Cancer Res Treat.  2013 Sep;45(3):186-192.

Prognostic Significance of Serum Carcinoembryonic Antigen Normalization on Survival in Rectal Cancer Treated with Preoperative Chemoradiation

• Chung MJ
• Chung SM
• Kim JY
• Ryu MR

Abstract

PURPOSE
The purpose of this retrospective study was to identify factors predictive of survival in rectal cancer patients who received surgery with curative intent after preoperative chemoradiotherapy (CRT).
MATERIALS AND METHODS
Between July 1996 and June 2010, 104 patients underwent surgery for rectal cancer after preoperative CRT. The median dose of radiotherapy was 50.4 Gy (range, 43.2 to 54.4 Gy) for 6 weeks. Chemotherapy was a bolus injection of 5-fluorouracil and leucovorin for the first and last week of radiotherapy (n=84, 77.1%) or capecitabine administered daily during radiotherapy (n=17, 16.3%). Low anterior resection (n=86, 82.7%) or abdominoperineal resection (n=18, 17.3%) was performed at a median 47 days from the end of radiotherapy, and four cycles of adjuvant chemotherapy was administered. The serum carcinoembryonic antigen (CEA) level was checked at initial diagnosis and just before surgery.
RESULTS
After a median follow-up of 48 months (range, 9 to 174 months), 5-year disease free survival (DFS) was 74.5% and 5-year overall survival (OS) was 86.4%. Down staging of T diagnoses occurred in 32 patients (30.8%) and of N diagnoses in 40 patients (38.5%). The CEA change from initial diagnosis to pre-surgery (high-high vs. high-normal vs. normal-normal) was a statistically significant prognostic factor for DFS (p=0.012), OS (p=0.002), and distant metastasis free survival (p=0.018) in a multivariate analysis.
CONCLUSION
Patients who achieve normal CEA level by the time of surgery have a more favorable outcome than those who retain a high CEA level after preoperative CRT. The normalization of CEA levels can provide important information about the prognosis in rectal cancer treatment.

Keyword

Carcinoembryonic antigen; Chemoradiotherapy; Rectal neoplasms

MeSH Terms

Carcinoembryonic Antigen
Chemoradiotherapy
Chemotherapy, Adjuvant
Deoxycytidine
Disease-Free Survival
Fluorouracil
Follow-Up Studies
Humans
Leucovorin
Neoplasm Metastasis
Prognosis
Rectal Neoplasms
Retrospective Studies
Capecitabine
Carcinoembryonic Antigen
Deoxycytidine
Fluorouracil
Leucovorin

Figure

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  Fig. 1 Overall survival rate by carcinoembryonic antigen level change.

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  Fig. 2 Distant metastasis free survival rate by carcinoembryonic antigen (CEA) level change.

Reference

1. Jung KW, Park S, Kong HJ, Won YJ, Lee JY, Park EC, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2008. Cancer Res Treat. 2011; 43:1–11. PMID: 21509157.

2. Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004; 351:1731–1740. PMID: 15496622.

3. Bosset JF, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, et al. Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results: EORTC 22921. J Clin Oncol. 2005; 23:5620–5627. PMID: 16009958.

4. Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006; 355:1114–1123. PMID: 16971718.

5. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Pudelko M, et al. Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiother Oncol. 2004; 72:15–24. PMID: 15236870.

6. Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006; 24:4620–4625. PMID: 17008704.

7. Lim SB, Choi HS, Jeong SY, Kim DY, Jung KH, Hong YS, et al. Optimal surgery time after preoperative chemoradiotherapy for locally advanced rectal cancers. Ann Surg. 2008; 248:243–251. PMID: 18650634.

8. Wong RK, Tandan V, De Silva S, Figueredo A. Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma. Cochrane Database Syst Rev. 2007; CD002102. PMID: 17443515.

9. Chen CC, Yang SH, Lin JK, Lin TC, Chen WS, Jiang JK, et al. Is it reasonable to add preoperative serum level of CEA and CA19-9 to staging for colorectal cancer? J Surg Res. 2005; 124:169–174. PMID: 15820244.

