- Email: [email protected]
Association of serum prostate-specific antigen levels with the results of the prostate needle biopsy
Bull Cancer 2016; 103: 730–734
Original article
en ligne sur / on line on www.em-consulte.com/revue/bulcan www.sciencedirect.com
Association of serum prostate-specific antigen levels with the results of the prostate needle biopsy Hamid Janbaziroudsari 1, Arezoo Mirzaei 1, Nasrollah Maleki 2
Received 18 October 2015 Accepted 16 May 2016 Available online: 23 June 2016
1. Imam Khomeini Hospital, Ardabil University of Medical Sciences, Department of Internal Medicine, Ardabil, Iran 2. Bushehr University of Medical Sciences, The Persian Gulf Marine Medicine Biotechnology Research Center, Department of Endocrinology, Bushehr, Iran
Correspondence: Nasrollah Maleki, Bushehr University of Medical Sciences, The Persian Gulf Marine Medicine Biotechnology Research Center, Department of Endocrinology, Bushehr, Iran. [email protected]
Association entre le taux d'antigène prostatique sérique et les résultats des biopsies prostatiques Keywords Prostate cancer Prostate specific antigen Prostate needle biopsy
Summary Aim > To investigate the relationship of serum prostate-specific antigen (PSA) levels with outcomes of prostate needle biopsy in men 50 or more years old. Methods > We measured serum PSA levels in 1472 healthy men 50 or more years old. Men who had serum PSA values 4.0 ng/mL or higher underwent digital rectal examination. If there were either an elevated PSA level ( 4 ng/mL) or abnormal digital rectal examination, a transrectal ultrasound-guided prostate biopsy was performed. Results > The mean serum total PSA level was 13.73 11.44 ng/mL, and the mean serum free PSA level was 4.99 0.97 ng/mL. Of the 260 men who had serum total PSA levels of 4 ng/mL, 139 underwent biopsy. Of these 139 men, 45 (32.4%) had prostate cancer. Benign prostatic hyperplasia with or without prostatitis was diagnosed in 94 patients (67.6%). There was no significant correlation between age and histologic results of prostate needle biopsy (Pvalue = 0.469). The serum free PSA showed no significant correlation with histologic results of prostate needle biopsy, whereas the serum total PSA level had a significant correlation in patients with adenocarcinoma compared with other diagnosis. Conclusions > The overall frequency of detection of prostate adenocarcinoma was 32.4%. This study revealed that no level of PSA was associated with a 100% positive predictive value and negative biopsy can occur virtually at any PSA level. There is a need to create awareness among the general population and health professionals for an early diagnosis of this common form of cancer.
730
Mots clés Cancer de la prostate Antigène prostatique Biopsie prostatique
tome 103 > n89 > September 2016 http://dx.doi.org/10.1016/j.bulcan.2016.05.006 © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
Prostate cancer is one of the most common cancers affecting men with > 1,100,000 new cases and 300,000 deaths worldwide each year [1]. About 9.7% of cancers in men are due to prostate cancer; in developed parts of world it increases to 15.3% and in the underdeveloped world it only accounts for 4.3% [2]. Prostate cancer often grows, so slowly that most men die of other causes before the disease becomes clinically advanced. Thus, a screening program that could identify asymptomatic men with aggressive localized tumors might be expected to substantially reduce prostate cancer morbidity, including urinary obstruction and painful metastases, and mortality. Most men with early stage prostate cancer have no symptoms attributable to the cancer. Prostate-specific antigen (PSA) testing revolutionized prostate cancer screening. Today, there are still no recommendations for mass screening from the health authorities. On the contrary, hesitation and downright negative attitudes are the rule due to the weaknesses of the PSA test, the side effects of treatment and the highly variable natural history of the cancer [3,4]. Screening for prostate cancer cannot be justified in low-risk populations, but the balance of benefit and harm will be more favourable after risk stratification. Prostate cancer screening can be justified only in research programmes designed to assess its effectiveness and help identify the groups who may benefit [5]. The majority of these newly-diagnosed cancers were clinically localized, which led to an increase in radical prostatectomy and radiation therapy, aggressive treatments intended to cure these early-stage cancers [6–8]. Men with abnormal prostate exams (nodules, induration, or asymmetry) should be referred to an urologist for a prostate biopsy, with a histologic diagnosis based upon tissue obtained from the biopsy. A prostate biopsy may also be indicated based upon abnormal PSA values. PSA-based screening commonly results in biopsy in patient with serum PSA levels of > 4.0 mg/ L with a detection rate of 30–35% for prostate cancer [9]. The aim of the present study was to investigate the role of abnormal PSA levels in the detection of prostate cancer in men and relationship of serum PSA levels with histologic results of prostate needle biopsy.
