Test Catalog

Test ID: PHI11    
Prostate Health Index (phi), Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Aids in distinguishing prostate cancer from benign prostate conditions in men with total 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

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test begins with the analysis of prostate-specific antigen (PSA). If the PSA is between 2.0 and 10.0 ng/mL, then the reflex test (PHI13) will be performed.

 

If the initial PSA is between 2.0 and 10.0 ng/mL, then free PSA and [-2]ProPSA will be reported.

If the initial PSA is between 4.0 and 10.0 ng/mL, then the percent free PSA and prostate health index (phi) will be calculated and reported.

If the initial PSA is between 2.0 and 4.0 ng/mL, then the percent free PSA and prostate health index (phi) will not be calculated or reported.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 increase glandular size and/or 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 (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.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Females: Not applicable

 

TOTAL 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 total 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 total 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%

Interpretation Provides information to assist in interpretation of the test results

Prostate health index (phi) may be used to determine the probability of prostate cancer on biopsy in men with total 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 clinically 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%

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Specimens for [-2]ProPSA (p2PSA) testing should be drawn 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.

Clinical Reference Recommendations for in-depth reading of a clinical nature

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, el al: Clinical utility of the (-2)proPSA and evaluation of the evidence: a systematic review. Clin Chem Lab Med 2015 Nov 26. pii available at /j/cclm.ahead-of-print/cclm-2015-0876/cclm-2015-0876.xml. 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