaynado, MD Advocare Colon and Rectal Surgical Specialists  WHAT IS COLON CANCER?

 WHAT CAUSES COLORECTAL CANCER?

 WHAT ARE THE RISK FACTORS

 SYMPTOMS

 DIAGNOSIS AND SCREENING

 STAGING OF COLON CANCER

 MEDICAL AND SURGICAL TREATMENT

 SURVIVORSHIP AND FOLLOW-UP

PREVIEW OF PRESENTATION Common Types Estimated New Estimated Rank HOW COMMON IS of Cancer Cases 2018 Deaths 2018 Breast Cancer COLORECTAL 1. 266,120 40,920 (Female) CANCER? Lung and 2. Bronchus 234,030 154,050 Cancer 3. Prostate Cancer 164,690 29,430 3rd most common cause of Colorectal 4. 140,250 50,630 Cancer cancer in men and women of Melanoma of the U.S. or 8.1% of all new 5. 91,270 9,320 the Skin cancer cases in 2018 6. Bladder Cancer 81,190 17,240

Non-Hodgkin 7. 74,680 19,910 Lymphoma 2nd leading cause of cancer Kidney and 8. Renal Pelvis 65,340 14,970 death among men and Cancer women of the U.S. or 8.3% of all 9. Uterine Cancer 63,230 11,350 cancer deaths in 2018 10. Leukemia 60,300 24,370

1 National Cancer Institute WHAT AGE GROUP GETS COLORECTAL CANCER?

Median age at diagnosis is 67

NCI, SEER 18 2011-2015 WHO DIES FROM COLORECTAL CANER?

Median age at death 73 Rates of newly diagnosed cases of CRC have been decreasing 2.6% per year over past 10 years

Rates of death from CRC cases have been decreasing 2.4% per year over past 10 years

TRENDS IN NEW CASES OF COLORECTAL CANCER AND DEATH RATES

NCI, SEER 9 1975-2015 TRENDS IN SURVIVAL RATES FOR COLORECTAL CANCER

Percent surviving past 5 years from diagnosis of CRC 64.5

NCI, SEER 1975-2010 Population Health Data from 2013-2015

 34.4/100,000 new cases diagnosed per year

 14.5/100,000 number of deaths per year

 4.5% lifetime risk of being diagnosed with colorectal cancer

 1,332,085 people diagnosed with CRC in U.S. in 2015

PREVALENCE OF COLORECTAL CANCER

1 National Cancer Institute WHAT IS COLON CANCER?

• Carcinoid tumors • Gastrointestinal stromal tumors (GIST) • Lymphomas • Sarcomas • Metestatic tumors (ie – endometrial, ovarian, melanoma, etc.) • Adenocarcinoma – 96% of all colorectal cancers

Cancer cells that arise from adenomatous polyps of mucous producing cells that normally help lubricate the inside lining of the colon and

Cancers can be caused by changes in the DNA inside our cells called DNA mutations

These mutations leads to uncontrolled cell growth and the development of cancerous tumors

Inherited gene mutations occurs in about 10% cases

Acquired gene mutations most common cause of CRC where a person acquires a mutation during a lifetime rather than inherited.

WHAT CAUSES COLORECTAL CANCER? SYMPTOMS OF  A change in bowel habits COLORECTAL CANCER  Rectal bleeding or blood in your stool

 Abdominal discomfort and/or fullness that persists or recurs

 Feelings of incomplete evacuation

 Progressive weakness or fatigue

 Unexplained weight loss

 Anemia on recent bloodwork  STOOL-BASED TESTS SCREENING FOR COLORECTAL CANCER  Highly sensitive fecal immunochemical test (FIT) every year

 Highly sensitive guaiac-based fecal American Cancer Society (ACS) occult blood test (gFOBT) every year recommends average risk screening for CRC to start at age 45 through to  Multi-targeted stool DNA test (MT-sDNA) age 75 at 10 year intervals every 3 years Ages 76 through 85 screening is based  VISUAL EXAMS OF THE COLON AND RECTUM on overall medical health and patient preferences  every 10 years

 CT colonoscopy () People over 85 should no longer get every 5 years colorectal screening

 Flexible (FSIG) every 5 years

2 American Cancer Society Average risk patients DO NOT have the following

 Personal history of colorectal cancer or colon polyps

 Family history of colorectal cancer

 Personal history of inflammatory bowel WHAT IS AVERAGE RISK disease SCREENING?

