management of colorectal cancer
TRANSCRIPT
Management of Colorectal CancerMohamed Abdulla M.D.
Prof. of Clinical Oncology
Cairo University
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.
Colon Cancer Mortality:
Why Improving Outcome?
1. Better life style.
Why Improving Outcome?
1. Better life style.
2. Risk groups and Screening utility.
High Risk Factors
Familial Adenomatous 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.
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
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.
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 BetterDFS & OAS.
Recurrence Rate Over Time:
0.14
2.63
7.64
6.92
5.44
3.68
2.97
2.071.7
1.32 1.230.86
0.6
0 1 2 3 4 5 6
Years
% RECURRENCE
> 80% of Recurrences Within the 1st 3 Years.
Sargent DJ, et al. J Clin Oncol. 2009;27(15S): Abstract 4011.
Who Needs Adjuvant Therapy?
60 m30 m0 monthStage
% Survival% Survival% Survival
93.296.1100I
84.791.0100IIa
72.280.2100IIb
83.491.4100IIIa
64.177.3100IIIb
52.367.1100IIIc
43.057.3100IIId
26.843.1100IIIe
8.117.3100IV
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.
Who Needs Adjuvant Therapy?
5-FU+
Calcium Leucovorin
Who Needs Adjuvant Therapy?
Stage III
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.
Stage II
Colon Cancer
80% Cured by Surgery only
16% will Recur Regardless Treatment
4% will Benefit of Treatment
Who Needs Adjuvant Therapy?
Who Needs Adjuvant Therapy? Stage II:
Uptodate.com 01/06/2014
• 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.
Who Needs Adjuvant Therapy? Stage II:
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 BetterDFS & OAS.
4. Identification of molecular key players of growth &aggressiveness Better RR, PFS and OAS.
The Adenoma-Carcinoma Process:
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.
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
Advances in the Treatment of StageIV CRC
0
5
10
15
20
25
30
35
1980 1985 1990 1995 2000 2005 2010 2015
OS
(mo
nth
as)
median overall survival
1980 1985 1990 1995 2000 2005 2010 2015
BSC
5-FU
Irinotecan
CapecitabineOxaliplatin
CetuximabBevacizumab
PanitumumabAflibercept
RegorafenibBBP
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
---
9697
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; Choti MA, et al. Ann Surg.2002;235(6):759-766; Pawlik TM, et al. Ann Surg. 2005;241(5):715-722.
mCRC with LLD: Key Players
Systemic Therapies Alone
Cures 1 – 2% of Patients
SurgeryAlone
Cures > 30% of Patients
Don’t Miss Surgical Intervention
The Race Toward More Responses
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 BetterDFS & OAS.
4. Identification of molecular key players of growth &aggressiveness Better RR, PFS and OAS.
5. MDT CURE in metastatic organ limited disease.
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. 2013 Mar;20(3):938-45
Why MDT?
Take Home Message:
• CRC is among disease associated withreduction of mortality over the past decade.
• Screening programs should be encouraged.
• Colorectal cancer is a highly treatable disease.
• CRC with organ limited disease should bemanaged with curative intent.
• Early MDT approach is highly appreciated.