II. Efficacy: PSA
- USPSTF Strength of Recommendation: D
-
Test Sensitivity
- Overall: 79-82% (72% for a PSA >4 ng/ml)
- Cancers >1 cm: 90%
- More sensitive than Digital Rectal Exam (30% for 1 cm tumor)
- Much more sensitive than Acid Phosphatase
-
Test Specificity
- Overall: 59% (93% for a PSA >4 ng/ml)
- Positive Predictive Value: 25% (for PSA>4 ng/ml)
- False Positive Rate: 70% (for PSA >4 ng/ml)
- Benign Prostatic Hyperplasia often increases PSA
- Outcomes uncertain despite effective screening
- Screening does not decrease overall or Prostate Cancer specific mortality
- Detection may not impact morbidity
- May actually increase morbidity due to Prostate Cancer treatment complications
- Absolute Risk Reduction: 1.28 deaths per 1,000 men screened for Prostate Cancer
- To prevent one death from Prostate Cancer
- References
- Additional tests that improve PSA efficacy
- See Elevated PSA management below (includes MRI, biomarkers)
- Free PSA to Total PSA ratio
- Normal range varies by age, but ratio <25% is higher risk
- Rate of PSA change
- Consider referral for higher rate of change, even if <4 ng/ml
III. Causes: Elevated PSA
- Prostate Cancer
- Benign Prostatic Hyperplasia (BPH)
- Prostatitis
- Prostate inflammation, Trauma, or manipulation
- Prostatic infarction
- Recent sexual activity
- Urologic procedures
IV. Screening: Recommendations
- Most organizations can not recommend for or against screening based on lack of evidence
- See Efficacy above
- US Preventive Task Force
- American College of Physicians
- American Society of Internal Medicine
- National Cancer Institute
- Centers for Disease Control and Prevention (CDC)
- American Academy of Family Physicians
- American College of Preventive Medicine
- Organizations that advocate Shared Decision Making for men ages 55 to 69 years old, but not routine screening
- American Cancer Society
- American Urological Association
- National Comprehensive Cancer Network
- Testing
- Digital Rectal Exam (optional, see Prostate Cancer for efficacy)
- Prostate Specific Antigen (PSA)
- Timing (if screening is performed)
- Start screening (some recommend every other year)
- Normal risk: Starting at age 50 years old (ACP, ACS) or age 55 (AUA)
- High Risk: Starting at age 40 years old (AUA) or 45 years old (ACS)
- See Prostate Cancer for risks factors
- Black Male
- Young first degree relative (<age 65 years old) with Prostate Cancer
- Known Genetic Syndromes (e.g. BRCA1, BRCA2, Lynch Syndrome)
- Stop screening
- Stop screening by age 70 years old OR
- Less than 10 to 15 years Life Expectancy (ACS/AUA)
- See Charlson Comorbidity Index (CALE)
- Frequency of testing
- Every 2 to 4 years is the interval recommended by most organizations
- Annual screening increases False Positive risk without mortality benefit
- ACS recommends every 2 years for PSA <2.5 ng/ml, and every year for PSA >=2.5 ng/ml
- High risk patients (e.g. BRCA2) may be considered for annual screening
- Screening every 4 years may be as effective as annual
- Every 2 to 4 years is the interval recommended by most organizations
- References
- Start screening (some recommend every other year)
V. Documentation: Informed Consent Discussion with Patient
-
Prostate Cancer is common
- Second most common cancer in U.S. men (Lung Cancer is first)
- Over 299,000 new cases of Prostate Cancer each year in the United States (as of 2024)
- Lifetime risk of Prostate Cancer is 17% (higher risk if Black or positive Family History)
- Most Prostate Cancer occurs in men over age 65 (60%)
- Blood Test improves detection of Prostate Cancer
- PSA is twice as effective as Digital Rectal Exam
- PSA blood test is far from perfect
- Most PSA level increases are not due to Prostate Cancer
- As high as 70% of men with an abnormal PSA do not have Prostate Cancer
- PSA misses as many as 15-20% of Prostate Cancers (PSA <4)
- Most PSA level increases are not due to Prostate Cancer
- Early detection, however may not save more lives
- Only 3% of men die from Prostate Cancer
- Most Prostate Cancers do not affect men who have them
- Prostate Cancer most often affects those over age 75 years old (70% of Prostate Cancer deaths)