Materials and methods Study design This was a prospective cross-sectional study carried out in the Department of Pathology, in collaboration with the Department of Urology at a medical college hospital, which is the largest public sector hospital in Ardabil City, Iran. The duration of the study was a period of 6 years from May 2008 to June 2013. A total of 1472 healthy men 50 or more years old were enrolled in this study. All patients were assessed by a thorough history, physical examination and routine laboratory investigations. Men with a history of prostate cancer, or a history of previous prostate surgery (transurethral resection of the prostate or open
tome 103 > n89 > September 2016
prostatectomy), and those with a history of prostatitis were excluded from the study. Patients were also excluded from the study if they had received 5-alpha-reductase inhibitors, or had an indwelling catheter or evidence of urinary tract infection. We measured serum PSA levels in 1472 healthy men 50 or more years old. Men who had serum PSA values 4.0 ng/mL or higher underwent digital rectal examination. If there were either an elevated PSA level ( 4 ng/mL) or abnormal digital rectal examination, a transrectal ultrasound (TRUS)-guided prostate biopsy was performed. Written informed consent was obtained from the participants.
Serum PSA measurement Serum PSA concentrations were measured by radioimmunoassay with kits (Tandem R-Prostate specific antigen) obtained from Hybritech. The Tandem-R assay is one of the original manual assays used for measurement of PSA. The PSA samples were reacted with a plastic bead coated with a monoclonal antibody that had an affinity for a specific PSA epitope. According to the manufacturer's recommendations, the normal range for PSA using this assay was 0 to 3.9 ng/mL.
Digital rectal examination The digital rectal examination is a relatively simple procedure. The patient undressed, then was placed in a position where the anus was accessible (lying on the side, squatting on the examination table, bent over the examination table, or lying down with feet in stirrups). Digital rectal examination findings were categorized as normal, abnormal but benign (including any enlargement or asymmetry), or arousing suspicion of cancer (including the presence of induration).
TRUS-guided prostate biopsy Each patient underwent eight-core biopsy with an 18-gauge automatic Tru-Cut biopsy needle (TSK, Tokyo, Japan) under local anesthetic infiltration peri-prostatic nerves with 10 mL of 1% lidocaine (without adrenaline). All biopsies were carried out by either a trainee or an experienced urologist while performing trans-rectal ultrasound with the patient in a lateral decubitus position. Hematoxylin-eosin-stained slides taken from archival sections of biopsied prostatic tissue were analyzed by one pathologist.
Statistical analysis The statistical analysis of the data was done using SPSS software (Version 19.SPSS Inc., United States). ANOVA analysis was performed using a two-sample t-test with equal variances for continuous variables and a Pearson x2 test to compare categorical variables. A P-value of < 0.05 was considered statistically significant. The results were expressed as means standard deviations.
