Earliest possible diagnosis of the recurrence

Curative second-look surgery

Improved overall survival

Follow-upThe purpose of tumor markers

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-upCRC tumor markers

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%

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

Sites Group 2 (%) n=325 (Not

Resectable)

Group 3 (%) n=96

(Resectable)

Total (%) n=421

Physician exam

1,5 0 1,2

CEA 40,3 31,2 38,2

Chest X ray 4,9 12,5 6,7

Colonoscopy 4,6 14,6 6,9

Patient symptoms

32,6 25,0 30,9

Multiple/other

16,0 16,7 16,2

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)

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.

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

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

Aggressive follow-up

Conventional follow-up

Clinically detected (refused participation)

Follow-upCEA-trial

Cancer Research Campaign; UKCancer Research Campaign; UK

Aggr. Conv. Clin. det.

No 108 No 108 No 195

2nd - look (number) 66 25 89Macroscopic cure 16 (25%) 7 (28%) 28

(31%)5-years survival 20 % 22 % 19 %Median surv. (years) 2.67 3.18 2.59

Cancer Research Campaign; UKCancer Research Campaign; UK

CEA-trial

Follow-up

Follow-upCEA-trial

Cancer Research Campaign; UKCancer Research Campaign; UK

Conclusion

No effect on survival

Same proportion curative 2nd - look op.

CEA cannot be recommended !

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.