Detection Of Recurrent Colorectal Cancer Research Articles

Diagnostic Performance of F-18 FDG PET/CT in the Detection of Recurrent Colorectal Cancer: Correlation with Biochemical Markers and Conventional Imaging Modalities.

Background/Objectives: Although the role of PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of F-18 FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, a retrospective study was performed including 134 CRC patients referred for PET/CT imaging on the suspicion of recurrence, based on elevated CEA and/or CA 19-9 and/or equivocal CIM findings. According to our institution's Tumor Board CRC protocol, after the initial treatment, which was dependent on the TNM stage (neoadjuvant therapy, primary resection, or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy, every six months. The statistics, including univariate and multivariate analyses were conducted using the IBM SPSS 20.0 statistical software. p-values < 0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. PET/CT showed high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA showed a high sensitivity of 98.1% but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy for CA 19-9 and CIM for diagnosis of CRC recurrence were 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p < 0.001), 0.844 (95% CI: 0.772-0.916; p < 0.001), 0.753 (95% CI: 0.612-0.844; p < 0.001), and 0.547 (95% CI: 0.442-0.652; p = 0.358), respectively. Univariate analysis showed that both PET/CT and CIM positive results were highly associated with CRC recurrence (p < 0.001 and p < 0.001, respectively). At the same time, gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) had no significance (p = 0.211, p = 0.158, p = 0.583, and p = 0.201, respectively). Our multivariate analysis showed that independent predictors for CRC recurrence are positive PET/CT scans (p < 0.001), positive CIM results (p = 0.001), and elevated CA 19-9 levels (p = 0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p = 0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting the CRC recurrence (p = 0.023). Conclusions: F-18 FDG PET/CT showed high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the post-operative follow-op in patients with elevated tumor markers.

Is frequent measurement of tumor markers beneficial for postoperative surveillance of colorectal cancer?

To determine whether frequent measurement of tumor markers triggers early detection of colorectal cancer recurrence. Of 1,651 consecutive patients undergoing colorectal cancer surgery between 2010 and 2016, 1,050 were included. CEA and CA 19-9 were considered to be postoperative tumor markers and were measured every 3months for 3years, and then every 6months for 2years. Sensitivity analysis of elevated CEA and CA19-9 levels and multivariate analysis of factors associated with elevated CEA and CA19-9 levels were performed. The proportion of triggers for detecting recurrence was determined. The median follow-up period was 5.3years. After applying the exclusion criteria, 1,050 patients were analyzed, 176 (16.8%) of whom were found to have recurrence. After excluding patients with persistently elevated CEA and CA19-9 levels before and after surgery from the 176 patients, 71 (43.6%) of 163 patients had elevated CEA levels and 35 (20.2%) of 173 patients had elevated CA19-9 levels. Sensitivity/positive predictive values for elevated CEA and CA19-9 levels at recurrence were 43.6%/32.3% and 20.2%/32.4%, respectively. Lymph node metastasis was a factor associated with both elevated CEA and CA19-9 levels at recurrence. Of the 176 patients, computed tomography triggered the detection of recurrence in 137 (78%) and elevated tumor marker levels in 13 (7%); the diagnostic lead interval in the latter 13 patients was 1.7months. Tumor marker measurements in surveillance after radical colorectal cancer resection contribute little to early detection, and frequent measurements are unnecessary for stage I patients with low risk of recurrence.

The Role of Circulating Biomarkers in the Early Detection of Recurrent Colorectal Cancer Following Resection of Liver Metastases.

On a global scale, colorectal cancer (CRC) is currently the fourth most commonly diagnosed cancer and despite progress in early diagnosis and treatment has the third highest mortality. Patients with oligometastatic disease to the liver may be suitable for liver resection with a curative intent. A sustained progress in perioperative management and surgical techniques, including staged liver resections, has increased the number of patients who may be offered hepatectomy. It is well recognised that early detection of any tumour, including recurrence, leads to a timely initiation of treatment with improved outcomes. Tumour biomarkers have long been desired in the search for a tool to aid cancer diagnosis, prognosis and follow-up. Currently, the only widely used biomarker for CRC, Carcinoembryonic Antigen (CEA), has multiple limitations, clearly illustrating the need for novel biomarkers. It is therefore unsurprising that much research has focused on identifying such markers with the literature being swamped with new and promising biomarkers. The aim of this study is to review the current status and role of circulating biomarkers in patients post hepatectomy for colorectal cancer metastasis including alternative cancer antigens to CEA, extracellular vesicles, circulating microRNA, circulating tumour cells and circulating tumour DNA.

