RECENT TRENDS INCOLO-RECTAL CANCERS TREATMENT

Dr. Manish Gandhi

MS, DNB (surgical gastroenterology)

Senior Consultant surgical gastroenterologist, HPB and Gastro-intestinal cancer surgeon

NH Multispeciality hospital

Duke’s staging

RECENT TRENDS

• Neoadjuvant / adjuvant therapy

• surgery

NEOADJUVANT THERAPY

• Given before surgical resection

• To prevent local recurrence

• To downstage disease

• To decrease bulk of disease

• To increase resectability/ conservation

• Either radiotherapy or chemotherapy

CHEMOTHERAPEUTIC AGENT

• 5 Fluorouracil (FU)

• Levamisole

• Leucovorine

• Oxaliplatin

• Irenotican

• Capecitabine

• Bevacizumab

• cetuximab

CARCINOMA COLON

• No role of neoadjuvant therapy

• Adjuvant radiotherapy is not advisable

COLON CANCER

• Adjuvant therapy

• High risk stage ll – Duke’s stage B - full thickness muscle invasion with negative node

• Poor histologic differentiation

• Lympho-vascular invasion, invasion of surrounding structure

• Obstruction, Perforation

• Inadequately examined(<12) lymph node

• DNA aneuploidy, high S –phase analysis, deletion of 18q

• Stage lll – Duke’s stage C – node positive

• Start within 6-7 weeks of surgery

CARCINOMA RECTUM

• Four major goal in treatment of ca rectum

Local control

Long-term survival

Preservation of anal sphincter, bladder and sexual function

Maintenance or improvement in quality of life

• Neoadjuvant – RT+ CT

• Adjuvant - RT+ CT

• In stage ll and stage lll disease (NIH consensus conference statement in 1990)

RADIOTHERAPY

• Short course intensive radiotherapy (Swedish concept)

• Neoadjuvant

• Short overall time and option of immediate surgery

• Used to decrease local recurrence

• Total dose of 25 Gy- 5 x 5 fraction

• Followed by surgery within a week or 10 days

• Not useful

• to down stage the disease the disease

• to increase resectibility

• to increase sphincter conservation

• Conventional radiotherapy • Neoadjuvant or adjuvant

• 45 – 50 Gy (1.8 to 2 Gy per dose for 25 – 26 dose) – 5 days a week over 5 week

• Neoadjuvant• followed by surgery within 6-8 week ( better clinical response)

• To downstage the disease

• To increase resectibility

• Adjuvant therapy • As early as possible

• To decrease local recurrence

PREOPERATIVE RADIOTHERAPY

• In stage ll and lll

• Short course / conventional

• Reduce the chance of implantation of viable cells in wound

• Tumor shrinkage and down staging may facilitate curative resection/ sphincter preserving surgery

• Less damage to small bowel

• No irradiation to anastomosis

• Effect is better as there is no tissue hypoxia

• No need to give radiation to perineal skin in pt. Who is a probable candidate of APR

• Radiotherapy alone – better control of local recurrence but no change in OS

• May over treat stage l

• Increase postop. morbidity

POSTOPERATIVE RADIOTHERAPY

• In stage ll and lll

• blood supply altered by dissection - Tissue hypoixa

• More small and large bowel resides in pelvis- more damage

• Both proximal and distal sides are irradiated (LAR)

• Need to apply RT in perineal area (APR)

NEOADJUVANT CHEMORADIOTHERAPY

• Survival benefit

• 5 FU as a radiosensitizer

• Complete clinical response – 19-38%

• Complete pathological response – 8-30%

• Patient who have >95% pathological response have significantly improve 10 yrOS and RFS then <95%

ADJUVANT CTRT

• In all pt. With stage ll or lll disease

• CT regimens

• Similar to colon cancer

• Mainly 5FU+ LV – proven by trials

• Oxaliplatin/irinotecan/xeloda – trials are going on

• In general

• preop. RT prefer than postop. RT• Marked tumor shrinkage

• Low complication

• Low local recurrence (14 vs 28 % at 5 yr)

• Radiotherapy combined with 5FU is more effective than RT alone

• Preoop. CTRT has better control on recurrence than postop. CTRT but no benefit of OS

Bowel preparation

10 RCT,7 meta analysis comparing preoperative bowel preparation to without preparation in terms of anastomotic leakage,

surgical infection,

reoperation were reviewed

preparation was associated with higher incidence of anastomotic leakage , infection and reoperation

Dig Surg. 2006;23(5-6):375-80. Epub 2006

PREOPERATIVE PREPARATION

MESORECTAL EXCISION

• Total Mesorectal Excision (TME) mandatory

• En masse excision of all primary drainage nodes and lymphatics

• Sharp dissection along the “holy”plane

• Reduces local recurrence to <10%

• Addition of pre op RT further reduces recurrence (2-5%)

Cecil TD et al Dis Colon Rectum 2004

Brekink et al Surg Endoscopy 2007

MINIMALLY INVASIVE SURGERY

ADVANTAGES OF LAPAROSCOPY

• Early recovery

• Decreased pain

• Less immunological response

• Short hospital stay

DISADVANTAGES

• Increased cost

• Learning curve

CONTROVERSIES

• Oncologic outcomes

• Survival

• Recurrence

• Surgical and port site recurrence

• Resection margins

• Lymph node retrieval

• General outcomes

• Conversion rates

• Operative time, hospital stay and cost

• Operative mortality and complications

• Quality of life

RCTS FOR COLON CANCER

• Barcelona trial

• COST

• COLOR

• MRC CLASSIC Trial

LAPAROSCOPIC TME

Brekink et al Surg Endoscopy 2007

LAPAROSCOPIC VS OPEN TMECOCHRANE REVIEW: BREUKINK 2008

LAP TME OPEN TME NO OF

STUDIES

5 YR SURVIVAL 75.3% 78.3% 17

LOCAL

RECURRENCE

17

MORTALITY 13

MORBIDITY 36

ANASTOMOTIC

LEAKAGE

29

DURATION OF

SURGERY

34

ADEQUACY OF

OCOLOGICAL

MARGINS

16

HOSPITAL STAY 39

COST 1

CONCLUSION

• All stage II and III carcinoma rectum should be treated with preoperative neoadjuvant chemo + radiotherapy

• Laparoscopic colorectal surgery is emerging with comparable result to open surgery

LAR

Specimen

with TME

APER Specimen

Neoadjuvant

Vs

no Neoadjuvant