Management of colorectal cancer

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.



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.




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.


5-FU+

Calcium Leucovorin


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? 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:





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





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.

Management of colorectal cancer

Health & Medicine

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