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    Prognostic value of preoperative carcinoembryonic antigen/tumor size in rectal cancer. Cai Du,Huang Zeng-Hong,Yu Hui-Chuan,Wang Xiao-Lin,Bai Liang-Liang,Tang Guan-Nan,Peng Shao-Yong,Li Ying-Jie,Huang Mei-Jin,Cao Guang-Wen,Wang Jian-Ping,Luo Yan-Xin World journal of gastroenterology BACKGROUND:Carcinoembryonic antigen (CEA) is a commonly used biomarker in colorectal cancer. However, controversy exists regarding the insufficient prognostic value of preoperative serum CEA alone in rectal cancer. Here, we combined preoperative serum CEA and the maximum tumor diameter to correct the CEA level, which may better reflect the malignancy of rectal cancer. AIM:To assess the prognostic impact of preoperative CEA/tumor size in rectal cancer. METHODS:We retrospectively reviewed 696 stage I to III rectal cancer patients who underwent curative tumor resection from 2007 to 2012. These patients were randomly divided into two cohorts for cross-validation: training cohort and validation cohort. The training cohort was used to generate an optimal cutoff point and the validation cohort was used to further validate the model. Maximally selected rank statistics were used to identify the optimum cutoff for CEA/tumor size. The Kaplan-Meier method and log-rank test were used to plot the survival curve and to compare the survival data. Univariate and multivariate Cox regression analyses were used to determine the prognostic value of CEA/tumor size. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), respectively. RESULTS:In all, 556 patients who satisfied both the inclusion and exclusion criteria were included and randomly divided into the training cohort (2/3 of 556, = 371) and the validation cohort (1/3 of 556, = 185). The cutoff was 2.429 ng/mL per cm. Comparison of the baseline data showed that high CEA/tumor size was correlated with older age, high TNM stage, the presence of perineural invasion, high CEA, and high carbohydrate antigen 19-9 (CA 19-9). Kaplan-Meier curves showed a manifest reduction in 5-year OS (training cohort: 56.7% 81.1%, < 0.001; validation cohort: 58.8% 85.6%, < 0.001) and DFS (training cohort: 52.5% 71.9%, = 0.02; validation cohort: 50.3% 79.3%, = 0.002) in the high CEA/tumor size group compared with the low CEA/tumor size group. Univariate and multivariate analyses identified CEA/tumor size as an independent prognostic factor for OS (training cohort: hazard ratio (HR) = 2.18, 95% confidence interval (CI): 1.28-3.73, = 0.004; validation cohort: HR = 4.83, 95%CI: 2.21-10.52, < 0.001) as well as DFS (training cohort: HR = 1.47, 95%CI: 0.93-2.33, = 0.096; validation cohort: HR = 2.61, 95%CI: 1.38-4.95, = 0.003). CONCLUSION:Preoperative CEA/tumor size is an independent prognostic factor for patients with stage I-III rectal cancer. Higher CEA/tumor size is associated with worse OS and DFS. 10.3748/wjg.v25.i33.4945
    Prognostic Value of Pretreatment Serum CA199 in Patients with Locally Advanced Rectal Cancer Treated with CRT Followed by TME with Normal Pretreatment Carcinoembryonic Antigen Levels. Huang Daxin,Lin Qingliang,Song Jianyuan,Xu Benhua Digestive surgery BACKGROUND:Elevated pretreatment carcinoembryonic antigen (CEA) levels are related to poor prognosis in patients with locally advanced rectal cancer (LARC) treated with neo-CRT followed by TME. In patients with normal pretreatment CEA levels, the prognostic significance of carbohydrate antigen 199 (CA199) is controversial. OBJECTIVES:The aim of this study was to explore the prognostic value of pretreatment serum CA199 in patients with LARC who had normal pretreatment CEA levels treated with neo-CRT followed by curative surgery. METHODS:A retrospective study of 456 patients with LARC treated with neo-CRT followed by TME between January 