Changes of Prostate-Specific Antigen and Prostate Size with Age: A Survey of 3367 Men
- I-shen Huang, Kuang-Kuo Chen*, and Alex T. L. Lin
Background To evaluate serum prostate-specific antigen (PSA) and prostate size distribution in age stratified men and further used as baseline value for normal individual.
Methods 3367 men who received health examination, transrectal ultrasonography and serum PSA testing in our hospital were enrolled. Age ranged from 20 to 90 years and was subdivided into 7 groups to study prostate size and PSA distribution among different ages.
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Results Median PSA raised from 0.80 ng/ml at age 30 to 1.77 ng/ml at age 80 years, and median prostate size increased from 20.03 ml at age 20 to 36.95 mL at age 90 years. Mean PSA density range from 0.04 to 0.08 and was associate with aging. 32 male with elevated PSA received prostate biopsy and 6 (18.8%) proved to be prostate adenocarcinoma.
Conclusions The results of this study revealed that in Taiwanese people, prostate size and PSA increased with age since 30s and mean PSA density remained constant through 21 to 80s. Age stratified PSA level can be applied to clinical practice and may further define the meaning of “elevation of PSA” of Taiwanese people.
Keywords: age; prostate; prostate specific antigen
Prostate cancer is the 5th leading cancer diagnosed and has cancer specific mortality at 7th place in Taiwan accounting for 1021 deaths in 2010. The incidence of prostate cancer is increasing yearly with merely 884 cases detected in 1995 and exceed to 4392 new cases diagnosed in 2010.1
Since 1979, purified of prostate-specific antigen (PSA) has become widely used as a marker for prostate cancer screening and disease assessment with treatment response.2-4 According to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) cancer statistic review, from 2003-2007, the median age at diagnosis for prostate cancer was 67 years of age. Approximately 0.0% was diagnosed under the age of 34; 0.6% between 35 and 44; 8.9% between 45 and 54; 29.9% between 55 and 64; 35.3% between 65 and 74; 20.7% between 75 and 84; and 4.6% 85 years or older of age. 5
As for benign prostatic hyperplasia (BPH), in which a well-known condition closely related to aging, functioning testes, central obesity, hypertension, ethnicity, cigarette smoking and diabetes mellitus, but negative correlated to exercise and moderate alcohol consumption.6-9 Berry et al reported that the normal prostate reaches 20 ± 6 gm in men between 21 and 30 years old, and this weight remains essentially constant with increasing age unless BPH develops. Average prostate weight increases from approximately 20 gm at age 40 to 38.8 gm in men older than 80 years.10
The prevalence of BPH increases with age though varied among different reports, owing to the lack of common definition and diagnostic criteria. Prostate size and PSA data in normal population were lacking in Taiwan, which prompted us to conduct this study.
Materials and methods:
In 2008, 3367 men came to our hospital for physical checkup. All male subjects received transrectal ultrasonography (TRUS) performed by different radiologists for prostate size measurement and a blood sample for PSA assay.
Prostate volume was assessed using the most common ellipsoid formula, requiring measurement of diameters of 3 prostatic dimensions. Dimensions are first determined in the axial plane by measuring the transverse and anteroposterior diameters in centimeter (cm) at the estimated point of widest distance. The longitudinal diameter is measured in the sagittal plane. The ellipsoid volume formula is then applied as following: volume = height X width X length X 0.52. The PSA density (ng/ml2) was defined as the quotient of PSA divided by gland volume.
Pearson product-moment correlation coefficients were used to test the association between age and prostate size, PSA, PSA density, respectively. Finally, linear regression models were performed for factors significantly correlated at Pearson or Spearman analysis.
The patients’ age was ranged from 20 to 90 years, and was divided into 7 subgroups: 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90 years.
Median PSA level was 0.87, 0.80, 0.91, 1.02, 1.27, 1.77, 1.76 ng/ml, and mean PSA was 0.965± 0.530, 0.943 ± 0.630, 1.216 ± 4.722, 1.349 ± 1.571, 1.845 ±1.690, 2.738 ± 3.324, 2.870 ± 4.815 ng/ml respectively for the 7 subgroups. Median prostate size was 20.03, 22.48, 24.94, 28.34, 31.11, 30.85, 36.95 ml and mean prostate size was 22.223 ± 13.698, 24.050 ± 10.204, 27.270 ±10.745, 31.428 ± 15.261, 35.244 ± 17.621, 40.056 ± 20.716, 44.705 ± 29.977 ml in age 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90 patient subgroups. Median PSA density is 0.05, 0.04, 0.03, 0.04, 0.04, 0.07, 0.04 ng/ml2 and mean PSA density is 0.20 ± 0.04, 0.04 ± 0.05, 0.04 ± 0.03, 0.05 ± 0.05, 0.06 ± 0.05, 0.06 ± 0.07, 0.08 ± 0.17 ng/ml2 in age 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90 patient subgroups (Table 1).
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A trend toward elevating PSA and prostate size as age increased from 30 years old was observed. Also we found a positive correlation between age and PSA (r=0.164, p=0.000), prostate size (r=0.316, p=0.000), PSA density (r=0.045, p=0.008), respectively (Figure 1).
In our study, 366 male had PSA > 2.5 ng/ml and 44 male having PSA above 4 ng/ml. Only 32 male (1 in group 21-30 years, 2 in group 31-40 years, 9 in group 51-60 years, 14 in group 61-70 years, 4 in group 71-80 years, 2 in group 81-90 years) with elevated PSA (> 4 ng/ml) received TRUS biopsy, which showed adenocarcinoma of prostate in 6 cases (18.8%). The age of the 6 prostate cancer patients was 60, 63, 63, 67, 79, and 79 years. PSA was 9.33, 5.38, 37.69, 2.85, 10.26, 3.59 ng/ml at the time when they accepted physical checkup. Gleason grade was 3+3 in 4 cases, 4+3 in one case and 4+5 in one case. Clinical staging was T2aN0M0, T2bN0M0, T2bN0M0, T2cN0M0, T3aN0M0, T2cN1M0, respectively. Notably, 4 cases accepted TRUS biopsy of prostate after elevation of PSA, and 2 of the 6 cases with PSA 2.85 and 3.59 ng/ml accepted TRUS biopsy of prostate due to a raise of PSA raise to 17.53 and 7.71 ng/ml , respectively 2 years later.
Four patients with age below 40 years (39,35,30,27) accepted TRUS biopsy of prostate. PSA was 6.97, 5.95, 11.8, 9.42 ng/ml, respectively and pathology disclosed benign prostatic tissue in 3 patients and atypical gland in 1 patient with PSA level 5.95 ng/ml.
Several studies have provided prostate size and average rate of prostate growth with age. Bosch et al.11 estimated 2% annual increase in prostate volume and doubling time of total prostatic volume to be 35 years among men aged 55-74 years. In men aged 40-79 years old, prostate size increased 1.6% annually, and the prostate growth rate correlated with baseline prostate volume.12 In the Baltimore Longitudinal Study of Aging, the median rate of volume change was 0.6 c.c per year, corresponding to a median growth of 2.5% per year. However, 64.6% of men with initial prostate size less than 40 cc had prostate growth compared to only 50.9% of men with prostate size exceed 40 cc, indicating a proportion of men have stationary prostate size.13 The future size of prostate can also be predicted according to the baseline prostate volume detected at a precise age.14 Instead of prediction of future prostate size by baseline prostate volume, baseline PSA level may also be useful for identification of long-term risk of prostate enlargement shown in the Baltimore longitudinal study of aging.15
Among men in their 40s, PSA level above the median value for age is a stronger predictor for further prostate cancer risk than family history or race.16,17 Consequently, the American Urological Association (AUA) stated determining baseline PSA for all asymptomatic men at age 40 years with an estimated life expectancy of more than 10 years for early detection and risk assessment for prostate cancer. 18 National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology also suggested that men with high risk for prostate cancer should accept annual PSA check and prostate examination since 40 years. Other men having baseline PSA > 1 ng/ml ought to be followed annually, whereas men with PSA <1 ng/ml may need early detection at their 45’s.19
In the prostate, Lung, Colorectal, and ovarian (PLCO) trial, 76,693 men aged 55 to 74 years were screened, with 6 years of PSA testing and 4 years of digital rectal examination. The results showed higher incidence of prostate cancer in the screened arm, but no statistically difference of mortality between the control and screened arm at 7 and 10 years of follow-up.20 The European Randomized Study of Screening for Prostate Cancer (ERSPC), a multinational trial of 8 European countries, begun in 1990s also came to a similar conclusion of an increased incidence of prostate cancer observed in the screening arm compared with controls, and no statistically significant reduction in prostate cancer mortality rate for men aged between 50 and 74 years. Nevertheless, in men aged 55 to 69 years, 20% relative prostate cancer mortality reduction was revealed in the screening group, meaning absolute reduction of 0.71 prostate cancer death per 1,000 men at 8.8 years of follow-up.21 However, 44% of men in the PLCO trial already received PSA testing prior to trial, which may decrease the detection rate of cancer and weaken the power to detect difference of mortality. Longer period of follow-up is required to reveal the benefit of PSA screening.
In our study, a trend of raising PSA from 0.80 to 1.77 ng/ml was found from the age of 30s to 80s. The prostate size also increased from 20.03 ml in their 20s years to 36.95 ml in their 80s, whereas PSA density range from 0.03 to 0.07 ng/ml2 and was not relevant to aging. Bosch et al22 predicted future PSA level based on men’s age and known history of PSA. In his study PSA increased from 0.9 ng/ml at age below 55 years to 2.0 ng/ml at age above 75 years, also prostate volume gained from 28.4 ml to 46.2 ml from age below 55 years to age above 75 years. Berges and Oelke23 studied 1,763 men aged 50-80 years, mean prostate volume continuously increased from 24 to 38 ml and mean PSA concentration from 1.1 to 2.5 ng/ml. The results of our study were compatible with the above 2 studies, representing an increase of PSA and prostate size increase with age. Interestingly, 3 studies enrolled German, Dutch and Taiwanese population, and the values of PSA and prostate size do not seem to be equivalent among different races.
This study might have several potential limitations to limit the utility of the results. First, it is a retrospective study. Most male subjects did not receive digital rectal examination and only 32 men received prostate biopsy, with 366 men having PSA level above 2.5 ng/ml. Second, we are unable to trace men who may receive prostate biopsy at other hospital; therefore the risk of prostate cancer in our study might be underestimated. Third, risk factors for elevating PSA level such as urinary tract infection and prostatitis were not excluded in the study. The strength of our study included all age of men from 20s to 80s, in which most of the other studies possessed data of PSA and prostate size of men at the age above 40s.
The results of this study revealed that in Taiwanese people, prostate size and PSA increased with age since 30s and mean PSA density remained constant through 21 to 80s. Age stratified PSA level can be applied to clinical practice and may further define the meaning of “elevation of PSA” of Taiwanese people.
Figure 1 Scatter diagram with trend line plotting positive correlation between age and (A) PSA ((r=0.164, p=0.000), (B) prostate size(r=0.316, p=0.000), (C) PSA density(r=0.045, p=0.008), respectively
- Altekruse SF, Kosary CL, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2007, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2007/,based on November 2009 SEER data submission, posted to the SEER web site, 2010.
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- Berges R, Oelke M. Age-stratified normal values for prostate volume, PSA, maximum urinary flow rate, IPSS, and other LUTS/BPH indicators in the German male community-dwelling population aged 50 years or older. World J Urol 2011;29:171-8.
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- Health promotion administration, Ministry of health and welfare, R.O.C (Taiwan); 2010. Available from: http://www.hpa.gov.tw/BHPNet/Portal/File/StatisticsFile/201305061037065219/99%E5%B9%B4%E7%99%8C%E7%97%87%E7%99%BB%E8%A8%98%E5%A0%B1%E5%91%8A.pdf
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- Platz E, Kawachi I, Rimm E, et al. Physical activity and benign prostatic hyperplasia. Arch Internal Med 1998; 158:2349–56.
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