- Increased PSA level triggers invasive evaluation
- Urology Consultation
- Transrectal Ultrasound with Prostate biopsies
- Most Prostate Cancer is treated surgically
- Prevents death in only 10% men with Prostate Cancer
- Prostate removal has high morbidity and a risk of mortality
- Death: 2%
- Erectile Dysfunction: 25%
- Urethral Stricture: 18%
- Incontinence: 6%
VI. Interpretation: Age specific Normal PSA values
- Age 40 to 49 years
- White: PSA <= 2.5
- Black: PSA < 2.0
- Asian: PSA < 2.0
- Age: 50 to 59 years
- White: PSA <= 3.5
- Black: PSA < 4.0
- Asian: PSA < 3.0
- Age 60 to 69 years
- White: PSA <= 4.5
- Black: PSA < 4.5
- Asian: PSA < 4.0
- Age 70 to 79 years
- White: PSA <= 6.5
- Black: PSA <5.5
- Asian: PSA <5.0
VII. Interpretation: Algorithym to evaluate PSA results
- PSA < 2 ng/ml
- Repeat PSA in 2 years
- Chance that PSA > 5 ng/ml in 2 years is <4%
- PSA 2.6 to 4.0 ng/ml
- Unclear guidelines as to approach this range of PSAs
- False Positive Rate would be 80% if PSA threshold were 2.5 ng/ml
- False Negative Rate 15% (of which 15% are high grade Prostate Cancers)
- Some groups have suggested referral in this range for ages 40 to 50 years (esp. black men)
- PSA 4.0 to 5.0 ng/ml
- Prostate Cancer "Curable" Range
- Test Sensitivity: 72%
- Test Specificity: 93%
- Positive Predictive Value: 25%
- False Positive Rate: 70%
- PSA >5.0 ng/ml
- Lower likelihood of Prostate Cancer "Cure"
VIII. Interpretation: PSA values predict Prostate size
-
Prostate size predicts BPH response to certain therapy
- 5a-Reductase Inhibitors (e.g. Finasteride) work best if Prostate >40 ml in volume
- PSA values suggesting Prostate >40 ml volume (Test Sensitivity and Specificity >70%)
- Age 50-59: PSA >1.6 ng/ml
- Age 60-69: PSA >2.0 ng/ml
- Age 70-79: PSA >2.3 ng/ml
- Roehrborn (1999) Urology 53(3):581-9 [PubMed]
IX. Prognosis: Prognostic Predictive Value of PSA
- PSA with associated Prostatectomy findings
- PSA <= 4.0 ng/ml
- Organ limited Prostate Cancer in 64%
- PSA 4.0-10.0 ng/ml
- Organ limited Prostate Cancer in 50%
- PSA 10.0 to 20.0 ng/ml
- Organ limited Prostate Cancer in 35%
- PSA >100 ng/ml
- Predicts bone metastases in 74% of cases
- PSA <= 4.0 ng/ml
- PSA in combination with Rectal Exam and biopsy
- PSA < 10 ng/ml (Non-palpable, Low Gleason grade)
- Organ limited disease in 60%
- PSA >20 ng/ml (Palpable, Gleason poor-moderate differentiated)
- Organ limited disease in 10%
- PSA < 10 ng/ml (Non-palpable, Low Gleason grade)
X. Management: Increased PSA
- Recheck elevated PSA (>4 ng/ml) in 3 months
- Transient PSA increase (e.g. due to BPH, Prostatitis) will normalize on recheck in 25 to 40% of patients
- Antibiotics are not recommended for elevated PSA unless symptomatic Prostatitis is present
- Additional Testing to consider on consistently elevated PSA (to further risk stratify to those who need biopsy)
- Multiparametric MRI (see Prostate Cancer)
- PSA Kinetics
- Biomarkers
- Blood Biomarkers (e.g. 4Kscore, isoPSA, Proclarix)
- Urine Biomarkers (e.g. PCA3, MPS, SelectMDx)
- Farha (2022) Ther Adv Urol 14:17562872221103988 +PMID: 35719272 [PubMed]
- MyProstateScore (MPS)
- Consider in patients referred for Prostate biopsy
- Estimates risk of Prostate Cancer using 2 urinary biomarkers
- Prostate CancerAntigen 3 (PCA3)
- TMPRSS2:ERG Gene Fusion
- Cost of $760 is not covered by Medicare or medicaid
- However private insurance may cover
- References
- Balloga (2022) Am Fam Physician 105(5): 542-3
-
Prostate Biopsy indications
- PSA >4 ng/ml or
- PSA 2.5 to 4.0 ng/ml and Prostate Cancer Risk Factor or
- Free PSA <8% of total PSA or
- Rapid PSA increase in one year
- Baseline PSA <4 ng/ml and PSA increase by more than 0.35 ng/ml in last year or
- Baseline PSA 4-10 ng/ml and PSA increase by more than 0.75 ng/ml in last year
XI. References
- Brawer (1995) CA Cancer J Clin 45(3):148-64 [PubMed]
- Gann (1995) JAMA 273(4):289-94 [PubMed]
- Lefevre (1998) Am Fam Physician 58(2): 432-8 [PubMed]
- Luttge (1996) Postgrad Med 100(3): 90-102 [PubMed]
- Mistry (2003) J Am Board Fam Pract 16(2): 95-101 [PubMed]
- Mohan (2011) Am Fam Physician 84(4): 413-20 [PubMed]
