C-reactive protein and Procalcitonin levels in Prostate Cancer
Aim: Prostate cancer (PCa) is one of the most common cancer
among men in the world. Prostate specific antigen is the most used
biomarker for PCa diagnosis. In this study we aimed to measure the
procalcitonin(PCT) and C-reactive protein (CRP) levels in patients with
PCa.
Methods: The patients who underwent transrectal prostate biopsy
and transurethral prostate surgery in the last 4 years were included in
the study. The patients were divided into two groups according to the
pathology reports, group1; benign prostate hyperplasia and group2;
prostate cancer. MedCalc Statistical Software version 17.6 was used for
statistical analyses.
Results: The current study includes 149 patients. There were
118 patients in group1 and 31 patients in group 2. The mean age of the
patients was 66.85 and 69.41 years in groups respectively. Serum CRP and
PCT levels was 3.33 and 0.01 in group 4.07 and 0.04 in group 2. Serum
PCT levels was significantly higher in patients with PCa.
Conclusion: We found that elevated procalcitonin levels was
associated with prostate cancer. Further studies are needed to define
the relationship between procalcitonin and prostate cancer.
What’s Known: Prostate cancer is the second most common cancer
among elderly men. Prostate specific antigen testisng is usually used in
screening and diagnosis. Unfortunately PSA is not cancer specific and
new biomarkers are needed for prostate cancer management.
What’s New: Procalcitonin is a precursor of calcitonin which is
produced by throid C-cells and some neuroendocrine cells. Elevated level
of procalcitonin is associated with bacteremia and sepsis. In this study
e investigated the procalcitonin levels in prostate cancer.
Key Words: prostate cancer, procalcitonin, C-reactive protein
Introduction: Prostate cancer(PCa) is one of the most common
cancer among males in the world and the fifth most common malignancy in
the general population (1). Serum prostate specific antigen (PSA)
testing is the most commonly used test for the diagnosis and screening
of PCa(2). The patients may be diagnosed as from clinically indolent to
metastatic disease (3).Digital rectal examination (DRE) and PSA testing
are important for early diagnosis of PCa (4). Unfortunatelly PSA is not
cancer specific marker, it is organ specific; so elevated levels are
seen in benign diseases such as prostatitis, benign prostate hyperplasia
and urinary retention (1,4).Despite its adequate sensitivity, the use of
PSA testing is limited and additional serum testing derivated from PSA (
PSA density, free/total PSA, PSA velocity) and new biomarkers
(prostatehealthindex, fourkallikrein and procalcitonin) were
investigated for diagnosis of PCa (2,4,5).
C-reactive protein (CRP) is an acute-phase proteinwhich is produced in
the liver (6). High levels of CRP (1000 fold) are usually associated
with microbial infection, trauma, infarction and autoimmun diseases. In
addition, elevated CRP levels have been linked to poor prognosis in some
malignancies; oral squamous cell carcinoma, esophagealcarcinoma,
non-small and small cell lung cancers, melanoma, hepatocellular
carcinoma, breast cancer, endometrial cancer, urogenital cancers.
Procalcitonin (PCT) is produced by throid C-cells and some
neuroendocrine cells and it is a precursor of calcitonin (2). In the
systemic inflammatory reaction and some malignancies such as thyroid and
renal cell carcinomas have an association with PCT levels. In this
study, we aimed to measure CRP and PCT levels in prostate cancer
patients and compared the patients without malignancy.
Methods: The patients who underwent transrectal prostate biopsy
and transurethral prostate surgery between January 2016 and June 2019
were included in the study. The patients history of radiotherapy,
dutasteride therapy, malignancy, chronic prostatitis and high level of
PSA (>100 ng/ml) were excluded. The biopsy was made under
local anesthesia with lateral decubitus position at least ten cores and
prostate surgery was made under spinal or general anestesia with
lithotomy position. The PSA, free PSA, CRP, PCT levels were measured
before the procedures. After the pathological examination; the patients
were divided into two groups. The patients with benign prostate
hyperplasia was in Group 1 and PCa was in group 2. The results of high
grade prostatic intraepithelial neoplasia (n:3) and atypical small
acinar proliferation(n:4) were excluded from the study.
Distribution normality was analyzed with the Kolmogorov-Smirnov test.
The normal distribution variable was compared with independent t test
and the others were compared with Mann-Whitney U test. The chi squared
test was used for percentage values. Data were expressed as mean ±
standard deviation for PSA, free PSA, CRP, PCT and sedimentation median
for the age, neutrophil and white blood cell and p< 0.05 as
considered with statistical significance. The receiver operating
characteristic(ROC) curves were analyzed to assess the diagnostic
utility total PSA,CRP and PCT levels in different PSA levels
(< 10 and >10 ng/ml). Statistical analyses
were performed using the demo version of MedCalc Statistical Software
version17.6 (MedCalc Software bvba, Ostend, Belgium; http://
www.medcalc.org; 2017).
