Clinical trial NCT02894801: Multistate Relative Survival Model
Official title: Multistate Relative Survival Modeling of Colorectal Cancer Progression and Mortality
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Cancer
Lead sponsor: Centre Hospitalier Universitaire Dijon
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2016-09-09
Enrollment: 5194
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients with invasive colorectal cancer

Brief summary: Colorectal cancer (CRC) has high incidence and is associated with high case fatality. In France, the 5-year survival, pooled across all cancer stages at diagnosis, ranges from 57% in men to 60% in women. About one third of patients diagnosed with CRC will develop a metachronous recurrence during the following years. It is of paramount importance to accurately identify factors associated with the increased risk of progression and death, in order to develop effective follow-up and treatment strategies. However, to accurately assess the role of patients' specific characteristics in the progression of cancer several methodological challenges need to be overcome.

One difficulty, common to prognostic studies of cancer, concerns the need to separate the effects of prognostic factors on different clinical endpoints, such as disease recurrence vs recurrence-free death. Another difficulty, encountered in prognostic studies, is that the cause of death is not available or not accurately coded. Yet, some patients are likely to die of causes not related to the disease of primary interest, especially in cancers with longer survival and in those that affect older subjects. Until recently, the existing statistical methodology was not able to simultaneously, deal with both difficulties, i.e. to account for (i) possibly different effects of prognostic factors on death vs recurrence, and (ii) unknown causes of death. However, this challenge has been addressed by the recent development of the Markov relative survival model (MRS) , which extends the Markov multi-state model to incorporate relative survival modelling. Simulations demonstrate that MRS is able to accurately estimate different effects of prognostic factors on the risk of each of several events, including separate effects on disease-specific vs other causes of death. To date, the MRS had not been applied in clinical or epidemiological studies.

The aim of this study was to assess the potential advantages of the new multi-state relative survival model (MRS), proposed by Huszti et al. (2012), in a prognostic cancer study. To this end, we compared the MRS results with those obtained with two more conventional analyses, based on Cox's proportional hazards model, and the multi-state Markov model proposed by Alioum and Commenges (2001). The three models were applied to explore the impact of prognostic factors on cancer-specific mortality and recurrence, in a large population-based French registry of colorectal cancer, with up to 25 years of follow-up.


Eligibility criteria: Inclusion Criteria:

patient with primary digestive cancer between 1985 and 2000, TNM I-III, resected for cure, residing in Burgundy or Calvados, France

Exclusion Criteria:

metastatic cancer, non adenocarcinoma, recurrence within 6 month

Primary outcomes:
measure: death due to cancer
timeFrame: 10 years after resection
measure: death due to recurrence
timeFrame: 10 years after resection
Secondary outcomes:
Other outcomes:
Locations:
city: Dijon
country: France
facility: Chu Dijon Bourgogne
Study officials:
References: