FOLLOW UP AFTER COLORECTAL CANCER SURGERY Andrew Luck Colorectal Surgeon Northern Adelaide Colorectal Unit Adelaide, South...
RATIONALE <ul><li>CRC patients at higher risk of a second primary (metachronous) tumour </li></ul><ul><ul><li>Beck et al (...
THE ARGUEMENTS <ul><li>Intensive versus routine follow-up </li></ul><ul><li>If intensive, what tests and when? </li></ul>
OVERVIEW <ul><li>Literature review </li></ul><ul><ul><li>Intensive vs routine follow-up </li></ul></ul><ul><li>Assessment ...
LITERATURE <ul><li>Randomised controlled trials comparing intensive vs minimal follow up </li></ul><ul><ul><li>None showed...
METHODS <ul><li>Medline </li></ul><ul><li>Embase </li></ul><ul><li>CANCERLIT </li></ul><ul><li>Cochrane controlled trials ...
INCLUSION CRITERIA <ul><li>Study design (RCT) </li></ul><ul><li>Target population </li></ul><ul><ul><li>patients with colo...
OUTCOME MEASURES <ul><li>Primary </li></ul><ul><ul><li>All cause mortality at 5 years </li></ul></ul><ul><li>Secondary </l...
SUITABLE RCT <ul><li>Makela et al  - Arch Surg 1995 </li></ul><ul><li>Ohlsson et al  - DCR 1995 </li></ul><ul><li>Schoemak...
MAKELA ET AL <ul><li>INTENSIVE </li></ul><ul><li>3/12 2 years, 6/12 </li></ul><ul><ul><li>Exam, FBC, FOBT, CEA, CXR, rigid...
OHLSSON ET AL <ul><li>INTENSIVE </li></ul><ul><li>3/12 2 years, 6/12 </li></ul><ul><ul><li>Exam, rigid sig, LFT, CEA, FOBT...
SCHOEMAKER ET AL <ul><li>INTENSIVE </li></ul><ul><li>3/12 2 years, 6/12 </li></ul><ul><ul><li>Exam, FBC, LFT, FOBT, CEA </...
PIETRA ET AL <ul><li>INTENSIVE </li></ul><ul><li>3/12 2 years, 6/12 </li></ul><ul><ul><li>Exam, US liver, CEA </li></ul></...
KJELDSEN ET AL <ul><li>INTENSIVE </li></ul><ul><li>6/12 3 years, 12/12 </li></ul><ul><ul><li>Exam, FBC, ESR, LFT, FOBT, CX...
ALL CAUSE MORTALITY 0.81 (0.70-0.94) 247/676 (37) 197/666 (30) POOLED DATA 0.93 (0.73-1.18) 100/307 (33) 88/290 (30) Kjeld...
ALL CAUSE MORTALITY <ul><li>Absolute reduction in mortality </li></ul><ul><ul><li>9-13% </li></ul></ul><ul><li>Number need...
TIME TO RELAPSE (MONTHS) -8.5  (-9.37 to –7.62 POOLED DATA -8.8 (-10.25 to –7.35) 26.5 17.7 Kjeldsen et al -9.9 (-11.19 to...
NHMRC GUIDELINES 2005 <ul><li>“ Intensive follow up is recommended for patients who have had surgery for potentially curab...
NHMRC GUIDELINES 2005 <ul><li>“… ..although optimal investigation and pathways are yet to be firmly established” </li></ul>
SURVEILLANCE OPTIONS <ul><li>For intraluminal recurrence and metachronous colorectal disease </li></ul><ul><ul><li>Colonos...
COLONOSCOPY <ul><li>At the time of diagnosis </li></ul><ul><ul><li>2-4% synchronous cancer rate </li></ul></ul><ul><ul><li...
COLONOSCOPY <ul><li>Timing of first post op colonoscopy </li></ul><ul><ul><li>NHMRC Guidelines </li></ul></ul><ul><ul><ul>...
 
FAECAL OCCULT BLOD TESTS <ul><li>No evidence that FOBT adds to the effectiveness of a colonoscopy follow up program </li><...