Detection of recurrent colorectal cancer with high specificity using a reporting threshold for circulating tumor DNA methylated in BCAT1 and IKZF1.

A blood assay measuring methylated BCAT1 and IKZF1 can detect recurrent colorectal cancer (CRC) with high sensitivity but suboptimal specificity. This study aimed to establish an upper reference limit (URL) of these biomarkers in a reference population without CRC, apply that threshold to detecting clinical recurrence in patients who had undergone definitive therapy for CRC, and compare the performance of the biomarkers with carcinoembryonic antigen (CEA). The level of methylation was reported as the aggregate methylated BCAT1 and IKZF1 expressed as a percentage of total plasma DNA. A reference population of patients confirmed to have no colorectal neoplasia (n = 857) was used to determine the URL. Test accuracy for clinical recurrence was determined in a post-treatment surveillance population (n = 549; 77 recurrence cases). A methylation level of 0.07%, corresponding to the 98th percentile in the reference population, was set as the URL. In the surveillance population, 60 patients had methylation levels above 0.07%, and 81.7% of these had recurrence. In comparison with no minimum threshold being applied, assay sensitivity with a URL of 0.07% yielded similar sensitivity (63.6% [CI, 51.9%-74.3%] vs 64.9% [CI, 53.8%-74.7%]; P = .87) and higher specificity (97.7% [CI, 95.9%-98.8%] vs 91.3% [CI, 88.4%-93.5%]; P < .001). The BCAT1/IKZF1 test was 2.5-fold more sensitive than CEA for detecting recurrences considered amenable to surgery with curative intent (50.0% vs 20.8%; P = .016). Applying a threshold for positivity to the methylated BCAT1/IKZF1 blood assay improved the specificity for CRC recurrence without compromising sensitivity. Both the sensitivity and the specificity were superior to those of CEA.

Combined 18-FDG-PET/Contrast-Enhanced CT in the Diagnosis of Recurrent Colorectal Cancer: A Prospective Monocentric Pilot Study

Contrast-enhanced CT scan and 18DG-PET are used in the staging and surveillance of Colorectal Cancer (CRC). We here evaluate the feasibility and performances of systematically combining 18-FDG-PET and contrastenhanced CT whether as a stand-alone diagnostic examination, or as 2 separate examinations, for the early detection of recurrent colorectal cancer. 45 patients underwent 159 planned diagnostic follow-up sessions: 109 (68%) were performed as a combined modality during the same examination and 50 were performed as two separate examinations and acquired at different timepoints. Fourteen patients experienced recurrence during the study period. The sensitivity of 18-FDG-PET and contrast-enhanced CT scan in detecting a recurrent disease was 84.4% and 86.6 % respectively with a specificity of 96% and 97% respectively. 18-FDG-PET and contrast-enhanced CT findings’ were concordant in 79% of cases. The overall sensitivity and specificity in detecting CRC recurrence were 80% and 99% respectively in the combined procedure and 89% and 98% respectively in the two-time procedure. The positive predictive value of the procedure (combined or two-time procedure) for the detection of recurrent CRC was 100% with, however a shorter delay for decision with the combined [7.7 vs. 12.2 days] (p&lt;0.05). The combined procedure is feasible in almost 2/3 of cases. When compared to the two-time procedure, it is performant in detecting recurrent CRC with shorter delay to therapy.

Evaluation of Circulating Tumor DNA for Methylated BCAT1 and IKZF1 to Detect Recurrence of Stage II/Stage III Colorectal Cancer (CRC).