Results A total of 1472 healthy men 50 or more years old with a mean age of 57.70 23.35 years (range: 50 to 89 years) were
731
Introduction
Original article
Association of serum prostate-specific antigen levels with the results of the prostate needle biopsy
Original article
H. Janbaziroudsari, A. Mirzaei, N. Maleki
enrolled in this study. The mean serum total PSA level was 13.73 11.44 ng/mL (range: 0.3 to 149.0 ng/mL) and the mean serum free PSA level was 4.99 0.97 ng/mL (range: 0.04 to 6.84 ng/mL). For the 1472 men enrolled in this study, the serum total PSA levels were < 4.0 ng/mL in 1212 (82.34 percent), 4.0 to 9.9 ng/mL in 174 (11.82 percent), and 10.0 ng/mL in 86 (5.84 percent). Of the 260 men who had serum total PSA levels of 4 ng/mL, 139 underwent biopsy. Of these 139 men, 45 (32.4 percent) had prostate cancer. Benign prostatic hyperplasia (BPH) with or without prostatitis was diagnosed in 94 patients (67.6 percent). After analyzing the data, it was observed that there was no significant correlation between age and histologic results of prostate needle biopsy (P-value = 0.469). Out of 1212 patient with PSA less than 4.0 ng/mL, 13 (1.1%) had nodular prostatic hyperplasia without prostatitis, 6 patients (0.5%) had nodular prostatic hyperplasia with prostatitis and 4 patients (0.3%) had adenocarcinoma. Table I shows the relationship between serum total PSA and histologic results of prostate needle biopsy. It was observed
that the serum total PSA levels were significantly higher in patients with adenocarcinoma compared with other diagnosis (P-value < 0.001). In this study, the serum total PSA level was divided into three intervals and in each interval, histologic results of prostate needle biopsy were studied. The results showed that in the serum total PSA level greater than 10, adenocarcinoma is the most common diagnosis, and the results were statistically significant (P-value = 0.001). Table II shows the relationship between total PSA intervals and histologic results of prostate needle biopsy. Table III shows the relationship between serum free PSA and histologic results of prostate needle biopsy. The results showed that there was no significant relationship between the level of free PSA and the histologic results of prostate needle biopsy (P-value = 0.176).
Discussion Prostate-specific antigen (PSA) is a glycoprotein produced by prostate epithelial cells. PSA levels may be elevated in men with
TABLE I The relationship between mean levels of serum total prostate-specific antigen (PSA) and histologic results of prostate needle biopsy Serum total PSA levels, ng/mL (mean W SD)
P-value
Nodular prostatic hyperplasia without prostatitis (n = 77)
10.33 7.70
< 0.001
Adenocarcinoma (n = 45)
49.87 40.04
Histologic results of prostate biopsy
7.89 5.24
Nodular prostatic hyperplasia with prostatitis (n = 17)
TABLE II The relationship between total prostate-specific antigen (PSA) intervals and histologic results of prostate needle biopsy Histologic results of prostate needle biopsy Nodular prostatic hyperplasia without prostatitis (n = 77)
PSA < 4 ng/mL, n (%)
PSA = 4–10 ng/mL, n (%)
PSA > 10 ng/mL, n (%)
P-value 0.001
13 (16.9)
31 (40.2)
33 (42.9)
Adenocarcinoma (n = 45)
4 (8.9)
6 (13.3)
35 (77.8)
Nodular prostatic hyperplasia with prostatitis (n = 17)
6 (35.3)
5 (29.4)
6 (35.3)
TABLE III The relationship between mean levels of serum free prostate-specific antigen (PSA) and histologic results of prostate needle biopsy
732
Histologic results of prostate biopsy
Serum free PSA levels, ng/mL (mean W SD)
P-value 0.176
Nodular prostatic hyperplasia without prostatitis (n = 77)
2.29 1.39
Adenocarcinoma (n = 45)
8.63 5.59
Nodular prostatic hyperplasia with prostatitis (n = 17)
2.03 1.41
tome 103 > n89 > September 2016
prostate cancer because PSA production is increased and because tissue barriers between the prostate gland lumen and the capillary are disrupted, releasing more PSA into the serum. However, PSA is also elevated in a number of benign conditions, particularly benign prostatic hyperplasia (BPH) and prostatitis. PSA has a half-life of 2.2 days [10]. Total prostate specific antigen (tPSA) is widely used to detect prostate cancer with a significant increase in the incidence of organ-confined disease at the time of diagnosis. The limitations of tPSA are low specificity and positive predictive value. Numerous attempts to enhance PSA's performance based on prostate volume, patient age, patient race, and PSA velocity have shown little clinical improvement. Percent free PSA has proven to be somewhat improved but still limited. Recently, the complexed PSA assay was developed and multisite institutional studies have shown that cPSA has improved specificity over tPSA [11]. Prostate cancer screening has been a controversial issue because decisions were made about adopting PSA testing in the absence of efficacy data from randomized trials [12]. Subsequently, the European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a small absolute survival benefit with PSA screening after nine years of follow-up [13]; however, 48 additional patients would need to be diagnosed with prostate cancer to prevent one prostate cancer death. Further sustaining the uncertainty surrounding screening, a report from the large United States trial, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, published concurrently with the European trial, found no benefit for annual PSA and digital rectal examination (DRE) screening after 7 to 10 years of follow-up [14]. In the present study, we found statistically significant inverse relationships between serum total PSA and histologic results of prostate needle biopsy. However, the relationship between the serum free PSA and prostate needle biopsy histologic results were not statistically significant. Moreover, we found that in the serum total PSA level greater than 10, adenocarcinoma is the most common diagnosis.
