Test Center

My Recent Searches

  • No Recent Search.

My Tests Viewed

  • No Test Viewed.

Prostate Cancer: Laboratory Support for Screening, Diagnosis, and Management

Prostate Cancer: Laboratory Support for Screening, Diagnosis, and Management

Clinical Focus

Prostate Cancer

Laboratory Support for Screening, Diagnosis, and Management

  

Contents:

Clinical Background

Individuals Suitable for Testing

Test Availability  - Table 1

Test Application - Table 2 - Table 3 - Table 4 - Table 5

 Figure 1 - Figure 2

Sample Collection Considerations  - Table 6

Test Interpretation Table 7 - Table 8 - Table 9

Appendix 1

Appendix 2

References
 

Clinical Background [return to contents]

Prostate cancer is the most commonly detected cancer in men in the United States, affecting approximately 1 out of every 6 men.1 It is the second leading cause of cancer death among men in the United States.1 Although prostate cancer is thought to begin when men are in their thirties and forties, it is most often diagnosed after age 65. Prevalence increases with age.1 

Prostate cancer typically progresses slowly over the course of 15 or more years. When organ-confined, it is potentially curable by radical prostatectomy or radiation therapy (ie, external-beam radiation or brachytherapy). Such therapy, however, may be associated with significant morbidity, including urinary incontinence and erectile dysfunction. For patients with a good prognosis, watchful waiting may be a better alternative. For metastatic disease, therapeutic options include androgen ablation, adjuvant hormone-radiotherapy, or chemotherapy. Prognosis for patients with metastatic disease is poor, nonetheless.

Laboratory testing can assist with screening, diagnosis, staging, prognosis, detection of residual or recurrent disease, and therapeutic monitoring. The primary test used for these purposes is prostate-specific antigen (PSA). PSA is an androgen-regulated, kallikrein-like serine protease produced by normal and malignant epithelium in the prostate as well as in the breast and salivary glands. When secreted into seminal fluid, PSA liquifies the gel-forming proteins in semen. The normal function of PSA in breast and salivary glands is not known.

Individuals Suitable for Testing [return to contents]

Screening

  • Average-risk men ≥40 years of age who have a life expectancy of ≥10 years

Patients should be actively involved in the decision to undergo prostate cancer screening and should be fully informed of the potential benefits, limitations, and risks associated with screening. Screening is not recommended for the general population. Recommendations regarding the age at which to start screening (and whether to screen at all) vary; see Test Application, Screeningsection. Screening is generally only appropriate for men who would be candidates for treatment (including active surveillance) if a potentially curable prostate cancer diagnosis was established (candidacy based on age, comorbidity, and an interest in being treated).

Other Applications

  • Symptomatic men

  • Men with a prostate cancer diagnosis

  • Men who are undergoing or have completed prostate cancer therapy

Test Availability [return to contents]

Laboratory tests that can be used to support screening, diagnosis, and management of prostate cancer are listed in Table 1.

Table 1. Laboratory Tests for Screening, Diagnosis, and Management of Prostate Cancer

Available Tests Method Description

Primary Tests

Free PSA

Total PSA

PSA Post-prostatectomy

PSA Post-prostatectomy  with HAMA Treatment

 

ICMA

ICMA

ICMA

ICMA

 

Includes free, total, and % free/total PSA

Analytical sensitivity: 0.1 ng/mL

Analytical sensitivity: 0.01 ng/mL

Analytical sensitivity: 0.01 ng/mL; eliminates interference from human anti-mouse antibodies (HAMA) that may be present in patients who have received mouse monoclonal antibody preparations

Secondary Tests

bcl-2

CellSearch® Circulating Tumor Cell, Prostate

DNA Cell Cycle Analysis

E-cadherin

FISH, Prostate Cancer

 

IHC

Immunomagnetic labeling/Immuno-fluorescent detection

Flow cytometry

IHC

FISH

 

Detects bcl-2 expression in tissue

Detects circulating tumor cells

Includes ploidy status and % S-phase in tissue

Detects E-cadherin protein in tissue

Detects 8p22 (lipoprotein lipase [LPL]) deletion, chromosome 8 aneusomy, 8q24 (C-MYC gene) gain, 7q31 deletion, and chromosome 7 aneusomy

Ki-67 (MIB-1)

p53 Oncoprotein

Testosterone, Total

IHC

IHC

LC/MS/MS

Detects MIB-1 protein in tissue

Detects mutated p53 oncoprotein in tissue

Suitable for measuring the low levels of testosterone associated with gonadotropin-releasing hormone analogs and antiandrogen therapies

ICMA, immunochemiluminometric assay; IHC, immunohistochemistry; FISH, fluorescence in situ hybridization;

LC/MS/MS, liquid chromatography, tandem mass spectrometry.

