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Original papers
Adv Clin Exp Med 2011, 20, 3, 295–303
ISSN 1230-025X
© Copyright by Wroclaw Medical University
Anil K. Agrawal1, Jerzy Rudnicki2, Dorota Zyśko3, Zygmunt Grzebieniak1,
Wojciech Kielan1, Joanna Słonina4
The Predictive Value of CA 19-9 Antigen Measurements
After Pancreatic Cancer Surgery
Oznaczanie antygenu CA 19-9 po operacji raka trzustki
– rola w rokowaniu
2nd Department and Clinic of General and Oncological Surgery, Wroclaw Medical University, Poland
Department of Minimally Invasive Surgery and Proctology, Wroclaw Medical University, Poland
3 Teaching Department for Emergency Medical Services, Wroclaw Medical University, Poland
4 Department of Radiology, Wroclaw Medical University, Poland
1 2 Abstract
Background. Prognosis in patients with pancreatic carcinoma is poor. The CA 19-9 antigen provides a marker of
pancreatic carcinoma.
Objectives. The study aimed at the evaluation of prognostic significance linked to measurements of CA 19-9 concentration during periodic control visits following surgical treatment of pancreatic carcinoma.
Material and Methods. The study was conducted on 74 patients subjected to surgery due to pancreatic carcinoma
in the years of 2000–2006, who survived until discharge from the hospital. In every patient, the plasma level of the
CA 19-9 antigen was estimated before and after surgery as well as during control check-ups.
Results. The surgery significantly decreased the mean level of CA 19-9 (p < 0.001). The extent of a decrease in the
CA 19-9 level following surgery provided prognosis of 12-month, 2-year and 5-year survival of the patients. Using
the analysis of ROC curves, the value of the CA 19-9 quotient could be estimated, which was linked to 2-year survival with the highest sensitivity and specificity. The value amounted to 0.67. The variables predicting death before
the subsequent visit of a patient were found to include the extent of lymph node involvement, a high level of CA
19-9 followed by the absence of a decrease in CA 19-9 level by at least 33% following surgery, longer duration of
observation and an increase in CA 19-9 level by at least 4 U/ml as compared to the preceding estimate. The level of
CA 19-9 above 29 U/ml in the period between the 3rd and 6th month following the surgery allows the prediction
of a patient’s death within 24 months with around 80 sensitivity and 70% specificity.
Conclusions. 1) Determination of the CA 19-9 level during control visits in patients subjected to surgery due to
pancreatic carcinoma manifests a prognostic value, 2) absence of at least a 33% decrease in CA 19-9 level following
surgery represents a prognostically unfavorable index, 3) increase in CA 19-9 level by over 4 U/ml as compared to
the estimate during the preceding visit is linked with moderate sensitivity and specificity to the occurrence of death
before the subsequent planned visit, 4) concentration of CA 19-9 below 29 U/ml in the period between the 3rd and
6th month after surgery indicates with moderate sensitivity and specificity elevated chances for 2-year survival of
a patient following surgical treatment of pancreatic carcinoma (Adv Clin Exp Med 2011, 20, 3, 295–303).
Key words: CA 19-9 antigen, pancreatic carcinoma, prognosis.
Streszczenie
Wprowadzenie. Rokowanie u pacjentów chorych na raka trzustki jest złe. Antygen CA 19-9 jest markerem raka
trzustki.
Cel pracy. Ocena prognostycznego znaczenia pomiarów stężenia CA 19-9 podczas okresowych kontrolnych wizyt
po leczeniu chirurgicznym raka trzustki.
Materiał i metody. Do badania zakwalifikowano 74 pacjentów leczonych chirurgicznie z powodu raka trzustki
w latach 2000–2006, które przeżyły do wypisania ze szpitala. U każdego pacjenta oznaczano poziom antygenu CA
19-9 w osoczu przed i po zabiegu chirurgicznym oraz w czasie kontrolnych wizyt.
