Aiding in distinguishing prostate cancer from benign prostate conditions in men with prostate-specific antigen (PSA) concentrations in the 4 to 10 ng/mL range and digital rectal examination (DRE) findings that are not suspicious for cancer
Calculation of prostate health index (phi) as a part of a reflex test when PSA concentrations are between 4 and 10 ng/mL
Prostate health index (phi) may be used to determine the probability of prostate cancer on biopsy in men with total prostate-specific antigen (PSA) in the 4.0 to 10.0 ng/mL range.
| Test Id | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| PHI13 | Prostate Health Index (phi) Reflex | No | No |
If the initial PSA concentration is between 2.0 and 10.0 ng/mL, then free PSA and [-2]pro-PSA isoform results will be reported.
If the initial PSA concentration is between 4.0 and 10.0 ng/mL, then the percent free PSA result and prostate health index (phi) will be calculated and reported.
If the initial PSA concentration is between 2.0 and 4.0 ng/mL, then the percent free PSA result and prostate health index (phi) will not be calculated or reported.
Immunoenzymatic Assay
P2PSA
PHI
Prostate Health Index
Pro-2-PSA
If the initial PSA concentration is between 2.0 and 10.0 ng/mL, then free PSA and [-2]pro-PSA isoform results will be reported.
If the initial PSA concentration is between 4.0 and 10.0 ng/mL, then the percent free PSA result and prostate health index (phi) will be calculated and reported.
If the initial PSA concentration is between 2.0 and 4.0 ng/mL, then the percent free PSA result and prostate health index (phi) will not be calculated or reported.
Serum Red
Patient Preparation:
1. Specimens for testing should be collected prior to prostate manipulations such as digital rectal examination (DRE), prostatic massage, transrectal ultrasound (TRUS), and prostatic biopsy.
2. A 6-week waiting period between needle biopsy and specimen collection is recommended.
3. Specimens should not be collected from patients receiving therapy with high biotin (vitamin B7) doses (ie, >5 mg/day) until at least 8 hours following the last biotin administration.
Collection Container/Tube: Red top (serum gel/SST are not acceptable)
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions: Centrifuge, aliquot serum into plastic vial, and refrigerate serum within 3 hours of collection. Freeze sample within 24 hours of collection and send frozen.
If not ordering electronically, complete, print, and send an Oncology Test Request (T729)
0.75 mL
| Gross hemolysis | Reject |
| Gross icterus | Reject |
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum Red | Frozen | 150 days |
Aiding in distinguishing prostate cancer from benign prostate conditions in men with prostate-specific antigen (PSA) concentrations in the 4 to 10 ng/mL range and digital rectal examination (DRE) findings that are not suspicious for cancer
Calculation of prostate health index (phi) as a part of a reflex test when PSA concentrations are between 4 and 10 ng/mL
If the initial PSA concentration is between 2.0 and 10.0 ng/mL, then free PSA and [-2]pro-PSA isoform results will be reported.
If the initial PSA concentration is between 4.0 and 10.0 ng/mL, then the percent free PSA result and prostate health index (phi) will be calculated and reported.
If the initial PSA concentration is between 2.0 and 4.0 ng/mL, then the percent free PSA result and prostate health index (phi) will not be calculated or reported.
Prostate-specific antigen (PSA) is a glycoprotein produced by the prostate gland, the lining of the urethra, and the bulbourethral gland. Normally, very little PSA is secreted in the blood. In conditions of increased glandular size and tissue damage, PSA is released into circulation. Measurement of serum PSA is useful for determining the extent of prostate cancer and assessing the response to prostate cancer treatment. PSA is also used as a screening tool for prostate cancer detection, although its use in screening has become controversial in recent years. While an elevated serum PSA is associated with prostate cancer, a number of benign conditions, such as benign prostatic hyperplasia (BPH) and prostatitis might lead to elevated serum PSA concentrations. As a consequence PSA lacks specificity for prostate cancer detection.