In 1993, Catalona et al. [15] measured serum PSA levels in 1653 healthy men 50 or more years old. Serum PSA levels ranged from 4.0 to 9.9 micrograms per liter in 6.5 percent of the 1653 men. Nineteen of the 85 men in this group (22 percent) who had prostatic biopsies had prostate cancer. Serum PSA levels were 10.0 micrograms per liter or higher in 1.8 percent of the 1653 men. Eighteen of the 27 men in this group (67 percent) who had prostatic biopsies had cancer. They recommended that the combination of measurement of the serum PSA concentration and rectal examination, with ultrasonography performed in patients with abnormal findings, provides a better method of detecting prostate cancer than rectal examination alone. The overall detection rate of prostatic adenocarcinoma in our patients was 32.4%. Prostate cancer incidence rates (per 100,000) for 2000–2004 from selected registries worldwide vary markedly, with rates ranging from < 10 in the Republic of Korea, Thailand, and Chennai, India, to > 100 in the United States and New Zealand [16]. Increasing prostate cancer incidence rates were observed in 32 of the 40 countries included in the analysis with the estimated average annual percent change ranging from 2 to 3% in Sweden, the United Kingdom, and Thailand to 12–16% in China, the Republic of Korea, and Lithuania [16].
Original article
Association of serum prostate-specific antigen levels with the results of the prostate needle biopsy
Conclusions In our study, the overall frequency of detection of prostate adenocarcinoma was 32.4%. This study revealed that no level of PSA was associated with a 100% positive predictive value and negative biopsy can occur virtually at any PSA level. There is a need to create awareness among the general population and health professionals for an early diagnosis of this common form of cancer. Disclosure of interest: the authors declare that they have no competing interest.
References
[2]
[3]
Tao ZQ, Shi AM, Wang KX, Zhang WD. Epidemiology of prostate cancer: current status. Eur Rev Med Pharmacol Sci 2015;19 (5):805–12. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63: 11–30. Andriole GL, Crawford ED, Grubb RL, et al. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up. J Natl Cancer Inst 2012;104:125–32.
tome 103 > n89 > September 2016
[4]
[5]
[6]
[7]
Lieberman SF, Karlberg I. Screening for cancer of the prostate: do we have a state of the art? Scand J Public Health 2015;43(6): 561–2. Frankel S, Smith GD, Donovan J, Neal D. Screening for prostate cancer. Lancet 2003; 361:1122–8. Lu-Yao GL, Greenberg ER. Changes in prostate cancer incidence and treatment in USA. Lancet 1994;343:251–4. Lu-Yao GL, Friedman M, Yao SL. Use of radical prostatectomy among Medicare beneficiaries before and after the introduction of
prostate specific antigen testing. J Urol 1997;157:2219–22. [8] Potosky AL, Miller BA, Albertsen PC, Kramer BS. The role of increasing detection in the rising incidence of prostate cancer. JAMA 1995;273:548–52. [9] Smith RA, Cokkinides V, von Eschenbach AC, Levin B, Cohen C, Runowicz CD, et al. American Cancer Society guidelines for the early detection of cancer. CA Cancer J Clin 2002;52(1):8–22. [10] Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E. Prostate-specific
733
[1]
734
Original article
H. Janbaziroudsari, A. Mirzaei, N. Maleki
antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987; 317:909–16. [11] Naya Y, Okihara K. Role of complexed PSA in the early detection of prostate cancer. J Natl Compr Canc Netw 2004;2(3):209–12. [12] Brett AS, Ablin RJ. Prostate-cancer screening–what the U.S. Preventive Services Task Force left out. N Engl J Med 2011;365: 1949–51.