Most recurrences of early-stage colorectal cancer detected with current surveillance measures are widespread and incurable. Circulating tumor DNA (ctDNA) may facilitate earlier diagnosis of recurrent colorectal cancer and improve cancer-related outcomes. Plasma from patients undergoing standard surveillance after definitive treatment for stage II/III colorectal cancer was assayed with COLVERA and carcinoembryonic antigen (CEA) at a single time point. Results were correlated with radiographic imaging. Assay performance, including sensitivity and specificity for recurrence, were compared. Impact of potentially confounding variables was also explored. 322 patients were included in the final analysis, and 27 recurrences were documented over a median follow-up period of 15 months. Sensitivity for recurrence was 63% [confidence interval (CI), 42.4-80.6] and 48% (CI, 28.7-68.1) for COLVERA and CEA (≥5 ng/mL), respectively (P = 0.046), while specificity was 91.5% (CI, 87.7-94.4) and 96.3% (CI, 93.4-98.1), respectively (P = 0.016). Smoking and age were independent predictors of CEA but not COLVERA positivity. COLVERA was more sensitive but less specific than CEA in detecting recurrent colorectal cancer. Short median follow-up may have been responsible for apparent false positives in COLVERA. Studies with serial sampling and longer follow-up are needed to assess whether earlier detection of colorectal cancer recurrence translates into clinical benefit. This prospective study showed that COLVERA (a two-gene ctDNA assay) was more sensitive for detection of recurrence in a cohort of patients undergoing surveillance after definitive therapy for stages II and III colorectal cancer.

Can PET/CT detect recurrence in post-operative colorectal carcinoma patients with elevated CEA level?

BackgroundPET is considered to be the most sensitive and specific modality for the detection of recurrent colorectal cancer. This study is to assess the role of F18-FDG PET/CT in post-operative assessment in a patient with colorectal cancer with elevated CEA level to rule out local recurrence and/or metastasis and hence guiding the clinician to the proper management strategy.ResultsThis study was performed on 45 patients who underwent surgical resection of the colon and/or rectal cancer; they were referred for PET/CT assessment at least 3 months after surgical resection. F18-FDG PET/CT sensitivity and specificity in detecting the recurrence and/or metastasis were 96.9 % and 83.3%, respectively. The positive predictive value was 94.2% while the negative predictive value was 90%.ConclusionFor post-operative detection of loco-regional recurrence and metastasis in patients with colorectal cancer and elevated CEA level, 18F-FDG PET/CT can be considered as an efficient diagnostic imaging tool due to its high sensitivity and specificity which extensively affect further management.

Circulating epigenetic biomarkers for detection of recurrent colorectal cancer.

BackgroundThe sensitive detection of recurrent colorectal cancer (CRC) by the measurement of circulating tumor DNA (ctDNA) might improve the chance of a cure. This study compared a quantitative methylated ctDNA test with carcinoembryonic antigen (CEA) in the setting of surveillance for recurrence.MethodsBlood samples collected either during surveillance or within 12 months of the confirmation of recurrence were assayed for ctDNA (methylated branched‐chain amino acid transaminase 1 [BCAT1]/Ikaros family zinc‐finger 1 protein [IKZF1]) and CEA. The optimal ctDNA threshold was determined by receiver operating characteristic analysis, and the test performance for the detection of recurrence was compared with CEA (5 ng/mL threshold).ResultsThe study cohort comprised 144 eligible patients and included 50 recurrence events. The sensitivity of the methylated ctDNA test for recurrence was 66.0% (95% confidence interval [CI], 57.1%‐69.3%), which was significantly higher than the sensitivity of CEA (31.9%; 95% CI, 22.8%‐36.6%; P < .001). The sensitivity for resectable recurrence (n = 20) was also higher (ctDNA, 60.0%; CEA, 20.0%; P = .01). The specificity did not differ between the tests (ctDNA, 97.9%; 95% CI, 93.2%‐99.6%; CEA, 96.4%; 95% CI, 91.4%‐99.0%). When adjustments were made for other predictors of the presence of recurrence, a positive ctDNA test was an independent predictor (odds ratio, 155.7; 95% CI, 17.9‐1360.6; P < .001), whereas CEA was not (odds ratio, 2.5; 95% CI, 0.3‐20.6; P = .407).ConclusionsThe quantitative ctDNA test showed superior sensitivity in comparison with CEA without a difference in the specificity for detecting recurrent CRC. Longitudinal studies are warranted to further assess the utility (specifically the survival benefit) of methylated BCAT1/IKZF1 ctDNA in the surveillance of patients with CRC.

