1. Colon and Rectal Cancer Update
Molly M. Cone, MD
Assistant Professor of Surgery
Vanderbilt Medical Center
November 14, 2014

2. Disclosures
No disclosures

3. Objectives
Review screening options and recommendations for colorectal cancer
Understand criteria for referral for genetic testing in patients with colon cancer
Learn about current surgical options for patients with colorectal cancer

4. Colon and Rectal cancer
Epidemiology:
In 2014:
96,830 colon cancer diagnosed
40,000 rectal cancer diagnosed
Lifetime risk 1/20 (5%)
3rd leading cause of cancer related deaths in US
50,310 expected to die of CRC in the US this year
Worldwide- responsible for over 650,000 deaths annually (WHO)

5. Colon and Rectal cancer
Both incidence and deaths from colon and rectal cancer have been declining
Except in those <50 yrs
Death rate decreasing
>1 million survivors in the US
Decreased death rate . There are a number of likely
reasons for this. One is that polyps are being found by screening and removed before they
can develop into cancers. Screening is also allowing more colorectal cancers to be found
earlier when the disease is easier to cure. In addition, treatment for colorectal cancer has improved over the last several years. As a result, there are now more than 1 million survivors
of colorectal cancer in the United States.
Except in those

6. Screening for colorectal cancer
Why screen?
Cost effective-
large number of incident cases, long duration of disease manifestation, and high mortality
simple methods for detection and reasonable treatment options
Saves lives-
screening for CRC not only detects cancer earlier, but also allows the clinician to intervene and change the course of the disease.

7. Adenoma-Carcinoma Sequence
APC 5q x
8-10 years x
K-ras 12p
DCC 18q
p53 17p

8. Screening Problems with screening-
multiple methods lead to considerable confusion regarding which method is best and the optimal timing .
confusion causes physicians to reduce the importance paid to CRC screening
This reduces the number of patients who ultimately get screened

9. Screening Physician Recommendation From National Cancer Institute:
Patients indicate as the single most important factor in deciding to undergo screening
From National Cancer Institute:
>42% of patients were unaware of potential screening options
only 35% of respondents were aware that colonoscopy could actually detect CRC
National surveys effort from NCI

10. Screening methods Fecal Occult Blood Test (FOBT)
only screening test which has shown efficacy in prospective randomized controlled trials
Fecal Immunochemical based stool Tests (FIT)
more specific for hemoglobin, this test avoids some of the false positive results of FOBT
DNA stool Assays (sDNA)
Cells shed from the polyp/cancer contain DNA mutations that can be used as a biological marker for cancer detection

11. Screening Serum Markers Barium Enema (double contrast)
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)
Good sensitivity for cancer %, questionable for polyps 32-60% depending on size

12. Screening CT Colonography
Must undergo complete bowel prep and have air/CO2 insufflated though a rectal catheter to distend the entire colon
May use barium per rectum to “tag” any residual stool in the colon

13. Screening Drawbacks to CT colonography
nontherapetic modality, and positive findings require intervention
No standardized protocol
Difficult to detect low rectal lesions
Pt still takes the prep

14. Screening Colonoscopy considered the gold standard test for detection
considered to have the highest sensitivity and specificity
there are NO randomized controlled trials

15. 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

16. Screening
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
CT Colonography
Flexible Sigmoidoscopy
Flexible Colonoscopy
Every 10 years
United States Preventive Services Task Force (USPSTF), American Society of Gastrointestinal Endoscopy (ASGE) , U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF)

17. Colorectal Carcinoma Cancer Environmental Factors Genetic
Susceptibility
Cancer
Age/Time

18. Environmental factors
Diet:
High fat
Low fiber
Red meat
Low calcium
Obesity
Smoking
Physical activity

19. Age

20. Genetic Susceptability
Sporadic (65-85%)
Familial
(10-30%)
Rare CRC
Syndromes (<0.1%)
HNPCC (2-5%)
FAP (1%)

21. Genetic Susceptibility
Hereditary Non-Polyposis Colon Cancer
2-5% of all colorectal cancers
Lynch 1
Colorectal cancers only
Lynch 2
Colorectal cancers
Other cancers (Endometrial, ovarian, pancreatic, gastric, transitional cell of kidney/ureter)

22. HNPCC 3 – 2 – 1 Rule Amsterdam II criteria
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

23. HNPCC Bethesda guidelines: Individuals with 2 HNPCC-related cancer
Meet Amsterdam criteria
Individuals with 2 HNPCC-related cancer
Individual with CRC and
1st degree relative with HNPCC-related CA <45yo or
1st degree relative with adenoma < 40yo
Individual with R-side CRC with undiff pattern <45yo
Individual with CRC or endometrial CA <45yo
Individual with signet cell CRC <45yo
Individual with adenoma <45yo