CARCINOEMBRYONIC ANTIGEN <ul><li>Antigen secreted by ~60% of colorectal cancers </li></ul><ul><ul><li>Useful if raised at ...
RADIOLOGY <ul><li>CT liver shown to detect liver metastases and to define a group where hepatic resection is possible with...
PET SCAN <ul><li>Nuclear medicine test </li></ul><ul><ul><li>Follow up of raised CEA where CT equivocal </li></ul></ul><ul...
PET SCAN <ul><li>Flanagan (1998) </li></ul><ul><ul><li>PET in patients with CEA rise </li></ul></ul><ul><ul><li>PET abnorm...
PET SCAN <ul><li>Oguinbiyi (1997) </li></ul><ul><ul><li>LOCAL Sensitivity PET 91% vs CT 52% </li></ul></ul><ul><ul><li>Spe...
CURRENT PRACTICE <ul><li>Clinical review  </li></ul><ul><ul><li>3/12 for 2 years </li></ul></ul><ul><ul><li>Yearly until 5...
CURRENT PRACTICE <ul><li>CEA </li></ul><ul><ul><li>3/12 for 2 years </li></ul></ul><ul><li>CT chest/abdomen/pelvis </li></...
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Follow Up After Colorectal Cancer Surgery

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Follow Up After Colorectal Cancer Surgery

  1. 1. FOLLOW UP AFTER COLORECTAL CANCER SURGERY Andrew Luck Colorectal Surgeon Northern Adelaide Colorectal Unit Adelaide, South Australia Honorary Secretary, Colorectal Surgical Society of Australia and New Zealand CSSANZ representative, National Bowel Cancer Screening Program Advisory Group CANCER SOCIETY OF NEW ZEALAND CANCER WEEK June 2009
  2. 2. RATIONALE <ul><li>CRC patients at higher risk of a second primary (metachronous) tumour </li></ul><ul><ul><li>Beck et al (1995) </li></ul></ul><ul><ul><ul><li>At 4 years </li></ul></ul></ul><ul><ul><ul><li>7.7% new primary cancer </li></ul></ul></ul><ul><ul><ul><li>62% new adenomatous polyp </li></ul></ul></ul><ul><li>Early detection of recurrence </li></ul><ul><ul><li>?still curable </li></ul></ul><ul><ul><ul><li>Eg single liver or lung metastasis </li></ul></ul></ul>
  3. 3. THE ARGUEMENTS <ul><li>Intensive versus routine follow-up </li></ul><ul><li>If intensive, what tests and when? </li></ul>
  4. 4. OVERVIEW <ul><li>Literature review </li></ul><ul><ul><li>Intensive vs routine follow-up </li></ul></ul><ul><li>Assessment of individual procedures </li></ul><ul><ul><li>Colonoscopy </li></ul></ul><ul><ul><li>Faecal occult blood tests (FOBT) </li></ul></ul><ul><ul><li>Carcinoembryonic antigen (CEA) </li></ul></ul><ul><ul><li>CT chest/abdomen/pelvis </li></ul></ul><ul><ul><li>Positron Emission Tomography (PET) </li></ul></ul><ul><li>Current Practice </li></ul>
  5. 5. LITERATURE <ul><li>Randomised controlled trials comparing intensive vs minimal follow up </li></ul><ul><ul><li>None showed a difference </li></ul></ul><ul><ul><li>? Insufficient statistical power </li></ul></ul><ul><li>Meta-analyses </li></ul><ul><ul><li>Ann Surg 1994 – non-randomised data </li></ul></ul><ul><ul><li>DCR 1998 – randomised and cohort studies </li></ul></ul><ul><ul><li>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’ </li></ul></ul>
