PSA determination (synonym: prostate-specific antigen) is a blood test (tumor marker) used in the early detection of prostate cancer with the aim of detecting the cancer at a curable stage. Tumor markers are substances produced naturally in the body by tumors and are detectable in the blood. They can provide an indication of a malignant neoplasm and are used as a follow-up test in cancer aftercare. The prostate, also called the prostate gland, is anatomically located in the male pelvis between the urinary bladder and the intestine. Older men in particular suffer from enlargement of the prostate gland, also called benign prostatic hyperplasia (BPH), which is associated with urination disorders. While 50% percent of all women regularly go for cancer screening, only 15% of all men do so, even though prostate cancer is the most common cancer in men. Prostate-specific antigen (PSA) is a protein (albumin) produced by the prostate glands. After ejaculation (ejaculation), it enters the semen with the prostatic secretion and liquefies it. This is a normal biochemical reaction. PSA is a physiologically present enzyme in healthy men.
The procedure
Material needed:
A variety of test systems are available. The values are usually given in ng/ml – nanograms/milliliter. However, comparability is only given if the same test system was used. The lower limit of detectability is usually 0.1ng/ml. Confounding factors (which increase the PSA value).
- There should be no mechanical stress on the prostate 48 hours prior to blood collection:
- Digital rectal examination (DRU) of the prostate (palpation of the prostate through the rectum).
- Rectal prostate sonography (ultrasound of the prostate by means of a probe inserted into the rectum (rectum)).
- Ejaculation
- Cycling
- Approximately 3-4 days after a prostate massage.
- Approximately 2 weeks after prostate biopsies (tissue sampling).
- Free PSA has a short half-life – only about 2.5 hours. This means that longer transport times can result in too low values!
- Cranberries (large-fruited cranberries) can lower PSA levels and interfere with the expression of androgen-responsive genes.
- Drugs that lead to lower PSA levels (PROBASE study).
- Angiotensin-converting-enzyme (ACE) inhibitors or other anithypertensives (excluding beta blockers, thiazide diuretics, calcium channel blockers, and angiotensin-1 receptor blockers)
- Insulin
- Metformin
- Finasteride (1 mg) and dutasteride (5α-reductase inhibitors): – During therapy with 5-alpha-reductase inhibitors (eg, in alopecia or benign prostatic hyperplasia):
- Lower the PSA level by about 50%.
- Reduce the frequency of detection of prostate cancer and preneoplasia (High-Grade Prostatic Intraepithelial Neoplasia (PIN) due tohalving serum PSA levels after a treatment period of 6-12 months.
- Delay in diagnosis up to 2.2 years; carcinomas were twice as likely to be detected at an advanced stage (4.7 versus 2.9% had reached stage 3); 25.2% versus 17.0% had Gleason grade 8 or higher; prostate cancer-specific mortality (mortality) at 12 years was 13% versus 8% among users of 5α-reductase inhibitors.
Forms of the PSA
Different forms of PSA exist in the blood serum. The total PSA is composed of.
- The so-called f-PSA (= free PSA), which has a proportion of about 5-40% and is elevated especially in benign (benign) prostate diseases and
- The c-PSA (= complexed PSA). which is bound to serine proteinase inhibitor a1-antichymotrypsin (ACT) and to a1-trypsin.
Bound c-PSA usually accounts for 60-95% of total PSA and is particularly elevated in prostate cancer.
Normal values
Age-specific PSA reference values according to Oesterling. The cutoff value increases with age because prostate volume increases with age.
| Age group | Limit |
| 40-49 years | < 2.5 ng/ml |
| 50-59 years | < 3.5 ng/ml |
| 60-69 years | <4.5 ng/ml |
| 70-79 years | <6.5 ng/ml |
Age-independent threshold* (despite negative digital rectal examination) according to the guideline of “German Urology”
| 4.0 ng/ml | Clarification by biopsy under sonographic control and antibiotic protection is recommended. |
* In younger patients, prostate biopsy may be recommended on an individual basis even at PSA levels below 4 ng /ml. Evaluation as a function of PSA level.