 A confirmed hereditary colorectal cancer syndrome

 Personal history of abdominal and/or pelvic radiation to treat prior cancer WHAT ARE THE RISK  Older age FACTORS FOR COLORECTAL CANCER?  African-American race  Personal history of colorectal cancer or polyps Crohn’s Disease  Inflammatory intestinal conditions  Inherited syndromes Lynch Syndrome  Family history of colon cancer Familial Adenomatous Polyposis (FAP)  Low-fiber, high fat diet  Sedentary lifestyle  Diabetes  Obesity  Smoking  Alcohol  Radiation therapy for cancer Patients at increased risk for SCREENING FOR PEOPLE colorectal cancer may need WHO ARE AT HIGHER RISK? screening prior to age 45 and screened at more frequent intervals with colonoscopy

 Strong family history of colon cancer or Start screening prior to age 45 polyps

 Personal history of colon cancer and/or Consider more frequent polyps screening, ie- every 3 to 5 years

 Personal history of inflammatory bowel Screening at earlier age disease and every 1 to 2 years

 Known family history of hereditary colorectal Start as early as teenage years with cancer syndrome more frequent intervals  Personal history of abdominal and/or pelvic radiation for treatment of prior cancer Earlier age of screening and every 3 to 5 years  PROS SCREENING MODALITIES • Stool collection can done at home Highly sensitive fecal immunochemical test (FIT) • No prep required

• No need for sedation

 CONS

• Fails to detect some polyps and cancers

• Certain foods and medications may need to be avoided

• If positive, additional tests are needed to determine the source

• False-positive results Check stool samples for hidden (occult) blood. Test is done annually  PROS SCREENING MODALITIES • Does not require a bowel prep Multi-targeted stool DNA test • You can eat, drink and take your (MT-sDNA) medications as usual before the test

• Stool collection done at home to avoid disruption of your daily routine

 CONS

• DNA stool test is less sensitive than colonoscopy at detecting precancerous polyps

• If abnormal, additional tests would be needed Stool sample is used to look for DNA • False-positive rates as high as 10-15% changes that would suggest the presence of colon cancer or precancerous conditions. Repeated every 3 years.  PROS • Sedation is not required • Less extensive bowel prep requirement SCREENING MODALITIES Flexible sigmoidoscopy (FSIG) • Biopsies and/or other therapies can be performed through the scope

 CONS • Upper colon abnormalities are not seen • An enema prep is usually required • You may need to change your diet and/or medication prior to test • Rare complication of bowel injury and/or bleeding can occur • Cramping and bloating after exam Tiny video camera that allows visualization of the rectum and lower part of the colon (sigmoid colon). Repeated every 5 years  PROS

• Test does not require sedation or insertion of SCREENING MODALITIES a scope into the rectum CT colonoscopy (virtual colonoscopy)  CONS

• Requires a thorough bowel cleansing before the test

• May not detect small polyps or cancers

• Dietary and/or medication changes would be required

• Radiation exposure

• Purely diagnostic procedure; abormal findings would need colonoscopy follow-up

• Cramping and bloating CT scan produces initial cross-section images of abdominal organs that can be reconstructed in 3D images by a computer to detect abnormalities. Repeated every 5 years.  PROS • The most sensitive test currently available for SCREENING colon cancer screening. MODALITIES • Visualize the entire colon Colonoscopy • Abnormal tissues can be biopsied and/or removed through the scope  CONS

• Thorough bowel cleansing is required before the test • Diet changes are required and medications may need to altered • Sedation is usually required and would require someone to take you home • Rare complication of bowel injury and/or bleeding from therapeutic sites • Cramping and bloating after procedure Flexible tube with fiberoptic video camera is inserted into the rectum to detect abnormalities. Repeated every 10 years. SHAPE o PEDUCULATED o SESSILE o SEMI-PEDUCULATED CELL PATTERN  TUBULAR  VILLOUS  TUBULOVILLOUS  HYPERPLASTIC DYSPLASIA  SERRATED  LOW-GRADE DYSPLASIA

 HIGH-GRADE ADENOMATOUS POLYPS DYSPLSIA Polyps are tissue growth from the inner lining of the colon that can be benign (non-cancerous) or grow into cancers (precancerous). Adenomatous feature is a description of a cell when viewed under a microscope that is different from normal cell appearance. DIFFERENTIATION

 WELL DIFFERENTIATED

 MODERTELY DIFFERENTIATED

 POORLY DIFFERENTIATED

HISTOLOGY INVASION  MUCIN PRODUCING  SIGNET-CELL  VASCULAR

 LYMPHATIC

 LYMPHOVASCUALR INVASIVE ADENOCARCINOMA Adenocarinoma is a type of cancer from cells that form mucous producing glands lining the colonic wall. Invasive is a cell description suggesting spread beyond the inner lining of the colon.

PRE-OP o < 5ng/mL STAGING TESTS o Can be higher in smokers  Radiographic staging of tumor

 Helps determine chemotherapy and/or radiation treatment plans

 Assess tumor resectability  Carcinoembryonic Antigen Test (CEA)  CT scan  3T MRI  TransRectal UltraSound (TRUS)  PET/CT Scan  85% of patients who present with colonic obstruction have CRC

 Only 40% of patients with obstructing left-sided colon cancer can be resected without the need of a

 Stent placement provides an effective solution to acute colonic obstruction

 Allows for bridge to elective and more favorable operative conditions

 Palliative treatment for advanced stage colon cancer

TREATMENTS AND COLONIC STENTING Open Segmental colon resection

Proximal diverting colostomy

Laparoscopic colon resection

Robotic colon resection

Transanal full-thickness excision

Transanal Endoscopic Microsurgery (TEM)

