Pretreatment Carcinoembryonic Antigen Level Research Articles

Conditional survival analysis and real-time prognosis prediction in stage III T3–T4 colon cancer patients after surgical resection: a SEER database analysis

BackgroundConditional survival (CS) takes into consideration the duration of survival post-surgery and can provide valuable additional insights. The aim of this study was to investigate the risk factors associated with reduced one-year postoperative conditional survival in patients diagnosed with stage III T3–T4 colon cancer and real-time prognosis prediction. Furthermore, we aim to develop pertinent nomograms and predictive models.MethodsClinical data and survival outcomes of patients diagnosed with stage III T3–T4 colon cancer were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, covering the period from 2010 to 2019. Patients were divided into training and validation cohorts at a ratio of 7:3. The training set consisted of a total of 11,386 patients for conditional overall survival (cOS) and 11,800 patients for conditional cancer-specific survival (cCSS), while the validation set comprised 4876 patients for cOS and 5055 patients for cCSS. Univariate and multivariate Cox regression analyses were employed to identify independent risk factors influencing one-year postoperative cOS and cCSS. Subsequently, predictive nomograms for cOS and cCSS at 2-year, 3-year, 4-year, and 5-year intervals were constructed based on the identified prognostic factors. The performance of these nomograms was rigorously assessed through metrics including the concordance index (C-index), calibration curves, and the area under curve (AUC) derived from the receiver operating characteristic (ROC) analysis. Clinical utility was further evaluated using decision curve analysis (DCA).ResultsA total of 18,190 patients diagnosed with stage III T3–T4 colon cancer were included in this study. Independent risk factors for one-year postoperative cOS and cCSS included age, pT stage, pN stage, pretreatment carcinoembryonic antigen (CEA) levels, receipt of chemotherapy, perineural invasion (PNI), presence of tumor deposits, the number of harvested lymph nodes, and marital status. Sex and tumor site were significantly associated with one-year postoperative cOS, while radiation therapy was notably associated with one-year postoperative cCSS. In the training cohort, the developed nomogram demonstrated a C-index of 0.701 (95% CI, 0.711–0.691) for predicting one-year postoperative cOS and 0.701 (95% CI, 0.713–0.689) for one-year postoperative cCSS. Following validation, the C-index remained robust at 0.707 (95% CI, 0.721–0.693) for one-year postoperative cOS and 0.700 (95% CI, 0.716–0.684) for one-year postoperative cCSS. ROC and calibration curves provided evidence of the model's stability and reliability. Furthermore, DCA underscored the nomogram’s superior clinical utility.ConclusionsOur study developed nomograms and predictive models for postoperative stage III survival in T3–T4 colon cancer with the aim of accurately estimating conditional survival. Survival bias in our analyses may lead to overestimation of survival outcomes, which may limit the applicability of our findings.

A prognostic nomogram integrating carcinoembryonic antigen levels for predicting overall survival in elderly patients with stage II-III colorectal cancer.

With the aging of the population, colorectal surgeons will have to face more elderly colorectal cancer (CRC) patients in the future. We aim to analyze independent risk factors affecting overall survival in elderly (age ≥65 years) patients with stage II-III CRC and construct a nomogram to predict patient survival. A total of 3,016 elderly CRC patients with stage II-III were obtained from the SEER database. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analyses were used to screen independent prognostic factors, and a survival prediction nomogram was constructed based on the results. The consistency index (C-index), decision curve analysis (DCA), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were used to compare the predictive ability between the nomogram and tumor-node-metastasis (TNM) stage system. All patients were classified into high-risk and low-risk groups based on risk scores calculated by nomogram. The Kaplan-Meier method was used to compare the survival differences between two groups. The 3- and 5-year area under the curve (AUC) values of the prediction nomogram model were 76.6% and 74.8%, respectively. The AIC, BIC, and C-index values of the nomogram model were 6,032.502, 15,728.72, and 0.707, respectively, which were better than the TNM staging system. Kaplan-Meier survival analysis showed a significant survival difference between high-risk and low-risk groups (P<0.0001). We constructed a prediction nomogram for stage II-III elderly CRC patients by combining pre-treatment carcinoembryonic antigen (CEA) levels, which can accurately predict patient survival. This facilitates clinicians to accurately assess patient prognosis and identify high-risk patients to adopt more aggressive and effective treatment strategies.

Integration of pretreatment tumor markers in a nomogram model for prognostic prediction of FIGO stage I endometrial cancer: A multi-institutional cohort study.

