title: Multi-state relative survival modelling of colorectal cancer progression and mortality.
abstract: Accurate identification of factors associated with progression of colorectal cancer remains a challenge. In particular, it is unclear which statistical methods are most suitable to separate the effects of putative prognostic factors on cancer progression vs cancer-specific and other cause mortality. To address these challenges, we analyzed 10 year follow-up data for patients who underwent curative surgery for colorectal cancer in 1985-2000. Separate analyses were performed in two French cancer registries. Results of three multivariable models were compared: Cox model with recurrence as a time-dependent variable, and two multi-state models, which separated prognostic factor effects on recurrence vs death, with or without recurrence. Conventional multi-state model analyzed all-cause mortality while new relative survival multi-state model focused on cancer-specific mortality. Among the 2517 and 2677 patients in the two registries, about 50% died without a recurrence, and 28% had a recurrence, of whom almost 90% died. In both multi-state models men had significantly increased risk of cancer recurrence in both registries (HR=0.79; 95% CI: 0.68-0.92 and HR=0.83; 95% CI: 0.71-0.96). However, the two multi-state models identified different prognostic factors for mortality without recurrence. In contrast to the conventional model, in the relative survival analyses gender had no independent association with cancer-specific mortality whereas patients diagnosed with stage III cancer had significantly higher risks in both registries (HR=1.67; 95% CI: 1.27-2.22 and HR=2.38; 95% CI: 1.29-3.27). In conclusion, relative survival multi-state model revealed that different factors may be associated with cancer recurrence vs cancer-specific mortality either after or without a recurrence.
authors.affiliation: Teaching Hospital, Department of Biostatistics and Medical Informatics (DIM), Dijon F-21000, France; Inserm, U866, University of Burgundy, Dijon F-21000, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Gilard-Pioc
authors.affiliation: McGill University, Department of Epidemiology, Biostatistics and Occupational Health, Montreal, Canada; Universite de l'océan Indien, Ile de la Reunion, France; CHU de La Reunion, Centre d'Etudes Périnatales de l'Océan Indien, 97 448 Saint-Pierre Cedex, France.
authors.forename: Michal
authors.initials: M
authors.lastname: Abrahamowicz
authors.affiliation: Teaching Hospital, Department of Biostatistics and Medical Informatics (DIM), Dijon F-21000, France; Inserm, U866, University of Burgundy, Dijon F-21000, France.
authors.forename: Amel
authors.initials: A
authors.lastname: Mahboubi
authors.affiliation: Inserm, U866, University of Burgundy, Dijon F-21000, France; University Hospital Dijon, Digestive Cancer Registry of Burgundy, Inserm U866, University of Burgundy, Dijon F-21079, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bouvier
authors.affiliation: CHU de Caen, Département de recherche épidémiologique et d'évaluation, Caen, France; University Hospital of Caen, U1086 INSERM UCBN "Cancers & Preventions", France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dejardin
authors.affiliation: Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Center, 610 University Avenue, Toronto, ON M5G 2M9, Canada.
authors.forename: Ella
authors.initials: E
authors.lastname: Huszti
authors.affiliation: Inserm, U866, University of Burgundy, Dijon F-21000, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Binquet
authors.affiliation: Teaching Hospital, Department of Biostatistics and Medical Informatics (DIM), Dijon F-21000, France; INSERM, CIC 1432, Dijon, France Dijon University Hospital, Clinical Investigation Center, Clinical Epidemiology/Clinical Trials Unit, Dijon, France. Electronic address: catherine.quantin@chu-dijon.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Quantin
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000401:mortality*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D015233:Models, Statistical; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000401:mortality*; D009367:Neoplasm Staging; D011379:Prognosis; D012042:Registries; D012307:Risk Factors; D015996:Survival Rate
keywords: Colorectal cancer; Multi-state Markov model; Prognostic studies; Progression; Relative survival