Test Application [return to contents]

Screening

Prostate cancer screening remains controversial. Proponents point to the high incidence, absence of preventive agents, ease of screening, potential curability of organ-confined disease, and lack of effective therapy for advanced disease. Opponents note the slow progression of many tumors, high number of false positives, overdiagnosis of indolent disease, and treatment side effects that diminish quality of life. Since screening commenced in the late 1980s, the incidence of metastatic disease has decreased while that of organ-confined, moderately differentiated disease has increased.2 This suggests screening has been effective in identifying clinically significant, potentially curable disease while reducing the incidence of incurable disease. Mortality has decreased as well,3 but this reduction may be due to factors other than screening and early detection.4 Results from the largest clinical trials to assess the effect of screening on prostate cancer mortality have reported conflicting results.5 In the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening study, prostate cancer–specific mortality was low in both the screening (2.0/10,000 person-years) and control (1.7/10,000 person-years) groups after 7 years of follow-up, suggesting that serial screening with PSA and DRE did not reduce prostate cancer-specific mortality.6 However, a relatively high proportion of men assigned to the control arm in this study underwent prostate cancer screening (52% by year 6) on their own, which could have reduced the study’s power to detect a significant effect from screening.7 In contrast to PLCO, the European Randomized Study of Screening for Prostate Cancer (ERSPC) study reported a 20% reduction in prostate cancer mortality from PSA screening.8

Current guidelines that provide guidance on timing of prostate cancer screening note the importance of informed decision-making by the patient, in collaboration with the healthcare provider.9-13 The American Cancer Society (ACS) has recommended that men with a life expectancy of at least 10 years should be informed of the risks and benefits of prostate cancer screening beginning at age 50, or earlier (eg, age 45 years) for African American men and those with an affected first-degree relative.9 The American Urological Association (AUA) 1) recommends shared decision-making re PSA screening for men aged 55 to 69 years who have a life expectancy of ≥10-15 years; 2) prefers a screening interval of ≥2 years; but 3) does not rule out PSA screening in younger and older men who are at high risk and may benefit.10 The National Comprehensive Cancer Network (NCCN) recommends offering baseline PSA testing to well-informed men beginning at age 40 years.11 NCCN recommendations for follow-up testing (PSA or PSA and DRE at specified frequencies) then depend on the PSA concentration and patient age, life expectancy, and risk of prostate cancer. Furthermore, NCCN strategies incorporate use of free PSA and PSA velocity (PSAV; see, “Diagnosis” section below) when making decisions to perform prostate biopsy; the NCCN notes that PSAV is not useful when the PSA level is >10 ng/mL. The American College of Preventive Medicine has not found sufficient evidence to recommend routine prostate cancer screening,12 and the US Preventive Services Task Force (USPSTF) recommends against it.13

Diagnosis

Prostate cancer diagnosis begins with DRE and total PSA. If either is suggestive of cancer, a transrectal ultrasound (TRUS)-guided biopsy is generally the next step (Figure 1). Investigators have attempted to reduce the number of unnecessary biopsies (ie, enhance the specificity of total PSA testing) without reducing the cancer detection rate. To this end, age-specific PSA reference ranges have been proposed as well as calculations of the prostate-specific antigen density (PSAD), PSAV, and the percentage of free to total PSA (% free PSA). Although conflicting studies have been published regarding the benefit of these strategies, guidelines for use and interpretation are provided herein for physicians who want to use them.

Figure 1. Indications for prostate biopsy following DRE and total PSA screen.

Age-related Reference Ranges

Serum PSA levels increase with increasing age and prostate size in healthy men. Use of age-related reference ranges (Table 2) theoretically would increase sensitivity in younger men and increase specificity (reducing unnecessary biopsies) in older men. Use of age-related reference ranges has not been widely adopted due to studies demonstrating diminished sensitivity in older men.18 Some investigators support the use of age-specific ranges only in men younger than 60 years of age.19

Table 2. Age- and Race-specific Reference Ranges

Age

Years

Free PSA14

(ng/mL)

Complexed PSA14

(ng/mL)

Total PSA (ng/mL)

Causasians15

African-Americans16

Asians17

40-49

<0.5

<1.0

<2.5

<2.0

<2.0

50-59

<0.7

<1.5

<3.5

<4.0

<3.0

60-69

<1.0

<2.0

<4.5

<4.5

<4.0

70-79

<1.2

<3.0

<6.5

<5.5

<5.0

PSA Density

Use of PSAD combines total PSA level with prostate gland volume to assess the probability of a positive biopsy. It is defined as the total PSA divided by the prostate gland volume as determined by TRUS. Levels ≤0.15 ng/mL/cm3 have been associated with a low likelihood of prostate cancer. PSAD has also been associated with tumor aggressiveness. Although not widely used, partly because of the need for ultrasound measurement of the prostate, PSAD may provide additional useful information for patient evaluation11; current AUA guidelines consider PSAD as a secondary test with potential utility for determining whether to perform biopsy.10