Traditionally, the prognosis of patients with FIGO stage I endometrial cancer is determined by clinicopathological risk factors. In this study, we assessed the potential contribution of pretreatment carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) levels to estimating the prognosis of these patients and aimed to develop and validate a prognostic nomogram. This retrospective study included patients with FIGO stage I endometrial cancer who underwent treatment between January 2009 and December 2021 in the four institutes of Chang Gung Memorial Hospital. To identify optimal cutoff values of CEA and CA-125 for predicting survival, receiver operating characteristic (ROC) curves were generated, the Kaplan-Meier method was used to estimate survival, and a Cox regression model was used to analyze the independent prognostic factors. Finally, a nomogram and calibration curve were constructed to predict patient survival probability. Of the 1559 patients evaluated, the optimal cutoff values of CEA and CA-125 were 1.44 ng/mL (area under the ROC curve [AUC] 0.601) and 39.77 U/mL (AUC 0.503), respectively. Multivariate Cox regression analysis showed that pretreatment CEA (hazard ratio [HR] 2.11, 95% confidence interval [95% CI] 1.35-3.28), CA-125 (HR 2.07, 95% CI 1.31-3.27), age >70 years (HR 12.54, 95% CI 5.05-31.11), myometrial invasion >50% (HR 1.69, 95% CI 1.03-2.73), non-endometrioid histology (HR 1.83, 95% CI 1.14-2.95), high-grade tumor (HR 2.41, 95% CI 1.46-3.97), and lymphovascular space invasion (HR 2.32, 95% CI 1.26-4.25) were significant variables associated with overall survival. These factors were used to construct the nomogram model, which showed good concordance and accuracy. Integration of pretreatment CEA and CA-125 in a prognostic nomogram is feasible. Our prediction model has the potential to assist clinicians in guiding appropriate clinical practice.

The correlation between pre-treatment CEA levels and the EGFR mutation status in advanced lung adenocarcinoma.

The discovery of the epidermal growth factor receptor (EGFR) mutation, especially in adenocarcinoma, has led to a major change in the treatment of non-small-cell lung cancer (NSCLC). This study investigated the relationship between the EGFR mutation status and the carcinoembryonic antigen (CEA) levels at the time of diagnosis. A total of 102 patients with EGFR mutation and tested CEA levels were recruited for this study. Of the patients, 24 were EGFR mutants (23.5%), while 78 patients (76.5%) did not harbor any EGFR mutations. The CEA levels did not differ across groups. Additionally, the CEA levels were analyzed between female and male patients separately due to EGFR mutations; no difference was observed. When the CEA levels were categorized as positive or negative based on different cut-off values, such as 5 and 10 ng/ml, no statistical difference was found between groups. In this study, no relationship between EGFR mutation and pre-treatment CEA levels was observed. Despite positive trials having shown a predictive value of CEA levels for EGFR mutation, more clinical trials are needed to elucidate the racial, clinical, and pathological differences of the study populations. Most studies have been located in the Far East, but new trials in Caucasian, African, and Hispanic populations are still lacking.

Clinical and pathological parameters predicting pathologic complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Objective The aim of this study is to identify possible clinical predictors of complete response after neoadjuvant treatment in locally advanced rectal cancer (LARC) patients. Background Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision and postoperative adjuvant chemotherapy for LARC is the standard of care with a local recurrence rate of only 5–10%. On the other hand, various people react differently to neoadjuvant CRT. Neoadjuvant CRT is well received by the majority of patients, with a pathologic complete response (pCR) occurring in 10–30% of cases. Predicting the response to neoadjuvant CRT is crucial from a clinical standpoint, since patients with pCR have a better prognosis and may require a different treatment plan than patients without pCR. As a result, predicting pCR following neoadjuvant CRT for rectal cancer continues to be extremely useful for treating physicians. To identify the clinical and pathological variables linked to a full response to preoperative CRT for rectal cancer, we assessed a group of patients with pCR in this study. Patients and methods The study included 153 patients with LARC that were enrolled in the study based on specific inclusion and exclusion criteria. Patients were treated by standard neoadjuvant therapy. Surgical resection was planned for 6–8 weeks after the completion of neoadjuvant CRT, irrespective of the response to CRT. Pathological examination was performed to assess pathological response in the resected specimen. pCR was defined as the absence of viable tumor cells in the surgical specimen, including lymph nodes. Results After neoadjuvant chemoradiation, the pCR rate for rectal cancer patients was 20.8%; patients were split into pCR and non-pCR groups. Age, sex, BMI, performance score, tumor stage, tumor differentiation, tumor location, and surgical method were all evenly distributed across the two groups. The results of the multivariate analysis showed that pretreatment lymph node status, tumor size, and a carcinoembryonic antigen level of less than or equal to 5 ng/ml were independent risk factors of an elevated likelihood of pCR, as was an interval of more than or equal to 8 weeks between the completion of chemoradiation and treatment. Conclusion The pCR in rectal cancer following neoadjuvant chemoradiation is predicted by pretreatment carcinoembryonic antigen level of less than or equal to 5 ng/ml, an interval of more than or equal to 8 weeks between the end of chemoradiation and surgical resection, tumor size greater than 5 cm, and pretreatment lymph node status. By utilizing these predictive variables, we are able to forecast patients’ outcomes and create flexible treatment plans. In certain, very specific situations, a wait-and-see policy might be appropriate.

Development and validation of prognostic nomograms for early-onset colon cancer in different tumor locations: a population-based study

ObjectiveThe prevalence of early-onset colon cancer (EOCC) among individuals below the age of 50 has shown a marked upward trend in recent years. The embryology, clinical symptoms, incidence, molecular pathways, and oncologic outcomes differ between right-sided and left-sided colon cancers. However, the differences have not been fully researched in EOCC. Our study aims to develop and validate prognostic nomograms predicting overall survival (OS) and cancer-specific survival (CSS) for EOCC in different tumor locations based on the Surveillance, Epidemiology, and End Results (SEER) database.MethodsUsing the SEER database, a total of 5,588 patients with EOCC were extracted and divided into development and validation cohorts in a random allocation ratio of 7:3 across three groups. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors influencing OS and CSS outcomes. These factors were then utilized to construct nomogram models. The prognostic capabilities of the three models were assessed through various evaluation metrics, including the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and validation cohorts respectively. Additionally, survival curves of the low- and high-risk groups were calculated using the Kaplan–Meier method together with the log-rank test.ResultsSignificant differences in clinical features were observed between right-sided and left-sided EOCCs, particularly in terms of OS (52 months vs 54 months) as demonstrated by Kaplan–Meier curves. Transverse-sided EOCCs exhibited clinical characteristics similar to right-sided EOCCs, suggesting a potential shared tumor microenvironment and therapeutic considerations. Advanced stage, liver metastasis, poor grade, elevated pretreatment carcinoembryonic antigen (CEA) level, chemotherapy, and perineural invasion were identified as independent prognostic factors across all three tumor locations and were incorporated into the nomogram model. Nomograms were constructed to predict the probability of 3- and 5-year OS and CSS. The C-index and calibration plots showed that the established nomograms had good consistency between actual clinical observations and predicted outcomes. ROC curves with calculated area under the curve (AUC) values exceeded 0.8 for all three groups in both the development and validation cohorts, indicating robust predictive performance for OS and CSS. Furthermore, decision curve analysis (DCA) plots revealed a threshold probability range of 0.1 to 0.9, within which the nomogram model exhibited maximum benefit. Kaplan–Meier curves exhibited significant differences between the low- and high-risk groups in EOCC for all three tumor locations in OS and CSS, further validating the prognostic value of the nomogram models.ConclusionsWe successfully developed three precise nomogram models for EOCCs in different tumor locations, providing valuable support for clinicians in guiding clinical treatments and facilitating further prospective follow-up studies.

Pretreatment carcinoembryonic antigen combined with cancer antigen-125 for predicting lymph node metastasis in endometrial carcinoma: a retrospective cohort study.

To investigate whether the cost-effective, pretreatment tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) can be used to predict lymph node metastasis (LNM) in endometrioid-type endometrial cancer (EC) and to develop a predictive model. This was a single-center retrospective study of patients with endometrioid-type EC who underwent complete staging surgery between January 2015 and June 2022. We identified the optimal cut-off values of CEA and CA-125 for predicting LNM using receiver operating characteristic (ROC) curves. Stepwise multivariate logistic regression analysis was used to identify independent predictors. A nomogram for predicting LNM was constructed and validated by bootstrap resampling. The optimal cut-off values of CEA and CA-125 were 1.4ng/mL (area under the ROC curve (AUC) 0.62) and 40 U/mL (AUC 0.75), respectively. Multivariate analysis showed that CEA (odds ratio (OR) 1.94; 95% confidence interval (CI) 1.01-3.74) and CA-125 (OR 8.75; 95% CI 4.42-17.31) were independent predictors of LNM. Our nomogram showed adequate discrimination with a concordance index of 0.78. Calibration curves for the probability of LNM showed optimal agreement between the predicted and actual probabilities. The risk of LNM for markers below the cut-offs was 3.6%. The negative predictive value and negative likelihood ratio were 96.6% and 0.26, respectively, with moderate ability to rule out the possibility of LNM. We report a cost-effective method of using pretreatment CEA and CA-125 levels to identify patients with endometrioid-type EC who are at a low risk for LNM, which may guide decision-making regarding aborting lymphadenectomy.