Performance comparison of the methylated BCAT1/IKZF1 ctDNA test (COLVERA) with the CEA assay for detection of recurrent colorectal cancer.

3589 Background: Early detection of recurrent colorectal cancer (CRC) will improve treatment options, but the current standard blood test of carcinoembryonic-antigen (CEA) has suboptimal sensitivity for recurrence. This study compared performance of a quantitative circulating tumor DNA (ctDNA) assay for methylated BCAT1 and IKZF1 (COLVERA) with that of CEA. Methods: 301 patients were monitored for recurrence after clearance of primary CRC. Blood was collected at scheduled intervals and concentrations of CEA and ctDNA were measured using the LIAISON CEA test (Diasorin) and the COLVERA ctDNA test (Clinical Genomics). Surveillance for recurrent disease was examined using regular CT scans. Sensitivity of each blood test for recurrence was assessed in the sample collected closest to the time of imaging confirming recurrence status. Absence of recurrence was defined as at least two consecutive clear CT scans. Receiver operator characteristic (ROC) analyses were used to determine optimal positivity threshold for Colvera. Results: 131 patients underwent satisfactory assessment for recurrence and had blood testing performed within 12 months of determining recurrence status (61.8% male, mean age 62.6 ±.12.2(SD)y). Of the 47 recurrence cases, 37 (74%) were distant. The areas under the ROC curves were 0.7761 and 0.8188 for CEA and COLVERA, respectively (each p &lt; 0.001). An optimal cut-off of 12.8pg/sample was determined for COLVERA and the standard 5ng/mL cut-off was selected for CEA. COLVERA had a significantly higher sensitivity for detecting recurrence as compared to CEA (68.1% vs 31.9%, p &lt; 0.001) with a similar specificity (97.6% Vs 96.4%, p = 0.6547). A multivariate analysis determined COLVERA to be a predictor of recurrence independent of CEA with positive COLVERA samples being 66.4 times (95%CI 14.0-315.8) more likely to have recurrence confirmed within the study timeframe, whereas CEA was not a significant predictor of recurrence (p = 0.228). Conclusions: These findings indicate that COLVERA, reporting in quantitative mode, is a more sensitive test than CEA. It provides a viable alternative for sensitive and early detection of recurrent CRC. Clinical trial information: 12611000318987.

Survival analysis of the CEAwatch multicentre clustered randomized trial.

The CEAwatch randomized trial showed that follow-up with intensive carcinoembryonic antigen (CEA) monitoring (CEAwatch protocol) was better than care as usual (CAU) for early postoperative detection of colorectal cancer recurrence. The aim of this study was to calculate overall survival (OS) and disease-specific survival (DSS). For all patients with recurrence, OS and DSS were compared between patients detected by the CEAwatch protocol versus CAU, and by the method of detection of recurrence, using Cox regression models. Some 238 patients with recurrence were analysed (7·5 per cent); a total of 108 recurrences were detected by CEA blood test, 64 (55·2 per cent) within the CEAwatch protocol and 44 (41·9 per cent) in the CAU group (P = 0·007). Only 16 recurrences (13·8 per cent) were detected by patient self-report in the CEAwatch group, compared with 33 (31·4 per cent) in the CAU group. There was no significant improvement in either OS or DSS with the CEAwatch protocol compared with CAU: hazard ratio 0·73 (95 per cent 0·46 to 1·17) and 0·78 (0·48 to 1·28) respectively. There were no differences in survival when recurrence was detected by CT versus CEA measurement, but both of these methods yielded better survival outcomes than detection by patient self-report. There was no direct survival benefit in favour of the intensive programme, but the CEAwatch protocol led to a higher proportion of recurrences being detected by CEA-based blood test and reduced the number detected by patient self-report. This is important because detection of recurrence by blood test was associated with significantly better survival than patient self-report, indirectly supporting use of the CEAwatch protocol.