PSA Velocity

In individuals with pre-clinical prostate cancer, there is an accelerated increase in serum PSA levels beginning 7 to 9 years before diagnosis. Thus, evaluation of the rate of change in PSA levels (ie, PSAV) may assist in early detection of cancer. Carter et al found that PSAV more accurately detected prostate cancer (sensitivity 72%, specificity 90%) than total PSA (sensitivity 78%, specificity 60%).20 Application of PSAV in routine screening remains controversial. Current NCCN guidelines incorporate use of PSAV in the early detection of prostate cancer, and AUA guidelines also include PSAV as a factor that may be considered when evaluating patients for biopsy.10 ACS guidelines do not recommend use of PSAV,9 on the basis of large-scale studies finding little or no benefit of PSAV in predicting a positive biopsy or significant prostate cancer.21,22 Instructions for calculating PSAV are provided in Appendix 1.

% Free PSA

Since the overlap in total PSA levels is substantial among men with benign prostatic hyperplasia (BPH) and prostate cancer, use of % free PSA may help distinguish BPH from cancer. PSA circulates in both free and bound, or complexed, forms. Immunoreactive PSA is primarily bound to the α1-antichymotrypsin (ACT) protease inhibitor; thus, PSA levels in healthy individuals mainly reflect complexed PSA. Individuals with benign prostatic hypertrophy (BPH) tend to have lower proportions of complexed PSA (ie, higher % free PSA) relative to those with prostate cancer. Studies using % free PSA (Table 3) have shown improved specificity in men with borderline total PSA levels (4.1–10.0 ng/mL), resulting in a 13% to 37% reduction in negative biopsies. Furthermore, in men with “normal” PSA levels (2.6 to 4.0 ng/mL) use of % free PSA may increase the sensitivity of PSA by detecting cancers that would have been missed by total PSA alone.23,26 NCCN guidelines approve use of % free PSA to determine need for biopsy in selected men with PSA levels in the 4.1–10.0 ng/mL or 2.6–4.0 ng/mL range.11

Table 3. Improved Specificity with % Free PSA

Reference Free PSA
Cut Point (%)
Sensitivity
(%)
Negative Biopsies
Avoided (%)

Catalona WJ, et al23

27a

90 18

Catalona WJ, et al24

25b

95 20

Luderer AA, et al25

25b

100 31

Roehl KA, et al26

25c

85 19

Van Iersel MP, et al27 

25b

90 25

Vashi AR, et al28

24b

95 13

Catalona WJ, et al29

23b

90 30

Catalona WJ, et al30

23b

90 31

Bangma CH, et al31

20b

89 37

a Total PSA 2.6–4.0 ng/mL.

b Total PSA 4.1–10.0 ng/mL.

c Total PSA 2.6–4.0 ng/mL; using a cut point of 30%, sensitivity was 93% but only 9% of negative biopsies could be avoided.

Staging

Tumor staging provides prognostic information and assists in selection of the therapeutic modality. In general, total PSA levels increase with increasing stage, although there is significant overlap (Table 4). A combination of markers has proved to be more useful than any single marker. Nomograms using patient-specific clinical (TNM) stage, biopsy data (eg, Gleason score), and pretreatment total PSA level are commonly used.33 Data from various imaging techniques (eg, bone scan) can also be used.

Table 4. Relation Between Total PSA Concentration and Localized Disease32

PSA ng/mL

Likelihood of Organ-confined Cancer (%)

<4.0

85

4.0–10.0

67

10.1–20.0

56

>20.0

30

Prognosis

The College of American Pathologists (CAP) and the World Health Organization (WHO) both recommend routine use of PSA as a prognostic factor in conjunction with TNM stage, Gleason score, and surgical margin status.34 The NCCN also recommends incorporating PSA levels when determining prognosis.35

PSA Kinetics

PSA kinetics are becoming more accepted for predicting disease-free survival, prostate cancer-related mortality, and local vs distant disease at time of biochemical relapse. These predictions are then used to help select appropriate therapeutic regimens.

The same PSAV used in the diagnosis of prostate cancer (see previous discussion) can be used to predict disease-free and cancer-related survival, irrespective of treatment. The cut points for interpretation, however are different; see Table 5  for the cut point used when determining prognosis. PSAV calculated from PSA levels obtained after primary therapy (eg, radical prostatectomy or radiotherapy) can help predict the extent of the recurrence (ie, local vs distant). The guidelines for interpretation are listed in Table 5.

PSA doubling time (PSADT) is the time required for total PSA levels to double. Instructions for calculating PSADT are provided in Appendix 2. Similar to PSAV, PSADT calculated using PSA concentrations obtained before diagnosis can be used to predict survival. PSADT calculated using PSA levels obtained after primary therapy can be used to predict both survival and the extent of the recurrence (Table 5).