An MRI Deep Learning Model Predicts Outcome in Rectal Cancer.

Background Deep learning (DL) models can potentially improve prognostication of rectal cancer but have not been systematically assessed. Purpose To develop and validate an MRI DL model for predicting survival in patients with rectal cancer based on segmented tumor volumes from pretreatment T2-weighted MRI scans. Materials and Methods DL models were trained and validated on retrospectively collected MRI scans of patients with rectal cancer diagnosed between August 2003 and April 2021 at two centers. Patients were excluded from the study if there were concurrent malignant neoplasms, prior anticancer treatment, incomplete course of neoadjuvant therapy, or no radical surgery performed. The Harrell C-index was used to determine the best model, which was applied to internal and external test sets. Patients were stratified into high- and low-risk groups based on a fixed cutoff calculated in the training set. A multimodal model was also assessed, which used DL model-computed risk score and pretreatment carcinoembryonic antigen level as input. Results The training set included 507 patients (median age, 56 years [IQR, 46-64 years]; 355 men). In the validation set (n = 218; median age, 55 years [IQR, 47-63 years]; 144 men), the best algorithm reached a C-index of 0.82 for overall survival. The best model reached hazard ratios of 3.0 (95% CI: 1.0, 9.0) in the high-risk group in the internal test set (n = 112; median age, 60 years [IQR, 52-70 years]; 76 men) and 2.3 (95% CI: 1.0, 5.4) in the external test set (n = 58; median age, 57 years [IQR, 50-67 years]; 38 men). The multimodal model further improved the performance, with a C-index of 0.86 and 0.67 for the validation and external test set, respectively. Conclusion A DL model based on preoperative MRI was able to predict survival of patients with rectal cancer. The model could be used as a preoperative risk stratification tool. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Langs in this issue.

Pretreatment Carcinoembryonic Antigen Level Serves as a Potential Biomarker to Guide Adjuvant Radiotherapy in pT4N+ Colon Cancer Patients.

The survival benefit of adjuvant radiotherapy in T4 colon cancer (CC) remains controversial, with conflicting results reported in the literature. This study aimed to explore the relationship between pretreatment carcinoembryonic antigen (CEA) level and overall survival (OS) of pT4N+ CC patients treated with adjuvant radiotherapy. Data of pT4N+ CC patients who received curative surgery between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The primary outcome was OS, and subgroup analysis was conducted according to pretreatment CEA level. A total of 8763 patients were eligible for our study. In the CEA-normal group, 151 patients received adjuvant radiotherapy, while 3932 patients did not. In the CEA-elevated group, 212 patients received adjuvant radiotherapy, while 4468 patients did not. In general, adjuvant radiotherapy was associated with better OS in pT4N+ CC patients (HR = 0.846, 95% CI = 0.733-0.976, P = 0.022). Intriguingly, only patients with an elevated pretreatment CEA level gained a survival benefit from adjuvant radiotherapy (HR = 0.782; 95% CI = 0.651-0.939; P = 0.008) while those with a normal pretreatment CEA level did not (HR = 0.907; 95% CI = 0.721-1.141; P = 0.403). Multivariable Cox regression analysis demonstrated that adjuvant radiotherapy was an independent protective factor in pT4N+ CC patients with an elevated pretreatment CEA level. Pretreatment CEA levels could serve as a potential biomarker to screen pT4N+ CC patients who would benefit from adjuvant radiotherapy.

A refined prediction of early recurrence combining tumor deposits in patients with resected rectal mucinous adenocarcinoma.

