molly m. cone, md assistant professor of surgery vanderbilt medical center november 14, 2014

Colon and Rectal Cancer

Update

Molly M. Cone, MDAssistant Professor of Surgery

Vanderbilt Medical Center

November 14, 2014

Disclosures No disclosures

Objectiveso Review screening options and recommendations for

colorectal cancero Understand criteria for referral for genetic testing in

patients with colon cancero Learn about current surgical options for patients with

colorectal cancer

Colon and Rectal cancer

Epidemiology:o In 2014:

• 96,830 colon cancer diagnosed• 40,000 rectal cancer diagnosed

o Lifetime risk 1/20 (5%)o 3rd leading cause of cancer related deaths in US

• 50,310 expected to die of CRC in the US this yearo Worldwide- responsible for over 650,000 deaths annually

(WHO)

Colon and Rectal cancer

• Both incidence and deaths from colon and rectal cancer have been declining

• Except in those <50 yrs

Screening for colorectal cancer

Why screen? Cost effective-

o large number of incident cases, long duration of disease manifestation, and high mortality

o simple methods for detection and reasonable treatment options

Saves lives-o screening for CRC not only detects cancer earlier, but

also allows the clinician to intervene and change the course of the disease.

Adenoma-Carcinoma Sequence

APC 5q

DCC 18q

p53 17p

DCC 18q

8-10 years

xxK-ras 12p

Screening Problems with screening-

o multiple methods lead to considerable confusion regarding which method is best and the optimal timing .

o confusion causes physicians to reduce the importance paid to CRC screening

This reduces the number of patients who ultimately get screened

Screening Physician Recommendation

o Patients indicate as the single most important factor in deciding to undergo screening

From National Cancer Institute:o >42% of patients were unaware of potential screening

options o only 35% of respondents were aware that colonoscopy

could actually detect CRC

Screening methods Fecal Occult Blood Test (FOBT)

o only screening test which has shown efficacy in prospective randomized controlled trials

Fecal Immunochemical based stool Tests (FIT)o more specific for hemoglobin, this test avoids some of

the false positive results of FOBT DNA stool Assays (sDNA)

o Cells shed from the polyp/cancer contain DNA mutations that can be used as a biological marker for cancer detection

Screening Serum Markers

o Two most studied- CEA, CA 19-9• CEA used as biologic marker for progression of cancer, but

only 30% sensitivity rate for detection• CA 19-9 not been found useful

Barium Enema (double contrast) o Good sensitivity for cancer- 85-97%, questionable for

polyps 32-60% depending on size

Screening CT Colonography

o Must undergo complete bowel prep and have air/CO2 insufflated though a rectal catheter to distend the entire colon

o May use barium per rectum to “tag” any residual stool in the colon

Screening Drawbacks to CT colonography

o nontherapetic modality, and positive findings require intervention

o No standardized protocolo Difficult to detect low rectal lesionso Pt still takes the prep

Screening Colonoscopy

o considered the gold standard test for detectiono considered to have the highest sensitivity and specificity o there are NO randomized controlled trials

Screening Multiple societies/ organizations have

recommendations, all that differ slightly Most agree that for average risk,

screening should begin at age 50 Screening ends by age 85, with a range

of 75-85

Screening

United States Preventive Services Task Force (USPSTF), American Society of Gastrointestinal Endoscopy (ASGE) , U.S. Multi-Society

Task Force on Colorectal Cancer (USMSTF)

Method Interval Society

Tests that detect Cancer Fecal Occult Blood Testing or FIT Yearly USPSTF, ASGE, USMSTF

Fecal DNA Unspecified USMSTF

Tests that detect

Cancer and Polyps

Double Contrast Barium Enema Every 5 years USMSTF

CT Colonography Every 5 years USMSTF

Flexible Sigmoidoscopy Every 5 years USPSTF, ASGE, USMSTF

Flexible Colonoscopy Every 10 years USPSTF, ASGE, USMSTF

Colorectal Carcinoma

Environmental Factors

Genetic Susceptibility

Age/Time

Cancer

Environmental factors Diet:

o High fato Low fibero Red meat o Low calciumo Obesityo Smokingo Physical activity

Age

Genetic SusceptabilitySporadic (65-85%)

Familial(10-30%)

HNPCC (2-5%)FAP (1%)

Rare CRCSyndromes (<0.1%)

Genetic Susceptibility Hereditary Non-Polyposis Colon Cancer 2-5% of all colorectal cancers

o Lynch 1• Colorectal cancers only

o Lynch 2• Colorectal cancers• Other cancers (Endometrial, ovarian, pancreatic, gastric,

transitional cell of kidney/ureter)

HNPCC• Most common inherited colon cancer syndrome Amsterdam II criteria • 3 – 2 – 1 Rule

– 3- family members with CRC or HNPCC associated CA

(2 first degree)

– 2- generations involved

– 1- family member < 50 years

HNPCC Bethesda guidelines:

o Meet Amsterdam criteriao Individuals with 2 HNPCC-related cancero Individual with CRC and

• 1st degree relative with HNPCC-related CA <45yo

or• 1st degree relative with adenoma < 40yo

o Individual with R-side CRC with undiff pattern <45yo

o Individual with CRC or endometrial CA <45yoo Individual with signet cell CRC <45yoo Individual with adenoma <45yo