  6. 6. METHODS <ul><li>Medline </li></ul><ul><li>Embase </li></ul><ul><li>CANCERLIT </li></ul><ul><li>Cochrane controlled trials register </li></ul><ul><li>Handsearches </li></ul><ul><ul><li>Reference lists </li></ul></ul><ul><ul><li>Reviews </li></ul></ul><ul><ul><li>Abstracts from meetings </li></ul></ul><ul><ul><li>National trial registers </li></ul></ul>
  7. 7. INCLUSION CRITERIA <ul><li>Study design (RCT) </li></ul><ul><li>Target population </li></ul><ul><ul><li>patients with colorectal cancer treated surgically with curative intent </li></ul></ul><ul><li>Timing of randomisation </li></ul><ul><ul><li>at or shortly after surgery </li></ul></ul><ul><li>Availability of cancer specific survival data </li></ul>
  8. 8. OUTCOME MEASURES <ul><li>Primary </li></ul><ul><ul><li>All cause mortality at 5 years </li></ul></ul><ul><li>Secondary </li></ul><ul><ul><li>Total number of recurrences </li></ul></ul><ul><ul><li>Any type of local recurrences </li></ul></ul><ul><ul><li>Isolated local recurrences </li></ul></ul><ul><ul><li>Any hepatic metastases </li></ul></ul><ul><ul><li>Isolated hepatic metastases </li></ul></ul><ul><ul><li>Lung metastases </li></ul></ul><ul><ul><li>Intraluminal recurrences </li></ul></ul><ul><ul><li>Metachronous colorectal cancers </li></ul></ul>
  9. 9. SUITABLE RCT <ul><li>Makela et al - Arch Surg 1995 </li></ul><ul><li>Ohlsson et al - DCR 1995 </li></ul><ul><li>Schoemaker et al - Gastro 1998 </li></ul><ul><li>Pietra et al – DCR 1998 </li></ul><ul><li>Kjeldsen et al – Br J Surg 1997 </li></ul>
  10. 10. MAKELA ET AL <ul><li>INTENSIVE </li></ul><ul><li>3/12 2 years, 6/12 </li></ul><ul><ul><li>Exam, FBC, FOBT, CEA, CXR, rigid sig. </li></ul></ul><ul><li>Colonoscopy 12/12 </li></ul><ul><li>USS liver 6/12 </li></ul><ul><li>CT 12/12 </li></ul><ul><li>CONTROL </li></ul><ul><li>3/12 2 years, 6/12 </li></ul><ul><ul><li>Exam, FBC, FOBT, CEA, CXR, rigid sig. </li></ul></ul><ul><li>Ba enema 12/12 </li></ul>
  11. 11. OHLSSON ET AL <ul><li>INTENSIVE </li></ul><ul><li>3/12 2 years, 6/12 </li></ul><ul><ul><li>Exam, rigid sig, LFT, CEA, FOBT, CXR </li></ul></ul><ul><li>Colonoscopy </li></ul><ul><ul><li>3, 15, 30, 60/12 </li></ul></ul><ul><li>CT </li></ul><ul><ul><li>3, 6, 12, 18, 24/12 </li></ul></ul><ul><li>CONTROL </li></ul><ul><li>No systematic follow up </li></ul>
  12. 12. SCHOEMAKER ET AL <ul><li>INTENSIVE </li></ul><ul><li>3/12 2 years, 6/12 </li></ul><ul><ul><li>Exam, FBC, LFT, FOBT, CEA </li></ul></ul><ul><li>CXR 12/12 </li></ul><ul><li>Colonoscopy 12/12 </li></ul><ul><li>CT liver 12/12 </li></ul><ul><li>CONTROL </li></ul><ul><li>3/12 2 years, 6/12 </li></ul><ul><ul><li>Exam, FBC, LFT, FOBT, CEA </li></ul></ul>
  13. 13. PIETRA ET AL <ul><li>INTENSIVE </li></ul><ul><li>3/12 2 years, 6/12 </li></ul><ul><ul><li>Exam, US liver, CEA </li></ul></ul><ul><li>Colonoscopy 12/12 </li></ul><ul><li>CXR 12/12 </li></ul><ul><li>CT scan 12/12 </li></ul><ul><li>CONTROL </li></ul><ul><li>3/12 2 years, 6/12 </li></ul><ul><ul><li>Exam, US liver, CEA </li></ul></ul><ul><li>Colonoscopy 12/12 </li></ul><ul><li>CXR 12/12 </li></ul>