Abstract B32: Longitudinal changes in plasma miRNA in patients with benign and malignant colorectal neoplasia

Abstract Introduction: The adenoma-carcinoma sequence is well-recognized as a stepwise pattern of mutational activation of oncogenes and inactivation of tumor suppressor genes resulting in sporadic colorectal cancer (CRC) development from colorectal adenomas (CRA) within the chromosomal instability pathway. MicroRNAs (miRNA) play an important role in oncogenesis by regulating gene expression and are known to be actively released from cells. They are found in body fluids such as plasma, saliva, feces and urine. We have previously demonstrated differential expression of plasma miRNAs in patients with CRC as compared to that of controls. Methods: Plasma was isolated from 10 patients: 5 patients with advanced colorectal adenoma (&amp;gt;0.6cm diameter) and 5 patients with stage II or III colorectal cancer prior to treatment and 4-6 weeks following endoscopic removal or surgical resection, respectively. RNA was extracted from plasma (Qiagen® miRNeasy), RT-PCR performed and 768 miRNAs were screened using microfluidic array technology (Applied BioSystems®) in pre- and post-treatment samples for each patient. Data were analyzed using paired t-tests after normalizing raw cycle threshold data to endogenous RNU6 for pre- and post-treatment samples. In addition, miRNA expression data from both pre- and post-treatment CRA and CRC samples were compared to that of plasma from 10 individuals without neoplasia (controls) (ANOVA). Results: Significant differential expression of plasma miRNAs was observed between pre- and post-treatment samples in both CRA and CRC groups. Interestingly, there was generalized miRNA upregulation in CRA when comparing pre-treatment samples to post-treatment samples. Conversely there was miRNA down-regulation in pre-treatment CRC plasma as compared to post-resection samples. Utilizing significantly dysregulated miRNAs, as well as p-values, AUC, fold-change and biological significance, miRNA panels were selected to facilitate detection of CRA recurrence (following complex polypectomy for large polyps) or for detection of recurrent CRC following resection. The resulting panel was able to differentiate between pre- and post-treatment samples for CRA (miR-186 and miR-623) with AUC 0.94 (95% CI 0.76 – 1.00) and for CRC (miR-324-5p, miR-30d and miR-766) with AUC 0.88 (95% CI 0.63 – 1.00). In addition, while miRNA expression of pre-treatment CRA and CRC samples differed significantly from controls, post-treatment CRA and CRC samples did not. Conclusion: Comparison of pre- and post-treatment plasma samples reveals differing patterns of changes in miRNA expression in benign colorectal neoplasms (CRA) as opposed to invasive neoplasia (CRC). The observed miRNA down-regulation prior to surgical resection of CRC might indicate decreased expression of miRNAs inhibiting oncogenes prior to cancer treatment, while the miRNA upregulation seen in pre-treatment CRA plasma could indicate inhibition of tumor suppressors. Such observations will perhaps elucidate the role of miRNA in carcinogenesis and may provide for a relatively non-invasive method of detecting such lesions. Further validation is needed to develop a miRNA panel that will allow monitoring for evidence of recurrent disease. Citation Format: Jane Carter, Vanessa States, Uri Netz, Jianmin Pan, Shesh Rai, Susan Galandiuk. Longitudinal changes in plasma miRNA in patients with benign and malignant colorectal neoplasia. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B32.

A General Cutoff Level Combined With Personalized Dynamic Change of Serum Carcinoembryonic Antigen Can Suggest Timely Use of FDG PET for Early Detection of Recurrent Colorectal Cancer.

FDG PET that has been used is good for diagnosing asymptomatic colorectal cancer (CRC) recurrence in patients with elevated serum carcinoembryonic antigen (CEA) level. However, there is no reference level of CEA rise that would universally suggest the necessity of a PET study. The purpose of this retrospective study was to identify the high-risk group of CRC recurrence through an examination of the dynamics of the CEA level rise as a recurrence indicator. Between July 2002 and May 2010, 112 patients (59 men, 53 women; age, 18-87 years) had FDG PET for suspicious CRC recurrence indicated by elevated CEA level. We reviewed the PET results and the medical records for recurrence verification and calculated the ratio of increase and the velocity of change in CEA levels for risk stratification. The patient-based sensitivity, specificity, and accuracy of PET are 96.6%, 91.3%, and 95.5%, respectively. The probability of recurrence positively correlated with the CEA level rise and the newly diagnosed disease stage. Carcinoembryonic antigen level greater than 13 ng/mL indicated significantly higher risks of recurrence. In patients with CEA level rise of 13 ng/mL or less, an increase over 3.34 times the individualized baseline also indicated high risks of recurrence. A posttreatment CEA level rise to greater than 13 ng/mL is suggestive of the optimal use of FDG PET, and so is a mild increase below 13 ng/mL at an increase rate over 3.34.

