Relations of Changes in Serum Carcinoembryonic Antigen Levels before and after Neoadjuvant Chemoradiotherapy and after Surgery to Histologic Response and Outcomes in Patients with Locally Advanced Rectal Cancer
Objectives: The histologic response to neoadjuvant chemoradiotherapy (nCRT) has been intimately related to outcomes in locally advanced rectal cancer. Serum carcinoembryonic antigen (CEA) levels change after nCRT and after surgery as compared with before nCRT. Methods: The subjects were 149 patients...
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| Published in | Oncology Vol. 94; no. 3; pp. 167 - 175 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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Basel, Switzerland
01.01.2018
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| Abstract | Objectives: The histologic response to neoadjuvant chemoradiotherapy (nCRT) has been intimately related to outcomes in locally advanced rectal cancer. Serum carcinoembryonic antigen (CEA) levels change after nCRT and after surgery as compared with before nCRT. Methods: The subjects were 149 patients with locally advanced rectal cancer who received nCRT between 2005 and 2013. The patients were divided into 4 groups according to the serum CEA levels: group 1, 55 patients with negative serum CEA levels before nCRT; group 2, 41 patients with positive serum CEA levels before nCRT that became negative after nCRT; group 3, 37 patients with positive serum CEA levels after nCRT that became negative after surgery; and group 4, 16 patients with positive serum CEA levels after nCRT as well as after surgery. Results: Pathological complete response, T downstaging, and tumor shrinkage were significantly higher in group 1 than in other groups. Disease-free survival was significantly poorer in group 4. The lack of a decrease in the serum CEA level in group 4 was most likely attributed to the persistence of micrometastases outside the resection field. Conclusions: Changes in serum CEA levels measured before nCRT, after nCRT, and after surgery can be used to reliably predict the histologic response to nCRT and outcomes. |
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| AbstractList | The histologic response to neoadjuvant chemoradiotherapy (nCRT) has been intimately related to outcomes in locally advanced rectal cancer. Serum carcinoembryonic antigen (CEA) levels change after nCRT and after surgery as compared with before nCRT.
The subjects were 149 patients with locally advanced rectal cancer who received nCRT between 2005 and 2013. The patients were divided into 4 groups according to the serum CEA levels: group 1, 55 patients with negative serum CEA levels before nCRT; group 2, 41 patients with positive serum CEA levels before nCRT that became negative after nCRT; group 3, 37 patients with positive serum CEA levels after nCRT that became negative after surgery; and group 4, 16 patients with positive serum CEA levels after nCRT as well as after surgery.
Pathological complete response, T downstaging, and tumor shrinkage were significantly higher in group 1 than in other groups. Disease-free survival was significantly poorer in group 4. The lack of a decrease in the serum CEA level in group 4 was most likely attributed to the persistence of micrometastases outside the resection field.
Changes in serum CEA levels measured before nCRT, after nCRT, and after surgery can be used to reliably predict the histologic response to nCRT and outcomes. Objectives: The histologic response to neoadjuvant chemoradiotherapy (nCRT) has been intimately related to outcomes in locally advanced rectal cancer. Serum carcinoembryonic antigen (CEA) levels change after nCRT and after surgery as compared with before nCRT. Methods: The subjects were 149 patients with locally advanced rectal cancer who received nCRT between 2005 and 2013. The patients were divided into 4 groups according to the serum CEA levels: group 1, 55 patients with negative serum CEA levels