title: Intensified follow-up in colorectal cancer patients using frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging: Results of the randomized "CEAwatch" trial.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands. Electronic address: c.j.verberne@umcg.nl.
authors.forename: C J
authors.initials: CJ
authors.lastname: Verberne
authors.affiliation: Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands. Electronic address: z.zhan01@umcg.nl.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhan
authors.affiliation: Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands. Electronic address: e.r.v.d.heuvel@tue.nl.
authors.forename: E
authors.initials: E
authors.lastname: van den Heuvel
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands. Electronic address: irenegrossmann@me.com.
authors.forename: I
authors.initials: I
authors.lastname: Grossmann
authors.affiliation: Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
authors.forename: P M
authors.initials: PM
authors.lastname: Doornbos
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Havenga
authors.affiliation: Department of Surgery, Medical Center Leeuwarden, Henri Dunantweg 2, 8934 AD, Leeuwarden, The Netherlands. Electronic address: e.r.manusama@znb.nl.
authors.forename: E
authors.initials: E
authors.lastname: Manusama
authors.affiliation: Department of Surgery, Medical Spectrum Twente, Haaksbergerstraat 55, 7513 ER, Enschede, The Netherlands. Electronic address: j.klaase@mst.nl.
authors.forename: J
authors.initials: J
authors.lastname: Klaase
authors.affiliation: Department of Surgery, Nij Smellinghe Hospital, Compagnonsplein 1, 9202 NN, Drachten, The Netherlands. Electronic address: h.mijle@nijsmellinghe.nl.
authors.forename: H C J
authors.initials: HC
authors.lastname: van der Mijle
authors.affiliation: Department of Surgery, Albert Schweitzer Hospital, Albert Schweitzerplaats 25, 3318 AT, Dordrecht, The Netherlands. Electronic address: b.lamme@asz.nl.
authors.forename: B
authors.initials: B
authors.lastname: Lamme
authors.affiliation: Department of Surgery, Jeroen Bosch Hospital, Henri Dunantstraat 1, 5223 GZ, Den Bosch, The Netherlands. Electronic address: k.bosscha@jbz.nl.
authors.forename: K
authors.initials: K
authors.lastname: Bosscha
authors.affiliation: Department of Surgery, Martini Hospital, Van Swietenplein 1, 9728 NT, Groningen, The Netherlands. Electronic address: p.c.baas@mzh.nl.
authors.forename: P
authors.initials: P
authors.lastname: Baas
authors.affiliation: Department of Surgery, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, The Netherlands. Electronic address: b.van.ooijen@meandermc.nl.
authors.forename: B
authors.initials: B
authors.lastname: van Ooijen
authors.affiliation: Department of Surgery, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands. Electronic address: grard.nieuwehuijzen@catharinaziekenhuis.nl.
authors.forename: G
authors.initials: G
authors.lastname: Nieuwenhuijzen
authors.affiliation: Department of Surgery, Medical Center Haaglanden, Postbus 432, 2501 CK, Den Haag, The Netherlands. Electronic address: andreas.marinelli@mch.nl.
authors.forename: A
authors.initials: A
authors.lastname: Marinelli
authors.affiliation: Department of Surgery, Gelre Hospital, Albert Schweitzerlaan 31, 7334 DZ, Apeldoorn, The Netherlands. Electronic address: e.van.der.zaag@gelre.nl.
authors.forename: E
authors.initials: E
authors.lastname: van der Zaag
authors.affiliation: Department of Surgery, Elisabeth Hospital, Hilvarenbeekseweg 60, 5022 GC, Tilburg, The Netherlands. Electronic address: d.wasowicz@elisabeth.nl.
authors.forename: D
authors.initials: D
authors.lastname: Wasowicz
authors.affiliation: Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands. Electronic address: g.h.de.bock@umcg.nl.
authors.forename: G H
authors.initials: GH
authors.lastname: de Bock
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands. Electronic address: t.wiggers@umcg.nl.
authors.forename: T
authors.initials: T
authors.lastname: Wiggers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood*; D002277:Carcinoma / Q000097:blood / Q000601:surgery*; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000097:blood / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis* / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen
keywords: CEA; Colorectal cancer; Follow-up; Stepped-wedge cluster randomized trial (SW-RCT)