fatty liver & CEA question - please share

[SoConfused]

Hi everyone,

I had my scans done last week ... today I met with my onc. All is well except for a fatty liver and degenerative disc disease noted on the scan.

My CEA at last check up a month ago was <0.5 which is where it has been for the past year. My CEA from two weeks ago is 0.7 ... is this rise significant? can it be attributed to the fatty liver? additionally, I have been suffering horribly from seasonal allergies - constant headache & all, could the allergies cause the CEA increase?

your thoughts and experiences would be greatly appreciated.

[jscho]

Many of us veteran have worried about CEA values from individual tests over the years, myself included. In 2010, I had a spike in my CEA level and worried about what it meant. The short answer was, fortunately, "not very much".

At my 1.3 year post-surgery checkup, my CEA suddenly rose 50% from a value of around 2.2 to 3.5.

I know, I know. This isn't the end of the world, the value is within normal ranges, CEA is a poor marker that is not necessarily meaningful, is influenced by other unknown factors, ... blah blah. Nonetheless, an increase of 50% is alarming when not in chemotherapy. My doctor says he isn't concerned, and that we will do a CT scan at the end of August. Of course he isn't - he doesn't have, and never has had, cancer! I will do my best to forget all about this issue for the next two months, since I won't be able to have another blood test done until August.

I've always wondered about what studies have been done on the natural fluctuations of CEA readings in healthy individuals. It seems like this would be something that has been carefully analyzed. Apparently not. I have found a number of small studies, and the best one seems to be:
http://www.ncbi.nlm.nih.gov/pubmed/17926198

This article is interesting because it analyzes both inter and intra-individual variations in CEA. CEA fluctuations show some bizarre features. For example, the standard deviation of CEA measurements is difficult to pin down: Some individuals, particularly those with low mean CEA levels, exhibit only small variations in CEA, while others show much larger fluctuations. This makes it nearly impossible to quantify the standard deviations, even when the standard deviations are normalized by the mean (so called reference change values, RCV, expressed as a percent). This suggests that the RCV itself is broadly distributed, making the mean RCV less meaningful. In fact the median and range of CEA shown for all subjects in the study (population of only 42) varies enormously (Figure 1 of article). The article quotes a mean RCV of around 30%, which would imply that my rise of 50% is worrisome (though not quite statistically significant).

I suspect my high baseline CEA is related to underlying chronic liver problems (I have PSC). Perhaps you are also in the population of individuals with high normal CEA levels with large fluctuations.

Remember, it is the generally the trend rather than the absolute number that is meaningful (unless the level is very high).

Best,
Jeremy

[gfpiv]

Hi there. Please allow me to be blunt, in hopes that it provides some comfort: increase to 0.7 CEA is insignificant, and WELL within normal range. I absolutely would not worry about it; your CEA could vary by 0.2 points between today and tomorrow just due to sampling, no need to trouble yourself even considering the cause.

[SoConfused]

Jeremy and Chip - I appreciate your responses ... informative and comforting. I hope you both have a great day.

[dianetavegia]

Jeremy, I have to admit that I didn't understand the article you shared. The percentages and inter vs intra were way over my head. Can you explain it for me?

[jscho]

The percentages and inter vs intra were way over my head. Can you explain it for me?

Sure. The article examines the reliability of various cancer markers by looking at how values of the markers are distributed in healthy individuals in two different ways. The intra-individual data from a 6 week period (4 samples per volunteer) were used to examine how values for a single individual are distributed. In addition, each sample was analyzed multiple times to find the variability and consistency of the analyzer. The results were analyzed in terms of both the mean and the coefficient of variability CV (the standard deviation divided by mean times 100, to get a percent). It was found that the machine itself had a CV = CVa = 5% for CEA measurement, which can be roughly interpreted as saying that individual measurements from the same sample are quite likely (probability around 30%) to vary by +/- 5% or so. The most important thing the article analyzes is the reference change values RCV, which is the total CV for an individual scaled to provide a limit for change in the value that can be attributed to random variation. The RCV is often interpreted as being the critical difference necessary between two values for them to be considered significantly different. The RCV for the CEA marker drawn from healthy individuals was computed to be 73%. This means that a healthy individual typically will have levels that differ by as much as 73%. I suspect that there are sub-populations as well with a much larger RCV, meaning that the RCV of 73% is not nailed down either. This is clear from Figure 1 in the text, which shows the mean and range of CEA readings of all individuals. For example it is not unusual for a subject to have a reading of over 4 even when their mean level is near 2. I think the study would benefit from a much larger population size to clarify this point.

The inter-individual measurements refer to all the data considered together, including the entire sample population. The CV for the CEA marker for the entire population is larger than that of a typical individual by roughly 20%. The authors conclude:

CVi and CVa determine what constitutes a significant difference between sequential results. For follow-up purposes, individuals are their own refer-
ences, and the clinician is mainly interested in increases or decreases of the concentration of tumour marker. Knowledge of within-person variation and
the critical difference (RCV) are important when tumour markers are used for follow-up. In this study, the calculated critical differences of AFP, CEA and
CA 19-9 between serial measurements were 62.62 %, 72.57 % and 64.71 %, respectively. These values are required before one can be sure that the difference between two measurements is significant.

I think the take-home message is that the CEA readings inherently fluctuate a great deal, with larger fluctuations seen in individuals who have a high baseline CEA level. If two readings do not differ by more than around 70%, they should not be considered as different. That suggests that the CEA is a pretty poor marker and patterns rather than levels should be used as a diagnostic tool.

Hope this helps,
Jeremy

[SoConfused]

well, here is an update ... not sure what caused the slight increase last time, but my CEA is back to being <0.5 and I couldn't be more relieved.

[Hapa]

Peace of mind is the best. Glad it was nothing!

[dianetavegia]

Thanks Jeremy! Wow.... I'm glad my onc only says 'stable' or 'normal' if I don't insist on numbers. I'm one of those who freaks out when it goes from 2.4 - 2.9 when my lab's normal is anything under 4.0.

[Bev G]

Jeremy has provided the best explanation I've seen, ever, about why too much worry about CEA values is rarely necessary (although hard to avoid). I've been saying for years here to NOT WORRY about any change to the right of the decimal point, and to try really hard not to worry about a point or two difference to the left. How fortunate we are to have a scientist among us who can back this up with hard data, then explain it. It's still HARD data, too (hard to process, that is). I wish we could put his wonderful explanation on the permanent thread at the top of the board. I suspect there would be far fewer sleepless nights around here! Thanks, Jeremy!

[SoConfused]

I agree with Bev and Diane ... thanks, Jeremy. This was the most thorough information about CEA that I came across. You explained it very well. Thank you.

[lydia123]

Glad you got posts to say that change in CEA is meaningless.

My husband has discovered one of the "down-sides" about being scanned so often: We get a close up and way too detailed look at his innards. Scan a middle-aged guy, and you find crap: Fatty liver, check. Intussusception, check (coulda been cancer, coulda been "just the way his gut has always been, and if you hadn't had cancer, we'd never have known..." talk about freak out). arthritis in hips, check...