The time to biochemical recurrence following primary therapy (eg, radical prostatectomy or radiation therapy) provides prognostic information regarding the extent of the recurrence (local vs distant) (Table 5). Following radical prostatectomy, biochemical recurrence is defined as failure to achieve undetectable PSA or an increase in PSA on at least two occasions post-prostatectomy.35 Following radiation therapy, biochemical recurrence is defined as an increase in PSA of at least 2 ng/mL above the nadir.35

Table 5. Use of PSA Kinetics in Assessing Prognosis37-42

PSA Kinetic Result Prognosis
PSADT

Pre diagnosis

<18 mo Decreased cancer-related survival

After primary therapy

<3 mo

10 mo

<10 mo

Decreased cancer-related survival

Recurrence likely to be local

Recurrence likely to be distant

PSAV

Pre diagnosis

>2.0 ng/mL/y

Decreased disease-free survival

Decreased cancer-related survival

After primary therapy

<0.75 ng/mL/y

>0.75 ng/mL/y

Recurrence likely to be local

Recurrence likely to be distant

Time to biochemical (PSA) recurrence after primary therapy

>2 y

2 y

Recurrence likely to be local

Recurrence likely to be distant

PSADT, PSA doubling time; PSAV, PSA velocity.

Initial Treatment Selection

PSA levels can be helpful in making initial treatment decisions when used in combination with TNM-stage, Gleason score, and life expectancy. Cut points most frequently used for such decision-making are 10 ng/mL and 20 ng/mL.35 PSA levels <20 ng/mL are associated with negative bone scans, and PSA levels <10 ng/mL are associated with local disease.

Therapeutic Monitoring, Residual and Recurrent Disease Detection

For men receiving active surveillance (ie, expectant management or watchful waiting), NCCN guidelines suggest that total PSA should be performed every 3 to 6 months for those with low-risk cancer and a life expectancy ≥10 years (or very low risk and a life expectancy ≥20 years); DRE should be performed at least annually in these patients. Because PSA kinetics may not provide accurate assessment of progression, frequent repeat biopsy (ie, up to once per year) may be appropriate.35 If life expectancy is <10 years, PSA testing should be performed at least every 6 months, with DRE at least annually.35

Following definitive therapy, ultrasensitive (post-prostatectomy) PSA levels help detect residual disease or document eradication of the tumor (Figure 2). Undetectable PSA or absence of rising PSA levels is the best indicator of total tumor eradication.45 A 6-month PSA testing interval (with annual DRE) is suggested for the first 5 years after curative treatment, followed by annual testing thereafter.34 For patients with metastatic disease, PSA testing (along with physical examination and DRE) should be performed every 3 to 6 months.35

Figure 2. Patient follow-up after radical prostatectomy.

Sample Collection Considerations [return to contents]

Serum PSA levels are affected by the relatively long half-life (2-3 days) of total PSA and various other factors. The adverse effects of many of these factors can be reduced or eliminated with proper timing of sample collection (Table 6). Furthermore, 3 analyses, each obtained from a separate collection, are recommended prior to biopsy to rule out effects of physiologic and assay variation.50

Table 6. Recommended Timing of Sample Collection46-49

Factor Effect on PSA Level Recommended Timing of Sample Collectiona

Cystoscopy

None or small

Prior to, or 24-48 hours after, procedure

DRE

None or small

Prior to the procedure

Ejaculation

48 hours after ejaculation

Prostate biopsy

Prior to, or 4-6 weeks after, biopsy

Prostate massage

2-fold

Prior to the procedure

Prostatitis

8 weeks after end of treatment

TRUS

None or small

Prior to, or 24-48 hours after procedure

TURPb

Prior to, or 6 weeks after, surgery

Urethral catheterization

None

Anytime

Urinary retention

4 days after relief

DRE, digital rectal exam; TRUS, transrectal ultrasonography; TURP, transurethral resection of prostate.

a To reduce or eliminate effect on PSA level.

b Includes electrovaporization techniques.

Test Interpretation [return to contents]

Total PSA levels >4.0 ng/mL are generally considered elevated, although lower cut points are sometimes used in younger men11 (Table 2) and the AUA does not recommend a single value as a threshold for considering biopsy. Elevated levels may be associated with BPH, acute urinary retention, urinary tract infections (including acute prostatitis), prostatic intraepithelial neoplasia, and prostate cancer. Transient elevations may be observed following DRE, ejaculation, prostate biopsy, or surgery (Table 6).

A 50% or greater change in serial PSA levels is considered clinically significant.48 Decreases in PSA not related to prostate cancer can be caused by medication and herbal supplementation (Table 7).