Early recurrence (ER) of rectal mucinous adenocarcinoma (MAC) has yet to be defined. We therefore explored risk factors for ER and constructed a predictive nomogram. A total of 145 rectal MAC patients undergoing radical surgery were included. The minimum P value method was used to determine the optimal cut-off point to discriminate between ER and late recurrence (LR). Risk factors for ER were determined by a logistic regression analysis, and a predictive nomogram was constructed. A total of 62 (42.8%) patients developed tumor recurrence. The optimal time to define ER was 12months. A pre-treatment tumor distance from the anal verge ≤ 7cm, pathological N stage, lymphovascular invasion, tumor deposits, and time to recurrence ≤ 12months were significantly associated with a poor post-recurrence survival in patients with recurrence. A pre-treatment serum carcinoembryonic antigen (CEA) level > 10ng/ml, pre-treatment tumor distance from the anal verge ≤ 7cm, pathological N + stage, perineural invasion, and tumor deposits were identified as independent risk factors associated with ER. A nomogram predicting ER was constructed (C-index 0.870). The pre-treatment serum CEA level, pre-treatment tumor distance from the anal verge, pathological N + stage, perineural invasion, and tumor deposits were significantly predictive of ER for rectal MAC patients.

ROLE OF CARBOHYDRATE ANTIGEN (CA19-9) AND CARCINOEMBRYONIC ANTIGEN (CEA) AS A PROGNOSTIC FACTORS IN PANCREATIC CARCINOMA

Objective:To investigate the potential utility of pre-treatment carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) as prognostic indicators to assess prognosis in pancreatic carcinoma. MaterialsandMethods:This retrospective observational study was carried out at the Department of General Surgery Hayatabad Medical Complex Peshawar from July 2017 to June 2022. A total of 70 patients with the diagnosis of pancreaticcarcinoma were enrolled.Allpatientswerehistologicallydiagnosedwithpancreaticcarcinoma. ThelevelsofCA19-9andCEAwereevaluatedbeforetreatment.Allpatientsreceivedeitheranoperation,chemotherapy or chemoradiotherapy (CRT), and patientswho only received supportive care, palliative surgery or othertreatmentswerenotincludedinthestudy.Patients with a history of other malignancies were excluded. Results:A total of 70 patients were included in this study. Age ranged between 25-75 years, with a mean age of 50 years. Included patients were stratified into 2 groups (35 each) in regard to their preoperative CEA &amp; CA 19-9 level. Group 1: (Normal serum level group, CEA level value &lt;5ng/ml &amp; CA19-9 &lt;37 U/ml), Group 2: (Elevated level group ≥5ng/ml &amp; ≥37 U/ml)There were 19(54.3%) males and 16(45.7%) females in group 1 with male to female ratio of 1.18:1 and 18(51.4%) male &amp; 17(48.6%) females in group 2 with male to female ratio 1.05:1. CA 19-9 and CEA were evaluated at initial diagnosis,andthemedianlevelswere37U/mL(range,0.1-20000U/mL) and 3.4 ng/mL (range, 0.04-8566 ng/mL), respectively. Conclusion:Patientswithelevated serum CEA levels at diagnosis demonstrated poor overall survival. Pre-treatment CEA level may predict the prognosis of patients with pancreatic adenocarcinoma.

Significance of serum carcinoembryonic antigen in metastatic breast cancer patients: A prospective study.

BACKGROUNDCarcinoembryonic antigen (CEA) is an important serum tumour marker with a substantial role in diagnosis and monitoring of various solid tumours. About 36%-70% of breast cancers have elevated serum CEA. And the available studies show discrepancy in addressing the prognostic significance of CEA in advanced breast cancer.AIMTo estimate the serum CEA level in our metastatic breast cancer patients and correlate it with response to treatment and clinical outcome.METHODSThis was a prospective clinical study conducted on 50 metastatic breast cancer patients treated at breast clinic, with newly diagnosed metastatic breast cancer planned for palliative chemotherapy, targeted therapy, and hormonal treatment. We estimated the proportion of patients with elevated serum CEA level at baseline and after palliative treatment and also studied the association of serum CEA levels with known prognostic factors. The response to treatment was correlated with the serum CEA levels in the context of responders and non-responders.RESULTSThe median pre-treatment and post-treatment CEA levels were 7.9 (1.8-40.7) ng/mL and 4.39 (1.4-12.15) ng/mL, respectively, in the whole study population (P = 0.032). No statistically significant difference was seen in baseline serum CEA between responders and non-responders. Even in the luminal group, pre-treatment serum CEA was not a predictor of response, but post-treatment CEA was a significant predictor of tumour progression. In patients with liver and lung metastases, post-treatment CEA level difference was not statistically significant in both responders and non-responders though the values were higher in non-responders. Among those with bone metastases, 69.5% had elevated post-treatment serum CEA, and only 37.5% had elevated serum CEA in those with no bone metastases.CONCLUSIONElevated post-treatment serum CEA levels are associated with disease progression and poor response to therapy. Persistently elevated post-treatment serum CEA levels are significantly associated with bone metastases. Elevated serum CEA and hormonal status are significant predictors of treatment response.