Wyniki. Średnie stężenie CA 19-9 zmniejszyło się istotnie po zabiegu (p < 0.001). Zmniejszenie stężenia CA 19-9
po operacji było czynnikiem przepowiadającym przeżycie 12-miesięczne, 2-letnie i 5-letnie. Za pomocą analizy
296
A.K. Agrawal et al.
krzywych ROC wyznaczono wartość ilorazu CA 19-9, która z największą czułością i swoistością była wiązana z uzyskaniem przeżycia 2-letniego i wynosiła 0,67. Wykazano, że czynnikami przepowiadającymi zgon przed następną
wizytą jest stopień zajęcia węzłów chłonnych, duże stężenie CA 19-9 przed, brak spadku CA 19-9 o co najmniej
33% po zabiegu, dłuższy czas obserwacji oraz wzrost stosunku do poprzedniego oznaczenia o co najmniej 4 U/ml.
Stężenie CA 19-9 powyżej 29 U/ml w okresie między 3. a 6. miesiącem po zabiegu przepowiada z około 80% czułością i 70% swoistością wystąpienie zgonu w okresie 24 miesięcy.
Wnioski. 1) Oznaczanie stężenia CA 19-9 podczas kontrolnych wizyt u pacjentów leczonych chirurgicznie z powodu raka trzustki ma wartość prognostyczną, 2) zmniejszenie stężenia CA 19-9 o co najmniej 33% jest czynnikiem niekorzystnym rokowniczo, 3) wzrost stężenia CA19-9 o ponad 4 U/ml (w stosunku do poprzedniej wizyty) z umiarkowaną czułością i swoistością jest związany z wystąpieniem zgonu przed kolejną planowaną wizytą,
4) stężenie CA 19-9 w okresie 3-6 miesiąca po zabiegu chirurgicznym poniżej 29 U/ml z umiarkowaną czułością
i specyficznością wskazuje na zwiększone szanse 2-letniego przeżycia po operacji raka trzustki (Adv Clin Exp Med
2011, 20, 3, 295–303).
Słowa kluczowe: antygen CA 19-9, rak trzustki, rokowanie.
The prognosis in patients with pancreatic carcinoma is poor and at present the only effective
method of treatment involves early surgical intervention which is often impossible, due to late
reporting of the patients to a doctor’s office and
difficulties in the diagnosis of atypical complaints
in the abdominal cavity [1].
At present, adjuvant treatment with chemotherapy and radiotherapy manifests low efficacy in
patients with pancreatic carcinoma but one cannot
rule out that subsequent progress in the field will
make it possible to save the lives of larger numbers
of patients. The application of adjuvant therapy,
particularly when associated with serious side effects, should be restricted to patients with a high
risk of an unfavorable course of the disease.
CA 19-9 represents a marker of pancreatic carcinoma and its high pre-operational level has been
shown to indicate a poor long-term prognosis [2].
Using our own material, in the previously published
study we demonstrated that the cut-off value of
> 106 U/ml indicates patients with an elevated death
risk in long-term observation [3]. Much less data is
available on the profile of antigen concentration in
patients following surgical treatment of pancreatic
carcinoma and whether there exists any relationship
between the changes in concentration of the antigen
in consecutive visits and a distant prognosis.
The aim of this study was an examination of
whether measurements of CA 19-9 concentration
in the course of control visits following surgical
treatment of pancreatic carcinoma carry prognostic significance in predicting the long-term survival of patients and during which visits such estimations carry the greatest predictive value.
Material and Methods
The studies were performed on our previously
described group of 81 patients with pancreatic
carcinoma, treated with surgery in the years of
2000–2006. For the purpose, 74 patients we qualified who survived till discharge from the hospital.
The demographic and clinical characteristics of the
group and plasma bilirubin levels are presented in
Table 1.
In every patient, the concentration of the
CA 19-9 antigen in plasma was estimated before
surgery (T0), before discharge from the hospital
(M0), after discharge from the hospital and during
control visits: after 4.5 ± 1.5 months (M6), after
7.5 ± 1.5 months (M9), after 10.5 ± 1.5 months
(M12), after 15 ± 3 months (M18), after 21 ±
3 months (M24), after 27 ± months (M30), after
33 ± 3 months (M36), after 39 ± 3 months (M42),
after 45 ± 3 months (M48), after 51 ± 3 months
(M54) and after 57 ± 3 months (M60).
