Colorectal CancerRobert Miller MD

www.aboutcancer.com

Third Most Common Cancer in Men and Women

Odds of Developing Colorectal cancer in the US (2007-9)~ 5%

Type Men Women

Any Cancer 45% (1in 2) 38% (1 in 3)

Breast 12% (1 in 8)

Colorectal 5% (1in 19) 4.8% (1 in 21)

Prostate 16% (1in 6)

Declining Incidence last 30y

Third Most Lethal Cancer in Men and Women

Declining Mortality in Men US Data 1930 to 2009

Declining Mortality in Women US Data 1930 to 2009

Odds of Dying of Colorectal cancer in the US (2007-9) ~ 2%

Type Men Women

Any Cancer 23% (1in 4) 19% (1 in 5)

Breast 2.8% (1 in 36)

Colorectal 2.11% (1in 47)

1.94% (1 in 52)

Prostate 2.8% (1in 36)

Most patients are diagnosed before they have symptoms because of screening or the findings of rectal blood (hematochezia) or anemia

Abdominal pain — 44 percentChange in bowel habit — 43 percentHematochezia or melena — 40 percentWeakness — 20 percentAnemia — 11 percentWeight loss — 6 percent

Patients who are symptomatic at diagnosis have a somewhat worse prognosis. In one report, the five-year survival rate for symptomatic (49%) and asymptomatic patients (71%)

Symptoms

Median Age of Patients with colon and rectal cancer (2005-2009)

Site Male Female

Colon 69y 73y

Rectum 64y 66y

Colon

8% less than 50y

Rectum

14% less than 50y

Age Distribution from the NCDB for 2000- 2012

Screening

Colonoscopy every 10 years starting at the age of 50 unless high risk

How should family history effect the age to start screening colonoscopy?

First-degree (share one half genes) = parent, child or siblingSecond-degree (share one quarter genes) = grandparents, uncle, niece

Workup or Evaluation Prior to Deciding on Treatment for Colon Cancer

Pathology Report• Confirm that it is malignant (usually adenocarcinoma)• Information about stage: depth in invasion and lymph nodes

involved (look at 12 nodes)• Surgical margins (to ensure complete removal)• Other prognostic risk factors: grade, vascular invasion,

perineural invasion• Genetic risk factors: MSI (microsatellite instability) testing/

MMR protein to look for Lynch syndrome• Gene mutation testing: KRAS and BRAF that will determine

whether the patient would benefit from anti EGFR drugs (cetuximab, panitumumab, regorafenib)

Workup or Evaluation Prior to Deciding on Treatment for Rectal Cancer

T2 T3

Nodes

Transrectal Endoscopic Ultrasound

Accuracy of Imaging in Staging Rectal Cancer

Site Ultrasound

CT MRI

Tumor 80-95% 65-75% 75-85%

Nodes 70-75% 55-65% 60-65%

Staging

Staging: T (tumor stage)

Stage Depth of Invasion

T1 submucosa

T2 muscularis propria

T3 Pericolorectal tissue

T4a Surface of visceral peritoneum

T4b Into other organs/structures

Staging: T (tumor stage)

Staging: N (lymph node stage)

Stage Nodes Involved

N0 0

N1a 1

N1b 2, 3

N2a 4, 6

N2b 7 or more

Staging: N (lymph node stage)

Colon Cancer Stage Distribution

Rectal Cancer Stage Distribution

NCCN.org

Treatment of colorectal cancer

• Early stages are treated with surgery• More advanced stages have surgery

followed by chemotherapy (colon) or radiation and chemotherapy prior to surgery (rectum)

• Metastatic or recurrent disease treated with chemotherapy or targeted therapy and possibly radiation, surgical resection or RF ablation

Survival in Months Drug Regimen

14.8 months bolus 5FU/LV17.4 months Infusional 5FU/LV20.1 months irinotecan (Camptosar) +5FU/LV20.3 months camptosar = 5FU + bevacizumab (Avastin)21.5 months FOLFIRI then FOLFOX25.1 months irinotecan/5FU + avastin +oxaliplatin (Eloxatin)

New Drugs for Colorectal Cancer

There are now seven different classes of drugs with significant antitumor activity:

• 5-fluorouracil [5-FU] which is usually given with leucovorin, capecitabine, (Xeloda) tegafur plus uracil

• Irinotecan (Camptosar)• Oxaliplatin (Eloxatin)• Cetuximab (Erbitux) and panitumumab (Vectibix), two

monoclonal antibodies (MoAbs) directed against the epidermal growth factor receptor (EGFR) if KRAS wild type

• Bevacizumab (Avastin), a MoAb targeting vascular endothelial growth factor (VEGF)

• Aflibercept, a recombinant fusion protein consisting of vascular endothelial growth factor (VEGF) binding portions from the human VEGF receptors 1 and 2 fused to the Fc portion of human immunoglobulin G1,

• Regorafenib, a small molecule inhibitor of multiple kinases

30 Year Trends in 5 Year Survival

Site 1975 2008

Colon 51% 65%

Rectum 48% 68%

Stage and 5 Year Survival US Data 2002- 2008

Stage Incidence Survival

All 100% 64%

Local 39% 90%

Regional 36% 70%

Distant 20% 12%

Survival with Colon Cancer

Survival with Rectal Cancer

5 Year Survival from NCDB

Stage Colon Rectum

I 77.5% 77.7%

II 66.6% 63.2%

III 54.5% 58.0%

IV 9.6% 9.8%

www.adjuvantonline.com

Colorectal CancerRobert Miller MD

www.aboutcancer.com