Prostatic specific antigen (PSA)

A serine protease and member of the kallikrein family.

A glycoprotein produced by prostate epithelial cells with high concentrations in male ejaculate.

A level greater than 4.0 ng/mL is found in approximately 10% of men.

PSA screening of approximately 19 million men annually, results in more than 1.3 million biopsy procedures and 240,000 diagnoses of prostate cancer.

The introduction of PSA screening was associated with a decline in the incidence of metastatic prostate cancer from 28 per hundred thousand men to 11 per hundred thousand men.

The widespread use of PSA testing has led to the overdiagnosis and treatment of the indolent prostate cancer, resulting in significant morbidity, health care costs and questionable survival benefits.

Has a low specificity for prostate cancer, ranging from 25-40%.

Prostate Cancer Prevention Trial (PCPT) with a PSA <4.0 15.2% had prostate cancer on biopsy and 15% had Gleason score of 7-10 (Thompson IM).

There is no PSA threshold below which there is no risk for prostate cancer.

Up to 70% of men presenting with an elevated PSA level between 4-7 ng/mL have false positive PSA tests that result in negative prostate biopsy.

PSA of 1.0 ng/mL has a high sensitivity for prostate cancer (82%) and a high false positive rate (59.4%), and a PSA threshold of 10 ng/mL has a low sensitivity (1%) and low false positive rate (0.5%).

PSA and may be elevated because of prostate cancer, infection, physical activity, or sexual activity.

PSA concentration may vary due to normal biological fluctuation or laboratory differences.

PSA is not adequate to monitor atypical or anaplastic carcinomas of the prostate that cause diminished or absent PSA production.

PSA testing is responsible for approximately 80% of the decline in distant and/or advanced Stage diagnoses.

NCCN 2018, recommended PSA screening for all patients age 45-75 years and discourages screening in patients aged greater than 75 years.

Levels may be increased with prostatitis, urinary retention, prostatic massage, following prostatic needle biopsy and transient elevations may occur after ejaculation, vigorous exercise, bike riding and constipation.

Serum levels persist for 48 hours after ejaculation.

Not elevated with routine digital rectal examination.

The positive predictive values of digital rectal exam and serum PSA value below 10 ng/mL is reported as less than 30% and 25-30%, respectively.

Elevations in the blood of patients with prostate cancer occur because production is increased and because tissue barriers between the prostate gland lumen and prostate blood vessels are damaged.

When measured in mass screening, 85-92% of cases have a PSA level of 4.0 ng/ml or less.

Value increases 45% per decade and by 38% per 10 cm3 of prostate gland volume.

Testing has nearly doubles the chance that a male will be diagnosed with prostate cancer in their lifetime.

62-71% of men undergoing PSA-based screening and found to have cancer have organ-confined disease.20% of men diagnosed with prostate cancer have PSA values of less than 4.0 ng/ml.

The proportion of free PSA to total PSA is lower in men with prostate cancer than in men with benign prostatic hyperplasia or without prostatic diseases.

Since the introduction of widespread screening for PSA, the median age at diagnosis has decreased by 1.7 years for whites and 1.3 years for African-Americans.

Pretreatment levels strongest independent predictor of treatment outcome after surgery and radiation.

20-30% of men with prostate cancer have PSA levels below 4.0 ng/mL.

Levels above 10 ng/mL markedly increase the odds that there is extracapsular prostatic tumor.

With values <10 ng/mL bone metastases never found.

Poorly differentiated prostate cancers are often PSA silent.

Occasionally a discrepancy exists between the prostate cancer volume or bulk of tumor in the amplitude of PSA, suggesting the presence of lower tumor bulk than is actually present.

Rapid PSA doubling time (≤ 10 months) is predictive of the development of metastatic disease in patients with nonmetastatic castrate resistant PC.

During the decades of PSA screening mortality from prostate cancer has decreased but it is not clear cut that the reduction is due to screening or other factors.

PSA doubling time andabsolute level of PSA are the only two factors known to predict for the time of onset of metastasis in the nonmetastatic prostate cancer population.

PSA doubling time is the most powerful predictor: PSA doubling time of less than three months is associated with the median time to metastasis of approximately nine months, while if a PSA doubling time is longer than 15 months, the time to metastasis is longer than four years.

Mortality for prostate cancer has dropped in countries where PSA is not commonly done and in the U.S. where different rates of PSA screening occur prostate cancer mortality rates are similar.

Biochemical relapse of prostate cancer is a continuous function of the PSA level with an approximate 2% increase in risk for each unit increase in PSA.

Utility of the test limited that PSA is a prostate marker and not a prostate cancer specific marker.

To date no study has shown that PSA screening has decrease prostate cancer specific mortality.

A long-term population study revealed that men who subsequently die of prostate cancer had significantly higher PSA levels 20 years previously compared to men who develop more stable disease.

Prostatic specific antigen doubling time requires several assays performed over 2 years to be accurate.

The half-life of PSA is around 3 days (Stamey TA).

Obese men have lower concentrations than men of normal weight.

C-reactive protein elevations associated with increased values of PSA in patients undergoing PSA screening.

Men who take aspirin have significantly lower levels than men who do not take the agent.

Statins may reduce PSA levels.

Use of aspirin and other nonsteroidal anti-inflammatory drugs significantly associated with lower levels than nonusers.

The Prostate, Lung, Colon, and Ovarian Cancer Screening Trial (PLCO) enrolled more than 76,600 men aged 55-74 years to receive annual prostate cancer screening or usual care, to be followed for at least 15 years: interim analysis found no benefit for annual PSA or DRE screening after a median of nine years of follow-up (Andriole GL et al).

The Prostate Cancer Prevention Trial (PCPT) screened patients for prostate cancer and found that a 28% cohort of men mainly in their 60s can be diagnosed with prostate cancer and SEER data suggest that the lifetime risk for a 60-year-old American man to die from prostate cancer is 3%: therefore this study provides strong evidence that overdiagnosis is a problem with prostate cancer screening (Thompson IM et al).

In the above study the PSA cut off point of 4.0 ng per milliliter has a sensitivity of 21% and a specificity of 94% for detecting prostate cancer.

In the PCPT study sensitivity was higher for detection of poorly differentiated cancers at 51%, with the specificity of 89%.

Men, aged 40-49 years, with a baseline Prostate-Specific Antigen below 1.0 ng/mL have a very low long-term risk of prostate cancer.

In a retrospective analysis of radical prostatectomy of 712 patients European database with a baseline PSA level > 20 ng/ml: Group A: Patients with a preoperative PSA level >100 ng/ml, Group B: Patients with a preoperative PSA level between 50.1 and 100 ng/ml , Group C: Patients with a preoperative PSA level between 20.1 and 50 ng/ml-10-year projected prostate cancer-specific survival appeared to be significantly affected by the baseline PSA level with 79.8 percent in Group A, 85.4 percent in Group B, 90.9 percent in Group C, 10-year projected overall survival was apparently not significantly affected by the baseline PSA level, 59.6 percent in Group A, 71.8 percent in Group B,75.3 percent in Group C, and at a median follow-up of 78.7 months, rates of biochemical progression-free survival were, 6.6 percent in Group A, 8.3 percent in Group B, 25.8 percent in Group C. (Gontero et al).

In the above study the authors conclude that 10-year prostate cancer-specific survival is high — even among men with baseline PSA levels >100 ng/ml, and that radical prostatectomy may be an appropriate treatment option even for some men whose baseline PSA level is >100 ng/ml.

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