Background: 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). Methods: 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. Results: 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. Conclusion: 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.@en

Background: The aim of the study was to evaluate psychological effects of the state-of-art intensified follow-up protocol for colorectal cancer patients in the CEAwatch trial. Method: At two time points during the CEAwatch trial questionnaires regarding patients’ attitude towards follow-up, patients’ psychological functioning and patients’ experiences and expectations were sent to participants by post. Linear mixed models were fitted to assess the influences and secular trends of the intensified follow-up on patients’ attitude towards follow-up and psychological functioning. As secondary outcome, odds ratios were calculated using ordinal logistic mixed model to compare patients’ experiences to their expectations, as well as their experiences at two different time points. Results: No statistical significant effects of the intensified follow-up were found on patients’ attitude towards the follow-up and psychological functioning variables. Patients had high expectations of the intensified follow-up and their experiences at the second time point were more positive compared to the scores at the first time point. Conclusion: The intensified follow-up protocol posed no adverse effects on patients’ attitude towards follow-up and psychological functioning. In general, patients were more nervous and anxious at the start of the new follow-up protocol, had high expectations of the new follow-up protocol and were troubled by the nuisances of the blood sample testing. As they spent more time in the follow-up and became more adapted to it, the nervousness and anxiety decreased and the preference for the frequent blood test became high in replacement of conversations with the doctors.@en

Aim: The study CEA Watch (Netherlands Trial Register 2182) has shown that an intensified follow-up schedule with more frequent carcinoembryonic antigen (CEA) measurements but fewer outpatient visits detects more curable recurrences compared with the usual follow-up protocol in colorectal cancer (CRC) patients. The aim of the study was to compare the cost and cost-effectiveness between various follow-up programmes. Method: In total, 3223 patients with stage I-III CRC were followed between October 2010 and October 2012. Direct medical costs were calculated per patient adding the costs for all visits, CEA measurements and imaging. Productivity losses and travel expenses were calculated using answers from questionnaires. The cost-effectiveness displayed the additional costs per additional patient with recurrent disease and used an incremental cost-effectiveness ratio (ICER) to compare them. Results: The mean yearly cost per patient was €548 in the intensified protocol and €497 in the control protocol. The ICER was €94 (95% CI €76-€157) per cent, to detect one additional patient with a recurrence in the intervention protocol compared with the control protocol would require an additional €9400. For curable recurrences, the ICER was €607 (95% CI €5695-€5728). Annual patient-reported costs were €509 per year in the intervention protocol and €488 in the control protocol. Conclusion: The current study demonstrates that the direct medical and patient-reported cost of a newly introduced, safe and effective way of CRC follow-up was comparable to that of standard care. The ICER per curable recurrence was considered acceptably low.@en

Abstract Aim The value of frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging for detecting recurrent disease in colorectal cancer (CRC) patients was investigated in search for an evidence-based follow-up protocol. Methods This is a randomized-controlled multicenter prospective study using a stepped-wedge cluster design. From October 2010 to October 2012, surgically treated non-metastasized CRC patients in follow-up were followed in eleven hospitals. Clusters of hospitals sequentially changed their usual follow-up care into an intensified follow-up schedule consisting of CEA measurements every two months, with imaging in case of two CEA rises. The primary outcome measures were the proportion of recurrences that could be treated with curative intent, recurrences with definitive curative treatment outcome, and the time to detection of recurrent disease. Results 3223 patients were included; 243 recurrences were detected (7.5%). A higher proportion of recurrences was detected in the intervention protocol compared to the control protocol (OR = 1.80; 95%-CI: 1.33-2.50; p = 0.0004). The proportion of recurrences that could be treated with curative intent was higher in the intervention protocol (OR = 2.84; 95%-CI: 1.38-5.86; p = 0.0048) and the proportion of recurrences with definitive curative treatment outcome was also higher (OR = 3.12, 95%-CI: 1.25-6.02, p-value: 0.0145). The time to detection of recurrent disease was significantly shorter in the intensified follow-up protocol (HR = 1.45; 95%-CI: 1.08-1.95; p = 0.013). Conclusion The CEAwatch protocol detects recurrent disease after colorectal cancer earlier, in a phase that a significantly higher proportion of recurrences can be treated with curative intent.@en

Background Due to changes in staging, (neo)-adjuvant treatment and surgical techniques for colorectal cancer (CRC), it is expected that the recurrence pattern will change as well. This study aims to report the current incidence of, and time to recurrent disease (RD), further the localization(s) and the eligibility for successive curative treatment. Methods A consecutive cohort of CRC patients, whom were routinely staged with CT and underwent curative treatment according to the national guidelines, was analyzed (n = 526). Results After a mean and median FU of 39 months, 20% of all patients and 16% of all AJCC stage 0-III patients had developed RD. The annual incidences were the highest in the first two years but tend to retain in the succeeding years for stage 0-III patients. The majority of RD was confined to one organ (58%) and 28% of these patients were again treated with curative intent. Conclusions In follow-up nowadays, less recurrences are found than reported in historical studies but these can more often be treated with curative intent. A main cause for the decreased incidence of RD, next to improvements in treatment, is probably stage shift elicited by pre-operative staging. The outcomes support continuation of follow-up in colorectal cancer.