CA 19-9 concentration was measured by an
automated, commercially available enzyme immunoassay on assay analyzer (Abbott Diagnostics
Laboratory). A value of 37 U/ml was used as the
upper limit of the normal level.
For every patient, his/her total survival time
was estimated when reporting for the consecutive
control visit and if the patient failed to report, by
phone contact with the patient’s family aimed at
establishing the causes for which the patient did
not appear for the control, or due to a spontaneous phone call by the family informing us about
the death of our patient, their family member.
The data permitted us to estimate for every
patient his/her survival for 12 months, 2 years or
5 years. Co-existing therapy was described in the
earlier study on the same material [3].
Statistical Analysis
Continuous variables were presented as means
and their standard deviation or median and interquartile range, according to their distribution.
Categorical variables were presented as numbers and percentages.
The Predictive Value of CA 19-9 Antigen Measurements After Pancreatic Cancer Surgery
Table 1. Demographics, histological characteristics and
biochemical data in the studied population, divided into
groups depending on the survival time
Tabela 1. Dane demograficzne, histologiczne i biochemiczne
Parameter
(Wskaźnik)
Value
(Wartość)
No. of patients
(Liczba pacjentów)
n
74
Age – years
Mean ± SD, range
(Wiek – lata, średnia ± odchylenie standardowe, zakres)
62.6 ± 7.8
(45–76)
Females (Kobiety)
Males (Mężczyźni)
n (%)
34 (45.9)
40 (54.1)
Site of primary lesion in pancreas
(Umiejscowienie zmiany pierwotnej
w trzustce)
n (%)
head (głowa)
body or tail (trzon lub ogon)
59 (79.7)
15 (20.3)
Tumor stage
(Wielkość guza)
n (%)
1
2
3
14 (18.9)
33 (44.6)
27 (36.5)
Nodal status
(Węzły chłonne)
n (%)
0
1
42 (56.8)
32 (43.2)
G stage
(Cecha G)
n (%)
0
1
2
3
10 (13.5)
21 (28.4)
25 (33.8)
18 (24.3)
Clinical stage
(Stopień kliniczny)
n (%)
IA
IIA
IB
IIB
9 (12.2)
12 (16.2)
21 (28.4)
32 (43.2)
Bilirubin level, mg%, mean ± SD
(Stężenie bilirubiny, średnia ± odchylenie
standardowe
8.3 ± 5.9
All continuous data was dichotomized around
the median value or according to significant cutoff points.
For every period between time points of visits the increment (change) in the CA 19-9 antigen
297
level was estimated, representing a difference between its levels during subsequent visits.
Since the numbers of estimations varied between the patients, reflecting differences in survival time, an analysis was also performed in which
every test was treated as a separate event, which
could be related to starting parameters, such as
age, sex, lymphadenopathy, tumor size, CA 19-9
before surgery, CA 19-9 level estimated during
a given visit and change in CA 19-9 level as compared to the previous period. It was also possible to
determine whether each examination represented
the last determination in a given patient or he/she
survived till the subsequent visit. Such a manner of
analysis made it possible to take into account the
time which elapsed after the surgery and its possible independent effect on prognosis.
An analysis of ROC curves was conducted in
order to find out the size of the increment (change)
in the CA 19-9 antigen level in a given period
which, with the highest sensitivity and specificity,
could predict 12-month and 2-year survival.
Increments in CA 19-9 levels were dichotomized according to the value obtained in ROC
analysis for logistic analysis in order to evaluate
the effects of individual variables on the chances
of 12-month and 2-year survival.
Survival probability was estimated according
to the Kaplan-Meier method, the log rank test was
used for comparison of survival in different subgroups. Multivariate analysis was performed using
Cox’s proportional hazard model.
P values less than 0.05 were considered significant.
Results
Plasma concentrations of the CA 19-9 antigen in
the studied periods of time are presented in Tables
2 and 3.
The mean level of CA 19-9 decreased significantly after surgery (p 0 001). The decrease in CA
19-9 was observed in 68 patients. The decrease in
CA 19-9 level following surgery made it possible
to predict 12-month, 2-year and 5-year survival.
