FOLLOW UP AFTER COLORECTAL CANCER

SURGERY

Andrew Luck

Colorectal SurgeonNorthern Adelaide Colorectal Unit

Adelaide, South Australia

Honorary Secretary, Colorectal Surgical Society of Australia and New ZealandCSSANZ representative, National Bowel Cancer Screening Program Advisory Group

CANCER SOCIETY OF NEW ZEALAND CANCER WEEK June 2009

RATIONALE

• CRC patients at higher risk of a second primary (metachronous) tumour– Beck et al (1995)

• At 4 years• 7.7% new primary cancer• 62% new adenomatous polyp

• Early detection of recurrence– ?still curable

• Eg single liver or lung metastasis

THE ARGUEMENTS

• Intensive versus routine follow-up

• If intensive, what tests and when?

OVERVIEW

• Literature review– Intensive vs routine follow-up

• Assessment of individual procedures– Colonoscopy– Faecal occult blood tests (FOBT)– Carcinoembryonic antigen (CEA)– CT chest/abdomen/pelvis– Positron Emission Tomography (PET)

• Current Practice

LITERATURE

• Randomised controlled trials comparing intensive vs minimal follow up– None showed a difference – ? Insufficient statistical power

• Meta-analyses– Ann Surg 1994 – non-randomised data– DCR 1998 – randomised and cohort studies– Renegan et al BMJ 2002 - ‘Impact on survival of

intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials’

METHODS

• Medline• Embase• CANCERLIT• Cochrane controlled trials register

• Handsearches– Reference lists– Reviews– Abstracts from meetings– National trial registers

INCLUSION CRITERIA

1. Study design (RCT)

2. Target population– patients with colorectal cancer treated

surgically with curative intent

3. Timing of randomisation– at or shortly after surgery

4. Availability of cancer specific survival data

OUTCOME MEASURES• Primary

– All cause mortality at 5 years

• Secondary– Total number of recurrences– Any type of local recurrences– Isolated local recurrences– Any hepatic metastases– Isolated hepatic metastases– Lung metastases– Intraluminal recurrences– Metachronous colorectal cancers

SUITABLE RCT

• Makela et al - Arch Surg 1995

• Ohlsson et al - DCR 1995

• Schoemaker et al - Gastro 1998

• Pietra et al – DCR 1998

• Kjeldsen et al – Br J Surg 1997

MAKELA ET AL

INTENSIVE

• 3/12 2 years, 6/12– Exam, FBC, FOBT,

CEA, CXR, rigid sig.

• Colonoscopy 12/12• USS liver 6/12• CT 12/12

CONTROL

• 3/12 2 years, 6/12– Exam, FBC, FOBT,

CEA, CXR, rigid sig.

• Ba enema 12/12

OHLSSON ET AL

INTENSIVE

• 3/12 2 years, 6/12– Exam, rigid sig, LFT,

CEA, FOBT, CXR

• Colonoscopy – 3, 15, 30, 60/12

• CT – 3, 6, 12, 18, 24/12

CONTROL

• No systematic follow up

SCHOEMAKER ET AL

INTENSIVE

• 3/12 2 years, 6/12– Exam, FBC, LFT,

FOBT, CEA

• CXR 12/12• Colonoscopy 12/12• CT liver 12/12

CONTROL

• 3/12 2 years, 6/12– Exam, FBC, LFT,

FOBT, CEA

PIETRA ET AL

INTENSIVE

• 3/12 2 years, 6/12– Exam, US liver,

CEA

• Colonoscopy 12/12• CXR 12/12• CT scan 12/12

CONTROL

• 3/12 2 years, 6/12– Exam, US liver,

CEA

• Colonoscopy 12/12• CXR 12/12

KJELDSEN ET AL

INTENSIVE

• 6/12 3 years, 12/12– Exam, FBC, ESR,

LFT, FOBT, CXR, colonoscopy

CONTROL

• 5 and 10 years– Exam, FBC, ESR,

LFT, FOBT, CXR, colonoscopy

ALL CAUSE MORTALITYTrial Intensive Control RR (95%)

Makela et al 23/52 (44) 27/54 (50) 0.88 (0.59-1.33)

Ohlsson et al 15/53 (28) 22/54 (41) 0.69 (0.41-1.19)

Schoemaker 43/167 (26) 55/158 (35) 0.74 (0.53-1.03)

