Describing the state of art in the neadjuvant and adjuvant therapy of rectal cancer.

1. MohamedAbdulla M.D.
Prof. of ClinicalOncology
Cairo University
GSO – Raffles Hotel – Istanbul – 28/03/2015

2.  Amgen.
 Merck Serono.
 Roche.
 Jansen Cilag.
 Astellas.
 MSD.
 pfizer.
 Novartis.

3.  Cecum 14 %
 Ascending colon 10 %
 Transverse colon 12 %
 Descending colon 7 %
 Sigmoid colon 25 %
 Rectosigmoid junct 0.9 %
 Rectum 23 %
CA Cancer J Clin 2011;61:69–90.VC 2011American Cancer Society, Inc.

4. CA Cancer J Clin 2011;61:69–90. VC 2011 American Cancer Society, Inc.
50
Years

5. Risk Factors
• Genetic
• FH
• IBD
• Obesity
• Smoking
• Alcohol
• Aspirin
• NSAIDS
• Vegetables
• Physical
Activity
• Adequate
Folate
• Decreased
Caloric
Intake
Primary prevention of colorectal cancer. Gastroenterology 2010; 138:2029.
Better Life
Style

6.  Good prognostic
factors
 Old age
 Gender(F>M)
 Asymptomatic pts
 Polypoidal lesions
 Non circumferential
lesions
 Diploid
 Poor prognostic factors
 Obstruction
 Perforation
 Ulcerative lesion
 Adjacent structures
involvement
 Positive margins
 LVSI
 Signet cell carcinoma
 High CEA
 Tethered and fixed cancer

7. Tis T1 T2 T3 T4
Extension to an adjacent organ
Mucosa
Muscularis mucosae
Submucosa
Muscularis propria
Subserosa
Serosa
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ: intraepithelial or invasion of lamina propria
T1 Tumor invades submucosa
T2 Tumor invades muscularis propria
T3 Tumor invades through the muscularis propria into pericolorectal tissues
T4a Tumor penetrates to the surface of the visceral peritoneum
T4b Tumor directly invades or is adherent to other organs or structures

9. Stage 5-year Survival (%)
0,1 Tis,T1;No;Mo > 90
I T2;No;Mo 80-85
II T3-4;No;Mo 70-75
III T2;N1-3;Mo 70-75
III T3;N1-3;Mo 50-65
III T4;N1-2;Mo 25-45
IV M1 <3

10.  History: Polyps & Colorectal Malignancy.
 Physical Examination: DRE.
 Routine laboratory investigations (CEA)
 Rigid Segmoidoscopy.
 Full Colonoscopy.
 Biopsy.
Journal of Surgical Oncology 2009;99:65–70

11.  80-95% accurate in tumor staging
 70-75% accurate in mesorectal lymph node
staging
 Use is limited to lesion < 14 cm from anus, not
applicable for upper rectum, for stenosing
tumor
 Very useful in determining extension of
disease into anal canal (clinical important for
planning sphincter preserving surgery)
Figure. Endorectal ultrasound
of a T3 tumor of the rectum,
extension through the
muscularis propria, and into
perirectal fat.

12.  Part of routine workup.
 Useful in identifying enlarged pelvic and extra-pelvic lymph-
nodes and visceral metastasis.
 Limited utility in:
1. small primary cancer.
2. T – Stage assessment.
3. Peri-rectal lymph nodes assessment.
 Sensitivity 50-80%
 Specificity 30-80%

13.  Shows promise as the most sensitive study for
the detection of metastatic disease in the
liver and elsewhere.
 Sensitivity of 97% and specificity of 76% in
evaluating for recurrent colorectal cancer.

14.  MRI may be Superior For:
1. Large field of view.
2. Better for proximal & stenotic lesions.
3. Less operator and technique dependent.
4. Size & morphologic characterization of peri-rectal nodes.
 EUS may be Superior for:
1. More specific for muscularis propria invasion (T1 versusT2).
2. Significantly higher sensitivity forT3 disease.
High Resolution MRI & EUS  Complementary Information.
Bipat et al.Radiology. 2004;232(3):773.