Diagnostic value of (18)F-FDG PET/CT as first choice in the detection of recurrent colorectal cancer due to rising CEA.

BackgroundThe diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) as the first imaging approach in the evaluation of rising carcinoembryonic antigen (CEA) is not clear. The objective of this study was to investigate the value of 18F-FDG PET/CT in patients with colorectal cancer (CRC) and suspected recurrence based on rising CEA.MethodsA total of 73 patients with CRC were referred to PET/CT after radical surgery. Generally, all patients were scheduled to follow a CT-based post-surgical follow-up regimen. In the case of rising CEA, 18F-FDG PET/CT was performed in most patients with contrast-enhanced CT. The PET/CT images were independently reviewed by two readers. The presence or absence of recurrence was based on histology and/or standardized clinical follow-up.ResultsAmong 35 patients who had confirmed recurrence of CRC, PET/CT demonstrated recurrence with a sensitivity of 85.7 %, a specificity of 94.7 %, a positive predictive value of 93.8 %, and a negative predictive value of 87.8 %. The SUVmax ranged from 1.3 to 19.9. The mean time since the last postoperative imaging and PET/CT was 8 months (median 4 months). CEA values at referral ranged from 1.5 to 164.0 μg/L (median 5.6 μg/L). The diagnostic properties of PET/CT were analyzed in subgroups of patients with a single rising CEA sample (30 patients, 41 %), 31 patients (43 %) with two or more consecutive increases, and 12 patients (16 %) with persistently elevated values.Conclusions18F-FDG PET/contrast-enhanced CT has high diagnostic accuracy in the diagnosis of recurrent CRC, even in patients in a conventional CT-based follow-up program.

Value of Dual Assessment of Carcinoembryonic Antigen and Fluorine-18-Fluoro-Deoxyglucose Positron Emission Tomography in Colorectal Cancer Recurrence

Globally, colorectal cancer is a common medical problem and improvement of survival in patients with colorectal carcinoma could be achieved by identifying disease recurrence and progression, as well as by specifying their treatment planning. The use of various biomarkers associated with radio diagnosis techniques is not common in daily clinical practice. The aim of the present study was to evaluate the usefulness of dual assessment of FDG-PET and CEA in detecting recurrence of colorectal carcinoma in patients subsequent to colonic resection or rectal amputation. One hundred sixty patients, 99 males and 61 females, the mean of their age was 55.76 ± 12.25 years with suspected recurrent colonrectal cancer (CRC) after previous colonic resection or rectal amputation for CRC were included in this prospective study from February 2011 to March 2015. The inclusion criteria were: histopathologically confirmed colorectal adenocarcinoma, curative resection of the primary tumor, at least 3 months before and availability for follow-up after 18F-FDG PET/CT and CEA for at least 12 months. The CEA levels were measured within the time of the FDG PET/CT study. Only 132 patients were confirmed by histopathology or 6 month clinical follow up had local recurrence or metastasis (47 patients were confirmed had Intra-abdominal extra-hepatic recurrence , 80 patients had extra-abdominal and/or hepatic recurrence , 30 patients had other form of recurrence (17 patients had metastasis at other sites as the neck, long bones , mediastinal lymph nodes and multiple metastases) .The PET/CT diagnosis of recurrence and metastasis in CRC patients included in the study. Out of 160 patients after CRC resection, 126 patients were diagnosed by PET/CT as true-positive cases (25.62% Stage II /53.13% and I Stage III/IV) and 34 patients as negative cases (21.25 %). The sensitivity of monitoring the recurrence and metastasis of patients with CRC by PET/CT was 95.45 %. However, the diagnostic value of CEA levels for recurrence and metastasis in CRC patients included in the study proved that 102 patients had increased value of CEA (63.8%) and 58 patients (36.2%) had normal CEA value. The sensitivity of the CEA levels for monitoring the recurrence of the patients with CRC was 77.27 %. The sensitivity of the 18F-FDG PET/CT scan is superior to CEA in detection of colorectal cancer recurrence and dual assessment is important in treatment planning.