Table 7. Pharmacologic Effects that Confound Interpretation of PSA Test Results9,51-55

Medication/Supplement

Clinical Indication

Effect on Total PSA

Finasteride

Male pattern hair loss (Propecia®)

BPH (Proscar®)

50% after 6-12 monthsa,b

Dutasteride (Avodart®)

BPH

~50% b

Terazosin

BPH

None

Antiandrogens (eg, flutamide, bicalutamide, megestrol

acetate)

Prostate cancer

50% for 3-14 months after

withdrawal of medication

Saw palmetto (Serenoa repens)

Herbal supplement for BPH and lower urinary tract symptoms

Possible , similar to finasteride

a May vary widely in individual men.

b % Free PSA not affected.

Screening and Diagnosis

Similar to other screening programs (eg, mammography), two-thirds of screened individuals with an elevated total PSA (>4.0 ng/mL) do not have prostate cancer (66% false-positive rate); however, most of the cancers that are detected are clinically localized (92%) and pathologically organ-confined (64%) and thus potentially curable.56 Approximately 90% are clinically significant tumors, being 1 cc or greater in size.23

Total PSA levels 4.0 ng/mL do not guarantee the absence of prostate cancer in asymptomatic individuals; 25% of men with cancer have a PSA level in this range. Indeed, there is no level of PSA at which clinically significant cancer does not occur (Table 8). Consequently, some proponents of screening recommend lowering the PSA cut point to 2.6 ng/mL58 and using % free PSA to reduce unnecessary biopsies. NCCN has adopted such a strategy.11

Table 8. Prevalence of Prostate Cancer in Men with PSA Levels <4.0 ng/mL57

PSA ng/mL

Prevalence (%) of Prostate Cancer

0–0.5

7

0.6–1.0

10

1.1–2.0

17

2.1–3.0

24

3.1–4.0

27

Among patients with borderline elevated PSA levels (4.1-10.0 ng/mL), approximately 25% will have cancer. Levels >10.0 ng/mL are associated with extracapsular cancer that is less likely to be curable.

Since free PSA is usually eliminated by the kidney, % free PSA can be increased in men with chronic renal failure and in those receiving dialysis. It can also be increased by DRE, prostate biopsy, and prostatectomy. False elevations can occur if the sample is collected prior to 48 to 72 hours after prostate manipulation.

Staging and Prognosis

Table 4 provides the risk of organ-confined prostate cancer associated with various concentrations of total PSA. Refer to Table 5 for suggested PSAV and PSADT cut points used to assign risk of local vs. distant recurrence and disease-free and cancer-related survival. Table 5 also includes a cut point based on time to PSA recurrence that predicts local vs. distant disease.

Therapeutic Monitoring, Residual and Recurrent Disease Detection

Following successful radical prostatectomy, total PSA levels should be undetectable. A rise in total PSA on at least 2 measurements post-prostatectomy is suggestive of biochemical recurrence,35 which can precede clinical recurrence by ≥5 years.

Following successful radiation therapy, PSA does not always reach undetectable levels; however, a nadir of 0.5 to 1.0 ng/mL is considered favorable. A rise in total PSA (≥2 ng/mL above nadir) indicates biochemical recurrence.35

Following successful antiandrogen therapy, there is an initial drop in PSA to normal or even undetectable levels. Relapse caused by androgen-independent tumor cells is characterized by castration levels of testosterone (<50 ng/mL) and 3 consecutive rises in PSA levels 2 weeks apart. Two of these increases should be 50% over the nadir level. Use of PSA for monitoring therapy in individuals with androgen-independent cancer is limited; however, a 50% decline from pretreatment levels is considered a sign of a better outcome, relative to a <50% decline, when maintained for 8 weeks.59

Additional interpretive information is provided in Table 9.

Table 9. Interpretation of Test Results11,20,24,26,36,45,57,60,61

Test

Result

Clinical Significance

Free PSAa

 

 

>30% of total PSA

21-30%

11-20%

1-10%

When total PSA is 2.6 to 4.0 ng/mL, probability for prostate cancer is:

20%

19%

25%

43%

  

   

When total PSA is 4.1-10.0 ng/mL, probability of prostate cancer is:

26% of total PSA

8%

Biopsy not recommended

21-25%

16-20%

11-15%

16% }
20% }

28% }

Indeterminate; consider other
factors before deciding to biopsy

0-10%

   

56%

  

Biopsy recommended

  

PSA Velocityb

<0.75 ng/mL/year
0.75 ng/mL/year

  

Low likelihood of prostate cancer

Suspicious for cancer; consider biopsy

  

Total PSAc

   

4.0 ng/mL

4.1–10.0 ng/mL

>10.0 ng/mL

20.0–29.9 ng/mL

30 ng/mL

         

Likelihood of prostate cancer:

15%

27%

59%

74%

96%

   

PSA, Post Prostatectomy

<0.02 ng/mL

Undetectable level of PSA; absence of recurrence

<0.10 ng/mL

Low likelihood of residual or recurrent cancer post radical prostatectomy

0.2 ng/mLd

Residual or recurrent cancer likely after radical prostatectomy

0.5-1.5 ng/mL

Consider 2nd line treatment with radiotherapye

a Not helpful in 2/3 of all men, ie, those who have % free PSA between 10% and 25%.

b See Table 5 for cut points associated with survival and local vs distant disease prognosis.

c See Table 8 for prostate cancer prevalence associated with PSA 4.0 ng/mL.

d NCCN guidelines recommend >0.3 ng/mL and rising on 2 or more measurements.35

e Initiate radiotherapy in patients with post prostatectomy recurrence while PSA is 1.5 ng/mL for best therapeutic response.