15. MDTSurgery
Radiation
Therapy
Systemic
Therapy
Imaging
Psychologist
&
Rehabilitation

16. MDT & MultimodalityTreatment  Outcome is improving over time
Sauer et al. N Engl J Med 2004;351:1731-40.

17.  High LR following APR and AR: 20-50% (35%).
 Sphincter preservation.
 To live with a stoma.
 Infections and sexual dysfunction.
 The perfect scenario.

18. Clinical Colorectal Cancer,Vol. 4, No. 4, 233-240, 2004

19.  Removal of peri-rectal
tissues involving lateral &
circumferential margins of
mesorectal envelop.
Dis Colon Rectum. 2013 May;56(5):535-50.

20. Clinical Colorectal Cancer,Vol. 4, No. 4, 233-240, 2004

21. Clinical Colorectal Cancer,Vol. 4, No. 4, 233-240, 2004

22.  GITSG.
 NCCTG.
 NSABP R-01.
N Engl J Med 1986; 315:1294.
FJ Natl Cancer Inst 1988; 80:21.
N Engl J Med 1991; 324:709.
Adjuvant
Fluoroupyremidine
X 2 months
CRT – 6Weeks
Adjuvant
Fluoroupyremidine
X 2 months

23. N Engl J Med 2004;351:1731-40.

24. 10 -Year RTh + S S P
LR 5% 11% < 0.0001
OAS 48% 49% 0.86
CCSD 17% 22% 0.04
Lancet Oncol 2011; 12: 575–82

25. Lancet Oncol 2011; 12: 575–82

26. 1. T3 –T4 Lesions:The only definitive indication.
2. cT3N0: Should be treated (understaging).
3. Depth of Extramural Invasion:
 T3 lesions (>5 mm)  ++ LNs involvement  Higher
Cancer Specific Survival (54%Versus 85%).
 Selection of high riskT3 for treatment.
 Approved outside US.
4. T1 – 2 lesions with Positive Nodes.
5. Low situated lesions.
6. Invasion of mesorectal fascia.
Br J Cancer 2000; 82:1131.

27. Grade Regression Fibrosis
0 No All cells are viable
1 Minor < 25% fibrosis
2 Moderate 26 – 50%nFibrosis
3 Good >50%
4 Total NoViable Cells
Grade 10 – year DM P 10 –Year DFS P
0 - 1 39.6%
0.005
63%
0.0082 - 3 29.3% 73.6%
4 10.5 % 89.5%
J Clin Oncol 32:1554-1562. © 2014

28. British Journal of Surgery 2012; 99: 918–928
Can we Avoid Surgery?

29. The Cancer Journal •Volume 13, Number 3, May/June 2007
EQUIVALEN
T

30. Curr Opin Oncol 2012, 24:441–447

31. Curr Opin Oncol 2012, 24:441–447

32. Curr Opin Oncol 2012, 24:441–447

33. PolishTrial
Trans-Tasman
Radiation
OncologyGroup
• Local Recurrence.
• DFS
• Distant Recurrence
• OAS
• Severe LateToxicity
EQUIVALENT
J Clin Oncol 2012; 30:3827.
Br J Surg 2006; 93:1215

34.  Rectal cancer should be treated by MDT.
 Surgery is still the mainstay of treatment.
 Neoadjuvant CRT is more appealing than
postoperative schedule regarding outcome and
toxicity profile for patients with stage II & III rectal
cancer.
 Fluoroupyremidine therapy is still the backbone of
any regimen and can be substituted by the oral form.
 Long course radiation therapy is still preferred by
majority of treating groups.
 pCR is associated with significant improvement in
outcome.
 Still more research is awaited.