Colon cancer is the second and third most common cancer in males and females. Screening programs have led to a reduction in late-stage diagnoses and mortality. Precise identification of prognostic patient groups allows for more targeted adjuvant therapy, improving disease-free and overall survival. Molecular markers of tumor aggressiveness aid in selecting optimal treatment approaches, increasing response rates, progression-free, and overall survival. A multidisciplinary team approach is essential for managing metastatic colon cancer with the goal of surgical cure in organ-limited disease.

1. Management of
Colorectal Cancer
Mohamed Abdulla M.D.
Prof. of Clinical Oncology
Cairo University

2. Colon Cancer:
Basic Facts & Figures:
• 2nd & 3rd most common cancers in females and males.
• 9% of cancer related deaths.
• The majority occurring around the age of 40 – 50 years.
• OAS for entire patients = 65%.
• Metastatic disease: 5-year OAS = 10%.
• Organ limited metastatic disease: 5-year OAS > 40%
• Median survival of metastatic disease > 24 - 30 months.
• Improved OAS with exposure to all available lines.
• Unified global ideal treatment algorhytm is still
controversial.

3. Colon Cancer Mortality:

4. Why Improving Outcome?
1. Better life style.

6. Why Improving Outcome?
1. Better life style.
2. Risk groups and Screening utility.

7. High Risk Factors
 FamilialAdenomatous Polyposis
 Hereditary Non Poliposis Colon Cancer
 Family history of Colo Rectal Carcinoma
 Previous Colorectal CA,Ovarian, Endometrial,
Breast CA
 Age >50 (3/1000 at the age of 80)
 Inflammatory Bowel Disease.
 Diet (increased fat, red meat, decreased fibre)
 Smoking
 Diabetes mellitus.
 HIV.
 Radiation therapy for prostate cancer.

8. Risk Assessment:
Ask The Following:
1. Have you had colorectal cancer or polyp?
2. Have you had inflammatory bowel disease or abdominal
irradiation during childhood?
3. Have any family members had colorectal cancer or polyp?
All Answers
are NO
Average Risk
Any Answer is
YES
Increased Risk

10. Screening of CRC: Cost –
Benefit:
US Data: Screening for CRC (1987 – 2010):
•  The incidence of late stage from 118 – 74/100000.
•  The incidence of early stage disease from 77 –
67/100000.
• Reduction of 550000 CRC cases over 3 decades.
Cancer 2014;120:2893-2901.

11. Why Improving Outcome?
1. Better life style.
2. Risk groups and Screening utility.
3. Identification of prognostic groups of patients 
More precise adoption of adjuvant therapy  Better
DFS & OAS.

12. Recurrence Rate Over Time:
2.63
0.14
7.64
6.92
5.44
3.68
% RECURRENCE
2.97
2.07
1.7
1.32 1.23
0.86
0.6
0 1 2 3 4 5 6
Years
> 80% of Recurrences Within
the 1st 3 Years.
Sargent DJ, et al. J Clin Oncol. 2009;27(15S): Abstract 4011.

13. Who Needs Adjuvant Therapy?
Stage 0 month 30 m 60 m
% Survival % Survival % Survival
I 100 96.1 93.2
IIa 100 91.0 84.7
IIb 100 80.2 72.2
IIIa 100 91.4 83.4
IIIb 100 77.3 64.1
IIIc 100 67.1 52.3
IIId 100 57.3 43.0
IIIe 100 43.1 26.8
IV 100 17.3 8.1
O’ConnellJB, Maggard MA, Ko CY: Colon Cancer Survival Rates with The New American Joint Committee on Cancer,
Sixth Edition Staging. J Natl Cancer Inst 2004;96:1423.

14. Who Needs Adjuvant Therapy?
5-FU
+
Calcium
Leucovorin

15. Who Needs Adjuvant Therapy?
Stage III

16. Who Needs Adjuvant Therapy?
Stage II
Colon Cancer
80% Cured by
Surgery only
16% will Recur
Regardless
Treatment
4% will Benefit of
Treatment
Quasar Collaborative G, Gray R, Barnwell J, et al. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a
randomized study. Lancet 2007; 370:2020-9.