Total neoadjuvant treatment approach and carcinoembryonic antigen level in locally advanced rectal cancer.

e15595 Background: Total Neoadjuvant therapy (TNT) has gained acceptance in the treatment of locally advanced rectal cancer, although the optimal sequencing of therapy chemoradiation (CRT) followed by consolidation chemotherapy (cChT) or induction chemotherapy followed by chemoradiation (iChT), remains a subject of ongoing debate. The effect of TNT sequencing and carcinoembryonic antigen (CEA) level on progression free survival (PFS) is uncertain. We conducted a retrospective analysis to examine these issues. Methods: Patients (n = 44) with locally advanced rectal cancer from June 2016 to December 2020 were reviewed. CEA level was compared against the primary outcome of response to TNT approaches. We categorized patients into 3 groups based on pre-TNT and post-TNT (i.e. pre-surgical) CEA: normal CEAPRE/normal CEAPOST, elevated CEA PRE/normal CEA POST, elevated CEA PRE/elevated CEA POST. 3-Year PFS was calculated using Kaplan-Meier method. Univariable and multivariable logistic regression analyses identified characteristics predictive of PFS and clinicopathologic variables associated with TNT sequencing. Results: The study cohort had a median age of 61 years and was predominantly male (70%) and Caucasian (94%). Pre-treatment stage was either II (27%) or III (72%), with the majority (65%) undergoing iChT. Downstaging occurred in 42/44 (95%). Baseline CEA was elevated in 40.9% of patients. On multivariable, logistic regression variable associated with receipt of CRT followed by cChT included: Age &gt; 61 years clinical T4 disease and lack of T downstaging (p &lt; 0.05 for all).There was no difference in 3-year PFS between patients receiving iChT versus patients receiving cChT (p = 0.53). When patients were stratified according to pretreatment CEA level, no difference in 3 year PFS were noted (p = 0.46). On multivariable analysis, lack of nodal downstaging following neoadjuvant treatment was associated with higher likelihood of progression (p = 0.02). Similarly, pretreatment CEA &gt; 4.25 ng/ml (p = 0.08) and failure of CEA to decrease by &gt;2 ng/ml following TNT (p = 0.07) trended toward higher likelihood of progression. Conclusions: Neither TNT sequencing, nor baseline CEA predicted the PFS although the power of our study was limited. Lack of nodal downstaging was identified as a predictor of worse PFS. Further areas of study should include plasma-based assays to quantitate circulating tumor DNA and next generation sequencing to assess prognosis with different sequencing of TNT.

The Correlation Between Survival Benefit of Preoperative Radiotherapy and Pretreatment Carcinoembryonic Antigen Level in Locally Advanced Rectal Cancer.

BackgroundPreoperative radiotherapy followed by radical surgery is the standard treatment for locally advanced rectal cancer; however, its long-term survival benefit remains controversial. This study aimed to determine the relationship between pretreatment carcinoembryonic antigen (CEA) levels and the long-term prognosis of preoperative radiotherapy in locally advanced rectal cancer (LARC) patients.MethodsData of LARC patients who underwent surgery between 2011 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database, and patients were accordingly divided into surgery (S) group and radiotherapy followed by surgery (RT+S) group. The primary outcomes were cancer-specific survival (CSS) and cancer-specific mortality (CSM). CSS was evaluated using Kaplan-Meier analysis, while CSM was evaluated using a competitive risk model. Subgroup analysis was also conducted, which was stratified by pretreatment CEA levels.ResultsA total of 2,760 patients were eligible for this study, including 350 (12.7%) patients in the S group and 2,410 (87.3%) in the RT+S group. There were no significant differences in the CSS and CSM rates at 1, 3, and 4 years between the S and RT+S groups before and after PSM (all p > 0.05). Pretreatment CEA levels were independently associated with CSS and CSM after adjusting for age, sex, stage, pathological factors, and treatment factors (all p < 0.05). Subgroup analysis showed that preoperative radiotherapy would benefit patients with elevated CEA in terms of CSS and CSM (both p < 0.05) but not those patients with normal CEA (both p > 0.05). Further analysis showed that preoperative radiotherapy was an independent protective factor for CSS and CSM in patients with elevated CEA levels (both p < 0.05).ConclusionsPretreatment CEA level may be considered a potential biomarker to screen LACR patients who would benefit from preoperative radiotherapy in terms of long-term prognosis.