Antígeno carcinoembrionario en la recurrencia y sobrevida de pacientes con resección curativa de cáncer colorrectal

Introduction: Carcinoembryonic antigen (CEA) has been associated with advanced stage, poor survival and early detection of recurrent colorectal cancer (CRC). Objectives: To determine relation between serum CEA and recurrence and survival of patients with curative resection of colorectal cancer. Design: Retrospective, correlational and explanatory study. Setting: Department of General and Oncology Surgery, Service of Colon and Rectum, Hospital Nacional Rebagliati Martins, EsSalud, Lima, Peru. Participants: Patients with curative resection of CRC. Methods: Patients with curative resection of CRC at Rebagliati Hospital during years 2000-2003 were followed until 2010. For variables quantitative comparison T test mean differences was used, and Kaplan-Meier method and Cox regression survival analysis techniques were used. Main outcome measures: Patients recurrence and survival. Results: Increased serum CEA in the pre and postoperative periods was related to significant increased recurrence of colorectal cancer (p <0.05). Survival in patients with pathological CEA was significantly lower than in patients with standard CEA (p <0.05). Conclusions: Elevated serum carcinoembryonic antigen was related to increased colorectal cancer recurrence. Serum CEA values in the preoperative period would be predictive of survival.

Future directions for the early detection of colorectal cancer recurrence.

Surgical resection remains a mainstay of treatment and is highly effective for localized colorectal cancer. However, ~30-40% of patients develop recurrence following surgery and 40-50% of recurrences are apparent within the first few years after initial surgical resection. Several variables factor into the ultimate outcome of these patients, including the extent of disease, tumor biology, and patient co-morbidities. Additionally, the time from initial treatment to the development of recurrence is strongly associated with overall survival, particularly in patients who recur within one year of their surgical resection. Current post-resection surveillance strategies involve physical examination, laboratory, endoscopic and imaging studies utilizing various high and low-intensity protocols. Ultimately, the goal is to detect recurrence as early as possible, and ideally in the asymptomatic localized phase, to allow initiation of treatment that may still result in cure. While current strategies have been effective, several efforts are evolving to improve our ability to identify recurrent disease at its earliest phase. Our aim with this article is to briefly review the options available and, more importantly, examine emerging and future options to assist in the early detection of colon and rectal cancer recurrence.

Early Detection of Colorectal Cancer Recurrence in Patients Undergoing Surgery with Curative Intent: Current Status and Challenges

Despite advances in neoadjuvant and adjuvant therapy, attention to proper surgical technique, and improved pathological staging for both the primary and metastatic lesions, almost half of all colorectal cancer patients will develop recurrent disease. More concerning, this includes ~25% of patients with theoretically curable node-negative, non-metastatic Stage I and II disease. Given the annual incidence of colorectal cancer, approximately 150,000 new patients are candidates each year for follow-up surveillance. When combined with the greater population already enrolled in a surveillance protocol, this translates to a tremendous number of patients at risk for recurrence. It is therefore imperative that strategies aim for detection of recurrence as early as possible to allow initiation of treatment that may still result in cure. Yet, controversy exists regarding the optimal surveillance strategy (high-intensity vs. traditional), ideal testing regimen, and overall effectiveness. While benefits may involve earlier detection of recurrence, psychological welfare improvement, and greater overall survival, this must be weighed against the potential disadvantages including more invasive tests, higher rates of reoperation, and increased costs. In this review, we will examine the current options available and challenges surrounding colorectal cancer surveillance and early detection of recurrence.

Use of FDG-PET or PET/CT to detect recurrent colorectal cancer in patients with elevated CEA: a systematic review and meta-analysis