| PSA value | Assessment | Proportion of carcinomas detected |
| PSA below age-specific norm (see table below). | No evidence of prostate carcinoma | Proportion of carcinomas detected is 10% |
| PSA between normal range and 10 ng/ml | Carcinoma cannot be excluded! Determination of the quotient f-PSA/total PSA, DRU and sonography if necessary biopsy. | Proportion of carcinomas detected is 25%. |
| PSA between 10-20 ng/ml | Carcinoma is not unlikely! Determination of the f-PSA/total PSA quotient, DRU, sonography, and biopsy. | Proportion of carcinomas detected is approximately 50-60%. |
| PSA increase of more than 0.75 ng/ml per year | Suspicion of prostate carcinoma! | Sensitivity (percentage of diseased patients in whom the disease is detected by use of the test, i.e., a positive test result occurs) 75%, specificity (probability that actually healthy individuals who do not have the disease in question are also detected as healthy in the test) 90%. |
Free PSA/Total PSA
| Calculation | Evaluation |
| Free PSA (ng/ml) divided by total PSA (ng/ml) x 100% Example: free PSA 1.3, total PSA 5.3. 1.3 / 5.3 = 0.25 * 100% = 25%. |
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Indications (areas of application)
PSA determination should be performed according to an American Association of Urology (AUA) guideline for/in:
- Determination of a baseline PSA level between the ages of 40 and 45.
- PSA screening (early detection).
- Between the ages of 55 and 69 in consultation with the physician; screening interval: two years or longer.
- From the age of 70, only in men with a presumed life expectancy of more than 10-15 years.
- Suspicion of prostate cancer
- Follow-up due to existing prostate cancer.
- Benign prostatic hyperplasia (BPH; benign prostate enlargement).
- Under hormone replacement therapy with testosterone
The 2014 German S3 guideline on early detection, diagnosis and treatment of prostate cancer recommends that men 45 and older (5 years earlier for high-risk patients) with a life expectancy of more than ten years should be informed about the possibility of early detection.For men at increased risk of prostate cancer, this age limit can be advanced by 5 years. According to the recommendations of the European Association of Urology (EAU) for early detection of prostate cancer, mass screening is not recommended. It recommends individual screening for the patient, citing a systematic literature review and meta-analysis of prospective and retrospective clinical trials on PSA level determination, early detection and screening of prostate cancer. She made the following statements:
- Early detection of prostate cancer reduces prostate cancer-specific mortality (mortality). The studies show a reduction in mortality between 21 and 44%.
- Early detection reduces the risk of diagnosis of advanced or metastatic prostate cancer. The risk reduction in various studies is 30% in 12 years and goes up to 48.9% in 10 years.
- Determination of a baseline PSA level should be performed from the age of 45 (and a life expectancy of > 10 years). The baseline PSA result should be estimated as follows:
- Baseline PSA < 1 ng/ml at 45 years → next PSA examination in 10 years.
- Baseline PSA ≥ 2 ng/ml at 60 years → increased risk of dying from prostate cancer or occurrence of advanced or metastatic prostate cancer in the next 25 years
- Age group 45 years and older and a life expectancy > 10 years (screening intervals) (see table).
- PSA screening should be offered to men with at least 10 years of life expectancy remaining.
- For men older than 70 years and a PSA < 1 ng/ml, further PSA-based screening is not recommended
- Risk assessment should also consider the rapidity of PSA rise. Other findings such as age, ethnicity, digital rectal examination (DRU), biopsy, and family history of prostate cancer must also be included in the risk assessment.
Time interval for measurement of the PSA value according to German S3 guideline prostate cancer.
| PSA value | Time interval |
| < 1 ng/ml | Every 4 years |
| 1-2 ng/ml | Every 2 years |
| > 2 ng/ml | Every year |
Ideally, the PSA determination should be supplemented by a digital rectal examination and, if necessary, a transrectal prostate sonography (TRUS) by the urologist.On the value of prostate cancer screening by PSA test: regular PSA screening from the age of 50 can, according to a European long-term study, reduce the mortality risk (risk of death) by more than one fifth. The reevaluation of the Prostate, Lung, Colorectal and Ovarian [PLCO] Cancer Screening Trial also demonstrated that PSA screening contributes to a reduction in prostate cancer mortality. The U.S. Preventive Services Task Force (USPSTF) advocates selective screening in younger men (recommendation grade C). Screening continues to be discouraged in men older than 70 (recommendation grade D).
Interpretation
Interpretation of Elevated Values
- Benign prostatic hyperplasia (BPH; benign prostatic enlargement).
- Prostate carcinoma (prostate cancer)
- Acute and chronic prostatitis (prostatitis).
- Sports – e.g. cycling, horseback riding (direct – acute; indirect – chronic).
- Sexual intercourse
- Constipation (constipation) – due to pressing.
- Prostate massage
- Digital rectal examination (DRU) – palpation of the prostate gland.