TREATMENTS SURGERY PRIMARY CURATIVE TREATMENT  Segmental colon resection  En bloc resection for negative radial margin  Complete mesenteric lymph node resection  High ligation of mesenteric pedicle  Minimum 13 lymph nodes in specimen  Total mesorectal excision  Adequate tissue margin  5cm proximal and distal margins in colon cancer  1cm for sphincter-saving resection in rectal cancer

TREATMENT ONCOLOGIC GOALS OF RESECTION  The weed

 Scan the lawn for other weeds

 Pull by the roots

 Normal turf around the weed

 Addition of fertilizer with weed killer  WHEN IS CHEMOTHERAPY GIVEN? TREATMENTS  Adjuvant chemo is given after surgery. The goal CHEMOTHERAPY is to target small cancer cells throughout the body and help reduce recurrent cancer rates . 5-Fluorouracil (5-FU)

 Neoadjuvant chemo is given before surgery, . Capecitabine (Xeloda) usually in combination with radiation, to reduce . Irinotecan (Camptosar) tumor size and improve resection . Oxaliplatin (Eloxatin)  Advanced cancers that has metastasized to other organs in efforts to improve quality of life . Trifluridine and Tipiracil (Lonsurf)  HOW IS CHEMOTHERAPY GIVEN?

 Systemic chemotherapeutic drugs are either IV or orally given. 5-FU + Leucovorin

 Regional drugs are put right into an artery FOLFOX leading to a specific body part, ie – , to FOLFIRI reduce systemic side effects CAPIRI TREATMENT  Anti-angiogenesis therapy TARGETED

 Bevacizumab (Avastin) CHEMOTHERAPY

 Regorafenib (Stivarga)  Treatment on the cancer’s specific  Ramucirumab (Cyramza) molecular targets (ie -genes and proteins)  Epidermal growth factor receptor (EGFR)  Blocks tumor cell growth and spread inhibitors  Limits damage to healthy cells  Cetuximab (Erbitux)

 Panitumumab (Vectibix)

 Humanized antibody

Pembrolizumab (Keytruda)  Hair loss

 Mouth sores

 Loss of appetite

 Nausea and vomiting

 Immunosuppression

 Easy bruising or bleeding

 Fatigue

 Neuropathy

SIDE EFFECTS OF CHEMOTHERAPY TREATMENTS  Before surgery given with chemotherapy to improve efficacy RADIATION THERAPY (usually for rectal cancer)

High-energy x-rays used to destroy  After surgery for cancer spread to tumor cells and decrease local other organs and/or peritoneal lining recurrence or spread of cancer

 During surgery, IORT to destroy tumor cells left behind after surgery

 Palliative radiation in advance cancers causing blockage, bleeding, or pain TREATMENT  External-beam radiation therapy (ERBT) TYPES OF RADIATION THERAPY  Internal radiation therapy (brachytherapy)

 Shrink tumors before surgery to  Stereotactic radiation therapy facilitate resection  Alternative to surgery for patients who are not good surgical  Endocavitary radiation therapy candidates

 Relieve symptoms of advance tumor growth such as pain and/or bleeding STAGING COLORECTAL CANCER TNM Staging System

T = Tumor

N = Lymph Node

M = Metastases(distant) LOCAL TUMOR STAGING (T) HOW DOES COLON CANCER METASTASIZE?

Cancer cells spread by:

 Blood

 Lymphatics – lymph nodes (N)

 Distant Organs – lung, liver, peritoneal cavity (M)

Medi Visuals, Inc., 2009  Stage 0 colorectal cancer Usual treatment with polypectomy alone with usually no additional surgery  Stage I colorectal cancer TREATMENT OPTION BY STAGE Segmental surgical resection of tumor and mesenteric lymph nodes alone  Stages 0, I, II, and III are curable by  Stage II colorectal cancer surgery Cure rates with segmental surgical resection  Stage II and III rectal cancer can alone are good and few benefit from receive radiation treatment before additional adjuvant chemotherapy surgery  Stage III colorectal cancer

Segmental surgical resection followed by adjuvant chemotherapy  Stage IV (Metastatic) colorectal cancer Non-curative surgical resection aimed at palliating symptoms; palliative chemotherapy and/or radiation goals for longevity with quality of life

SURVIVAL RATES BASED ON STAGE

5-year survival rates for colorectal cancer based on initial stage of tumor  Regular physical examinations every 3-6 months WHAT IS THE FOLLOW-UP  CEA test Every 3-6 months CARE AFTER TREATMENT?  CT scan annually for 3 years

 Sigmoidoscopy every 6 months  80% of recurrences are found within  Colonoscopy one year after surgery; then the first 2-3 years after surgery every 3-5 years depending on previous  Primary goal of follow-up is early test result detection of recurrent cancer

UPDATE IN THE MANAGEMENT AND TREATMENT OF COLORECTAL CANCER

Edwin A. Empaynado, MD, FACS Advocare Colon and Rectal Surgical Specialists