Several PSA isoforms have been identified that can further increase the specificity of PSA for prostate cancer. In particular, the [-2] form of proPSA (p2PSA) shows improved performance over either total or free PSA for prostate cancer detection on biopsy. The prostate health index (phi) is a formula that combines all 3 PSA forms (total PSA, free PSA, and p2PSA) into a single score. phi is calculated using the following formula: (p2PSA/free PSA) x square root of PSA.
In a multicenter study that compared the performance of PSA, free PSA, p2PSA, and phi in men undergoing prostate biopsy due to a serum PSA concentration between 4 and 10 ng/mL, phi was the best predictor of any prostate cancer, high-grade cancer, and clinically significant cancer. At 95% clinical sensitivity, the clinical specificity of phi was 16.0%, compared to 8.4% for free PSA and 6.5% for PSA.
Prostatic biopsy is required for diagnosis of cancer.
Females: Not applicable
PROSTATE-SPECIFIC ANTIGEN (PSA)
Males:
| Age | Reference range |
| <40 years | < or =2.0 ng/mL |
| 40-49 years | < or =2.5 ng/mL |
| 50-59 years | < or =3.5 ng/mL |
| 60-69 years | < or =4.5 ng/mL |
| 70-79 years | < or =6.5 ng/mL |
| > or =80 years | < or =7.2 ng/mL |
PERCENT FREE PSA
Males:
When PSA is in the range of 4-10 ng/mL
| % Free PSA | Probability of cancer |
| < or =10% | 56% |
| 11-15% | 28% |
| 16-20% | 20% |
| 21-25% | 16% |
| >25% | 8% |
PROSTATE HEALTH INDEX (phi)
Males:
When PSA is in the range of 4-10 ng/mL
| phi range | Probability of cancer | 95% Confidence interval |
| 0-26.9 | 9.8% | 5.2-15.4% |
| 27.0-35.9 | 16.8% | 11.3-22.2% |
| 36.0-54.9 | 33.3% | 26.8-39.9% |
| > or =55.0 | 50.1% | 39.8-61.0% |
Prostate health index (phi) may be used to determine the probability of prostate cancer on biopsy in men with total prostate-specific antigen (PSA) in the 4 to 10 ng/mL range. Low phi scores are associated with a lower probability of finding prostate cancer on biopsy and higher phi scores are associated with an increased probability of finding prostate cancer on biopsy. The choice of an appropriate phi score to be used in guiding clinical decision-making may vary for each patient and may depend on other clinical factors or on family history of disease. The table below indicates the probability of finding prostate cancer on biopsy when PSA is the in range of 4 to 10 ng/mL and may be used as guidance for interpreting the phi score.
| phi range | Probability of cancer | 95% Confidence interval |
| 0-26.9 | 9.8% | 5.2%-15.4% |
| 27.0-35.9 | 16.8% | 11.3%-22.2% |
| 36.0-54.9 | 33.3% | 26.8%-39.9% |
| 55.0+ | 50.1% | 39.8%-61.0% |
Specimens for [-2]pro-prostate-specific antigen (p2PSA) testing should be collected prior to prostate manipulations such as digital rectal examination (DRE), prostatic massage, transrectal ultrasound (TRUS), and prostatic biopsy. DRE may cause a transient increase in p2PSA, free PSA, and PSA.
Transrectal needle biopsy has also been shown to cause transient increases in p2PSA, free PSA, and PSA elevations, thus a 6-week waiting period between needle biopsy and p2PSA, free PSA, and PSA sampling is recommended.
The prostate health index (phi) results should be interpreted in light of the total clinical presentation of the patient, including symptoms, clinical history, data from additional tests, and other appropriate information. phi should not be interpreted as absolute evidence for the presence or absence of prostate cancer. Elevated PSA concentrations, increased phi, or decreased free PSA may be observed in patients with nonmalignant disorders, as well as those with prostate cancer.
Routine use of 5 alpha-reductase inhibitor drugs typically lower PSA, free PSA, and p2PSA levels in patients. Other drugs used to treat benign prostatic hyperplasia (BPH) may also affect PSA levels. Care should be taken in interpreting results from patients taking these drugs.
