***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Surgical resection is the primary treatment modality for patients with localized colorectal cancer , but unfortunately one-third to one-half of these patients will develop a recurrence . If detected early , recurrent disease may be amenable to surgical resection and this provides the rationale for a follow-up strategy in patients with resected colorectal cancer . Despite eight published r and omized controlled trials and six published systematic review s evaluating different follow-up strategies , there is still no consensus as to the appropriateness of follow-up in colorectal cancer patients . In the present article the authors explore the reasons behind the controversy and the arguments used to support each side . They outline the current published guidelines and the data to support these recommendations , including the use of  carcinoembryonic antigen ( CEA ) levels , liver imaging , and colonoscopy .  Finally , they speculate on the future developments that may impact on this debate PURPOSE Three-year disease-free survival ( DFS ) was significantly improved in patients who had undergone resection with curative intent for stage II or III colon cancer who received bolus plus continuous-infusion fluorouracil plus leucovorin ( LV5FU2 ) with the addition of oxaliplatin ( FOLFOX4 ) . Final results of the study , including 6-year overall survival ( OS ) and 5-year up date d DFS , are reported . PATIENTS AND METHODS A total of 2,246 patients were r and omly assigned to receive LV5FU2 or FOLFOX4 for 6 months . The primary end point was DFS . Secondary end points were OS and safety . Results Five-year DFS rates were 73.3 % and 67.4 % in the FOLFOX4 and LV5FU2 groups , respectively ( hazard ratio [ HR ] = 0.80 ; 95 % CI , 0.68 to 0.93 ; P = .003 ) . Six-year OS rates were 78.5 % and 76.0 % in the FOLFOX4 and LV5FU2 groups , respectively ( HR = 0.84 ; 95 % CI , 0.71 to 1.00 ; P = .046 ) ; corresponding 6-year OS rates for patients with stage III disease were 72.9 % and 68.7 % , respectively ( HR = 0.80 ; 95 % CI , 0.65 to 0.97 ; P = .023 ) . No difference in OS was seen in the stage II population . The incidence of second noncolorectal cancers was 5.5 % and 6.1 % in the FOLFOX4 and LV5FU2 groups , respectively . Among patients receiving oxaliplatin , the frequency of grade 3 peripheral sensory neuropathy was 1.3 % 12 months after treatment and 0.7 % at 48 months . CONCLUSION Adding oxaliplatin to LV5FU2 significantly improved 5-year DFS and 6-year OS in the adjuvant treatment of stage II or III colon cancer and should be considered after surgery for patients with stage III disease Following curative treatment for colorectal cancer ( CRC ) , 30 % to 50 % of patients will develop recurrent disease . For CRC there are several lines of evidence supporting the hypothesis that early detection of metachronous disease offers a second opportunity for cure . This paper revisits the potential role of serum carcinoembryonic antigen ( CEA ) in follow-up . A comprehensive review of the literature ( 1978–2008 ) demonstrates that the initial promise of serum CEA as an effective surveillance tool has been tarnished through perpetuation of poorly design ed studies . Specific limitations included : testing CEA as only an ‘ add-on ’ diagnostic tool ; lack of st and ardization of threshold values ; use of static thresholds ; too low measurement frequency . Major changes in localizing imaging techniques and treatment of metastatic CRC further cause a decrease of clinical applicability of past trial outcomes . In 1982 , Staab hypothesized that the optimal benefit of serum CEA as a surveillance tool is through high-frequency triage using a dynamic threshold ( HiDT ) . Evidence supporting this hypothesis was found in the biochemical characteristics of serum CEA and retrospective studies showing the superior predictive value of a dynamic threshold . A multi-centred r and omized phase III study optimizing the usage of HiDT against resectability of recurrent disease is commencing recruitment in the Netherl and IMPORTANCE Intensive follow-up after surgery for colorectal cancer is common practice but is based on limited evidence . OBJECTIVE To assess the effect of scheduled blood measurement of carcinoembryonic antigen ( CEA ) and computed tomography ( CT ) as follow-up to detect recurrent colorectal cancer treatable with curative intent . DESIGN , SETTING , AND PARTICIPANTS R and omized clinical trial in 39 National Health Service hospitals in the United Kingdom ; 1202 eligible participants were recruited between January 2003 and August 2009 who had undergone curative surgery for primary colorectal cancer , including adjuvant treatment if indicated , with no evidence of residual disease on investigation . INTERVENTIONS Participants were r and omly assigned to 1 of 4 groups : CEA only ( n = 300 ) , CT only ( n = 299 ) , CEA+CT ( n = 302 ) , or minimum follow-up ( n = 301 ) .  