Appendix 1. PSA Velocity (PSAV) Calculations [return to contents]

PSAV can be calculated using linear regression.42 Alternatively, calculate PSAV using 3 consecutive PSA measurements20:

1. PSAV = [PSAt – PSAt-1] ÷ [yeart – yeart-1] where t is the most recent PSA level and t-1 is the

previous, consecutive measurement.

2. Average PSAV = [PSAVt + PSAVt-1] ÷ 2 where t is the most recent PSAV and t-1 is the previous,

consecutive PSAV.

Use PSA measurements from 3 samples collected over at least 18 to 24 months. All PSA test results should be generated using reagents and method from the same manufacturer.

Appendix 2. PSA Doubling Time (PSADT) Calculations [return to contents]

PSADT can be calculated using one of the following 2 methods44

1. PSADT = natural log of 2 (ie, 0.693) ÷ slope of the line derived from a plot of log[PSA] vs time

of PSA measurement.

2. PSADT = (natural log of 2)(time interval) ÷ (log[final PSA] – log[initial PSA]) where the time

interval is the period between initial and final PSA measurements.

References [return to contents]

  1. American Cancer Society. Cancer Facts & Figures 2013. Atlanta: American Cancer Society; 2013. Available at: http://www.cancer.org/docroot/STT/stt_0.asp. Accessed May 8, 2013.

  2. Farkas A, Schneider D, Perrotti M, et al. National trends in the epidemiology of prostate cancer, 1973 to 1994; evidence for the effectiveness of prostate-specific antigen screening. Urology. 1998;52:444-449.

  3. Brenner H, Arndt V. Long-term survival rates of patients with prostate cancer in the prostate-specific antigen screening era: population-based estimates for the year 2000 by period analysis. J Clin Oncol. 2005;23:441-447.

  4. Etzioni R, Legler JM, Feuer EJ, et al. Cancer surveillance series: interpreting trends in prostate cancer – Part III: quantifying the link between population prostate-specific antigen testing and recent declines in prostate cancer mortality. J Natl Cancer Inst. 1999;91:1033-1039.

  5. Chou R, Croswell JM, Dana T, et al. Screening for prostate cancer: a review of the evidence for the US Preventive Services Task Force. Ann Intern Med. 2011;155:762-771.

  6. Andriole GL, Crawford ED, Grubb RL 3rd, et al; PLCO Project Team. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310-1319..

  7. Crawford ED, Grubb R 3rd, Black A, et al. Comorbidity and mortality results from a randomized prostate cancer screening trial. J Clin Oncol. 2011;29:355-361.

  8. Schröder FH, Hugosson J, Roobol MJ, et al; ERSPC Investigators. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320-1328.

  9. Wolf AM, Wender RC, Etzioni RB, et al; American Cancer Society Prostate Cancer Advisory Committee. American Cancer Society guideline for the early detection of prostate canc-er: update 2010. CA Cancer J Clin. 2010;60:70-98.

  10. Carter HB, Albertsen PC, Barry MJ, et al. Early detection of prostate cancer: AUA guideline. http://www.auanet.org/common/pdf/education/clinical-guidance/Prostate-Cancer-Detection.pdf  April 2013. Accessed May 8, 2013.

  11. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™). Prostate cancer early detection, v.2.2012. Available at http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed May 8, 2013.

  12. Lim LS, Sherin K, ACPM Prevention Practice Committee. Screening for prostate cancer in US men: ACPM position statement on preventive practice. Am J Prev Med. 2008;34:164–170.

  13. U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. http://www.uspreventiveservicestaskforce.org/prostatecancerscreening/
    prostatefinalrs.htm. May 2012. Accessed May 8, 2013.

  14. Oesterling JE, Jacobsen SJ, Klee GG, et al. Free, complexed and total serum prostate specific antigen: the establishment of appropriate reference ranges for their concentrations and ratios. J Urol. 1995;154:1090-1095.

  15. Oesterling JE, Jacobsen SJ, Chute CG, et al. Serum prostate-specific antigen in a community-based population of healthy men. Establishment of age-specific reference ranges. JAMA. 1993;270:860-864.