[13] Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320–8. [14] Andriole GL, Crawford ED, Grubb 3rd RL, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310–9. [15] Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan JJ, et al. Measurement of
prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med 1991;324:1156–61. [16] Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, et al. International variation in prostate cancer incidence and mortality rates. Eur Urol 2012;61:1079–92.
tome 103 > n89 > September 2016
Original article
en ligne sur / on line on www.em-consulte.com/revue/bulcan www.sciencedirect.com
Association of serum prostate-specific antigen levels with the results of the prostate needle biopsy Hamid Janbaziroudsari 1, Arezoo Mirzaei 1, Nasrollah Maleki 2
Received 18 October 2015 Accepted 16 May 2016 Available online: 23 June 2016
1. Imam Khomeini Hospital, Ardabil University of Medical Sciences, Department of Internal Medicine, Ardabil, Iran 2. Bushehr University of Medical Sciences, The Persian Gulf Marine Medicine Biotechnology Research Center, Department of Endocrinology, Bushehr, Iran
Correspondence: Nasrollah Maleki, Bushehr University of Medical Sciences, The Persian Gulf Marine Medicine Biotechnology Research Center, Department of Endocrinology, Bushehr, Iran. [email protected]
Association entre le taux d'antigène prostatique sérique et les résultats des biopsies prostatiques Keywords Prostate cancer Prostate specific antigen Prostate needle biopsy
Summary Aim > To investigate the relationship of serum prostate-specific antigen (PSA) levels with outcomes of prostate needle biopsy in men 50 or more years old. Methods > We measured serum PSA levels in 1472 healthy men 50 or more years old. Men who had serum PSA values 4.0 ng/mL or higher underwent digital rectal examination. If there were either an elevated PSA level ( 4 ng/mL) or abnormal digital rectal examination, a transrectal ultrasound-guided prostate biopsy was performed. Results > The mean serum total PSA level was 13.73 11.44 ng/mL, and the mean serum free PSA level was 4.99 0.97 ng/mL. Of the 260 men who had serum total PSA levels of 4 ng/mL, 139 underwent biopsy. Of these 139 men, 45 (32.4%) had prostate cancer. Benign prostatic hyperplasia with or without prostatitis was diagnosed in 94 patients (67.6%). There was no significant correlation between age and histologic results of prostate needle biopsy (Pvalue = 0.469). The serum free PSA showed no significant correlation with histologic results of prostate needle biopsy, whereas the serum total PSA level had a significant correlation in patients with adenocarcinoma compared with other diagnosis. Conclusions > The overall frequency of detection of prostate adenocarcinoma was 32.4%. This study revealed that no level of PSA was associated with a 100% positive predictive value and negative biopsy can occur virtually at any PSA level. There is a need to create awareness among the general population and health professionals for an early diagnosis of this common form of cancer.
730
Mots clés Cancer de la prostate Antigène prostatique Biopsie prostatique
tome 103 > n89 > September 2016 http://dx.doi.org/10.1016/j.bulcan.2016.05.006 © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
Prostate cancer is one of the most common cancers affecting men with > 1,100,000 new cases and 300,000 deaths worldwide each year [1]. About 9.7% of cancers in men are due to prostate cancer; in developed parts of world it increases to 15.3% and in the underdeveloped world it only accounts for 4.3% [2]. Prostate cancer often grows, so slowly that most men die of other causes before the disease becomes clinically advanced. Thus, a screening program that could identify asymptomatic men with aggressive localized tumors might be expected to substantially reduce prostate cancer morbidity, including urinary obstruction and painful metastases, and mortality. Most men with early stage prostate cancer have no symptoms attributable to the cancer. Prostate-specific antigen (PSA) testing revolutionized prostate cancer screening. Today, there are still no recommendations for mass screening from the health authorities. On the contrary, hesitation and downright negative attitudes are the rule due to the weaknesses of the PSA test, the side effects of treatment and the highly variable natural history of the cancer [3,4]. Screening for prostate cancer cannot be justified in low-risk populations, but the balance of benefit and harm will be more favourable after risk stratification. Prostate cancer screening can be justified only in research programmes designed to assess its effectiveness and help identify the groups who may benefit [5]. The majority of these newly-diagnosed cancers were clinically localized, which led to an increase in radical prostatectomy and radiation therapy, aggressive treatments intended to cure these early-stage cancers [6–8]. Men with abnormal prostate exams (nodules, induration, or asymmetry) should be referred to an urologist for a prostate biopsy, with a histologic diagnosis based upon tissue obtained from the biopsy. A prostate biopsy may also be indicated based upon abnormal PSA values. PSA-based screening commonly results in biopsy in patient with serum PSA levels of > 4.0 mg/ L with a detection rate of 30–35% for prostate cancer [9]. The aim of the present study was to investigate the role of abnormal PSA levels in the detection of prostate cancer in men and relationship of serum PSA levels with histologic results of prostate needle biopsy.
Materials and methods Study design This was a prospective cross-sectional study carried out in the Department of Pathology, in collaboration with the Department of Urology at a medical college hospital, which is the largest public sector hospital in Ardabil City, Iran. The duration of the study was a period of 6 years from May 2008 to June 2013. A total of 1472 healthy men 50 or more years old were enrolled in this study. All patients were assessed by a thorough history, physical examination and routine laboratory investigations. Men with a history of prostate cancer, or a history of previous prostate surgery (transurethral resection of the prostate or open
tome 103 > n89 > September 2016
prostatectomy), and those with a history of prostatitis were excluded from the study. Patients were also excluded from the study if they had received 5-alpha-reductase inhibitors, or had an indwelling catheter or evidence of urinary tract infection. We measured serum PSA levels in 1472 healthy men 50 or more years old. Men who had serum PSA values 4.0 ng/mL or higher underwent digital rectal examination. If there were either an elevated PSA level ( 4 ng/mL) or abnormal digital rectal examination, a transrectal ultrasound (TRUS)-guided prostate biopsy was performed. Written informed consent was obtained from the participants.
Serum PSA measurement Serum PSA concentrations were measured by radioimmunoassay with kits (Tandem R-Prostate specific antigen) obtained from Hybritech. The Tandem-R assay is one of the original manual assays used for measurement of PSA. The PSA samples were reacted with a plastic bead coated with a monoclonal antibody that had an affinity for a specific PSA epitope. According to the manufacturer's recommendations, the normal range for PSA using this assay was 0 to 3.9 ng/mL.
Digital rectal examination The digital rectal examination is a relatively simple procedure. The patient undressed, then was placed in a position where the anus was accessible (lying on the side, squatting on the examination table, bent over the examination table, or lying down with feet in stirrups). Digital rectal examination findings were categorized as normal, abnormal but benign (including any enlargement or asymmetry), or arousing suspicion of cancer (including the presence of induration).
TRUS-guided prostate biopsy Each patient underwent eight-core biopsy with an 18-gauge automatic Tru-Cut biopsy needle (TSK, Tokyo, Japan) under local anesthetic infiltration peri-prostatic nerves with 10 mL of 1% lidocaine (without adrenaline). All biopsies were carried out by either a trainee or an experienced urologist while performing trans-rectal ultrasound with the patient in a lateral decubitus position. Hematoxylin-eosin-stained slides taken from archival sections of biopsied prostatic tissue were analyzed by one pathologist.
Statistical analysis The statistical analysis of the data was done using SPSS software (Version 19.SPSS Inc., United States). ANOVA analysis was performed using a two-sample t-test with equal variances for continuous variables and a Pearson x2 test to compare categorical variables. A P-value of < 0.05 was considered statistically significant. The results were expressed as means standard deviations.