- Acute urinary retention
- Urinary bladder catheter
- Urethrocystoscopy (urethral and bladder endoscopy).
- Prostate biopsy (tissue sampling from the prostate).
Elevated PSA levels do not mean a prostate carcinoma (prostate cancer) in every case. This must be verified in individual cases by a prostate biopsy (tissue sampling from the prostate). Interpretation of decreased values
- See under interfering factors: cranberries and drugs.
- After surgical removal of prostate tissue.
- After radiation or hormone therapy of the prostate gland
- In overweight men – Men with a higher BMI consistently have higher blood volumes than those with a lower BMI. As a result, blood PSA concentrations are also significantly lower in overweight men than in thinner men, although the absolute amount of PSA in the blood is similar in both groups.
Further notes
- Patients with a low-risk tumor (tumor stage ≤ 2a and a Gleason score ≤ 6) and PSA level > 10 or even > 20 ng/ml (intermediate or high-risk range, respectively) are at higher risk for pathologic and oncologic outcomes. The risk depends crucially on the PSA density (PSAD = total PSA / prostate volume in ml): Men with a PSA between 10 and 20 ng/ml but a PSAD below 0.15 ng/ml/g are comparable to patients who have a low-risk tumor.
- A PSA level > 1 ng/ml at age 40 to 50 years is associated with a 5-fold increased risk of cancer.
- In prostate cancer, the concentration of preoperative prostate-specific antigen (PSA) in the blood correlates with the location of the tumor confined to the organ:
- PSA values: < 4 ng/ml → prostate carcinomas in the apex (tip) and peripheral zone.
- PSA levels: 10.1-20 ng/ml → prostate carcinomas in the anterior (“front”) region as well as at the base (compared to men with a PSA level <10 ng/ml).
Regression analysis showed that PSA levels 4-10 ng/dl and < 4 ng/dl were significantly less likely to have carcinoma in the anterior region near the base of the prostate (OR < 1) than levels between 10- 20 ng/dl (16.4% versus 10% and 6%, respectively)
- Based on nearly a quarter of a million patients from the Surveillance, Epidemiology, and End Results(SEER) Program database, the mortality curve related to PSA concentration was calculated for the collective of patients with a Gleason score of 8-10. The reference value was the PSA level of 4.1-10.0 ng/ml; here, the 5-year cumulative mortality was calculated to be around 5%. Subsequent results showed a U-shaped mortality curve:
- PSA > 40.0 ng/ml: mortality risk (risk of death) 3-fold.
- PSA 20-40 ng/ml: mortality risk 2.08-fold
- PSA 10.1-20.0 ng/ml: mortality risk 1.6-fold
- PSA value < 2.5 ng/ml: mortality risk 2.15-fold [probably indicative of aggressively growing, extremely poorly differentiated, or anaplastic carcinomas that produce little PSA].
- In men at increased genetic risk for prostate cancer due to a BRCA mutation, PSA levels have a higher predictive value than in men without a BRCA mutation.
- After the U.S. Preventive Services Task Force made a general recommendation in 2012 to forgo PSA screening regardless of age, the proportion of metastatic tumors in older men (>75 years) has increased from 6.6% to 12%, and an increase in the rate of metastases to 5% has also been demonstrated in young men
- Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP): a single PSA test in England and Wales 189,386 men aged 50 to 69 years increased the number of cancer diagnoses but did not reduce mortality in patients in the first 10 years.
- See also under prostate risk calculator.
Biochemical recurrence
Interpretation of PSA levels in recurrent or metastatic prostate cancer (when prostate cancer recurs or daughter tumors appear):
- After radical prostatectomy (complete removal of the prostate including the capsule, seminal vesicles (vesiculae seminales), and regional lymph nodes), a PSA level confirmed in at least two measurements to be >0.2 ng/mL denotes biochemical recurrence/recurrence of tumor disease. In a cohort study with a total of 13,512 prostatectomized patients (cT1-2N0M0), it was shown that the optimal threshold is a single PSA level of ≥ 0.4 ng/ml. This was said to be both a marker for continued PSA rise and a strong predictor (predictive value) for metastasis (formation of daughter tumors) of prostate carcinoma.→ Biooptical backup (sampling and fine tissue examination) of biochemical recurrence is not required.
- After radiotherapy alone (radiatio)a PSA increase of > 2 ng/ml confirmed in at least two measurements above the postinterventional PSA nadir characterizes a biochemical recurrence.→ Bioptic confirmation of biochemical recurrence in patients after radiotherapy with the option of local recurrence therapy should be sought.
