1.  Earliest possible diagnosis of the recurrence  Curative second-look surgery  Improved overall survival Follow-up The purpose of tumor markers

2.  CEA, Ca 19-9, Ca 242, Ca 72-4, cytokeratins, VEGF, p 53  The role of these markers: -Diagnosis -Staging -Prognosis -Detection of the recurrence  At the present there`s no ideal tumor marker! Follow-up CRC tumor markers

3. Carcinoembryonic antigen (CEA)  Discovered in 1965, seen as THE marker for CRC -in 25% of the cases with known CRC proved to be negative  Preoperative assessment of the extent and outcome of the disease  Postoperative follow-up -Plasma CEA level, earliest single sign of the recurrence in 13-89% -CEA directed second-look surgery, resectability rate 44-58% with 5- year survival 30%

4. R. Graham, Ann Surg 1998. First indicators of recurrent disease Follow-up Follow-up of 421 patients who developed recurrent disease Eastern Cooperative Oncology Group SitesGroup 2 (%) n=325 (Not Resectable) Group 3 (%) n=96 (Resectable) Total (%) n=421 Physician exam1,501,2 CEA40,331,238,2 Chest X ray4,912,56,7 Colonoscopy4,614,66,9 Patient symptoms 32,625,030,9 Multiple/other16,016,716,2

5. Results from Intergroup Study 0114 First Smptoms of the Recurrence 1792 patients; 8,9 years follow-up 715 (42%) with recurrence of the disease No specific symptoms 56% Elevated CEA 17% Pain 15% Obstruction 4% Rectal bleeding 2% Tepper, J Clin Oncol 2003. Carcinoembryonic antigen (CEA)

6.  Elevation of CEA preoperatively 218 (103) 47% >5ng/ml  Recurrence rate higher in Dukes B and C with CEA levels >5 ng/ml, preoperatively Preoperative carcinoembryonic antigen (CEA) Preoperative CEA in CRC WS. Wang et al. Jpn J Clin Oncol 2000.

7. CEA- benefits  Sensitive plasma marker becomes abnormal while disease in asymptomatic phase  In cases of advanced stages of the disease, plasma CEA level- indicator for response to chemotherapy  Postoperative rise of CEA level might be used to detect the recurrence Follow-up

8. CEA  The facts confirm earlier detection of recurrence using CEA but -does such detection result in higher percent of curative second-look procedures? -is CEA based monitoring strategy of early detection of recurrence cost effective? Follow-up

9.  Aggressive follow-up  Conventional follow-up  Clinically detected (refused participation) Follow-up CEA-trial Cancer Research Campaign; UK

10. Aggr. Conv.Clin. det. No 108 No 108 No 195 2nd - look (number) 66 25 89 Macroscopic cure16 (25%)7 (28%) 28 (31%) 5-years survival 20 % 22 % 19 % Median surv. (years) 2.67 3.18 2.59 Cancer Research Campaign; UK CEA-trial Follow-up

11. CEA-trial Cancer Research Campaign; UK Conclusion  No effect on survival  Same proportion curative 2nd - look op.  CEA cannot be recommended !

12. Tumor markers  Cytokeartins as a tumor marker for CRC demonstrate greater sensitivity than CEA  Several antigens have been used for the detection of cytokeratins: TPA, TPS, TPA-M  Cytokeratins cannot identify patients with poor prognosis, before radical surgery for CRC  They present a step towards the perfect tumor marker for CRC Follow-up Luis C. WJG 2005.