  16. Morgan TO, Jacobsen SJ, McCarthy WF, et al. Age-specific reference ranges for serum prostate-specific antigen in black men. N Engl J Med. 1996;335:304-310.

  17. Oesterling JE, Kumamoto Y, Tsukamoto T, et al. Serum prostate-specific antigen in a community-based population of healthy Japanese men: lower values than for similarly aged white men. Br J Urol. 1995;75:347-353.

  18. Catalona WJ, Hudson MA, Scardino PT, et al. Selection of optimal prostate specific antigen cutoffs for early detection of prostate cancer: receiver operating characteristic curves. J Urol. 1994;152:2037-2042.

  19. Partin AW, Criley SR, Subong EN, et al. Standard versus age-specific prostate specific antigen reference ranges among men with clinically localized prostate cancer: a pathological analysis. J Urol. 1996;155:1336-1339.

  20. Carter HB, Pearson JD, Metter EJ, et al. Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. JAMA. 1992;267:2215-2220.

  21. Wolters T, Roobol MJ, Bangma CH, et al. Is prostate-specific antigen velocity selective for clinically significant prostate cancer in screening? European Randomized Study of Screening for Prostate Cancer (Rotterdam). Eur Urol. 2009;55:385-392.

  22. Vickers AJ, Wolters T, Savage CJ, et al. Prostate-specific antigen velocity for early detection of prostate cancer: result from a large, representative, population-based cohort. Eur Urol. 2009;56:753-760.

  23. Catalona WJ, Smith DS, Ornstein DK. Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Enhancement of specificity with free PSA measurements. JAMA. 1997; 277:1452-1455.

  24. Catalona WJ, Partin AW, Slawin KM, et al. Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease. A prospective multicenter clinical trial. JAMA. 1998;279:1542-1547.

  25. Luderer AA, Chen YT, Soriano TF, et al. Measurement of the proportion of free to total prostate-specific antigen improves diagnostic performance of prostate-specific antigen in the diagnostic gray zone of total prostate-specific antigen. Urology. 1995;46:187-194.

  26. Roehl KA, Antenor JOV, Catalona WJ. Robustness of free prostate specific antigen measurements to reduce unnecessary biopsies in the 2.6 to 4.0 ng/mL range. J Urol. 2002;168:922-925.

  27. Van Iersel MP, Witjes WPJ, Thomas CMG, et al. Review on the simultaneous detection of total prostate-specific antigen and free prostate-specific antigen. Prostate Suppl. 1996;7:48-57.

  28. Vashi AR, Wojno KJ, Henricks W, et al. Determination of the “reflex range” and appropriate cutpoints for percent free prostate-specific antigen in 413 men referred for prostatic evaluation using the AxSYM system. Urology. 1997;49:19-27.

  29. Catalona WJ. Clinical utility of measurement of free and total prostate-specific antigen (PSA): a review. Prostate Suppl. 1996;7:64-69.

  30. Catalona WJ, Smith DS, Wolfert RL, et al. Evaluation of percentage of free serum prostate-specific antigen to improve specificity of prostate cancer screening. JAMA. 1995;274:1214-1220.

  31. Bangma CH, Kranse R, Blijenberg BG, et al. The value of screening tests in the detection of prostate cancer. Part II: retrospective analysis of free/total prostate-specific analysis ratio, age-specific reference ranges, and PSA density. Urology. 1995; 46:779-784.

  32. Narayan P, Gajendran V, Taylor S, et al. The role of transrectal ultrasound-guided biopsy-based staging, preoperative serum prostate-specific antigen, and biopsy Gleason score in prediction of final pathologic diagnosis in prostate cancer. Urology. 1995; 46:205-212.

  33. Huang Y, Isharwal S, Haese A, et al. Prediction of patient-specific risk and percentile cohort risk of pathological stage outcome using continuous prostate-specific antigen measurement, clinical stage and biopsy Gleason score. BJU Int. 2011;107:1562-1569. Erratum in: BJU Int. 2011;108:1232.

  34. Bostwick DG, Foster CS. Predictive factors in prostate cancer: current concepts from the 1999 College of American Pathologists Conference on Solid Tumor Prognostic Factors and the 1999 World Health Organization Second International Consultation on Prostate Cancer. Semin Urol Oncol. 1999;17:222-272.

  35. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines™). Prostate Cancer. v.2.2013. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed May 8, 2013.

  36. Freedland SJ, Sutter ME, Dorey F, et al. Defining the ideal cutpoint for determining PSA recurrence after radical prostatectomy. Prostate-specific antigen. Urology. 2003;61:365-369.

  37. Consensus statement: guidelines for PSA following radiation therapy. American Society for Therapeutic Radiology and Oncology Consensus Panel. Int J Radiat Oncol Biol Phys. 1997;37:1035-1041.

  38. Sengupta S, Myers RP, Slezak JM, et al. Preoperative prostate specific antigen doubling time and velocity are strong and independent predictors of outcomes following radical prostatectomy. J Urol. 2005;174:2191-2196.