24. Genetic susceptibility
Genetic testing should be considered when
Individual meets Amsterdam criteria
Individual meets Bethesda guidelines
Tumor is MSI +

25. Treatment of colon cancer
Pre-operative workup
Colonoscopy- evaluate for other polyps/cancers
CEA level
CT scan of chest/abd/pelvis

26. Treatment of colon cancer
Surgical principles
Exploration- either lap or via open techniques
Evaluate peritoneum, adjacent organs, and liver
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

27. 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

28. Survival After Operation
5 year survival
T1N0M0 }
Stage I
95%
T2N0M0
T3N0M0
Stage II
80%
TxN1M0
Stage III
40%
Node +
Distant mets
TxNxM1
Stage IV
<5%

29. Chemotherapy for Colon Cancer
5 year survival
T1N0M0 }
Stage I
95%
T2N0M0
T3N0M0
Stage II
80%
TxN1M0
Stage III
40%
Node +
Distant mets
TxNxM1
Stage IV
<5%

30. Rectal Cancer Differs from colon cancer Pelvic anatomy
Radiation therapy
Surgical treatment options

31. Rectal Cancer Pre-op work-up
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

32. Rectal Cancer
DRE information-
Location
Position
Size
Fixed vs. mobile

33. Rectal Cancer Determine the need for Neoadjuvant 5FU/Radiation
Endorectal ultrasound/MRI:
the most important pre-operative component
ERUS % 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+)

34. Before the 1970’s rectal cancer was treated with surgery alone
1975 trial comparing surgery with chemo, XRT, or both
Surgery only- 55% recurrence
46% with chemotherapy,
48% with radiation therapy
33% with combined modality
NIH Consensus Statement 1990
Stage II and III rectal adenocarcinoma should be treated with adjuvant chemoradiotherapy

35. Rectal cancer
At the same time- specifically in the 1990s, there became a realization that not all surgery was being performed equally
“Total mesorectal excision”

36. Proctectomy for Rectal Cancer: Margins
Distal Mural Resection Margin
1-2 cm
Tumors do not spread longitudinally in wall of rectum
Radial Margin
Critical to ensure complete tumor removal
Pathologists must measure and report
Mesorectal Margin

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

38. Preop vs. Postop Chemoradiotherapy
German rectal cancer trial update 2004
Preop XRT Postop XRT n
Local pelvic failure 6% %
Survival No difference
Anastomotic leak No difference
Toxicity (acute) Lower Higher
Toxicity (late) Lower Higher
So then the question was, when is the best time to give the radiation?

39. 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

40. Dutch Rectal Cancer Trial NEJM 2001
Prospective, Randomized, n=1748
Pre-Op XRT vs. surgery alone (TME)
Local pelvic failure (recurrence)
XRT + Surgery Surgery
2.4% % yrs
5.8% % yrs
Published in 2001/2011.

41. Rectal cancer surgery
Laparoscopic vs. open resection for rectal cancer
1 major trial, 1 underway

42. UK MRC CLASSIC Trial ACASOG Z6051 Trial
Prospective, randomized, experienced surgeons
n=794 overall
n=242 rectal
Disease free survival and local control (3 years)
No difference between laparoscopic and open
Local failure open lap
Anterior resection 7% 8%
APR 21% 15%
________________________________________________
ACASOG Z6051 Trial
American College of Surgeons Oncology Group
650 pts, randomized, multi-center trial of open vs. HALS resection for rectal cancer

43. Robotic Surgery for Rectal Cancer
Pros-
good visualization
precise movements
better ergonomics
Cons-
hard to move from one quadrant to another
costly
lack of stapler/vessel sealing device
Especially in pts with increased BMI in a fixed space (pelvis)

44. 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.

45. Abdominoperineal resection
Appropriate if tumor invades anal sphincter or levator ani

46. Rectal Cancer Coloanal anastomosis
Same dissection, but instead of removal of the anus, the colon is hand sewn to the anal mucosa

47. TEMS/TAMIS Transanal Endoscopic Micro Surgery
Can do full thickness excision of rectal wall
Ideal for
Unresectable adenomas
Carcinoid tumors
T1 rectal cancer
T2 rectal cancer?

48. TEMS/TAMIS

49. Summary
In the past 3 decades significant changes in the diagnosis and treatment of colon and rectal cancer has resulted in:
Decrease in incidence
Decrease in mortality
Less invasive procedures with shorter hospital stay