before nCRT; group 2, 41 patients with positive serum CEA levels before nCRT that became negative after nCRT; group 3, 37 patients with positive serum CEA levels after nCRT that became negative after surgery; and group 4, 16 patients with positive serum CEA levels after nCRT as well as after surgery. Results: Pathological complete response, T downstaging, and tumor shrinkage were significantly higher in group 1 than in other groups. Disease-free survival was significantly poorer in group 4. The lack of a decrease in the serum CEA level in group 4 was most likely attributed to the persistence of micrometastases outside the resection field. Conclusions: Changes in serum CEA levels measured before nCRT, after nCRT, and after surgery can be used to reliably predict the histologic response to nCRT and outcomes. |
| Author | Suzuki, Toshiyuki Ogimi, Takashi Tanaka, Akira Miyakita, Hiroshi Sadahiro, Sotaro Okada, Kazutake Saito, Gota |
| Author_xml | – sequence: 1 givenname: Gota surname: Saito fullname: Saito, Gota – sequence: 2 givenname: Sotaro orcidid: 0000-0002-7800-3880 surname: Sadahiro fullname: Sadahiro, Sotaro email: Sadahiro@is.icc.u-tokai.ac.jp – sequence: 3 givenname: Takashi orcidid: 0000-0001-9819-5149 surname: Ogimi fullname: Ogimi, Takashi – sequence: 4 givenname: Hiroshi surname: Miyakita fullname: Miyakita, Hiroshi – sequence: 5 givenname: Kazutake surname: Okada fullname: Okada, Kazutake – sequence: 6 givenname: Akira surname: Tanaka fullname: Tanaka, Akira – sequence: 7 givenname: Toshiyuki surname: Suzuki fullname: Suzuki, Toshiyuki |
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| CitedBy_id | crossref_primary_10_1016_j_jtumed_2022_06_009 crossref_primary_10_1186_s12885_023_10855_w crossref_primary_10_1111_codi_15694 crossref_primary_10_21294_1814_4861_2018_17_5_60_66 crossref_primary_10_1007_s11605_018_3815_9 crossref_primary_10_3393_ac_2020_11_27 crossref_primary_10_1007_s00268_019_05309_z crossref_primary_10_1093_dote_doac029 crossref_primary_10_3390_jcm10215124 crossref_primary_10_1007_s00261_019_02129_6 crossref_primary_10_4103_ijpm_ijpm_63_22 crossref_primary_10_1007_s10147_021_01919_7 crossref_primary_10_1007_s12029_022_00861_9 crossref_primary_10_1038_s41598_024_83166_0 crossref_primary_10_1002_jso_27667 crossref_primary_10_2147_OTT_S474855 |
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| Copyright | 2017 S. Karger AG, Basel 2017 S. Karger AG, Basel. |
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| Issue | 3 |
| Keywords | Carcinoembryonic antigen Rectal cancer Overall survival Chemoradiotherapy Disease-free survival Histologic response |
| Language | English |
| License | This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. 2017 S. Karger AG, Basel. |
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Kaminsky-Forrett MC, Conroy T, Luporsi E, Peiffert D, Lapeyre M, Boissel P, Guillemin F, Bey P: Prognostic implications of downstaging following preoperative radiation therapy for operable T3-T4 rectal cancer. Int J Radiat Oncol Biol Phys 1998;42:935-941. Kim CW, Yu CS, Yang SS, Kim KH, Yoon YS, Yoon SN, Lim SB, Kim JC: 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. Sadahiro S, Suzuki T, Tanaka A, Okada K, Kamijo A, Murayama C, Akiba T, Nakayama Y: Phase I/II study of preoperative concurrent chemoradiotherapy with S-1 for locally advanced, resectable rectal adenocarcinoma. Oncology 2011;81:306-311. Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, Roussel A, Jacob JH, Segol P, Samama G, et al: Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 1994;73:2680-2686. Gold P, Freedman SO: Specific carcinoembryonic antigens of the human digestive system. J Exp Med 1965;122:467-481. Huh JW, Kim HR, Kim YJ: Clinical prediction of pathological complete response after preoperative chemoradiotherapy for rectal cancer. Dis Colon Rectum 2013;56:698-703. Park YA, Sohn SK, Seong J, Baik SH, Lee KY, Kim NK, Cho CW: Serum CEA as a predictor for the response to preoperative chemoradiation in rectal cancer. J Surg Oncol 2006;93:145-150. Labianca R, Nordlinger B, Beretta GD, Mosconi S, Mandala M, Cervantes A, Arnold D: Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013;24(suppl 6):vi64-vi72. Wang JY, Lu CY, Chu KS, Ma CJ, Wu DC, Tsai HL, Yu FJ, Hsieh JS: Prognostic significance of pre- and postoperative serum carcinoembryonic antigen levels in patients with colorectal cancer. Eur Surg Res 2007;39:245-250. Lee JH, Kim DY, Kim SH, Cho HM, Shim BY, Kim TH, Kim SY, Baek JY, Oh JH, Nam TK, Yoon MS, Jeong JU, Kim K, Chie EK, Jang HS, Kim JS, Kim JH, Jeong BK: Carcinoembryonic antigen has prognostic value for tumor downstaging and recurrence in rectal cancer after preoperative chemoradiotherapy and curative surgery: a multi-institutional and case-matched control study of KROG 14-12. Radiother Oncol 2015;116:202-208. Mohiuddin M, Hayne M, Regine WF, Hanna N, Hagihara PF, McGrath P, Marks GM: Prognostic significance of postchemoradiation stage following preoperative chemotherapy and radiation for advanced/recurrent rectal cancers. Int J Radiat Oncol Biol Phys 2000;48:1075-1080. Yoon SM, Kim DY, Kim TH, Jung KH, Chang HJ, Koom WS, Lim SB, Choi HS, Jeong SY, Park JG: Clinical parameters predicting pathologic tumor response after preoperative chemoradiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys |
| References_xml | – reference: Meyerhardt JA, Mangu PB, Flynn PJ, Korde L, Loprinzi CL, Minsky BD, Petrelli NJ, Ryan K, Schrag DH, Wong SL, Benson AB 3rd: Follow-up care, surveillance protocol, and secondary prevention measures for survivors of colorectal cancer: American Society of Clinical Oncology clinical practice guideline endorsement. J Clin Oncol 2013;31:4465-4470. – reference: Li M, Li JY, Zhao AL, He JS, Zhou LX, Li YA, Gu J: Comparison of carcinoembryonic antigen prognostic value in serum and tumour tissue of patients with colorectal cancer. Colorectal Dis 2009;11:276-281. – reference: Park YA, Lee KY, Kim NK, Baik SH, Sohn SK, Cho CW: Prognostic effect of perioperative change of serum carcinoembryonic antigen level: a useful tool for detection of systemic recurrence in rectal cancer. Ann Surg Oncol 2006;13:645-650. – reference: Wang JY, Lu CY, Chu KS, Ma CJ, Wu DC, Tsai HL, Yu FJ, Hsieh JS: Prognostic significance of pre- and postoperative serum carcinoembryonic antigen levels in patients with colorectal cancer. Eur Surg Res 2007;39:245-250. – reference: Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rodel C: Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 2012;30:1926-1933. – reference: Kim JY, Kim NK, Sohn SK, Kim YW, Kim KJ, Hur H, Min BS, Cho CH: Prognostic value of postoperative CEA clearance in rectal cancer patients with high preoperative CEA levels. Ann Surg Oncol 2009;16:2771-2778. – reference: Yang KL, Yang SH, Liang WY, Kuo YJ, Lin JK, Lin TC, Chen WS, Jiang JK, Wang HS, Chang SC, Chu LS, Wang LW: Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery. Radiat Oncol 2013;8:43. – reference: Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suarez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL: Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 2010;11:835-844. – reference: Garland ML, Vather R, Bunkley N, Pearse M, Bissett IP: Clinical tumour size and nodal status predict pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Int J Colorectal Dis 2014;29:301-307. – reference: Lee JH, Kim DY, Kim SH, Cho HM, Shim BY, Kim TH, Kim SY, Baek JY, Oh JH, Nam TK, Yoon MS, Jeong JU, Kim K, Chie EK, Jang HS, Kim JS, Kim JH, Jeong BK: Carcinoembryonic antigen has prognostic value for tumor downstaging and recurrence in rectal cancer after preoperative chemoradiotherapy and curative surgery: a multi-institutional and case-matched control study of KROG 14-12. Radiother Oncol 2015;116:202-208. – reference: Lee JH, Kim SH, Kim JG, Cho HM, Shim BY: Preoperative chemoradiotherapy (CRT) followed by laparoscopic surgery for rectal cancer: predictors of the tumor response and the long-term oncologic