2006 and May 2017 was performed. We employed the maximal χ2 method to determine the CA199 threshold of 9.1 U/mL based on the difference in survival and divided patients into 2 groups. Group 1: patients with pretreatment s-CEA < 5 ng/mL and CA199 ≥ 9.1 U/mL. Group 2: patients with pretreatment s-CEA < 5 ng/mL and CA199 < 9.1 U/mL. Overall survival (OS) across CA199 was assessed using Cox proportional hazard regression models (PS:CEA ≥ 5 ng/mL was seen as elevated). RESULTS:Multivariate analyses demonstrated that the following factors were significantly related to OS in patients with LARC with normal pretreatment CEA levels: ypT (odds ratio [OR] 1.863, p = 0.030), ypN (OR 1.622, p = 0.026), and pretreatment CA199 levels (OR 1.886, p = 0.048). CONCLUSION:Pretreatment CA199 is an independent factor for OS in patients with LARC with normal pretreatment CEA levels, which may reach the clinic to guide individualized decision-making. 10.1159/000508442
    Prognostic value of changes in serum carcinoembryonic antigen levels for preoperative chemoradiotherapy response in locally advanced rectal cancer. Cheong Chinock,Shin Jun Sang,Suh Kwang Wook World journal of gastroenterology BACKGROUND:Preoperative chemoradiotherapy (CRT) is a standard treatment modality for locally advanced rectal cancer. However, CRT alone cannot improve overall survival. Approximately 20% of patients with CRT-resistant tumors show disease progression. Therefore, predictive factors for treatment response are needed to identify patients who will benefit from CRT. We theorized that the prognosis may vary if patients are classified according to pre- to post-CRT changes in carcinoembryonic antigen (CEA) levels. AIM:To identify patients with locally advanced rectal cancer for preoperative chemoradiotherapy based on carcinoembryonic antigen levels. METHODS:We retrospectively included locally advanced rectal cancer patients who underwent preoperative CRT and curative resection between 2011 and 2017. Patients were assigned to groups A, B, and C based on pre- and post-CRT serum CEA levels: Both > 5; pre > 5 and post ≤ 5; and both ≤ 5 ng/mL, respectively. We compared the response to CRT based on changes in serum CEA levels. Receiver operating characteristic curve analysis was performed to determine optimal cutoff for neutrophil-lymphocyte ratio and platelet-lymphocyte ratio. Multivariate logistic regression analysis was used to evaluate the prognostic factors for pathologic complete response (pCR)/good response. RESULTS:The cohort comprised 145 patients; of them, 27, 43, and 65 belonged to groups A, B, and C, respectively, according to changes in serum CEA levels before and after CRT. Pre- ( < 0.001) and post-CRT ( < 0.001) CEA levels and the ratio of down-staging ( = 0.013) were higher in Groups B and C than in Group A. The ratio of pathologic tumor regression grade 0/1 significantly differed among the groups ( 0.003). Group C had the highest number of patients showing pCR ( < 0.001). Most patients with pCR showed pre- and post-CRT CEA levels < 5 ng/mL ( < 0.001, = 0.008). Pre- and post-CRT CEA levels were important risk factors for pCR (OR = 18.71; 95%CI: 4.62-129.51, < 0.001) and good response (OR = 5.07; 95%CI: 1.92-14.83, = 0.002), respectively. Pre-CRT neutrophil-lymphocyte ratio and post-CRT T ≥ 3 stage were also prognostic factors for pCR or good response. CONCLUSION:Pre- and post-CRT CEA levels, as well as change in CEA levels, were prognostic markers for treatment response to CRT and may facilitate treatment individualization for rectal cancer. 10.3748/wjg.v26.i44.7022