Using the analysis of ROC curves made it possible to estimate the value of the CA 19-9 quotient,
which was linked, with the highest sensitivity and
specificity, to survival for 2 years and the value
of the quotient amounting to 0.67. In a unifactorial analysis of survival curves, a decrease in CA
19-9 following surgery to levels below 0.67 was
associated with more than 1-year, 2-year survival
and 5-year survival (Fig. 1), but in multifactorial
analysis in which dependent variables included
sex and whether metastasis to lymph nodes were
298 2. Plasma concentrations of CA 19-9 antigen expressed in U/ml
Table
A.K. Agrawal et al.
Tabela 2. Stężenia antygenu CA 19-9 w osoczu, w U/ml
Period
(Czas)
Number of patients
(Liczba pacjentów)
Mean ± SD
(Średnia ± odchylenie standardowe)
Median – IQR
(Mediana)
T0
M0
M6
M9
M12
M18
M24
M30
M36
M42
M48
M54
M60
74
74
73
67
62
51
38
27
22
15
12
9
5
283.3 ± 294.2
148.2 ± 215.8
112.7 ± 175.7
131.2 ± 164.0
153.3 ± 192.2
158.4 ± 207.7
147.9 ± 180.2
153.7 ± 247.0
96.9 ± 129.3
125.7 ± 162.1
86.3 ± 105.8
47.3 ± 61.5
14.8 ± 8.9
143 (54–279)
45.5 (21–181)
33 (15–145)
59 (20–201)
78.5 (21–239)
71 (15–267)
66.5 (23–208)
45 (17–256)
26 (15–112)
39 (14–132)
31.5 (12–115)
24 (11–38)
9–15
T0 – before surgery.
M0 – before discharge from hospital.
– following discharge from hospital during control visit.
M6 – after 4.5 ± 1.5 months.
M9 – after 7.5 ± 1.5 months
M12 – after 10.5 ± 1.5 months.
M18 – after 15 ± 3 months.
M42 – after 39 ± 3 months
T0 – przed zabiegiem chirurgicznym.
M0 – przed wypisaniem ze szpitala
– po wypisaniu ze szpitala w czasie kontrolnych wizyt.
M6 – po 4,5 ± 1,5 miesiąca.
M9 – po 7,5 ± 1,5 miesiąca.
M12 – po 10,5 ± 1,5 miesiąca.
M18 – po 15 ± 3 miesiącach.
Table 3. Concentration of CA 19-9 at the beginning of a period with subdivision of patients into subgroups who died and
those who survived till the next visit. CA 19-9 was expressed in U/ml and presented in the form of median value plus interquartile range (IQR)
Tabela 3. Stężenie CA 19-9 na początku okresu z podziałem na podgrupy pacjentów, którzy w tym okresie zmarli i którzy
przeżyli do następnej wizyty. CA 19-9 przedstawiono w U/ml jako medianę i rozstęp międzykwartylowy (IQR)
M0–M6
M6–M9
M9–M12
M12–M18
M18–M24
M24–M30
M30–M36
M36–M42
M42–M48
M48–M54
M54–M60
Number of surviving patients
(Liczba osób,
które przeżyły)
Number of patients who died
(Liczba osób,
które zmarły)
CA 19-9 in the group of
patients who survived
(W grupie osób, które
przeżyły)
CA 19-9 in the group of
patients who died
(W grupie osób, które
zmarły)
p
73
67
62
51
38
27
22
15
12
9
5
1
6
5
11
13
11
5
7
3
3
4
42 (21–71)
33 (15–139)
49.5 (19–201)
42 (19–198)
28 (13–185)
29 (17–143)
32 (13–101)
25 (12–112)
26 (12.5–98.5)
22 (9–32)
15 (5–32)
637 (637–637)
126 (12–328)
96 (52–186)
178 (87–503)
310 (76–423)
187 (113–431)
312 (194–433)
45 (16–312)
389 (39–524)
254 (109–328)
68 (20–113)
< 0.01
< 0.01
n.s.
< 0.01
< 0.01
n.s.
< 0.01
n.s.
< 0.01
< 0.01
NS
M0–M6 – period between examination before discharge
from the hospital and M6 visit.
M6–M9 – period between M6 visit and M9 visit.