Prognostic risk factors and survival models for T3 locally advanced rectal cancer: what can we learn from the baseline MRI?

To evaluate the baseline MRI characteristics for predicting survival outcomes and construct survival models for risk stratification to facilitate personalized treatment and follow-up strategies in patients with MRI-defined T3 (mrT3) locally advanced rectal cancer (LARC). We retrospectively reviewed 256 mrT3 LARC patients evaluated between 2008 and 2012 in our institution, with an average follow-up period of 6.8 ± 1.2 years. The baseline MRI characteristics, clinical data, and follow-up information were evaluated. The patients were randomized into a training cohort (TC, 186 patients) and validation cohort (VC, 70 patients). The TC dataset was used to develop multivariate nomograms for disease-free survival (DFS) and overall survival (OS), while the VC dataset was used for independent validation of the models. Harrell concordance (C) indices and Hosmer-Lemeshow calibration were used to evaluate the performances of the models. Baseline mrT3 substage, extramural venous invasion (EMVI) grading, mucinous adenocarcinoma, mesorectal fascia involvement, elevated pretreatment carcinoembryonic antigen level, and neoadjuvant chemoradiotherapy (NCRT) were independent predictors of DFS. T3 substage, EMVI grading, and NCRT were also independent predictors of OS. The nomograms constructed permitted the individualized prediction of 3-year and 5-year DFS and 5-year OS with high discrimination (C-index range, 0.833-0.892) and good calibration in the TC and VC. We have identified baseline MRI characteristics that help independently predict survival outcomes in patients with mrT3 LARC. The survival models based on these characteristics allow for the individualized pretreatment risk stratification in patients with mrT3 LARC. • Baseline MRI characteristics can independently stratify risk and predict survival outcomes in patients with mrT3 LARC. • The nomograms built using selected baseline MRI characteristics facilitate the individualized pretreatment risk stratification and help with clinical decision-making in patients with mrT3 LARC. • MR-defined risk factors should, therefore, be carefully reported in the baseline MRI evaluation.

Predictive Factors for Pathologic Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer.

Background:An accurate assessment of potential pathologic complete response(pCR) following neoadjuvant chemoradiotherapy(NCRT) is important for the appropriate treatment of rectal cancer. However, the factors that predict the response to neoadjuvant chemoradiotherapy have not been well defined. Therefore, this study analyzed the predictive factors on the development of pCR after neoadjuvant chemoradiation for rectal cancer. Methods: From January 2008 to January 2018, a total of 432 consecutive patients from a single institution patients who underwent a long-course neoadjuvant chemoradiotherapy were reviewed in this study. The clinicopathological features were analyzed to identify predictive factors for pathologic complete response in rectal cancer after neoadjuvant chemoradiation. Results:The rate of pathologic complete response in rectal cancer after neoadjuvant chemoradiation was 20.8%, patients were divided into the pCR and non-pCR groups. The two groups were well balanced in terms of age, gender, body mass index, ASA score, tumor stage, tumor differentiation, tumor location, surgical procedure, chemotherapy regimen and radiation dose. The multivariate analysis revealed that a pretreatment carcinoembryonic antigen (CEA) level of ≤5 ng/mL and an interval of ≥8 weeks between the completion of chemoradiation and surgical resection were independent risk factors of an increased rate of pCR. Conclusions: Pretreatment carcinoembryonic antigen (CEA) level of ≤5 ng/mL and an interval of ≥8 weeks between the completion of chemoradiation and surgical resection are predictive factors for pathologic complete response in rectal cancer after neoadjuvant chemoradiation. Using these predictive factors, we can predict the prognosis of patients and develop adaptive treatment strategies. A wait-and-see policy might be possible in highly selective cases.

No benefit of more intense follow-up after surgery for colorectal cancer in the risk group with elevated CEA levels – An analysis within the COLOFOL randomized clinical trial