  14. 14. KJELDSEN ET AL <ul><li>INTENSIVE </li></ul><ul><li>6/12 3 years, 12/12 </li></ul><ul><ul><li>Exam, FBC, ESR, LFT, FOBT, CXR, colonoscopy </li></ul></ul><ul><li>CONTROL </li></ul><ul><li>5 and 10 years </li></ul><ul><ul><li>Exam, FBC, ESR, LFT, FOBT, CXR, colonoscopy </li></ul></ul>
  15. 15. ALL CAUSE MORTALITY 0.81 (0.70-0.94) 247/676 (37) 197/666 (30) POOLED DATA 0.93 (0.73-1.18) 100/307 (33) 88/290 (30) Kjeldsen et al 0.64 (0.44-0.95) 43/103 (42) 28/104 (27) Pietra et al 0.74 (0.53-1.03) 55/158 (35) 43/167 (26) Schoemaker 0.69 (0.41-1.19) 22/54 (41) 15/53 (28) Ohlsson et al 0.88 (0.59-1.33) 27/54 (50) 23/52 (44) Makela et al RR (95%) Control Intensive Trial
  16. 16. ALL CAUSE MORTALITY <ul><li>Absolute reduction in mortality </li></ul><ul><ul><li>9-13% </li></ul></ul><ul><li>Number needed to treat </li></ul><ul><ul><li>(the number of patients needed to prevent one death) </li></ul></ul><ul><ul><li>8-11 patients </li></ul></ul>
  17. 17. TIME TO RELAPSE (MONTHS) -8.5 (-9.37 to –7.62 POOLED DATA -8.8 (-10.25 to –7.35) 26.5 17.7 Kjeldsen et al -9.9 (-11.19 to –8.61) 20.2 10.3 Pietra et al -3.6 (-6.45 to –0.75) 24.0 20.4 Ohlsson et al -5.0 (-7.99 to –2.01) 15.0 10.0 Makela et al Diff means (95%) Control Intensive Trial
  18. 18. NHMRC GUIDELINES 2005 <ul><li>“ Intensive follow up is recommended for patients who have had surgery for potentially curable disease” </li></ul><ul><li>Level of evidence I </li></ul><ul><li>Strength of recommendation A </li></ul>
  19. 19. NHMRC GUIDELINES 2005 <ul><li>“… ..although optimal investigation and pathways are yet to be firmly established” </li></ul>
  20. 20. SURVEILLANCE OPTIONS <ul><li>For intraluminal recurrence and metachronous colorectal disease </li></ul><ul><ul><li>Colonoscopy </li></ul></ul><ul><ul><li>Faecal occult blood tests </li></ul></ul><ul><li>For locoregional and distant metastases </li></ul><ul><li>(NB 85% of recurrences by 2 years, 98.5% by 5 years DCR 2008) </li></ul><ul><ul><li>Carcinoembryonic antigen </li></ul></ul><ul><ul><li>Radiology </li></ul></ul><ul><ul><ul><li>CT chest/abdomen/pelvis </li></ul></ul></ul><ul><ul><ul><li>Ultrasound liver </li></ul></ul></ul><ul><ul><ul><li>Chest X-ray </li></ul></ul></ul><ul><ul><li>PET scan </li></ul></ul>
  21. 21. COLONOSCOPY <ul><li>At the time of diagnosis </li></ul><ul><ul><li>2-4% synchronous cancer rate </li></ul></ul><ul><ul><li>40% synchronous adenoma rate </li></ul></ul><ul><li>If not possible (obstructing cancer) </li></ul><ul><ul><li>3 to 6 months post operatively </li></ul></ul><ul><li>Timing of subsequent colonoscopy contentious </li></ul><ul><li>Then 3 yearly, unless pathology found </li></ul>
  22. 22. COLONOSCOPY <ul><li>Timing of first post op colonoscopy </li></ul><ul><ul><li>NHMRC Guidelines </li></ul></ul><ul><ul><ul><li>3 years </li></ul></ul></ul><ul><li>But, </li></ul><ul><ul><li>Early metachronous lesions (Beck et al) </li></ul></ul><ul><ul><li>Quality of initial colonoscopy </li></ul></ul><ul><ul><ul><li>Not performed by same specialist </li></ul></ul></ul><ul><ul><ul><li>Medicolegal consequences </li></ul></ul></ul><ul><li>‘ Baseline’ colonoscopy at 12 months </li></ul><ul><li>Then 3 yearly unless pathology found </li></ul>