Genetic susceptibility Genetic testing should be considered when

o Individual meets Amsterdam criteriao Individual meets Bethesda guidelineso Tumor is MSI +

Treatment of colon cancer

Pre-operative workupo Colonoscopy- evaluate for other polyps/cancerso CEA levelo CT scan of chest/abd/pelvis

Treatment of colon cancer

Surgical principleso Exploration- either lap or via open techniques

• Evaluate peritoneum, adjacent organs, and livero Resection

• Removal of primary lesion with “adequate” margins• Removal of the zone of lymphatic drainage- defined by

arterial blood supply, resected at or near origin

Treatment for Colon Cancer

Laparoscopic vs. open? Literature- Laparoscopic colectomy is equivalent

cancer related survival to open colectomy Benefits of laparoscopic methods for

postoperative recovery

Rectal Cancer Differs from colon cancer

o Pelvic anatomyo Radiation therapyo Surgical treatment options

Rectal Cancer Pre-op work-up

o Very important, as stage effects order/components of treatment

• Colonoscopy- evaluate for other polyps/cancers• CEA level• CT scan of chest/abd/pelvis• Endorectal ultrasound or MRI • Physical exam/flex sig

Rectal Cancer DRE information-

o Locationo Positiono Sizeo Fixed vs. mobile

Rectal Cancer Endorectal ultrasound/MRI:

o the most important pre-operative component• ERUS- 67-95% sensitivity for T stage• MRI (with EndoCoil) 60-95% sensitivity

• Both modalities are less sensitive for N stage

• Determine the need for Neoadjuvant 5FU/Radiation

• Stage II and III (T3, T4, and/or N+)

Before the 1970’s rectal cancer was treated with surgery aloneo 1975 trial comparing surgery with chemo, XRT, or both

• Surgery only- 55% recurrence• 46% with chemotherapy, • 48% with radiation therapy• 33% with combined modality

o NIH Consensus Statement 1990• Stage II and III rectal adenocarcinoma should be

treated with adjuvant chemoradiotherapy

Rectal cancer At the same time- specifically in the 1990s, there

became a realization that not all surgery was being performed equallyo “Total mesorectal excision”

Proctectomy for Rectal Cancer: Margins

Distal Mural Resection Margino 1-2 cmo Tumors do not spread longitudinally

in wall of rectum

Radial Margino Critical to ensure complete tumor

removalo Pathologists must measure and

report

Mesorectal Margin

Total Mesorectal Excision

A review of 51 surgical series showed that TME reduced the median local recurrence rate from 18.5 to 7.1%.

Preop vs. Postop Chemoradiotherapy

German rectal cancer trial update 2004Preop XRT

Postop XRTn 405 392Local pelvic failure 6%

12%Survival No differenceAnastomotic leak No differenceToxicity (acute) Lower

HigherToxicity (late) Lower Higher

Neoadjuvant Therapy: Benefits

• Shrink tumor prior to removal• Downsizing• Downstaging

• Sterilize margins prior to pelvic dissection

• More effective than postop XRT• oxygenated field

• Better functional result• Radiate only one side of

anastomosis• More patients complete

treatment course

Dutch Rectal Cancer TrialNEJM 2001

Prospective, Randomized, n=1748 Pre-Op XRT vs. surgery alone (TME)

Local pelvic failure (recurrence) XRT + Surgery Surgery

2.4% 8.3% 2 yrs5.8% 11.4% 5 yrs

Rectal cancer surgery Laparoscopic vs. open resection for rectal cancer

1 major trial, 1 underway

UK MRC CLASSIC Trial Prospective, randomized, experienced surgeons

• n=794 overall• n=242 rectal

Disease free survival and local control (3 years)o No difference between laparoscopic and open

o Local failure open lap• Anterior resection 7% 8% • APR 21% 15%

________________________________________________ ACASOG Z6051 Trial

o American College of Surgeons Oncology Groupo 650 pts, randomized, multi-center trial of open vs. HALS resection for

rectal cancer

Robotic Surgery for Rectal Cancer

Pros-o good visualizationo precise movementso better ergonomics

Cons- o hard to move from one quadrant to anothero costlyo lack of stapler/vessel sealing device

Sphincter Preservation Unless directly invaded

by tumor, skeletal muscle is not at risk for tumor implantation.

Therefore, there is no reason to excise the anus or levators…

… if it will not improve oncologic outcome.

Abdominoperineal resection

Appropriate if tumor invades anal sphincter or levator ani

Rectal Cancer Coloanal anastomosis

Same dissection, but instead of removal of the anus, the colon is hand sewn to the anal mucosa

TEMS/TAMIS Transanal Endoscopic Micro Surgery

o Can do full thickness excision of rectal wallo Ideal for

• Unresectable adenomas• Carcinoid tumors• T1 rectal cancer• T2 rectal cancer?

TEMS/TAMIS

Summary In the past 3 decades significant changes in the

diagnosis and treatment of colon and rectal cancer has resulted in:o Decrease in incidence o Decrease in mortalityo Less invasive procedures with shorter hospital stay