BackgroundPatients with colorectal cancer were examined to determine (1) whether elevated carcinoembryonic antigen (CEA) levels, either before treatment or after surgery, was associated with an increased risk of overall or colorectal cancer-specific mortality or recurrence, and (2) whether high intensity follow-up would benefit those patients. Materials and methodsPost-hoc analysis based on 2509 patients that underwent surgery for colorectal cancer, stage II or III, in the COLOFOL randomized trial with 5-year follow-up. Serum CEA levels were ascertained before treatment and one month after surgery. Follow-up examinations included computed tomography of the thorax and abdomen and serum CEA sampling. Patients were randomized to examinations at either 6, 12, 18, 24, and 36 months (high-intensity group) or at 12 and 36 months after surgery (low-intensity group). Levels of CEA >5 μg/l were defined as elevated. ResultsElevated CEA levels before treatment were associated with increased risk of recurrence (hazard ratio [HR], 1.49; 95% confidence interval [CI]: 1.22–1.83), colorectal cancer-specific mortality (HR, 1.44; 95% CI: 1.08–1.91), and overall mortality (HR, 1.38; 95% CI: 1.07–1.78). Elevated CEA levels after surgery were associated with increased colorectal cancer-specific mortality (HR, 1.68; 95% CI: 1.08–2.61) and overall mortality (HR, 1.79; 95% CI: 1.22–2.63). The intensity of the follow-up regimen had no effect on 5-year outcomes in patients with elevated CEA levels. ConclusionBoth pre-treatment and post-surgery elevated serum CEA levels were associated with increased overall and cancer-specific mortality. Intensified follow-up showed no benefit over low-intensity follow-up in this high-risk group of patients with elevated CEA levels.

TFAP2E and MLH1 Genes Methylation Pattern and Microsatellite Instability as Predictors of Rectal Cancer Response to Neoadjuvant Chemoradiotherapy

Background: Neoadjuvant chemoradiotherapy (nCRT) prior to surgery in rectal cancer has several adverse effects. Predictive biomarkers for response to nCRT are needed to save patients unnecessary toxicities and to take a timely tailored treatment decision. Epigenetic modifications like DNA methylation patterns have been suspected to be potential predictive biomarkers. Aim: To determine the role of TFAP2E and MLH1 genes’ methylation status and microsatellite instability (MSI) in predicting response to 5-fluorouracil – based nCRT in rectal cancer. Methods: DNA was extracted from 80 patients with newly diagnosed stage II / III rectal cancer. The methylation status of TFAP2E and MLH1 genes was determined by pyrosequencing and MSI was determined using 5 micro­satellite loci by conventional polymerase chain reaction and capillary electrophoresis. Results: The cut-off values for TFAP2E & MLH1 genes’ methylation level were 40% and 15% by receiver operating characteristic curve analysis. Hypermethylated TFAP2E and MLH1 gene promotors and MSI were predominant among non-responders (p <0.001, <0.001 and =0.022; respectively). Other factors associated with significantly higher pathological response to nCRT were well/moderately differentiated adenocarcinoma, pretreatment carcinoembryonic antigen level ≤5 ng/ml and rectal tumor ≤5 cm from the anal verge. Conclusion: Hypermethylated TFAP2E and MLH1 gene promotors and MSI in rectal cancer tissue were associated with poor response to 5-fluorouracil – based nCRT. They might be of value in predicting the response of rectal cancer to nCRT and in tailoring its treatment.

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

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.

Limited Role for Routine Restaging After Neoadjuvant Therapy in Locally Advanced Rectal Cancer

BackgroundAlthough many patients with locally advanced rectal cancer undergo restaging imaging after neoadjuvant chemoradiotherapy and before surgery, the benefit of this practice is unclear. The purpose of this study was to examine the impact of reimaging on outcomes. Materials and methodsWe performed a retrospective analysis of consecutive patients with stage 2 and 3 rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy between May 2005 and April 2018. Patient and disease characteristics, imaging, treatment, and oncologic outcomes were compared between those who underwent restaging and those who went directly to surgery. Predictors of outcomes and cost effectiveness of restaging were determined. ResultsOf 224 patients, 146 underwent restaging. Six restaged patients had findings leading to a change in management. There was no difference in freedom from recurrence (P = 0.807) and overall survival (P = 0.684) based on restaging. Pretreatment carcinoembryonic antigen level >3 ng/mL (P = 0.010), clinical T stage 4 (P = 0.016), and pathologic T4 (P = 0.047) and N2 (P = 0.002) disease increased the risk of death, whereas adjuvant chemotherapy decreased the risk of death (P < 0.001) on multivariate analysis. Disease recurrence was lower with pelvic exenteration (P = 0.005) and in females (P = 0.039) and higher with pathologic N2 (P = 0.003) and N3 (P = 0.002) disease. The average cost of reimaging is $40,309 per change in management; however, $45 is saved per patient when downstream surgical costs are considered. ConclusionsImaging restaging after neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer rarely changes treatment and does not improve survival. In a subset of patients at higher risk for worse outcome, reimaging may be beneficial.