M0–M6 – okres między badaniem przed wypisaniem ze
szpitala a wizytą M6.
M6–M9 – okres między wizytą M6 a M9.
299
CA_19_9_in_M0_and_T0_quotient
present or absent, the parameter of CA 19-9 level
before surgery dichotomized as ≤ 106 U/ml or >
106 U/ml proved to be statistically insignificant
for evaluation of 2-year survival chances (Table 4)
but gained significance in survival analysis in the
studied group in the entire evaluated period using
analysis by Cox’s regression method (Table 5).
The factors predicting death before the next visit
involved the extent of lymph node involvement, a high
level of CA 19-9 followed by lack of a decrease in CA
19-9 level after the surgery by at least 33%, longer time
of observation and an increase in CA 19-9 level since
the preceding estimation by at least 4 U/ml (Table 6).
An analysis of ROC curves disclosed that a CA
19-9 level above 29 U/ml in the M6 period corresponded to death within 24 months with 82.9% sensitivity
and 71.1% specificity while concentration of CA 19-9
in the period M9 above 40 U/ml corresponded to such
death with 89.7% sensitivity and 73.3% specificity.
100
sensitivity
(czułość)
80
sensitivity: 69.4
specificity: 66.7
criterion : ≤ 0.67
60
40
20
0
0
20
40
60
80
100
100-specificity
(swoistość)
Fig. 1. ROC curve analysis. The quotient of CA 19-9 in
period M0 and in period T0 and 2 year survival
Discussion
cumulative probability of survival
(skumulowane prawdopodobieństwo przeżycia)
Ryc. 1. Krzywa ROC. Iloraz stężenia CA 19-9 w okresie M0
i w okresie T0 a przeżycie 2-letnie. Stwierdzono 69,4 % czułość
i 66,7% specyficzność dla kryterium iloraz CA19-9 w okresie
M0 do T0 ≤ 0,67 w przewidywaniu przeżycia 2-letniego
complete
1,0
Pancreatic carcinoma represents a disease
with poor prognosis and only surgery at the earli-
censored
Fig. 2. Survival probability in patients with
and without decrease of CA 19-9 antigen
level in period M0 at least to 67% of the
level in period T0 (p < 0.05)
CA 19-9 in period M0 > 67% in period T0
CA 19-9 in period M0 ≤ 67% in period T0
0,9
0,8
0,7
0,6
Ryc. 2. Prawdopodobieństwo przeżycia
pacjentów z i bez spadku poziomu antygenu
Ca 19-9 w okresie M0 do co najmniej 67%
poziomu w okresie T0 (p < 0,05)
0,5
0,4
0,3
0,2
0,1
0,0
-0,1
0
200
400
600
800
1000
1200
1400
1600
1800
2000
survival – days
(czas przeżycia – dni)
Table 4. Analysis of Cox’s proportional hazard regressions for 2-year survival
Tabela 4. Analiza przeżycia 2-letniego metodą regresji proporcjonalnego hazardu Coxa
Hazard ratio
(Ryzyko względne)
95% CI
(95% przedział
ufności)
P value
(Istotność
stytystyczna)
Gender
(Płeć)
female
male
1
43.9
4.3–447.5
< 0.005
N
N0
N1
1
17.9
2.6–123.3
< 0.005
CA 19-9
≤ 106 U/ml
> 106 ml
1
64.1
6.5–632.7
< 0.005
Age
(Wiek)
≤ 65 years
> 65 years
1
5.7
1.0001–28.8
< 0.05
CA 19-9 in period
T0/in period M0
≤ 0.67
> 0.67
1
2.7
0.55–12.8
= 0.22
300
A.K. Agrawal et al.
Table 5. Regression of Cox’s proportional hazards. Analysis of 5-year survival
Tabela 5. Regresja proporcjonalnego hazardu Coxa. Analiza przeżycia 5-letniego
Hazard ratio
(Ryzyko względne)
95% CI
P value
T
T1
T2 or T3
1
2.49
1.2–5.2
< 0.02
N
N0
N1
1
2.68
1.53–4.70
< 0.001
CA 19-9
≤ 106 U/ml
> 106 U/ml
1
2.23
1.29–3.85
< 0.005
CA 19-9 in period
T0/in period M0
≤ 0.67
> 0.67
1
2.68
1.62–4.42
< 0.001
An increase in CA 19-9 level by at least 4 U/ml was found to be linked to an increased risk of death before the next visit.