10. Takagawa R, Fujii S, Ohta M, Nagano Y, Kunisaki C, Yamagishi S, et al. Preoperative serum carcinoembryonic antigen level as a predictive factor of recurrence after curative resection of colorectal cancer. Ann Surg Oncol. 2008; 15:3433–3439. PMID: 18846401.

11. Secco GB, Fardelli R, Gianquinto D, Bonfante P, Baldi E, Ravera G, et al. Efficacy and cost of risk-adapted follow-up in patients after colorectal cancer surgery: a prospective, randomized and controlled trial. Eur J Surg Oncol. 2002; 28:418–423. PMID: 12099653.

12. Huh JW, Oh BR, Kim HR, Kim YJ. Preoperative carcinoembryonic antigen level as an independent prognostic factor in potentially curative colon cancer. J Surg Oncol. 2010; 101:396–400. PMID: 20119979.

13. Moureau-Zabotto L, Farnault B, de Chaisemartin C, Esterni B, Lelong B, Viret F, et al. Predictive factors of tumor response after neoadjuvant chemoradiation for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2011; 80:483–491. PMID: 21093174.

14. Farnault B, Moureau-Zabotto L, de Chaisemartin C, Esterni B, Lelong B, Viret F, et al. Predictive factors of tumour response after neoadjuvant chemoradiation for locally advanced rectal cancer and correlation of these factors with survival. Cancer Radiother. 2011; 15:279–286. PMID: 21515083.

15. Das P, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, Wolff RA, et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer. 2007; 109:1750–1755. PMID: 17387743.

16. Park YA, Sohn SK, Seong J, Baik SH, Lee KY, Kim NK, et al. Serum CEA as a predictor for the response to preoperative chemoradiation in rectal cancer. J Surg Oncol. 2006; 93:145–150. PMID: 16425302.

17. Thomas SN, Zhu F, Schnaar RL, Alves CS, Konstantopoulos K. Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E- and L-selectin in shear flow. J Biol Chem. 2008; 283:15647–15655. PMID: 18375392.

18. Thomas SN, Tong Z, Stebe KJ, Konstantopoulos K. Identification, characterization and utilization of tumor cell selectin ligands in the design of colon cancer diagnostics. Biorheology. 2009; 46:207–225. PMID: 19581728.

19. Lee JW, Park KD, Im JA, Hwang HJ, Kim SH. Serum carcinoembryonic antigen is associated with metabolic syndrome in female Korean non-smokers. Clin Chim Acta. 2011; 412:527–530. PMID: 21138741.

20. Jang NY, Kang SB, Kim DW, Kim JH, Lee KW, Kim IA, et al. The role of carcinoembryonic antigen after neoadjuvant chemoradiotherapy in patients with rectal cancer. Dis Colon Rectum. 2011; 54:245–252. PMID: 21228676.

21. Kim CW, Yu CS, Yang SS, Kim KH, Yoon YS, Yoon SN, et al. Clinical significance of pre- to post-chemoradiotherapy s-CEA reduction ratio in rectal cancer patients treated with preoperative chemoradiotherapy and curative resection. Ann Surg Oncol. 2011; 18:3271–3277. PMID: 21537868.

22. Wiratkapun S, Kraemer M, Seow-Choen F, Ho YH, Eu KW. High preoperative serum carcinoembryonic antigen predicts metastatic recurrence in potentially curative colonic cancer: results of a five-year study. Dis Colon Rectum. 2001; 44:231–235. PMID: 11227940.

23. Lin JK, Lin CC, Yang SH, Wang HS, Jiang JK, Lan YT, et al. Early postoperative CEA level is a better prognostic indicator than is preoperative CEA level in predicting prognosis of patients with curable colorectal cancer. Int J Colorectal Dis. 2011; 26:1135–1141. PMID: 21538056.

24. Kim JY, Kim NK, Sohn SK, Kim YW, Kim KJ, Hur H, et al. Prognostic value of postoperative CEA clearance in rectal cancer patients with high preoperative CEA levels. Ann Surg Oncol. 2009; 16:2771–2778. PMID: 19657698.

25. Ha YH, Jeong SY, Lim SB, Choi HS, Hong YS, Chang HJ, et al. Influence of preoperative chemoradiotherapy on the number of lymph nodes retrieved in rectal cancer. Ann Surg. 2010; 252:336–340. PMID: 20647928.