Blood CEA  was measured every 3 months for 2 years , then every 6 months for 3 years ; CT scans of the chest , abdomen , and pelvis were performed every 6 months for 2 years , then annually for 3 years ; and the minimum follow-up group received follow-up if symptoms occurred . MAIN OUTCOMES AND MEASURES The primary outcome was surgical treatment of recurrence with curative intent ; secondary outcomes were mortality ( total and colorectal cancer ) , time to detection of recurrence , and survival after treatment of recurrence with curative intent . RESULTS After a mean 4.4 ( SD , 0.8 ) years of observation , cancer recurrence was detected in 199 participants ( 16.6 % ; 95 % CI , 14.5%-18.7 % ) overall ; 71 of 1202 participants ( 5.9 % ; 95 % CI , 4.6%-7.2 % ) were treated for recurrence with curative intent , with little difference according to Dukes staging ( stage A , 5.1 % [ 13/254 ] ; stage B , 6.1 % [ 34/553 ] ; stage C , 6.2 % [ 22/354 ] ) . Surgical treatment of recurrence with curative intent was 2.3 % ( 7/301 ) in the minimum follow-up group , 6.7 % ( 20/300 ) in the CEA group , 8 % ( 24/299 ) in the CT group , and 6.6 % ( 20/302 ) in the CEA+CT group . Compared with minimum follow-up , the absolute difference in the percentage of patients treated with curative intent in the CEA group was 4.4 % ( 95 % CI , 1.0%-7.9 % ; adjusted odds ratio [ OR ] , 3.00 ; 95 % CI , 1.23 - 7.33 ) , in the CT group was 5.7 % ( 95 % CI , 2.2%-9.5 % ; adjusted OR , 3.63 ; 95 % CI , 1.51 - 8.69 ) , and in the CEA+CT group was 4.3 % ( 95 % CI , 1.0%-7.9 % ; adjusted OR , 3.10 ; 95 % CI , 1.10 - 8.71 ) . The number of deaths was not significantly different in the combined intensive monitoring groups ( CEA , CT , and CEA+CT ; 18.2 % [ 164/901 ] ) vs the minimum follow-up group ( 15.9 % [ 48/301 ] ; difference , 2.3 % ; 95 % CI , -2.6 % to 7.1 % ) . CONCLUSIONS AND RELEVANCE Among patients who had undergone curative surgery for primary colorectal cancer , intensive imaging or CEA screening each provided an increased rate of surgical treatment of recurrence with curative intent compared with minimal follow-up ; there was no advantage in combining CEA and CT . If there is a survival advantage to any strategy , it is likely to be small . TRIAL REGISTRATION is rct n.org Identifier : 41458548 The concept of second‐look surgery was introduced by Wangensteen 25 years ago , and 17 % of patients were reported to be converted to a cancer‐free state . Instead of an arbitrary time interval for reoperation , serial CEA values were used as the indicator of colon cancer recurrence and second‐look operation . Twenty‐two retrospective and 18 prospect i ve patients were evaluable .  There was no operative mortality . The CEA Nomogram was used to determine whether the CEA change was significant . All patient‐ sample s were analyzed in duplicate , stored , and compared with the most recent sample ; therefore , each patient served as his own control . The prospect i ve results emphasize the importance of minimizing the time delay between a significant change in CEA values and reoperation . Equally important are the frequency of serial determinations ( every one or two months ) , a thorough underst and ing of the limitations of the CEA radioimmunoassay , and the clinical condition of the patient Objective To evaluate the diagnostic accuracy of a single CEA ( carcinoembryonic antigen ) blood test in detecting  colorectal cancer recurrence .  