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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