Friday, 4 August 2017

Interval cancers

Interval cancers are those that occur following a negative screening episode, in the interval before the next invitation to screening is due. For faecal occult blood testing interval cancers may occur following a negative FOBT, or following a positive test result with negative further assessment (colonoscopy). Rates of interval cancers reflect both the sensitivity of the screening test (false negatives), and the incidence of newly-arising cases not present at the time of screening. With increasing time since negative test, the rate and proportion of the latter will increase. In the absence of repeat screening, incidence rates would eventually reach the background level again. Rates of interval cancers should therefore be presented by time period (years) since previous screen.

Rates of interval cancers will depend on the underlying incidence in the population. They will also depend on the extent of selection bias, whereby rates in those not participating in screening differ from the general population rates. 

For this reason it is important that (age- and gender-specific) incidence rates in non-responders are also monitored, to allow for the underlying incidence in responders to be estimated. Background incidence rates can be estimated from rates prior to the introduction of screening (although time trends need to be considered) or from areas not covered by the screening programme (when geographic differences need to be considered).  

The interval cancer rate can therefore be expressed as a proportion of the background incidence rate, standardised for age and gender, by dividing the number of interval cancers in the specific age/gender group (I) by the ones expected based on the background incidence for that age/gender group (C), or as a proportion of the background incidence rate adjusted for non-participants (C*). The adjusted rate can be calculated as:

C* = (C – (1 – P) N) / P 
P: participation rate 
N: rate in non-responders  

The comparisons can be adjusted for differences in age and gender.
The rate of interval cancers in the period after a negative screening provides information on the sensitivity of the programme. The sensitivity of gFOBT-based program for detection of cancer has been estimated as 55%–57% using this method. In the Nottingham trial the estimate was based on overall rates of interval cancers of 0.64 per 1000 person-years in the two year period after screening (Moss et al. 1999). Using the same method, the sensitivity of iFOBT-based programme has been reported as 82% 

No data are available yet on the sensitivity of FS or colonoscopy-based programmes. 

CRC incidence rates  

Immediately following the introduction of a screening programme, incidence rates in the target age range should increase due to the detection of prevalent disease by screening. At re-screening, rates should return to background level apart from the advancement of the age of diagnosis by screening. 
Age- and gender-specific incidence rates should therefore be reported over time. FS screening should eventually lead to a reduction in incidence rates due to detection and removal of adenomas of the distal colon, but as discussed above this is a long-term effect. Screening FOBT may also have an eventual impact in reducing incidence rates, but the effect will be less due to lower detection rates of adenomas. 
Cumulative incidence rates or proxies should be used to monitor potential over-diagnosis of cancer that is cancer that would not otherwise appear during the lifetime of the individual. 

Rates of advanced-stage disease 
Screening (both FOBT and FS) should result in a reduction in the overall population incidence of late stage disease (DUKES C & D) prior to any reduction in mortality and can therefore be used as an early indicator of effectiveness. Because screening will result in the detection of a large number of early stage cases, and hence a reduction in the proportion of late stage disease, it is preferable to monitor rates of late stage disease. The ability to do this will depend on the completeness of stage information that ideally should be available for a sufficiently lengthy period immediately prior to the introduction of the screening programme, to allow trends to be studied.

Projected mortality based on stage-adjusted cancer incidence. 
Models have been developed to use prognostic information provided by Dukes stage and age at diagnosis to predict cancer mortality.  

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