    Prognostic Role of Carcinoembryonic Antigen Level after Preoperative Chemoradiotherapy in Patients with Rectal Cancer. Huh Jung Wook,Yun Seong Hyeon,Kim Seok Hyung,Park Yoon Ah,Cho Yong Beom,Kim Hee Cheol,Lee Woo Yong,Park Hee Chul,Choi Doo Ho,Park Joon Oh,Park Young Suk,Chun Ho-Kyung Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract BACKGROUND:The prognostic role of post-chemoradiotherapy (CRT) carcinoembryonic antigen (CEA) level is not clear. We evaluated the prognostic significance of post-CRT CEA level in patients with rectal cancer after preoperative CRT. METHODS:We reviewed 659 consecutive patients who underwent preoperative CRT and total mesorectal excision for non-metastatic rectal cancer. Patients were categorized into two groups according to post-CRT serum CEA level: low CEA (< 5 ng/mL) and high CEA (≥ 5 ng/mL). RESULTS:Median post-CRT CEA level was 1.7 ng/mL (range, 0.1-207.0). A high post-CRT level was significantly associated with ypStage, ypT category, tumor regression grade, and pre-CRT CEA level. The 5-year overall survival rate of the 659 patients was 87.8% with a median follow-up period of 57.0 months (range, 1.4-176.4). When the post-CRT CEA groups were divided into groups according to pre-CRT CEA level, the 5-year overall survival rates were significantly different (P < 0.001 and P = 0.001, respectively). Post-CRT CEA level was an independent prognostic factor for overall survival. Multivariate analysis revealed that operation method, differentiation, perineural invasion, postoperative chemotherapy, tumor regression grade, and post-CRT CEA level were independent prognostic factors for overall survival. CONCLUSION:The level of serum CEA after preoperative CRT was an independent prognostic factor for overall survival in patients with rectal cancer. 10.1007/s11605-018-3815-9
    Clinical significance of pre- to post-chemoradiotherapy s-CEA reduction ratio in rectal cancer patients treated with preoperative chemoradiotherapy and curative resection. Kim Chan Wook,Yu Chang Sik,Yang Song-Soo,Kim Kyung Ho,Yoon Yong Sik,Yoon Sang Nam,Lim Seok-Byung,Kim Jin Cheon Annals of surgical oncology PURPOSE:To evaluate the clinical significance of a reduction in serum carcinoembryonic antigen (s-CEA) concentration ratio from before to after preoperative chemoradiotherapy (CRT) in terms of recurrence and prognostic factors in rectal cancer patients. METHODS:We retrospectively evaluated 333 rectal cancer patients who received preoperative CRT followed by surgery with curative intent between January 2000 and December 2006. Patients were divided into three groups: those with pre-CRT s-CEA≤6 ng/mL (group 1), those with pre-CRT s-CEA>6 mg/mL and post-CRT s-CEA≥70% lower than pre-CRT s-CEA (group 2), and those with pre-CRT s-CEA>6 mg/mL and post-CRT s-CEA<70% lower or higher than pre-CRT s-CEA (group 3). RESULTS:The 5-year disease-free survival rate was similar in group 1 (76.0%) and group 2 (66.0%), but significantly lower in group 3 (39.5%) (p<0.001). Multivariate analysis showed that CEA group 3, ypT stage, ypN stage, and type of surgery were independent prognostic factors for disease-free survival. CONCLUSIONS:The reduction ratio of pre- to post-CRT s-CEA concentration may be an independent prognostic factor for disease-free survival following preoperative CRT and surgery in rectal cancer patients with initial s-CEA>6 ng/mL. 10.1245/s10434-011-1740-1
    Analysis of unexplained carcinoembryonic antigen elevation after curative treatment of locally advanced rectal cancer. Lee Sung Uk,Jwa Eunjin,Kim Dae Yong,Kim Tae Hyun,Baek Ji Yeon,Cha Yongjun,Chang Hee Jin,Oh Jae Hwan International journal of clinical oncology BACKGROUND:To analyze the causes and patterns of unexplained carcinoembryonic antigen (CEA) elevation after curative treatment in locally advanced rectal cancer patients. METHODS:Among the 1309 locally advanced rectal cancer patients treated with curative resection and radiotherapy between January 2001 and June 2011, 325 patients who postoperatively