The purpose of the present study was to conduct a systematic review and meta-analysis of the published literature to assess the diagnostic performance of FDG-PET or PET/CT in the detection of recurrent colorectal cancer (CRC) rising in patients with elevated CEA. The authors conducted a systematic MEDLINE search of published articles. Two reviewers independently assessed the methodological quality of each study. We estimated pooled sensitivity and specificity and positive and negative likelihood ratios, and summary receiver-operating characteristic curves in the detection of recurrent CRC in patients with elevated CEA. Eleven studies with a total of 510 patients met the inclusion criteria. One hundred and six patients (106/510 = 20.8%) had true-negative FDG-PET (PET/CT) results in detection of recurrent CRC when rising CEA. The pooled estimates of sensitivity and specificity and positive and negative likelihood ratios of FDG-PET in the detection of tumor recurrence in CRC patients with elevated CEA were 90.3% (95% CI, 85.5-94.0%), 80.0% (95% CI, 67.0-89.6%), 2.88 (95% CI, 1.37-6.07), and 0.12 (95% CI, 0.07-0.20), respectively. The pooled estimates of sensitivity and specificity and positive and negative likelihood ratios of FDG-PET/CT in the detection of tumor recurrence in CRC patients with elevated CEA were 94.1% (95% CI, 89.4-97.1%), 77.2% (95% CI, 66.4-85.9%), 4.70 (95% CI, 0.82-12.13), and 0.06 (95% CI, 0.03-0.13), respectively. Whole-body FDG-PET and PET/CT are valuable imaging tools for the assessment of patients with suspected CRC tumor recurrence based on the increase of CEA.

Early detection of recurrence after curative resection for colorectal cancer – obstacles when using soluble biomarkers?

Objective. Results from monitoring studies using biomarkers in blood samples aiming at early detection of recurrent colorectal cancer (CRC) are presently evaluated. However, some serological biomarker levels are influenced by the surgical trauma, which may complicate translation of the levels in relation to recurrence. The primary purpose of the present study was to evaluate the frequency of postoperative surgical interventions during a follow-up period of patients who have undergone surgery for primary CRC. Methods.In a prospective multicenter, clinical study, 634 patients resected for primary CRC were followed in the outpatient clinic every third month. Blood samples were drawn at each visit. A subgroup of 165 stage II and III patients, who had been followed for at least 3 years, was selected. Any recent surgical intervention associated with the primary disease and/or other diseases were recorded at each visit to the outpatient clinic. Results. Among the 165 patients, 49 developed recurrence (R+), 107 did not (R-) and 11 developed a new primary cancer, including 2 in the R+ group. Within the 3 years of observation, 78 (47.3%) of the 165 patients underwent 117 (range 1–5) postoperative surgical interventions. Seventy-five operations were related to CRC and 42 to benign diseases, while none were related to a new primary, malignant disease. Conclusion.Patients resected for CRC are frequently undergoing surgical procedures in the postoperative follow-up period. Therefore, postoperative monitoring using soluble biomarker levels, which may be influenced by the surgical trauma, must be adjusted in relation to postoperative surgical interventions.

Diagnostic Value of Positron Emission Tomography-Computed Tomography (PET/CT) in Detection of Recurrence after Curative resection for Colorectal Cancer

Introduction : Accurate detection of recurrent colorectal cancer remains a diagnostic challenge. The purposes of this study were to evaluate the diagnostic value of Positron Emission Tomography-Computed Tomography (PET/CT) using fluor-18-deoxyglucose (FDG) in Detection of Recurrence after Curative resection for Colorectal Cancer. Material and Methods : We performed a retrospective review of 248 patients who underwent PET/CT for surveillance of colorectal cancer after curative resection between June 2008 and April 2011. Recurrence of colorectal cancer was validated by histopathologic examination or serial imaging study follow-up. Results : Of the 248 patients (149 males) included in the study, thirty-six patients (14.5%) were confirmed as recurrence. Liver was the most common site of recurrence (n=13). A total 472 PET/CT were conducted in 248 patients during follow-up period. The sensitivity and specificity of PET/CT were 0.921(95% CI 0.908-0.934) and 0.981(95% CI 0.975-0.987) for detecting tumor recurrence. The sensitivity and specificity of contrast enhanced computed tomography (CECT) were 0.902(95% CI 0.888-0.916) and 0.952(95% CI 0.942-0.952). CEA elevation was shown in only 13 cases (36.1%) of patients with recurrence. The treatment plans of 26 cases (10.5%) were altered by PET/CT findings. The curative surgical tumor resection procedure was performed in 15 out of 36 patients. In 3 cases which CECT showed negative findings, PET/CT had detected unexpected metachronous cancer (one colon, two bladders). Conclusions : Additional PET/CT on CECT seems to provide high detection rate of tumor recurrence after curative resection for colorectal cancer and other critical information such as unexpected secondary malignancy.