Results A total of 1472 healthy men 50 or more years old with a mean age of 57.70 23.35 years (range: 50 to 89 years) were
731
Introduction
Original article
Association of serum prostate-specific antigen levels with the results of the prostate needle biopsy
Original article
H. Janbaziroudsari, A. Mirzaei, N. Maleki
enrolled in this study. The mean serum total PSA level was 13.73 11.44 ng/mL (range: 0.3 to 149.0 ng/mL) and the mean serum free PSA level was 4.99 0.97 ng/mL (range: 0.04 to 6.84 ng/mL). For the 1472 men enrolled in this study, the serum total PSA levels were < 4.0 ng/mL in 1212 (82.34 percent), 4.0 to 9.9 ng/mL in 174 (11.82 percent), and 10.0 ng/mL in 86 (5.84 percent). Of the 260 men who had serum total PSA levels of 4 ng/mL, 139 underwent biopsy. Of these 139 men, 45 (32.4 percent) had prostate cancer. Benign prostatic hyperplasia (BPH) with or without prostatitis was diagnosed in 94 patients (67.6 percent). After analyzing the data, it was observed that there was no significant correlation between age and histologic results of prostate needle biopsy (P-value = 0.469). Out of 1212 patient with PSA less than 4.0 ng/mL, 13 (1.1%) had nodular prostatic hyperplasia without prostatitis, 6 patients (0.5%) had nodular prostatic hyperplasia with prostatitis and 4 patients (0.3%) had adenocarcinoma. Table I shows the relationship between serum total PSA and histologic results of prostate needle biopsy. It was observed
that the serum total PSA levels were significantly higher in patients with adenocarcinoma compared with other diagnosis (P-value < 0.001). In this study, the serum total PSA level was divided into three intervals and in each interval, histologic results of prostate needle biopsy were studied. The results showed that in the serum total PSA level greater than 10, adenocarcinoma is the most common diagnosis, and the results were statistically significant (P-value = 0.001). Table II shows the relationship between total PSA intervals and histologic results of prostate needle biopsy. Table III shows the relationship between serum free PSA and histologic results of prostate needle biopsy. The results showed that there was no significant relationship between the level of free PSA and the histologic results of prostate needle biopsy (P-value = 0.176).
Discussion Prostate-specific antigen (PSA) is a glycoprotein produced by prostate epithelial cells. PSA levels may be elevated in men with
TABLE I The relationship between mean levels of serum total prostate-specific antigen (PSA) and histologic results of prostate needle biopsy Serum total PSA levels, ng/mL (mean W SD)
P-value
Nodular prostatic hyperplasia without prostatitis (n = 77)
10.33 7.70
< 0.001
Adenocarcinoma (n = 45)
49.87 40.04
Histologic results of prostate biopsy
7.89 5.24
Nodular prostatic hyperplasia with prostatitis (n = 17)
TABLE II The relationship between total prostate-specific antigen (PSA) intervals and histologic results of prostate needle biopsy Histologic results of prostate needle biopsy Nodular prostatic hyperplasia without prostatitis (n = 77)
PSA < 4 ng/mL, n (%)
PSA = 4–10 ng/mL, n (%)
PSA > 10 ng/mL, n (%)
P-value 0.001
13 (16.9)
31 (40.2)
33 (42.9)
Adenocarcinoma (n = 45)
4 (8.9)
6 (13.3)
35 (77.8)
Nodular prostatic hyperplasia with prostatitis (n = 17)
6 (35.3)
5 (29.4)
6 (35.3)
TABLE III The relationship between mean levels of serum free prostate-specific antigen (PSA) and histologic results of prostate needle biopsy
732
Histologic results of prostate biopsy
Serum free PSA levels, ng/mL (mean W SD)
P-value 0.176
Nodular prostatic hyperplasia without prostatitis (n = 77)
2.29 1.39
Adenocarcinoma (n = 45)
8.63 5.59
Nodular prostatic hyperplasia with prostatitis (n = 17)
2.03 1.41
tome 103 > n89 > September 2016
prostate cancer because PSA production is increased and because tissue barriers between the prostate gland lumen and the capillary are disrupted, releasing more PSA into the serum. However, PSA is also elevated in a number of benign conditions, particularly benign prostatic hyperplasia (BPH) and prostatitis. PSA has a half-life of 2.2 days [10]. Total prostate specific antigen (tPSA) is widely used to detect prostate cancer with a significant increase in the incidence of organ-confined disease at the time of diagnosis. The limitations of tPSA are low specificity and positive predictive value. Numerous attempts to enhance PSA's performance based on prostate volume, patient age, patient race, and PSA velocity have shown little clinical improvement. Percent free PSA has proven to be somewhat improved but still limited. Recently, the complexed PSA assay was developed and multisite institutional studies have shown that cPSA has improved specificity over tPSA [11]. Prostate cancer screening has been a controversial issue because decisions were made about adopting PSA testing in the absence of efficacy data from randomized trials [12]. Subsequently, the European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a small absolute survival benefit with PSA screening after nine years of follow-up [13]; however, 48 additional patients would need to be diagnosed with prostate cancer to prevent one prostate cancer death. Further sustaining the uncertainty surrounding screening, a report from the large United States trial, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, published concurrently with the European trial, found no benefit for annual PSA and digital rectal examination (DRE) screening after 7 to 10 years of follow-up [14]. In the present study, we found statistically significant inverse relationships between serum total PSA and histologic results of prostate needle biopsy. However, the relationship between the serum free PSA and prostate needle biopsy histologic results were not statistically significant. Moreover, we found that in the serum total PSA level greater than 10, adenocarcinoma is the most common diagnosis.