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Background: The present paper is a first evaluation of the use of "CEAwatch", a clinical support software system for surgeons for the follow-up of colorectal cancer (CRC) patients. This system gathers Carcino-Embryonic Antigen (CEA) values and automatically returns a recommendation based on the latest values. Methods. Consecutive patients receiving follow-up care for CRC fulfilling our in- and exclusion criteria were identified to participate in this study. From August 2008, when the software was introduced, patients were asked to undergo the software-supported follow-up. Safety of the follow-up, experiences of working with the software, and technical issues were analyzed. Results: 245 patients were identified. The software-supported group contained 184 patients; the control group contained 61 patients. The software was safe in finding the same amount of recurrent disease with fewer outpatient visits, and revealed few technical problems. Clinicians experienced a decrease in follow-up workload of up to 50% with high adherence to the follow-up scheme. Conclusion: CEAwatch is an efficient software tool helping clinicians working with large numbers of follow-up patients. The number of outpatient visits can safely be reduced, thus significantly decreasing workload for clinicians.@en

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 meta chronous disease offers a second opportunity for cure. This paper revisits the potential role of serum carcinoem bryonic 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 designed studies. Specific limitations included: testing CEA as only an 'add-on' diagnostic tool; lack of standardization 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 randomized phase III study optimizing the usage of HiDT against resectability of recurrent disease is commencing recruitment in the Netherlands.

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Background: Carcinoembryonic antigen (CEA) as a marker in the follow-up after curative resection of colorectal carcinoma (CRC) is often omitted from follow-up despite guideline recommendations. One reason is the assumption that when a normal CEA value exists before curative resection of CRC, it will neither rise during follow-up. This study investigates this relationship. Method: Data were derived from a study initiated to evaluate treatment regimes for rectal carcinoma (Dutch TME trial, n = 1861) from which 954 were eligible for analysis. Recurrent disease occurred in 272 of these patients (29.5%). The pre-operative CEA value was compared to CEA values during follow-up, using threshold values of 2.5 and 5.0 ng/ml. Results: Normal pre-operative CEA values were present in 63% (CEA < 5.0) and 39% (CEA < 2.5) of patients with recurrent disease. Patients with a normal pre-operative CEA and recurrent disease had elevated CEA values during follow-up in 41% (CEA < 5.0), 50% (CEA < 2.5) and in 60% with both threshold values when the last measurement was done within 3 months before recurrent disease was diagnosed. Conclusion: A normal pre-operative CEA is common in patients with rectal carcinoma. CEA does rise due to recurrent disease in at least 50% of patients with normal pre-operative values. Serial post-operative CEA testing cannot be discarded based on a normal pre-operative serum CEA.

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Objective: Follow-up after curative resection of colorectal carcinoma (CRC) has been subjected to debate concerning its effectiveness to reduce cancer mortality. Current national and international guidelines advise CEA measurements every 3 months during 3 years after surgery. The common clinical practice and opinion about follow-up for colorectal carcinoma, was evaluated by means of a survey among Dutch general surgeons. Method: A web-based survey of follow-up after treatment of CRC was sent to all registered Dutch general surgeons. A reply from 246 surgeons treating patients for colorectal carcinoma in 105 out of 118 hospitals was received (response rate 91%). Questions related to actual follow-up protocol, opinion about serum CEA monitoring, liver and/or lung metastasectomy, and motivation to participate in a new trial concerning follow-up. Results: For the majority of surgeons the length of follow-up was influenced by age of the patient (62%) and physical condition (76%) prohibiting hepatic metastasectomy. The generally accepted follow-up protocol consisted of CEA measurements every 3 months in the first year and six-monthly thereafter, and ultrasound examination of the liver every 6 months. Nearly all surgeons (92%) were willing to participate in a new study of follow-up protocol. Conclusion: The adherence to national guidelines for the follow-up of colorectal carcinoma is low. The indistinctness about follow-up after curative treatment of colorectal carcinoma also affects clinical practice. Recent advancements in imaging techniques, liver and lung surgery have changed circumstances, which are not yet anticipated upon in current guidelines. Renewal of follow-up based upon scientific evidence is required.@en