Evidence-base approach in the perioperative management and follow-up strategy for colon cancer...

Evidence-base approach in the Evidence-base approach in the perioperative management and perioperative management and

follow-up strategy for colon cancerfollow-up strategy for colon cancer

Hester YS CheungHester YS CheungDepartment of surgeryDepartment of surgery

Pamela Youde Nethersole Eastern HospitalPamela Youde Nethersole Eastern Hospital

Common scenarioCommon scenario M/54 No family history of carcinoma of colon Presented with dizziness P/E Pale looking, left upper quadrant mass

Blood testHb 4g/dL

Liver function test normal

Carcinoma of transverse colonCarcinoma of transverse colon

Pre-operative assessmentPre-operative assessment

CEA

Bowel Preparation

CT scanChestX-ray

Prophylactic Antibiotic

Blood Transfusion

Carcinoma of colonCarcinoma of colon

Carcinoembryonic antigen Carcinoembryonic antigen (CEA)(CEA)

Elevated in a variety of conditions Proximal gastrointestinal cancer, lung and breast cancers,

smoking etc.

Proven useful in individuals diagnosed with colorectal cancer

Recommended before resection of colorectal cancerLevel of evidence Class II A

Graham RA, Ann Surg 1998

Wiratkapun S. Dis Colon Rectum 2001

Pre-operative CEAPre-operative CEA

Returning to normal after operation is associated with complete tumor resection

Persistently elevated values indicate the presence of visible or occult residual disease

Lavin PT. Cancer 1981

Steele G. Ann Surg 1982

Pre-operative CEAPre-operative CEA

An independent prognostic indicator of poor outcome Predictive of poor survivalPredictive of poor survival shorter disease-free survivalshorter disease-free survival

Metastases in 37% patients with elevated preoperative CEA Metastases in 37% patients with elevated preoperative CEA vs. 7.5% in patients with normal CEAvs. 7.5% in patients with normal CEA

Wiratkapun S. Dis Colon Rectum 2001

Harrison LE. J Am Coll Surg 1997

Chest x-raysChest x-rays

Overall pre-operative assessment Evaluate lungs for metastatic disease

Routine pre-operative chest x-ray is acceptableLevel of evidence Class III C

The Standards Practice Task Force

Dis Colon Rectum 2004

Low costLow yield for

metastatic disease

Computed tomography (CT Computed tomography (CT scan)scan)

Evaluate local extension of tumor, regional lymphadenopathy and the presence of hepatic metastases

Accuracy of CT scan

McAndrew MR. Am Surg 1999

Hundt W. Eur Radiol 1999

Ward J. Radiology 1999

SensitivityLocal extension Limited dataLimited dataMetastatic lymphadenopathy 19-67%19-67%Liver metastases >1cm 90-95%90-95%

Computed tomography (CT scan)Computed tomography (CT scan)

No impact on the decision to operate Not affect the operative approach Information readily obtained at the time of

surgery

Routine pre-operative CT scan is optionalLevel of evidence Class II B



Computed tomography (CT scan)Computed tomography (CT scan)

Suspicion of invasion of adjacent organs Palpable massPalpable mass Unexplained biochemical abnormalitiesUnexplained biochemical abnormalities Nearly obstructing cancerNearly obstructing cancer

Used in selected patients for pre-operative planning



Peri-operative blood transfusionPeri-operative blood transfusion

Established immunosuppressive effect Higher incidence of infection

Wound infectionWound infection Intra-abdominal sepsisIntra-abdominal sepsis PneumoniaPneumonia

Greater risk of cancer recurrence Decreased survival

Is it harmful?

Jensen LS. Br J Surg 1992

Van Twuyver E. N Eng J med 1991

Perioperative blood transfusionPerioperative blood transfusion

STUDIES Patients5-year

SurvivalDisease-free

SurvivalCancer

RecurrenceLocal

RecurrencePost-operative

Infection

Van de Watering LMVan de Watering LM20012001 697697 ↓↓ ↓↓ ↑↑

SAKKSAKK19971997 450450 ↓↓

Hobiers JGHobiers JG19971997 697697

↑↑Dose responseDose responseRR 1.6 (1-3U)RR 1.6 (1-3U)RR 3.6 (>3U)RR 3.6 (>3U)