Results: There were 149 patients in this study. Of these
patients; 118 patients were in Group1 and 31 patients were in Group 2.
The mean age of the patients was 66.85+ 8.19 and 69.41+ 6.20
years in groups respectively (p=0.10). Table 1 shows the patients’
characteristics. The PSA level was significantly higher in group 2.
Serum CRP and PCT levels was 3.3 mg/L and 0.01 ng/ml in group 1, 4.07
mg/L and 0.04 ng/ml in group 2 (p=0.08 for CRP and p<0.05 for
PCT).
The diagnosis was made by prostate biopsy in 92 patients and prostate
surgery in 57 patients (Table-2). There was significant difference for
diagnosis method in groups (p<0.05). In group 2; GS 6 and 7
was detected in 11 and 7 patients respectively. Gleason score was
reported as 8,9 and 10 in7,4 and 2 patients.
Discussion: PCa is the most common malignancy in men older than
60 years and the second most common cause of cancer deaths after lung
cancer in worldwide (7).The main cause of PCa is unknown but age,
genetic factors, diet and environmental factors are focused on the
etiology (8). Serum PSA testing is the most widely accepted and used
biomarker for prostatic diseases especially PCa (9). But PSA is not
cancer specific marker, increases in benign prostate diseases and there
is no threshold value of PSA for cancer diagnosis(1). In general PSA
over 4 ng/ml is recommended for biopsy, the cancer detection rate is
between 20-25% in patients with a PSA value of 4-10 ng/ml. In our
previous study, the cancer detection rate was 22.3, 34.5 and 54.2% in
patients with PSA level of 4-10, 10.01-20 and 20.01-50 ng/ml
respectively(10). To reduce the unnecessary biopsies; new molecules and
markers which have higher positive predictive value than PSA have been
investigated (1). Prostate health index, four kallikrein score test, PSA
density and velocity, free/total PSA ratio, PCA3 marker was used to
differentiate benign prostate diseases from PCa(4).We found that
free/total PSA ratio has significant diagnostic efficacy for PCa
diagnosis in PSA level 4.01-10 ng/ml (5).
C-reactive protein is an acutphase protein which is mainly produced in
liver and rarely in atherosclerotic lesions, kidney, neurons and
alveolarmacrophages in the body (11). Synthesis of CRP is associated
with interleukin 6 (IL-6) secretion from macrophages and T-cells. In the
inflammation;activation of IL-6 increases the serum level of CRP.
Systemic inflammation has an important role in cancer initiation,
promotion, progression, metastasis stimulates endocrine cells to
hyperplasia and neoplastic transformation (12). C-reactive protein can
predict the urological cancers such as renal cell carcinoma, bladder
cancer, prostate cancer and upper urinary tract cancers. On the contrary
the authors found no association between PCa risk and CRP levels(13).
The authors demonstrated that CRP was a prognostic factor in PCa and
correlated with patients who had bone metastasis than without metastasis
(12).
Procalcitonin is a 116 amino-acid protein with a weight of 13 kDa which
is a precursor of the calcitonin hormone (14). During bacterial and
fungal infections; circulating and cytokines increases the level of PCT
and it has been investigated as a marker for bacteremia and sepsis
(14,15). The studies showed that inflammation plays an important role
for tumorgenesis and relationship between PCT and medullary carcinoma
and nun-small cell lung cancer were investigated (16,17). In addition,
the authors reported that PCT value may be a biomarker for prediction of
localized clearr cell carcinoma (15). The authors from Turkey found that
PCT can be used to diagnose of PCa with a PSA level of 2-20 ng/ml (2).
We found a high diagnostic efficacy of PCT in patients with a PSA level
>10 ng/ml and no significant difference between PSA and
PCT.
There ara some limitations in the current study. This study includes a
small number of patients from one center and the parameters (CRP, PCT)
were not checked again after first measuring the levels .The stage of
the patients with PCa was not homogenous.
We found that serum PCT levels were higher in patients with prostate
cancer. If further studies support our findings serum PCT can be a new
biomarker to diagnose prostate cancer in the future.
Funding: None
Acknowledgements : None
REFERENCES
1)Selvi I, Basar H, Baydilli N,Murat K, Kaymaz O. The importance of
plasma arginine level and its downstream metabolites in diagnosing
prostate
cancer. Int
Urol Nephrol. 2019; 51(11): 1975-1983.