  39. D’Amico AV, Moul J, Carroll PR, et al. Prostate specific antigen doubling time as a surrogate end point for prostate cancer specific mortality following radical prostatectomy or radiation therapy. J Urol. 2004;172:S42-S47.

  40. Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281:1591-1597.

  41. Patel DA, Presti JC Jr, McNeal JE, et al. Preoperative PSA velocity is an independent prognostic factor for relapse after radical prostatectomy. J Clin Oncol. 2005;23:6157-6162.

  42. D’Amico AV, Chen MH, Roehl KA, et al. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med. 2004;351:125-135.

  43. Partin AW, Pearson JD, Landis PK, et al. Evaluation of serum prostate-specific antigen velocity after radical prostatectomy to distinguish local recurrence from distant metastases. Urology. 1994;43;649-659.

  44. Cannon GM Jr, Walsh PC, Partin AW, et al. Prostate-specific antigen doubling time in the identification of patients at risk for progression after treatment and biochemical recurrence for prostate cancer. Urology. 2003;62(Suppl 6B):2-8.

  45. Cox JD, Gallagher MJ, Hammond EH, et al. Consensus statements on radiation therapy of prostate cancer: guidelines for prostate re-biopsy after radiation and for radiation therapy with rising prostate-specific antigen levels after radical prostatectomy. American Society for Therapeutic Radiology and Oncology Consensus Panel. J Clin Oncol. 1999;17:1155-1163.

  46. Caplan A, Kratz A. Prostate-specific antigen and the early diagnosis of prostate cancer. Am J Clin Pathol. 2002;117(Suppl 1):S104-S108.

  47. Talic RF, El-Tiraifi AM, Altaf S, et al. Changes of serum prostate-specific antigen following high energy thick loop prostatectomy. Int Urol Nephrol. 2000;32:271-274.

  48. Oesterling JE, Rice DC, Glenski WJ, et al. Effect of cystoscopy, prostate biopsy, and transurethral resection of prostate on serum prostate-specific antigen concentration. Urology. 1993;42:276-282.

  49. Dew T, Coker C, Saadeh F, et al. Influence of investigative and operative procedures on serum prostate-specific antigen concentration. Ann Clin Biochem. 1999;36(Pt3):340-346.

  50. Soletormos G, Semjonow A, Sibley PEC, et al. Biological variation of total prostate-specific antigen: a survey of published estimates and consequences for clinical practice. Clin Chem. 2005;51:1342-1351.

  51. Gormley GJ, Stoner E, Bruskewitz RC, et al. The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group. N Engl J Med. 1992;327:1185-1191.

  52. Pannek J, Marks LS, Pearson JD, et al. Influence of finasteride on free and total serum prostate specific antigen levels in men with benign prostatic hyperplasia. J Urol. 1998;159:449-453.

  53. Andriole GL, Kirby R. Safety and tolerability of the dual 5alpha-reductase inhibitor dutasteride in the treatment of benign prostatic hyperplasia. Eur Urol. 2003;44:82-88.

  54. Brawer MK, Lin DW, Williford WO, et al. Effect of finasteride and/or terazosin on serum PSA: results of VA Cooperative Study #359. Prostate. 1999;39:234-239.

  55. Paul R, Breul J. Antiandrogen withdrawal syndrome associated with prostate cancer therapies: incidence and clinical significance. Drug Saf. 2000;23:381-390.

  56. Mettlin C. The American Cancer Society National Prostate Cancer Detection Project and national patterns of prostate cancer detection and treatment. CA Cancer J Clin. 1997;47:265-272.

  57. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level ≤4.0 ng per milliliter. N Engl J Med. 2004;350:2239-2246.

  58. Krumholtz JS, Carvalhal GF, Ramos CG, et al. Prostate-specific antigen cutoff of 2.6 ng/mL for prostate cancer screening is associated with favorable pathologic tumor features. Urology. 2002;60:469-474.

  59. Smith DC, Dunn RL, Strawderman MS, et al. Change in serum prostate-specific antigen as a marker of response to cytotoxic therapy for hormone-refractory prostate cancer. J Clin Oncol. 1998;16:1835-1843.

  60. Catalona WJ, Smith DS, Ratliff TL, et al. Detection of organ-confined prostate cancer is increased through prostate-specific antigen-based screening. JAMA. 1993;270:948-954.

  61. Gerstenbluth RE, Seftel AD, Hampel N, et al. The accuracy of the increased prostate specific antigen level (greater than or equal to 20 ng/mL) in predicting prostate cancer: is biopsy always required? J Urol. 2002;168:1990-1993.

     

Content reviewed 05/2013

* The tests listed by specialist are a select group of tests offered. For a complete list of Quest Diagnostics tests, please refer to our Directory of Services.