In 1993, Catalona et al. [15] measured serum PSA levels in 1653 healthy men 50 or more years old. Serum PSA levels ranged from 4.0 to 9.9 micrograms per liter in 6.5 percent of the 1653 men. Nineteen of the 85 men in this group (22 percent) who had prostatic biopsies had prostate cancer. Serum PSA levels were 10.0 micrograms per liter or higher in 1.8 percent of the 1653 men. Eighteen of the 27 men in this group (67 percent) who had prostatic biopsies had cancer. They recommended that the combination of measurement of the serum PSA concentration and rectal examination, with ultrasonography performed in patients with abnormal findings, provides a better method of detecting prostate cancer than rectal examination alone. The overall detection rate of prostatic adenocarcinoma in our patients was 32.4%. Prostate cancer incidence rates (per 100,000) for 2000–2004 from selected registries worldwide vary markedly, with rates ranging from < 10 in the Republic of Korea, Thailand, and Chennai, India, to > 100 in the United States and New Zealand [16]. Increasing prostate cancer incidence rates were observed in 32 of the 40 countries included in the analysis with the estimated average annual percent change ranging from 2 to 3% in Sweden, the United Kingdom, and Thailand to 12–16% in China, the Republic of Korea, and Lithuania [16].
Original article
Association of serum prostate-specific antigen levels with the results of the prostate needle biopsy
Conclusions In our study, the overall frequency of detection of prostate adenocarcinoma was 32.4%. This study revealed that no level of PSA was associated with a 100% positive predictive value and negative biopsy can occur virtually at any PSA level. There is a need to create awareness among the general population and health professionals for an early diagnosis of this common form of cancer. Disclosure of interest: the authors declare that they have no competing interest.
References
[2]
[3]
Tao ZQ, Shi AM, Wang KX, Zhang WD. Epidemiology of prostate cancer: current status. Eur Rev Med Pharmacol Sci 2015;19 (5):805–12. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63: 11–30. Andriole GL, Crawford ED, Grubb RL, et al. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up. J Natl Cancer Inst 2012;104:125–32.
tome 103 > n89 > September 2016
[4]
[5]
[6]
[7]
Lieberman SF, Karlberg I. Screening for cancer of the prostate: do we have a state of the art? Scand J Public Health 2015;43(6): 561–2. Frankel S, Smith GD, Donovan J, Neal D. Screening for prostate cancer. Lancet 2003; 361:1122–8. Lu-Yao GL, Greenberg ER. Changes in prostate cancer incidence and treatment in USA. Lancet 1994;343:251–4. Lu-Yao GL, Friedman M, Yao SL. Use of radical prostatectomy among Medicare beneficiaries before and after the introduction of
prostate specific antigen testing. J Urol 1997;157:2219–22. [8] Potosky AL, Miller BA, Albertsen PC, Kramer BS. The role of increasing detection in the rising incidence of prostate cancer. JAMA 1995;273:548–52. [9] Smith RA, Cokkinides V, von Eschenbach AC, Levin B, Cohen C, Runowicz CD, et al. American Cancer Society guidelines for the early detection of cancer. CA Cancer J Clin 2002;52(1):8–22. [10] Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E. Prostate-specific
733
[1]
734
Original article
H. Janbaziroudsari, A. Mirzaei, N. Maleki
antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987; 317:909–16. [11] Naya Y, Okihara K. Role of complexed PSA in the early detection of prostate cancer. J Natl Compr Canc Netw 2004;2(3):209–12. [12] Brett AS, Ablin RJ. Prostate-cancer screening–what the U.S. Preventive Services Task Force left out. N Engl J Med 2011;365: 1949–51.
[13] Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320–8. [14] Andriole GL, Crawford ED, Grubb 3rd RL, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310–9. [15] Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan JJ, et al. Measurement of
prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med 1991;324:1156–61. [16] Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, et al. International variation in prostate cancer incidence and mortality rates. Eur Urol 2012;61:1079–92.
tome 103 > n89 > September 2016