The use of the prostate health index (phi) has not been validated when PSA values are outside of the range of 4 to 10 ng/mL.
In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies (HAMA) or heterophile antibodies), which may cause interference in some immunoassays. Caution should be used in interpretation of results and the laboratory should be alerted if the result does not correlate with the clinical presentation.
1. Catalona WJ, Partin AW, Sanda MG, et al: A multicenter study of [-2]pro-prostate-specific antigen combined with prostate-specific antigen and free prostate-specific antigen for prostate cancer detection in the 2.0 to 10.0 ng/mL prostate-specific antigen range. J Urol. 2011 May;185:1650-1655
2. Pecoraro V, Roli L, Plebani M, Trenti T: Clinical utility of the (-2)proPSA and evaluation of the evidence: a systematic review. Clin Chem Lab Med. 2016 Jul 1;54(7):1123-1132. doi: 10.1515/cclm-2015-0876
3. Loeb S, Catalona WJ: The Prostate Health Index: a new test for the detection of prostate cancer. Ther Adv Urol. 2014 Apr;6(2):74-77. doi: 10.1177/1756287213513488
Prostate Specific Antigen (PSA):
The Access Hybritech prostate-specific antigen (PSA) assay is a 2-site immunoenzymatic (sandwich) assay. A sample is added to mouse monoclonal anti-PSA alkaline phosphatase conjugate and paramagnetic particles coated with a second mouse monoclonal anti-PSA antibody. The PSA in the sample binds to the immobilized monoclonal anti-PSA on the solid phase while the monoclonal anti-PSA alkaline phosphatase conjugate reacts with a different antigenic site on the sample PSA. After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. The chemiluminescent substrate Lumi-Phos* 530 is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of PSA in the sample and is determined from a stored, multipoint calibration curve.(Instruction manual: Beckman Coulter Access Total PSA Instructions for Use. Beckman Coulter Inc; 2019)
Free Prostate Specific Antigen:
The Access Hybritech free PSA assay is a 2-site immunoenzymatic (sandwich) assay. A sample is added to mouse monoclonal anti-free PSA-alkaline phosphatase conjugate and paramagnetic particles coated with a second mouse monoclonal anti-PSA antibody. The free PSA in the sample binds to the immobilized monoclonal anti-PSA on the solid phase while the monoclonal anti-free PSA-alkaline phosphatase conjugate reacts with different antigenic sites on the free PSA molecule. After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. The chemiluminescent substrate Lumi-Phos 530 is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of free PSA in the sample and is determined from a stored, multipoint calibration curve.(Instruction manual: Beckman Coulter Access Free PSA Instructions for Use. Beckman Coulter Inc; 2019)
[-2]ProPSA:
The Access Hybritech p2PSA is a 2-site immunoenzymatic (sandwich) assay. A sample is added to mouse monoclonal anti-PSA-alkaline phosphatase conjugate, paramagnetic particles coated with a mouse monoclonal anti-[-2]proPSA antibody, and a blocking reagent. The [-2]proPSA in the sample binds to the immobilized monoclonal anti-[-2]proPSA on the solid phase while the monoclonal anti-PSA-alkaline phosphatase conjugate reacts with different antigenic sites on the [-2]proPSA molecule. After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. The chemiluminescent substrate Lumi-Phos*530 is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of [-2]proPSA in the sample and is determined from a stored, multipoint calibration curve.(Instruction manual: Beckman Coulter Access P2PSA Instructions for Use. Beckman Coulter Inc; 2019)
The free PSA concentration is divided by the total PSA to derive the percent free PSA. The percentage is provided only when the total PSA is in the range of 4.0 to 10.0 ng/mL.
Prostate health index (phi) is calculated in the laboratory information system, SCC Soft. phi is provided only when the total PSA is in the range of 4.0 to 10.0 ng/mL.
Monday through Saturday
This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.
84153 - Total PSA
84154 - Free PSA (if appropriate)
86316 - [-2]ProPSA (if appropriate)
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| PHI11 | Prostate Health Index Reflex, S | 53764-7 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| PHI12 | Prostate Specific Antigen, S | 83112-3 |