- Mulhem (2015) Am Fam Physician 92(8): 683-8 [PubMed]
- Roehrborn (1999) Urology 53(3):473-80 [PubMed]
- Roehrborn (1999) Urology 53(3):581-9 [PubMed]
- Slawin (1995) CA Cancer J Clin 45(3):134-47 [PubMed]
- Thompson (2004) N Engl J Med 350:2239-46 [PubMed]
- Vashi (1997) Mayo Clin Proc 72:337-44 [PubMed]
- Wilbur (2008) Am Fam Physician 78(12): 1377-4 [PubMed]
- Xu (2024) Am Fam Physician 110(5): 493-9 [PubMed]
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Related Studies
Definition (NCI_NCI-GLOSS) | A protein made by the prostate gland and found in the blood. Prostate-specific antigen blood levels may be higher than normal in men who have prostate cancer, benign prostatic hyperplasia (BPH), or infection or inflammation of the prostate gland. |
Definition (NCI) | Prostate-specific antigen (261 aa, ~29 kDa) is encoded by the human KLK3 gene. This protein plays a role in both proteolysis and seminal fluid liquefaction. |
Definition (MSH) | A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. |
Definition (CSP) | a tissue kallikrein related sequence enzyme used as a biomarker for prostate cancer or benign prostate hyperplasia. |
Concepts | Amino Acid, Peptide, or Protein (T116) , Enzyme (T126) , Immunologic Factor (T129) |
MSH | D017430 |
SnomedCT | 102687007, 130634002, 143526001, 166158002 |
CPT | 1011648 |
LNC | LP18193-0, MTHU001466 |
English | Prostate-Specific Antigen, Prostate Specific Antigen, Semenogelase, Seminin, gamma Seminoprotein, gamma-Seminoprotein, PSA-Prostate specific antigen, HK 003 KALLIKREIN, KALLIKREIN HK 003, P-30 antigen, prostate specific antigen, gamma seminoprotein, Kallikrein hK3, Kallikrein, hK3, hK3 Kallikrein, Prostate-Specific Antigen [Chemical/Ingredient], prostate specific antigen (PSA), prostate specific ag, psa antigen, Kallikrein-3, EC 3.4.21.77, Semenogelase (substance), Prostate specific antigen (procedure), Prostate specific Ag, Prostate specific Antigen, Prostate specific antigen (PSA), Prostate-specific antigen, prostate-specific antigen, PSA, Prostate specific antigen, PSA - Prostate specific antigen, Prostate specific antigen (substance), Antigen, Prostate-Specific, Gamma-Seminoprotein, KLK3, P-30 Antigen, Prostate Specific Antigen Preproprotein |
Swedish | Prostataspecifikt antigen |
Czech | prostatický specifický antigen, specifický antigen nádorů prostaty, PSA |
Spanish | APE - antígeno prostático específico, seminina, semenogelasa, antígeno P - 30, semenogelasa (sustancia), Antígeno Específico de la Próstata, Antígeno Próstata-Específico, antígeno prostático específico (sustancia), antígeno prostático específico, Antígeno Prostático Específico, Calicreína hK3, gamma Seminoproteína |
Finnish | Prostataspesifinen antigeeni |
Russian | PROSTATY SPETSIFICHESKII ANTIGEN, KALLIKREIN HK3, PREDSTATEL'NOI ZHELEZY SPETSIFICHESKII ANTIGEN, ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ СПЕЦИФИЧЕСКИЙ АНТИГЕН, ПРОСТАТЫ СПЕЦИФИЧЕСКИЙ АНТИГЕН, КАЛЛИКРЕИН HK3 |
French | Antigène spécifique de la prostate, Kallikréine hK3, Semenogelase, Antigène PSA, gamma-Séminoprotéine, Kallikréine-3, Séminine, Kallikréine-3 humaine |
German | HK 003 KALLIKREIN, KALLIKREIN HK 003, Antigen, prostataspezifisches, Kallikrein,hK3-, Prostataspezifisches Antigen, hK3-Kallikrein, Gamma-Seminoprotein, PSA |
Polish | Antygen swoisty dla prostaty, PSA, Antygen sterczowy specyficzny, Antygen specyficzny gruczołu krokowego, Specyficzny antygen prostaty, Swoisty antygen sterczowy |
Croatian | PSA, PROSTATA SPECIFIČNI ANTIGEN |
Japanese | 前立腺特異抗原, セメノゲラーゼ, ガンマ-セミノプロテイン, ガンマセミノプロテイン, 前立腺特異性抗原, γ-セミノプロテイン, 抗原-前立腺特異, 抗原-前立腺特異性 |
Norwegian | PSA-test |
Portuguese | PSA, Antígeno Específico da Próstata, Antígeno Prostático Específico, Calicreína hK3, gama-Seminoproteína, hK3 Calicreína |
Italian | Antigene specifico della prostata |
Ontology: prostate cancer prevention (C0281413)
Concepts | Therapeutic or Preventive Procedure (T061) |
English | Prostate Cancer Prevention, cancer prevention prostate, cancer prostate prevention, prevention prostate cancer, prevention of prostate cancer, prostate cancer prevention, Prevention of Prostate Cancer |