Pietra et al 28/104 (27) 43/103 (42) 0.64 (0.44-0.95)

Kjeldsen et al 88/290 (30) 100/307 (33) 0.93 (0.73-1.18)

POOLED DATA

197/666 (30)

247/676 (37)

0.81

(0.70-0.94)

ALL CAUSE MORTALITY

• Absolute reduction in mortality– 9-13%

• Number needed to treat (the number of patients needed to

prevent one death)– 8-11 patients

TIME TO RELAPSE (MONTHS)

Trial Intensive Control Diff means (95%)

Makela et al 10.0 15.0 -5.0 (-7.99 to –2.01)

Ohlsson et al 20.4 24.0 -3.6 (-6.45 to –0.75)

Pietra et al 10.3 20.2 -9.9 (-11.19 to –8.61)

Kjeldsen et al 17.7 26.5 -8.8 (-10.25 to –7.35)

POOLED DATA

-8.5

(-9.37 to –7.62

NHMRC GUIDELINES2005

“Intensive follow up is recommended for patients who have had surgery

for potentially curable disease”

Level of evidence I

Strength of recommendation A

NHMRC GUIDELINES2005

• “…..although optimal investigation and pathways are yet to be firmly established”

SURVEILLANCE OPTIONS

• For intraluminal recurrence and metachronous colorectal disease– Colonoscopy– Faecal occult blood tests

• For locoregional and distant metastases(NB 85% of recurrences by 2 years, 98.5% by 5 years DCR

2008)– Carcinoembryonic antigen– Radiology

• CT chest/abdomen/pelvis• Ultrasound liver• Chest X-ray

– PET scan

COLONOSCOPY

• At the time of diagnosis– 2-4% synchronous cancer rate– 40% synchronous adenoma rate

• If not possible (obstructing cancer)– 3 to 6 months post operatively

• Timing of subsequent colonoscopy contentious

• Then 3 yearly, unless pathology found

COLONOSCOPY

• Timing of first post op colonoscopy– NHMRC Guidelines

• 3 years

• But, – Early metachronous lesions (Beck et al)– Quality of initial colonoscopy

• Not performed by same specialist• Medicolegal consequences

• ‘Baseline’ colonoscopy at 12 months• Then 3 yearly unless pathology found

FAECAL OCCULT BLOD TESTS

• No evidence that FOBT adds to the effectiveness of a colonoscopy follow up program

CARCINOEMBRYONIC ANTIGEN

• Antigen secreted by ~60% of colorectal cancers– Useful if raised at time of diagnosis– Less useful if not raised

• Serial CEA shown to decrease mortality from metastatic and recurrent disease (Renehan et al 2002)

• Perform 3-6 monthly

RADIOLOGY

• CT liver shown to detect liver metastases and to define a group where hepatic resection is possible with the intent to cure

• USS liver not fully assessed• Chest Xray – insufficient data

• Why not CT chest/abdomen/pelvis?– Assessment of liver, lung and locoregional recurrence

in one investigation– Radiological investigation of choice

PET SCAN

• Nuclear medicine test– Follow up of raised CEA where CT equivocal– PET/CT now available

• 2-[18F]fluoro-2-deoxy-D-glucose(F-18-FDG)

– Radiolabelled analogue of glucose– Preferentially transported into malignant cells– Trapped in CRC cancer cells– Detected by gamma camera

PET SCAN

• Flanagan (1998)– PET in patients with CEA rise– PET abnormal in 17/22– Biopsy or follow-up confirmed

recurrence– 4 patients had curative resections– PPV 89% NPV 100%

PET SCAN

• Oguinbiyi (1997)– LOCAL Sensitivity PET 91% vs CT 52%

Specificity PET 100% vs CT 80%– LIVER Sensitivity PET 95% vs CT 74%

Specificity PET 100% vs CT 85%

• Schiepers (1995)– LOCAL Sensitivity PET 93% vs CT 60%– Specificity PET 97% vs CT 72%– LIVER Sensitivity PET 94% vs CT 85%

CURRENT PRACTICE

• Clinical review – 3/12 for 2 years– Yearly until 5 years– Encourage review if symptoms occur

• Colonoscopy– At diagnosis

• At 3-6 months if incomplete preop– At 12 months– Every 3 years

CURRENT PRACTICE

• CEA– 3/12 for 2 years

• CT chest/abdomen/pelvis– At 12 and 24 months

• PET/CT– If CEA rises