outcomes. Int J Radiat Oncol Biol Phys 2011;81:431-438. – reference: Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, Roussel A, Jacob JH, Segol P, Samama G, et al: Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 1994;73:2680-2686. – reference: Kim CW, Yu CS, Yang SS, Kim KH, Yoon YS, Yoon SN, Lim SB, Kim JC: 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. – reference: Mohiuddin M, Hayne M, Regine WF, Hanna N, Hagihara PF, McGrath P, Marks GM: Prognostic significance of postchemoradiation stage following preoperative chemotherapy and radiation for advanced/recurrent rectal cancers. Int J Radiat Oncol Biol Phys 2000;48:1075-1080. – reference: Restivo A, Zorcolo L, Cocco IM, Manunza R, Margiani C, Marongiu L, Casula G: Elevated CEA levels and low distance of the tumor from the anal verge are predictors of incomplete response to chemoradiation in patients with rectal cancer. Ann Surg Oncol 2013;20:864-871. – reference: Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, Somerfield MR, Hayes DF, Bast RC Jr: ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol 2006;24:5313-5327. – reference: Labianca R, Nordlinger B, Beretta GD, Brouquet A, Cervantes A: Primary colon cancer: ESMO Clinical Practice Guidelines for diagnosis, adjuvant treatment and follow-up. Ann Oncol 2010;21(suppl 5):v70-v77. – reference: Suzuki T, Sadahiro S, Tanaka A, Okada K, Kamata H, Kamijo A, Murayama C, Akiba T, Kawada S: Biopsy specimens obtained 7 days after starting chemoradiotherapy (CRT) provide reliable predictors of response to CRT for rectal cancer. Int J Radiat Oncol Biol Phys 2013;85:1232-1238. – reference: Sadahiro S, Suzuki T, Tanaka A, Okada K, Kamijo A, Murayama C, Akiba T, Nakayama Y: Phase I/II study of preoperative concurrent chemoradiotherapy with S-1 for locally advanced, resectable rectal adenocarcinoma. Oncology 2011;81:306-311. – reference: Al-Sukhni E, Attwood K, Mattson DM, Gabriel E, Nurkin SJ: Predictors of pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Ann Surg Oncol 2016;23:1177-1186. – reference: Jang NY, Kang SB, Kim DW, Kim JH, Lee KW, Kim IA, Kim JS: The role of carcinoembryonic antigen after neoadjuvant chemoradiotherapy in patients with rectal cancer. Dis Colon Rectum 2011;54:245-252. – reference: Gold P, Freedman SO: Specific carcinoembryonic antigens of the human digestive system. J Exp Med 1965;122:467-481. – reference: Yoon SM, Kim DY, Kim TH, Jung KH, Chang HJ, Koom WS, Lim SB, Choi HS, Jeong SY, Park JG: Clinical parameters predicting pathologic tumor response after preoperative chemoradiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 2007;69:1167-1172. – reference: Kim CW, Yoon YS, Park IJ, Lim SB, Yu CS, Kim JC: Elevation of preoperative s-CEA concentration in stage IIA colorectal cancer can also be a high risk factor for stage II patients. Ann Surg Oncol 2013;20:2914-2920. – reference: Huh JW, Kim HR, Kim YJ: Clinical prediction of pathological complete response after preoperative chemoradiotherapy for rectal cancer. Dis Colon Rectum 2013;56:698-703. – reference: Kleiman A, Al-Khamis A, Farsi A, Kezouh A, Vuong T, Gordon PH, Vasilevsky CA, Morin N, Faria J, Ghitulescu G, Boutros M: Normalization of CEA levels post-neoadjuvant therapy is a strong predictor of pathologic complete response in rectal cancer. 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| Snippet | Objectives: The histologic response to neoadjuvant chemoradiotherapy (nCRT) has been intimately related to outcomes in locally advanced rectal cancer. Serum... The histologic response to neoadjuvant chemoradiotherapy (nCRT) has been intimately related to outcomes in locally advanced rectal cancer. Serum... |
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| Title | Relations of Changes in Serum Carcinoembryonic Antigen Levels before and after Neoadjuvant Chemoradiotherapy and after Surgery to Histologic Response and Outcomes in Patients with Locally Advanced Rectal Cancer |
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