Wykazano, że zwiększenie stężenia Ca 19-9 o co najmniej 4 U/ml jest związane ze zwiększonym ryzykiem zgonu przed
następną wizytą.
Fig. 3. ROC curve analysis. The increase of CA 19-9 in comparison to previous level for prediction the death before the
next planned visit
CA_19_9_increase
100
Ryc. 3. Krzywa ROC. Wzrost stężenia CA 19-9 w porównaniu do stężenia w poprzednim okresie jako czynnik predykcyjny zgonu przed następną planowaną wizytą.
sensitivity
(czułość)
80
sensitivity: 67,6
specificity: 60,4
criterion : > 4
60
40
20
0
0
20
40
60
80
area under the ROC curve (AUC) 0.668
standard error 0.0379
95% Confidence interval 0.622 to 0.711
z statistics 4.31
significance level P (area = 0.5)
0.0001
100
100-specificity
(swoistość)
est stages of advancement of the disease makes full
recovery possible [1]. Nevertheless, the development of therapeutic approaches in the future may
increase the survival rate in patients of the disease.
Appropriate management of the patients in the
post-operative period is of key significance for
early diagnosis of relapse and rapid implementation of radiotherapy or chemotherapy. One of the
methods with a recognized diagnostic significance
used in patients with pancreatic carcinoma for
evaluation of the dynamics of neoplastic spread involves estimation of CA 19-9 levels during control
visits following the surgery [2]. However, the CA
19-9 antigen is thought to be insufficiently specific
to be evaluated as a singular index in suspicions
of pancreatic carcinoma. Nevertheless, such estimations may be of high value in the monitoring
of the dynamic spread of pancreatic carcinoma [4,
5]. Both before surgery and following resection of
the pancreas, higher levels of CA 19-9 were shown
to be linked with an abbreviated total survival [6,
7]. Literature data related to cut-off points, sensitivity and specificity of the points in predicting
progression of the disease are insufficient. Our
studies have been conducted in a group of patients subjected to surgery due to carcinoma of the
pancreas in whom, during follow-up, levels of CA
19-9 have been monitored. Analysis of the results
has justified the conclusion that a longer distant
survival of the patients has been associated with
three parameters: a decrease in CA 19-9 levels by
at least 33% as compared to pre-operational level,
CA 19-9 levels not greater than 29 U/ml in the
M6 period and 40 U/ml in the M9 period following surgery and absence of even a small increase
in the concentration (amounting to 4 U/ml) as
compared to preceding estimations, repeated
every 3 to 6 months.
301
Table 6. Logistic regression. A dependent variable: death in the period after the last determination of CA 19-9 level
and before the next planned visit
Tabela 6. Regresja logistyczna. Zmienna zależna: zgon w okresie po ostatnim ocenionym stężeniu CA 19-9
i przed następną planowaną wizytą
Nodal involvement
(Przerzuty
do węzłów
chłonnych)
CA 19-9 > 106
CA 19-9 in
period
M0/in period
T0 ≤ 0.64
(CA 19-9 w
okresie M0/
okresie T0
≤ 0.64)
Observation
time – number
of visits
(Czas
obserwacji
– liczba wizyt)
CA 19-9 increase of
at least 4 U/ml in
comparison to the
last visit
(Wzrost CA 19-9
o co najmniej 4 U/
ml w stosunku do
wartości na
poprzedniej wizycie)
Quotient of chances
with unit
(Iloraz szans z jednością)
2.82
2.37
0.37
1.49
3.36
–95%
1.47
1.26
0.20
1.30
1.86
+95%
5.40
4.45
0.68
1.70
6.07
Quotient of chances
within the range of
(Iloraz szans zakresu)
2.82
2.37
0.37
53.6
3.36
–95%
1.47
1.26
0.20
14.3
1.86
+95%
5.40
4.45
0.68
201.8
6.07
p
< 0.003
< 0.01
< 0.002
< 0.001
< 0.001
The results of other authors related to the decrease in CA 19-9 following surgery and distant
prognosis are consistent with our observations [8].