developed abnormal CEA elevation were reviewed. The unexplained CEA elevation was defined as a CEA level higher than 5 ng/mL with no evidence of cancer recurrence at the time of elevation. RESULTS:Of the 325 patients, 143 (44%) had unexplained CEA elevations. The causes were categorized as delayed recurrence (n = 29, 20%), non-colorectal malignancy (n = 10, 7%), and non-malignancy-related conditions (n = 104, 73%). Shorter intervals between treatment and the first CEA elevation, and a higher peak CEA level, were observed in the delayed recurrence group compared with the non-colorectal malignancy or non-malignancy-related group (intervals of 6.8 vs. 44.9 vs. 23.2 months, respectively, p = 0.002; and peak CEA levels of 9.9 vs. 7.1 vs. 6.2 ng/mL, respectively, p = 0.034). In patients who showed delayed recurrence, the interval between the first CEA elevation and diagnosis of recurrence was a median of 13.0 months (range 3.8-60.6 months). Smoking was the most common cause for non-malignancy-related conditions. The patterns of unexplained CEA elevations were defined as sporadic (n = 78, 55%), stationary (n = 37, 26%), and increasing (n = 28, 20%). The patterns were significantly different depending on the cause (p < 0.001). CONCLUSIONS:Analysis of the patterns of unexplained CEA elevations is a reasonable approach to predict the cause of the cancer. 10.1007/s10147-018-1293-4
    Prognostic value of postoperative CEA clearance in rectal cancer patients with high preoperative CEA levels. Kim Jeong Yeon,Kim Nam Kyu,Sohn Seung Kook,Kim Yong Wan,Kim Kim Jin Soo,Hur Hyuk,Min Byung Soh,Cho Chang Hwan Annals of surgical oncology PURPOSE:We determined the prognostic value of carcinoembryonic antigen (CEA) clearance after tumor resection with serial evaluation of postoperative CEA levels in rectal cancer. METHODS:Between 1994 and 2004, we retrospectively reviewed 122 patients with rectal cancer whose serum CEA levels were measured on the preoperative day and postoperative days 7 and 30. Patients with preoperative CEA levels <5.0 ng/ml were excluded. An exponential trend line was drawn using the three CEA values. Patients were categorized into three groups based on R(2) values calculated through trend line, which indicates the correlation coefficient between exponential graph and measured CEA values: exponential decrease group (group 1: 0.9 < R(2) < or = 1.0), nearly exponential decrease group (group 2: 0.5 < R(2) < or = 0.9), and randomized clearance group (group 3: 0.5 < or = R(2)). We then analyzed the CEA clearance pattern as a prognostic indicator. RESULTS:With a median follow-up of 57 months, the 5-year overall survival was 62.3% vs. 48.1% vs. 25% and the 5-year disease-free survival was 58.6% vs. 52.7% vs. 25% among groups 1, 2, and 3 (P = 0.014, P = 0.027, respectively) in patients with stage III rectal cancer. For those with stage II rectal cancer, the 5-year overall survival rate of group 1 was significantly better than groups 2 and 3 (88.8% vs. 74.1%, respectively, P = 0.021). CONCLUSIONS:The postoperative pattern of CEA clearance is a useful prognostic determinant in patients with rectal cancer. Patients with a randomized pattern of CEA clearance after tumor resection should be regarded as having the possibility of a persistent CEA source and may require consideration of intensive follow-up or adjuvant therapy. 10.1245/s10434-009-0651-x