Background Patients who have undergone curative resection for primary colorectal cancer are typically followed up with scheduled CEA testing for 5 years . Decisions to investigate further ( usually by CT imaging ) are based on single test results , reflecting international guidelines . Methods A secondary analysis was undertaken of data from the FACS trial ( two arms included CEA testing ) . The composite reference st and ard applied included CT-CAP imaging , clinical assessment and colonoscopy . Accuracy in detecting recurrence was evaluated in terms of sensitivity , specificity , likelihood ratios , predictive values , time-dependent area under the ROC curves , and operational performance when used prospect ively in clinical practice are reported . Results Of 582 patients , 104 ( 17.9 % ) developed recurrence during the 5 year follow-up period . Applying the recommended threshold of 5μg/L achieves at best 50.0 % sensitivity ( 95 % CI : 40.1–59.9 % ) ; in prospect i ve use in clinical practice it would lead to 56 missed recurrences ( 53.8 % ; 95 % CI : 44.2–64.4 % ) and 89 false alarms ( 56.7 % of 157 patients referred for investigation ) . Applying a lower threshold of 2.5μg/L would reduce the number of missed recurrences to 36.5 % ( 95 % CI : 26.5–46.5 % ) but would increase the false alarms to 84.2 % ( 924/1097 referred ) . Some patients are more prone to false alarms than others — at the 5μg/L threshold , the 89 episodes of unnecessary investigation were clustered in 29 individuals . Conclusion Our results demonstrated very low sensitivity for CEA , bringing to question whether it could ever be used as an independent triage test . It is not feasible to improve the diagnostic performance of a single test result by reducing the recommended action threshold because of the workload and false alarms generated . Current national and international guidelines merit re-evaluation and options to improve performance , such as making clinical decisions on the basis of CEA trend , should be further assessed Abstract The relationship between the pattern of carcinoembryonic antigen ( CEA ) changes and the types of recurrence was investigated in a prospect i ve study of 146 patients who underwent curative operations for adenocarcinoma of the colon or rectum .  Recurrences developed in 51 patients ( 34.9 % ) and was local in 14 , distant in 23 , and both local and distant in 14 of them . CEA slope values were individually calculated beginning with an initial rise of more than 1 ng/ml , and expressed as the % rise in CEA per month . Patients who relapsed had significantly higher slopes than those who remained well ( median 20.0 % versus 0.3 % rise , p<0.001 ) . A slope value of 5 % rise per month broadly separated the two groups with an overall accuracy of 79.4 % , sensitivity rate for recurrence of 86.3 % , and specificity rate for no relapse of 75.8 % . Median CEA slope values did not differ significantly among patients with different types of relapse . However , compared with patients who had any distant recurrence , more patients with localized recurrence had slope values of less than 5 % rise per month ( 8.1 % versus 28.6 % , respectively ; one-tailedp=0.04 ) . Nevertheless , a slope exceeding a 5 % rise per month was observed in 10 of the 14 patients with local recurrence . We conclude that serial postoperative CEA monitoring is useful in detecting both local as well as distant recurrence . Furthermore , the use of slope analysis may enhance the sensitivity of postoperative CEA monitoring for detecting relapse . RésuméLa relation entre les variations du taux de l'antigène carcino-embryonnaire et les divers types de récidive ont été étudiés chez 146 sujets qui avaient subi une opération à visée curative pour cancer du colon ou du rectum . La récidive s'est manifestée chez 51 opérés ( 34,9 % ) , locale dans 24 cas , à distance dans 23 cas , locale et à distance dans 14 cas . La pente des valeurs de l'antigène fut calculée pour chaque sujet dès que le taux de l'antigène atteignait 1 ng/ 
    Output:
    
Making decisions to further investigate based on the trend in serial CEA measurements is better ( AUC for positive trend 0.85 , 95 % CI 0.78 to 0.91 ) , but to maintain approximately 70 % sensitivity with 90 % specificity it is necessary to increase the frequency of testing in year 1 and to apply a reducing threshold for investigation as measurements accrue .
The results suggest that ( 1 ) CEA testing should not be used alone as a triage test ; ( 2 ) in year 1 , testing frequency should be increased ( to monthly for 3 months and then every 2 months ) ; ( 3 ) the threshold for investigating a single test result should be raised to 10 µg/l ; ( 4 ) after the second CEA test , decisions to investigate further should be made on the basis of the trend in CEA levels ; ( 5 ) the optimal threshold for investigating the CEA trend falls over time ; and ( 6 ) continuing smokers should not be monitored with CEA testing .