iris lansdorp-vogelaar janneke wilschut marjolein van ballegooijen
DESCRIPTION
Stage-specific survival of screen-detected versus clinically diagnosed colorectal cancer - evidence from the FOBT screening trials-. Iris Lansdorp-Vogelaar Janneke Wilschut Marjolein van Ballegooijen Methods and Applications for Population Based Survival Frascati, 20 September 2010. Outline. - PowerPoint PPT PresentationTRANSCRIPT
Stage-specific survival of screen-detected versus clinically diagnosed colorectal cancer
- evidence from the FOBT screening trials-
Iris Lansdorp-Vogelaar
Janneke Wilschut
Marjolein van Ballegooijen
Methods and Applications for Population Based Survival
Frascati, 20 September 2010
Outline
Background
Microsimulation modeling and length and lead-time bias
Analysis
Results
Future work
Colorectal Cancer
Colorectal cancer (CRC) 2nd leading cause of cancer death worldwide
CRC develops through adenoma-carcinoma pathway:
NormalColorectum
SmallAdenoma
ColorectalCancer
AdvancedAdenoma
FOBT Screening
Three randomized trials showed 15-33% reduction in CRC mortality
from fecal occult blood testing (FOBT)
Mortality reduction assumed to be result of more favorable stage
distribution with screening
Mapp et al. found different survival between screendetected CRC and
CRC in control group after correcting for stage (Mapp et al, Br J Surg; 1999)
Lead-time and length bias
Lead-time bias: longer survival of screendetected CRC because of
earlier detection and not by later death
Length bias: longer survival of screendetected CRC because slower-
growing tumors are detected by screening
Correcting for lead-time and length bias
Kafadar & Prorok: Compare survival of cases in screen and control
groups of randomized trial using time since entry of the trial (Kafadar & Prorok, Stat Med; 1994)
Key assumption:
Cases in two groups are comparable
Limitations:
No correction for overdiagnosis
Comparison stage-specific survival not possible
Research objective
To test hypothesis that stage-specific survival of screen-detected CRC
is the same as of clinically diagnosed CRC.
Microsimulation modeling of colorectal cancer
Simulation of a life-history
Simulating the effect of screening
Microsimulation modeling & lead-time bias
Microsimulation modeling & length bias
Screening Intervention
Validation of MISCAN-Colon model
Used model to try and reproduce results of randomized trials of
Minnesota, Nottingham and Funen simultaneously
Model was adjusted to account for differences in demography,
background incidence, and trial design
The model with a higher sensitivity shortly before clinical diagnosis
gave the best fit
This model reproduced CRC incidence and detection rates by stage
well
Analysis
Use validated MISCAN-colon model that reproduces observed
incidence and CRC detection by stage for three trials
Assume same stage-specific survival for screendetected and clinically
diagnosed CRC
Compare simulated mortality reduction with observed for three trials
Results
Observed mortality
reduction
Simulated mortality
reduction
Minnesota, annual
screening
32.5% 20.6%
Minnesota, biennial
screening
17.3% 11.3%
Nottingham 13.4% 5.1%
Funen 17.8% 8.9%
First approach to modeling within stage shift
Model validation suggested higher screendetection in the stage in
which the cancer would have been diagnosed in the absence of
screening than in earlier stages
Of the screendetected cancers, the cases that are detected in the same
stage as they would have become clinical, are the most likely
candidates for better survival because of within stage-shift
Survival assumptions for within stage shift
Assumed following survival for these screendetected cancers:
Survival in stage I is 100%
Survival in stage II = Survival in stage I of clinical cases
Survival in stage III = Survival in stage II of clinical cases
Survival in stage IV of these cases was not improved
Results with within-stage shift
Observed mortality
reduction
Simulated
mortality reduction
(no within shift)
Simulated
mortality reduction
(within shift)
Minnesota, annual
screening
33% 20.6% 33.5%
Minnesota, biennial
screening
21% 11.3% 21.2%
Future work
Current approach for effect of within-stage shift quite arbitrary
Estimate effect of within-stage shift through hazard ratio for survival of
cancers screendetected in same stage as clinical diagnosis
Explore alternative approaches to obtain estimate for improvement that
is independent of screening intensity
Conclusions
The improvement in stage-distribution from FOBT screening is
insufficient to explain the observed mortality reduction
Even after correcting for lead-time en length bias, stage-specific
survival of screendetected cases needs to be better than of clinically
diagnosed cases