Busch ORBusch OR19941994 420420 ↑↑

Heiss MMHeiss MM19941994 120120 ↓↓ ↑↑

Randomized controlled trialsRandomized controlled trials


STUDIES Papers SurvivalCancer

Recurrence

PoorPrognostic

Factor

Post-operativeInfection

Amato ACAmato ACDis Colon Rectum 1998Dis Colon Rectum 1998 3232 ↑↑

Odds ratio 1.68Odds ratio 1.68√√

McAlister FAMcAlister FABr J Surg 1998Br J Surg 1998 88

No No differencedifference

No No differencedifference

Vamvakas ECVamvakas ECTransfusion 1995Transfusion 1995 6060 Discrepancies explained by study design and confounding factorsDiscrepancies explained by study design and confounding factors

Fernadez LFernadez L

Rev Esp Enferm Dig 1992Rev Esp Enferm Dig 1992 No No

differencedifference

Meta-analysesMeta-analyses


Strongly questioned whether there is a true causal effect Factors in patients requiring transfusion might be the

cause for increased recurrence Extent of resectionExtent of resection Location of tumorLocation of tumor Experience of surgeonExperience of surgeon

Meta-analyses




Simon TL. Arch Pathol Lab Med 1998

Red Blood Cell Administration Practice Guideline Development Task Red Blood Cell Administration Practice Guideline Development Task Force of the College of American PathologistsForce of the College of American Pathologists

Peri-operative transfusionPeri-operative transfusionAsymptomatic anaemia and haemoglobin ≤ 7 g/dL

may need to be transfused if:

A. Scheduled surgery is expected to produce significant blood lossB. Risks associated with general anaesthesia are high

Pre-operative blood transfusionPre-operative blood transfusion

Blood transfusion should be based on physiological neede.g. starting haemoglobin, physiological status and extent of intra-operative blood loss

Level of evidence Class III C

Vignali A. Eur J Surg 1995

Houbiers JG. Lancet 1994

The Standards Practice Task Force Dis Colon Rectum 2004

Mechanical bowel preparationMechanical bowel preparation

Year Anastomostic Leakage Wound Infection

Prep No Prep Prep No Prep

Brownson et alBrownson et al 1992 8/67 1/67 5/86 7/93

Burke et alBurke et al 1994 3/82 4/87 4/82 3/87

Santos et alSantos et al 1994 7/72 4/77 17/72 9/77

Fillmann et alFillmann et al 1995 2/30 1/30 1/30 2/30

Miettinen et alMiettinen et al 2000 5/138 3/129 5/138 3/129

Tabusso et alTabusso et al 2002 5/24 0/23 2/24 0/23

Zomera et alZomera et al 2003 7/187 4/193 12/187 11/193

Bucher et alBucher et al 2003 4/47 1/46 4/47 1/46

Fa-Si-Oen et alFa-Si-Oen et al 2003 7/125 6/125 9/125 7/125

No definite benefit for pre-operative mechanical preparation of bowel

9 RCTs showed no decrease in Infection rateInfection rate Leakage rateLeakage rate Mortality rateMortality rate

Mechanical bowel preparationMechanical bowel preparation

Ease of handling prepared colon Proven safety for colon cleansing Low cost

Mechanical bowel preparation is nearly universally used in elective surgery

Level of evidence Class II A



Prophylactic antibioticsProphylactic antibiotics Proven effectiveness in decreasing

Infective complicationsInfective complications MortalityMortality Cost of hospitalization after colonic resectionCost of hospitalization after colonic resection

Parenteral antibiotic regimen Given before the start of operationGiven before the start of operation

Need not be continued longer than 24 hours post-operativelyNeed not be continued longer than 24 hours post-operatively

Single dose of Cefotaxime and Metronidazole is as effective as 3 Single dose of Cefotaxime and Metronidazole is as effective as 3 dosesdoses

Baum ML. N Eng J Med 1981

Stone HH. Ann Surg 1976, Polk HC. Surgery 1969

Stone HH. Ann Surg 1979

Rowe-Jones DC. BMJ 1990

Prophylactic antibioticsProphylactic antibiotics

Prophylactic antibiotics are recommended for patients undergoing colon resection

Level of evidence Class I A



Post-operative surveillancePost-operative surveillance

Follow-up

Colonoscopy

Imaging

Carcinoma of colonCarcinoma of colon

Laboratory Tests

Intensive follow-upIntensive follow-up

85% recurrences diagnosed within the first 3 years after resection of primary tumor

Sargent DJ. J Clin Oncol 2004

Frequency Duration

Desch et al. J Clin Oncol 2005

American Society of Clinical Oncology Practice GuidelineAmerican Society of Clinical Oncology Practice GuidelineFollow-up strategyFollow-up strategyFirst 3 yearsFirst 3 years Every 3-6 months4th and 5th year4th and 5th year Every 6 monthsAfter 5th yearAfter 5th year Discretion of surgeon

Post-operative follow-upPost-operative follow-up

Intensive follow-up 3 high-quality meta-analyses

20-30% reduction in risk of death from all causes for patients who received more intensive follow-up

Intensive follow-upIntensive follow-up Earlier documentation of recurrences Increase in operability of recurrent disease

Patient health-related quality of life (HRQL) Limited dataLimited data No difference in cohort studiesNo difference in cohort studies


Stiggelbout AM. Br J Cancer 1997

Kjeldsen BJ. Scand J Gastroenterol 1999

Laboratory testsLaboratory tests Haemoglobin

1% recurrence No survival benefit

Liver function test < 10% recurrence Resectable recurrence: 2-3 patients per 1000 followed-up

Faecal occult blood test 10-30% recurrence/metachronous lesions Resectable recurrence: 0-9 per 1000 patients followed-up

Kjelden BJ. Br J Surg 1997

Goldberg RM. Ann Intern med 1998

Peethambaram P. Oncology 1997

Graffner H. J Surg Oncol 1985

Jahn H. Dis Colon Rectum 1992

Not recommended for routine blood testLevel of evidence Class II A

Laboratory testsLaboratory tests Carcinoembryonic antigen (CEA)

Positive predictive value of 70-80% for recurrent disease if level > 5ng/ml

First indicator of recurrence First abnormal test in 38-66% recurrences Lead-time 4-6 months

Survival advantage not demonstrated False positive rate 7-16%

ProsPros

ConsCons

McCall JL. Dis Colon Rectum 1994, Moertel CG. JAMA 1993

Ohlsson B. Dis Colon Rectum 1995

McCall JL. Dis Colon Rectum 1994



Used as a part of follow-upLevel of evidence Class II B

Laboratory testsLaboratory tests

Carcinoembryonic antigen (CEA)

American Society of Clinical Oncology Practice GuidelineAmerican Society of Clinical Oncology Practice GuidelinePost-operative CEA testingPost-operative CEA testing

Every 3 months in patients withEvery 3 months in patients with

Stage II/III disease for at least 3 yearsStage II/III disease for at least 3 yearsCandidate for surgery or systemic therapyCandidate for surgery or systemic therapy

ImagingImaging

STUDIES PatientsAsymptomatic

HepaticMetastases

Hepatic Resection

RateSurvival

Chau IChau IJ Clin Oncol 2004J Clin Oncol 2004 530530 No differenceNo difference ↑↑ ↑↑

Schoemaker DSchoemaker DGastroenterology 1998Gastroenterology 1998 325325

↑↑60%60%

NoNo differencedifference No differenceNo difference

Computed tomography (CT scan) 2 RCTs addressed the impact of CT scan on

survival

25% lower mortality


ImagingImaging

American Society of Clinical Oncology Practice GuidelineAmerican Society of Clinical Oncology Practice GuidelineCT in colon cancer surveillance (2005)CT in colon cancer surveillance (2005)

Annual CT for 3 years after primary therapyAnnual CT for 3 years after primary therapy

For patients withFor patients withHigher risk of recurrenceHigher risk of recurrenceCandidates for curative-intent surgeryCandidates for curative-intent surgery

Colonoscopy Colonoscopy Identify metachronous cancers and polyps

American Society of Clinical Oncology Practice GuidelineAmerican Society of Clinical Oncology Practice GuidelineEndoscopic surveillanceEndoscopic surveillance

Following surgeryFollowing surgery At 3 yearsif normal, then every 5 years

High-risk genetic syndromesHigh-risk genetic syndromes

In conclusionsIn conclusions

CEA is recommended CXR CT abdomen is optional Mechanical bowel

preparation is still a common practice

Prophylactic antibiotics is recommended

Blood transfusion based on physiological need

high risk patients & candidates for curative surgery or systemic treatment

Intensive follow up CEA Annual CT scan Surveillance colonoscopy at

3 years and then 5 years

Pre-operative Post -operative

Thank youThank you

Level of evidenceLevel of evidence

Evidence-base approach in the perioperative management and follow-up strategy for colon cancer...

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