Maisey et al. demonstrated that already a 20% decrease in CA 19-9 level was linked to longer total
survival in the patients [9]. The relationship noted
by us between distant survival and a decrease in
CA 19-9 following surgery could not be observed
by some other authors who could not note better prognosis in patients manifesting at least 50%
decrease in CA 19-9 levels than that observed in
patients who demonstrated no such a decrease in
CA 19-9 levels [10].
The CA 19-9 antigens is secreted by cells of
pancreatic carcinoma and a decreased concentration of the antigen following surgery reflects the
removal of cells which produce the antigen. In
cases of incomplete resection, a relapse is expected to take place within a few months after surgery
and therefore CA 19-9 level in that period may
be of prognostic significance which we have been
able to demonstrate by our results. Decreased
concentrations of CA 19-9 following treatment
of pancreatic carcinoma were noted both after
surgical resection of the tumor and after chemotherapy [11–14].
Our results have also shown that even a slight
increase in CA 19-9 antigen level of just 4 U/ml
between subsequent estimations foretells an in-
ability to survive until the subsequent visit with
a moderate sensitivity and specificity. Studies of
other authors related to the course of changes in
the CA 19-9 antigen and prognosis are few. Tian
et al. showed that in 65% of the patients, death
was preceded by elevated concentrations of the
CA 19-9 antigen [15]. The authors did not present mean values of increments in CA 19-9 antigen
levels but the examples of changes in concentration of the antigen presented indicated that the
increment might be higher than that in our study.
The differences might reflect more frequent testing by the authors (every two months) while in our
study estimations were performed every 6 months
and only at the beginning every three months. We
have also shown that concentrations of the CA
19-9 antigen above 29 U/ml in the period of 3 to
6 months following surgery were linked to less favorable 2-year survival. The value is situated very
close to the cut-off point for normal values, which
amounts to 37 U/ml. Compared to our study, other authors accepted a slightly lower cut-off point:
in the study of Kondo et al. a value of 37 U/ml
was used [16]. Slight differences noted between
the results of studies might reflect selection of the
examined population, differences in preliminary
advancement of the disease and various times of
performing studies following surgery. The results
obtained by us point to a high significance of esti-
302
A.K. Agrawal et al.
mating CA 19-9 levels during control visits following resection of pancreatic carcinoma for purposes
of monitoring progress of the disease and defining
prognosis for the patient, consistent with the results obtained by other authors [17]. Determination of CA 19-9 levels in the post-operative period
in patients with pancreatic carcinoma is consistent
with recommendations by The National Academy
of Clinical Biochemistry (NACB; USA) [2]. The
results obtained by us make it possible to suggest
values of threshold levels used in interpretation of
the results.
Restrictions of the Study
Confirmation of the parameters suggested by
us of CA 19-9 concentration alterations would
require prospective estimations on a subsequent
group of patients. Absence of such studies represents a restriction and until our results are confirmed it points to the need for caution in application of the suggested cut-off values and types of
estimated parameters in clinical practice.
The authors concluded that 1) estimation of
CA 19-9 level during control visits in patients subjected to surgery due to carcinoma of the pancreas
carries a prognostic value, 2) absence of at least
a 33% decrease in CA 19-9 level represents a prognostically unfavorable index, 3) increase in CA 199 level by over 4 U/ml is linked to development
of death before the subsequent planned visit with
moderate sensitivity and specificity, 4) CA 19-9
concentration below 29 U/ml in the period of 3 to
6 months following surgery points with moderate
sensitivity and specificity to augmented chances of
2-year survival following surgery due to carcinoma
of the pancreas.
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Address for correspondence:
Anil K. Agrawal
2nd Department of General and Oncological Surgery
Wroclaw Medical University
Borowska 213
50-556 Wrocław
Poland
Tel.: 48 71 734 35 40, 609 289 027
E-mail: [email protected]
Conflict of interest: None declared
Received: 8.03.2011
Revised: 4.05.2011
Accepted: 2.06.2011

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