17. Who Needs Adjuvant Therapy?
Stage II:
Uptodate.com 01/06/2014

18. Who Needs Adjuvant Therapy?
Stage II:
• Molecular Markers:
1. Tumors with Microsatellite Instability have better prognosis
than those with Microsatellite stable tumor cells. MSI  Poor
response to fluoroupyremidine therapy.
2. Chromosomal Instability: Worse outcome.
3. LOH 18q: Worse outcome.
• Genetic Expression Profiling:
1. Oncotype DX:
7 Recurrence Genes.
5 Reference Genes +
5 Treatment Benefit Genes.
2. Coloprint.

19. Why Improving Outcome?
1. Better life style.
2. Risk groups and Screening utility.
3. Identification of prognostic groups of patients 
More precise adoption of adjuvant therapy  Better
DFS & OAS.
4. Identification of molecular key players of growth &
aggressiveness  Better RR, PFS and OAS.

20. The Adenoma-Carcinoma Process:
Normal colonic epithelium
Dysplastic aberrant crypt foci
Initial adenoma develops
Intermediate adenoma
Late adenoma
Carcinoma
Metastasis
Mutation in APC
Mutation in K-ras
Mutation in DCC
Mutation in p53
Other alteration?
EGFR & VEGF
Kinzler KW, et al. New York, The genetic basis of human cancer. NY: McGraw-Hill, 1998:565-87. Vogelstein B, et al. N Engl J Med.
1988;319:525-532. Fearon ER, et al. Cell. 1990;61:759-767.

21. Advances in the Treatment of Stage
IV CRC
1980 1985 1990 1995 2000 2005 2010 2015
35
30
25
20
15
10
5
0
1980 1985 1990 1995 2000 2005 2010 2015
OS (monthas)
median overall survival
BSC
5-FU
Irinotecan
Capecitabine
Oxaliplatin
Cetuximab
Bevacizumab
Panitumumab
Aflibercept
Regorafenib
BBP

22. Results of Hepatic Resection for Patients
with mCRC:
Survival (%)
Author (year) No. Patients Mortality,% Median Survival 1-year 5-year
Hughes et al (86) 607 --- --- --- 33
Gayowski et al (94) 204 0 33 mo 91 32
Scheele et al (95) 469 4 40 mo 83 39
Fong et al (95) 577 4 40 mo 85 35
Jamison et al (97) 280 4 33 mo 84 27
Fong et al (99)
Choti et al (02)
Pawlik et al (05)
1001
226
557
3
1
1
42 mo
46 mo
74 mo
---
96
97
36
40
58
Hughes KS, et al. Surgery. 1986;100(2):278-284. Gayowski TJ, et al. Surgery. 1994;116(4):703-710. Scheele J, et al.World J Surg. 1995;19(1):59-71. Fong Y, et al.
Ann Surg. 1995;222(4):426-434.; Jamison RL, et al. Arch Surg. 1997;132:505–510. Fong Y, et al. Ann Surg 1999;230:309-318; ChotiMA, et al. Ann Surg.
2002;235(6):759-766; Pawlik TM, et al. Ann Surg. 2005;241(5):715-722.

23. mCRC with LLD: Key Players
Systemic
Therapies Alone
Cures 1 – 2%
of Patients
Surgery
Alone
Cures > 30%
of Patients
Don’t Miss Surgical Intervention
The Race Toward More Responses

24. Why Improving Outcome?
1. Better life style.
2. Risk groups and Screening utility.
3. Identification of prognostic groups of patients 
More precise adoption of adjuvant therapy  Better
DFS & OAS.
4. Identification of molecular key players of growth &
aggressiveness  Better RR, PFS and OAS.
5. MDT  CURE in metastatic organ limited disease.

25. Why MDT?
It’s MANDATORY!
 Greater accuracy of staging
 Fewer treatment delays
 Better outcome!
Fleissing A, et al. Lancet Oncol. 2006; 7(11): 935 – 943; Du CZ, et al.Worl J Gastroenterol. 2011;17(15):2013-2018;
MacDermid E, et al. Colorectal Dis. 2009;11(3):291-295; Viganò L, et al. Ann Surg Oncol. 2013Mar;20(3):938-45

26. Take Home Message:
• CRC is among disease associated with
reduction of mortality over the past decade.
• Screening programs should be encouraged.
• Colorectal cancer is a highly treatable disease.
• CRC with organ limited disease should be
managed with curative intent.
• Early MDT approach is highly appreciated.