2)Canat L, Atalay HA, Can O,Alkan I, Otunctemur A. Serum procalcitonin
levels in prostate cancer: A new biomarker?. Urologia
Journal.2018; 85(2):46-50.
3) Verep S,Erdem S, Ozluk Y,Kilicaslan I, Sanli O, Ozcan F. The
pathological upgrading after radical prostatectomy in low-risk prostate
cancer patients who are eligible for active surveillance: How safe is it
to depend on bioptic
pathology? Prostate. 2019;79(13):1523-1529.
4) Ceylan
C, Doluoglu
OG, Yahşi
S. A different perspective: Can urine pH be important in the diagnosis
of prostate
cancer?Urologia. 2019
Jul 31:391560319865724.
5)CaliskanS.Diagnostic efficacy of free prostate-specific antigen/total
prostate-specific antigen ratio for the diagnosis of prostate cancer in
low concentration (≤4 ng/ml) and intermediate levels of total
prostate-specificantigen (4.01–10.0ng/ml). J Can ResTher
2017;13:279-83.
6)
Schnoeller
TJ, Steinestel
J, Steinestel
K, Jentzmik
F, Schrader
AJ. Do preoperative serum C-reactive protein levels predict the
definitive pathological stage in patients with clinically localized
prostate cancer? 2015 ;47(5):765-70.
7) Memis A, Ugurlu O, Ozden C, Oztekin CV, Aktas BK, Akdemir AO. The
correlation among the percentage of positive biopsy cores from the
dominant side of prostate, adverse pathology, and biochemical failure
after radical prostatectomy. Kaohsiung J MedSci 2011;27:307-13.
8) Benli
E, Cirakoglu
A, Ayyıldız
SN, Yüce
A Comparison of serum uric acid levels between prostate cancer patients
and a control
group. Cent European
J Urol. 2018;71(2):242-247.
9) Elzanaty
S, Rezanezhad
B, Borgquist
R. Association between PSA Levels and Biomarkers of Subclinical
Systemic Inflammation in Middle-Aged Healthy Men from the General
Population.Curr
Urol. 2016 Oct;9(3):148-152.
10)Çalışkan S. Prevelance of prostate cancer among Turkish men with
prostate‑specific antigen level of ≤100 ng/ml. J Can ResTher
2018;14:1256-9.
11)Schimmack
S, Yang
Y, Felix
K, Herbst
M, Li
Y, Schenk
M, Bergmann
F, Hackert
T, Strobel
O. C-reactive protein (CRP) promotes malignant properties in pancreatic
neuroendocrine neoplasms.
Endocr
Connect. 2019:8;1007-1019.
12) Dai
J1, Tang
K, Xiao
W, Yu
G, Zeng
J, Li
W, Zhang
YQ, Xu
H, Chen
ZQ, Ye
ZQ. Prognostic significance of C-reactive protein in urological
cancers: a systematic review and
meta-analysis.Asian
Pac J Cancer Prev. 2014;15(8):3369-75.
13)Van
Hemelrijck
M, Jungner
I, Walldius
G, Garmo
H, Binda
E, Hayday
A, Lambe
M, Holmberg
L, Hammar
N. Risk of prostate cancer is not associated with levels of C-reactive
protein and other commonly used markers of inflammation.
IntJ Cancer.2011:15;129(6):1485-92.
14) Sbrana
A1, Torchio
M2, Comolli
G3, Antonuzzo
A1, Danova
M2; Italian
Network for Supportive Care in Oncology (NICSO). Use of procalcitonin
in clinical oncology: a literature
review. New
Microbiol. 2016 Jul;39(3):174-180.
15) Hamidi N, Gokce MI, Suer E, Baltacı S. Evaluation of increased
preoperative serum high sensitive C-reactive protein and procalcitonin
levels on grade and stage of clear cell renal cell carcinoma.
2015;83(4):225-230.
16) Giovanella L, Verburg FA, Imperiali M, Valabre - ga S,
Trimboli P, Ceriani L. Comparison of serum calcitonin and procalcitonin
in detecting medul - lary thyroid carcinoma among patients with thy -
roid nodules. Clin Chem Lab Med. 2013; 51: 1477-1481.
17) Walter MA, Meier C, Radimerski T, Iten F, Kränz - lin M,
Müller-Brand J, de Groot JW, Kema IP, Links TP, Müller B. Procalcitonin
levels predict clinical course and progression-free survival in patients
with medullary thyroid cancer. Cancer. 2010; 116: 31-40.