    Postoperative carcinoembryonic antigen level has a prognostic value for distant metastasis and survival in rectal cancer patients who receive preoperative chemoradiotherapy and curative surgery: a retrospective multi-institutional analysis. Jeong Songmi,Nam Taek Keun,Jeong Jae Uk,Kim Sung Hwan,Kim Kyubo,Jang Hong Seok,Jeong Bae Kwon,Lee Jong Hoon Clinical & experimental metastasis The cut-off value and prognostic significance of postoperative carcinoembryonic antigen (CEA) level in rectal cancer after preoperative chemoradiotherapy (CRT) and curative surgery are still unclear. 1559 rectal cancer patients staged with cT3-4N0-2M0 received preoperative CRT and total mesorectal excision (TME). CEA levels were measured before CRT and 3-4 weeks after surgery. Clinicopathologic factors that could be associated with tumor recurrence and patient survival were analyzed. The cumulative probability of tumor recurrence showed a steep increase with a cutoff value of 2.5 ng/mL for postoperative CEA level, and the gradient decreased as the CEA levels increased above 2.5 ng/mL. After a median follow-up time of 46.7 months, patients with postoperative CEA level >2.5 ng/mL had significantly lower relapse-free survival (RFS) (65.2 vs. 75.6 %, P < 0.001) and overall survival (OS) (78.1 vs. 88.3 %, P < 0.001) at 5 years than patients with postoperative CEA level ≤2.5 ng/mL. On the multivariate analysis, postoperative CEA level was a significant prognostic factor for RFS (HR 1.561; 95 % CI 1.221-1.996; P < 0.001) and OS (HR 2.073; 95 % CI 1.498-2.869; P < 0.001). Postoperative CEA level independently affected RFS irrespective of pre-CRT CEA level. Postoperative CEA level was a significant predictor for distant recurrence (P = 0.004), but not for locoregional recurrence (P = 0.472). Postoperative CEA level >2.5 ng/ml is a predictor of distant metastasis and a negative prognostic factor for survival in rectal cancer patients who receive preoperative CRT and curative surgery. 10.1007/s10585-016-9818-6
    Prognostic impact of preoperatively elevated and postoperatively normalized carcinoembryonic antigen levels following curative resection of stage I-III rectal cancer. Nakamura Yuya,Shida Dai,Tanabe Taro,Takamizawa Yasuyuki,Imaizumi Jun,Ahiko Yuka,Sakamoto Ryohei,Moritani Konosuke,Tsukamoto Shunsuke,Kanemitsu Yukihide Cancer medicine BACKGROUND:Preoperative and early postoperative serum carcinoembryonic antigen (CEA) levels are known prognostic factors in rectal cancer. Recently, a large-scale study on colon cancer revealed that "preoperatively elevated and postoperatively normalized CEA levels" is not an indicator of poor prognosis. However, whether this hold true in rectal cancer patients is unknown. This study aimed to investigate the prognostic significance of preoperatively elevated and postoperatively normalized CEA levels in rectal cancer patients undergoing curative resection. METHODS:Subjects were consecutive stage I-III rectal cancer patients who underwent curative resection without preoperative treatment at National Cancer Center Hospital between 2000 and 2015. Overall survival (OS) and the hazard function of recurrence or death were analyzed according to the CEA levels, as follows: normal preoperative CEA (normal group), preoperatively elevated but postoperatively normalized CEA (normalized group), and preoperatively and postoperatively elevated CEA (elevated group). RESULTS:The normalized group (n =235) had worse OS (HR 1.49, 95% CI 1.08-2.04; P = .0142) compared to the normal group (n = 1208), and better OS compared to the elevated group (n = 47) (HR 0.53, 95% CI 0.31-0.91; P = .0208). The elevated group had the highest and earliest peak in hazard function, followed by the normalized group and the normal group, with median times to recurrence of 8.8, 15.5, and 18.5 months, respectively (P = .0223). CONCLUSIONS:Prognosis after resection of rectal cancer was worse in patients with preoperatively elevated and postoperatively normalized CEA compared to those with normal preoperative CEA. Patients with elevated preoperative CEA might require intensive follow-up even if levels normalize after resection, especially in earlier periods, for early detection of recurrence. 10.1002/cam4.2758