  23. 24. FAECAL OCCULT BLOD TESTS <ul><li>No evidence that FOBT adds to the effectiveness of a colonoscopy follow up program </li></ul>
  24. 25. CARCINOEMBRYONIC ANTIGEN <ul><li>Antigen secreted by ~60% of colorectal cancers </li></ul><ul><ul><li>Useful if raised at time of diagnosis </li></ul></ul><ul><ul><li>Less useful if not raised </li></ul></ul><ul><li>Serial CEA shown to decrease mortality from metastatic and recurrent disease (Renehan et al 2002) </li></ul><ul><li>Perform 3-6 monthly </li></ul>
  25. 26. RADIOLOGY <ul><li>CT liver shown to detect liver metastases and to define a group where hepatic resection is possible with the intent to cure </li></ul><ul><li>USS liver not fully assessed </li></ul><ul><li>Chest Xray – insufficient data </li></ul><ul><li>Why not CT chest/abdomen/pelvis? </li></ul><ul><ul><li>Assessment of liver, lung and locoregional recurrence in one investigation </li></ul></ul><ul><ul><li>Radiological investigation of choice </li></ul></ul>
  26. 27. PET SCAN <ul><li>Nuclear medicine test </li></ul><ul><ul><li>Follow up of raised CEA where CT equivocal </li></ul></ul><ul><ul><li>PET/CT now available </li></ul></ul><ul><li>2-[ 18 F]fluoro-2-deoxy-D-glucose (F-18-FDG) </li></ul><ul><ul><li>Radiolabelled analogue of glucose </li></ul></ul><ul><ul><li>Preferentially transported into malignant cells </li></ul></ul><ul><ul><li>Trapped in CRC cancer cells </li></ul></ul><ul><ul><li>Detected by gamma camera </li></ul></ul>
  27. 28. PET SCAN <ul><li>Flanagan (1998) </li></ul><ul><ul><li>PET in patients with CEA rise </li></ul></ul><ul><ul><li>PET abnormal in 17/22 </li></ul></ul><ul><ul><li>Biopsy or follow-up confirmed recurrence </li></ul></ul><ul><ul><li>4 patients had curative resections </li></ul></ul><ul><ul><li>PPV 89% NPV 100% </li></ul></ul>
  28. 29. PET SCAN <ul><li>Oguinbiyi (1997) </li></ul><ul><ul><li>LOCAL Sensitivity PET 91% vs CT 52% </li></ul></ul><ul><ul><li>Specificity PET 100% vs CT 80% </li></ul></ul><ul><ul><li>LIVER Sensitivity PET 95% vs CT 74% </li></ul></ul><ul><ul><li> Specificity PET 100% vs CT 85% </li></ul></ul><ul><li>Schiepers (1995) </li></ul><ul><ul><li>LOCAL Sensitivity PET 93% vs CT 60% </li></ul></ul><ul><ul><li>Specificity PET 97% vs CT 72% </li></ul></ul><ul><ul><li>LIVER Sensitivity PET 94% vs CT 85% </li></ul></ul>
  29. 30. CURRENT PRACTICE <ul><li>Clinical review </li></ul><ul><ul><li>3/12 for 2 years </li></ul></ul><ul><ul><li>Yearly until 5 years </li></ul></ul><ul><ul><li>Encourage review if symptoms occur </li></ul></ul><ul><li>Colonoscopy </li></ul><ul><ul><li>At diagnosis </li></ul></ul><ul><ul><ul><li>At 3-6 months if incomplete preop </li></ul></ul></ul><ul><ul><li>At 12 months </li></ul></ul><ul><ul><li>Every 3 years </li></ul></ul>
  30. 31. CURRENT PRACTICE <ul><li>CEA </li></ul><ul><ul><li>3/12 for 2 years </li></ul></ul><ul><li>CT chest/abdomen/pelvis </li></ul><ul><ul><li>At 12 and 24 months </li></ul></ul><ul><li>PET/CT </li></ul><ul><ul><li>If CEA rises </li></ul></ul>

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