Elevated PSA (Prostate Specific Antigen)

Prostate cancer is the most commonly diagnosed non skin cancer in American men. It is estimated that around 300,000 patients will be diagnosed with prostate cancer this years and and 30-40,000 men will die of the disease. Significant advances have been made in early detection, especially with the increasing availability and usage of biomarkers as well as mpMRI, but the PSA blood test remains the first-line screening test of choice based on randomized trials of PSA-based screening showing reductions in metastasis and prostate cancer death.

Prostate cancer screening is an important health consideration for men, particularly as they age. The PSA is a blood test. The test measures the level of PSA concentration in the blood, Elevated PSA levels can indicate the presence of prostate cancer but they may also result from benign conditions such as prostatitis (infection or inflammation) or benign prostatic hyperplasia (BPH or enlarged prostate).

Prostate-specific antigen (PSA) is a protein produced by cells of the prostate gland. It is primarily found in semen where it functions to liquefy the semen to help fertilization. Small amounts of PSA circulate in the blood as a result of blood flowing through the prostate. The PSA does not have a function in the bloodstream. A high level is not harmful to you, it is simply an indication you may have prostate cancer.

Recommendations for PSA Screening

The decision to undergo PSA screening should be based on individual factors, including age, family history of prostate cancer, and overall health. The general guidelines recommend:

  • Men aged 50 and older: Discuss the benefits and risks of PSA screening with a healthcare provider.

  • Men at higher risk (e.g., African American men or those with a family history of prostate cancer): Consider screening starting at age 45.

  • Men with a significantly higher risk: For those with multiple family members affected by prostate cancer, starting screening as early as age 40 may be advisable.

Interpreting PSA Test Results

A PSA below 1.5 ng/ml means a man’s risk of prostate cancer is very low. As the number rises above 1.5 the risk of having prostate cancer also increases. As men age the average PSA levels also increase because our prostates grow and tend to leak more PSA into the bloodstream. Historically a cutoff PSA level below 4.0 ng/mL was typically considered normal, but this threshold can vary based on age and other factors. We tend to use age-specific PSA criteria to help assess a man’s risk of prostate cancer.

Here are some of the generally accepted age-specific PSA thresholds:

  • Ages 40-49: A PSA level of 0 to 2.5 ng/mL is considered normal. Levels above 2.5 ng/mL may warrant further investigation, given the lower baseline levels in this age group.

  • Ages 50-59: Normal PSA levels are typically between 0 and 3.5 ng/mL. Levels above this range may indicate a higher risk of prostate pathology.

  • Ages 60-69: PSA levels should generally be between 0 and 4.5 ng/mL. Elevated levels require further evaluation due to an increased risk of prostate cancer.

  • Ages 70 and older: A normal PSA level may range from 0 to 6.5 ng/mL. Higher levels may suggest an increased probability of prostate issues, including cancer.

These criteria are not absolute; individual factors such as family history, race, and previous prostate conditions also play significant roles in the interpretation of PSA results.

What happens when the PSA is elevated?

An elevated prostate-specific antigen (PSA) level can be a concern for many individuals, as it may indicate potential prostate issues, including prostatitis, benign prostatic hyperplasia (BPH), or prostate cancer.

Next Steps After an Elevated PSA:

  1. Repeat Testing: A repeat PSA test may be recommended to confirm that the elevation is consistent.

  2. Digital Rectal Exam (DRE): A DRE can help assess the prostate's size, shape, and texture to identify any abnormalities.

  3. Imaging Tests: Depending on the situation, ultrasound or MRI might be utilized to visualize the prostate and identify potential problems.

  4. Other Blood or Urine Tests: Other tests can help determine overall cancer risk. Tests such as an iso-PSA or 4K score can help determine if a prostate biopsy should be done.

  5. Biopsy: If there is a sustained elevation or other concerning signs, a prostate biopsy may be necessary to determine the presence of cancer.

Prostate MRI

A prostate MRI (Magnetic Resonance Imaging) is a non-invasive imaging technique used to obtain detailed images of the prostate gland and surrounding tissues. This procedure is particularly valuable for diagnosing prostate conditions, including prostate cancer, benign prostatic hyperplasia (BPH), and prostatitis.

During the MRI, the patient lies on a table that slides into a cylindrical machine. The MRI machine uses strong magnetic fields and radio waves to create detailed images without the use of ionizing radiation. The entire procedure typically lasts between 30 to 60 minutes.

Before the MRI, patients may be asked to avoid certain foods or medications and to inform their healthcare provider about any metal implants, pacemakers, or claustrophobia. In some cases, an intravenous contrast agent may be administered to enhance the images of the prostate.

The results of the prostate MRI can provide valuable information for guiding diagnosis A prostate MRI (Magnetic Resonance Imaging) is a non-invasive imaging technique used to obtain detailed images of the prostate gland and surrounding tissues. This procedure is particularly valuable for diagnosing prostate conditions, including prostate cancer, benign prostatic hyperplasia (BPH), and prostatitis.

During the MRI, the patient lies on a table that slides into a cylindrical machine. The MRI machine uses strong magnetic fields and radio waves to create detailed images without the use of ionizing radiation. The entire procedure typically lasts between 30 to 60 minutes.

Before the MRI, patients may be asked to avoid certain foods or medications and to inform their healthcare provider about any metal implants, pacemakers, or claustrophobia. In some cases, an intravenous contrast agent may be administered to enhance the images of the prostate.

The results of the prostate MRI can provide valuable information for guiding diagnosis and treatment decisions. The images can help identify the size, shape, and specific characteristics of any abnormalities, aiding in determining the need for further evaluation or intervention. Following the MRI, a radiologist will analyze the images and generate a report for the patient’s healthcare provider, who will discuss the findings and recommend next steps.and treatment decisions. The images can help identify the size, shape, and specific characteristics of any abnormalities, aiding in determining the need for further evaluation or intervention. Following the MRI, a radiologist will analyze

Prostate Biopsy

During the biopsy, small tissue samples are taken from the prostate gland for laboratory analysis.

The procedure is typically performed in our outpatient clinic. There are several methods for conducting a prostate biopsy, the most common of which is transrectal ultrasound-guided biopsy. A small ultrasound probe is inserted into the rectum to allow the physician to visualize the prostate and guide a needle to collect samples from specific areas.

Other techniques include transperineal biopsy, where samples are taken through the skin between the scrotum and rectum, and saturation biopsy, which involves taking more samples than standard methods to ensure thorough examination.

Patients may experience some discomfort or minor pain during and after the procedure. Serious complications of infection and bleeding can occur after the procedure but are uncommon.

The biopsy results help determine whether cancer is present, the aggressiveness of the disease, and guide treatment decisions if necessary.

  • GUIDELINE STATEMENTS from the AUA/SUO Guidelines for early detection of prostate cancer.

    PSA Screening

    1. Clinicians should engage in shared decision-making (SDM) with people for whom prostate cancer screening would be appropriate and proceed based on a person’s values and preferences. (Clinical Principle)

    2. When screening for prostate cancer, clinicians should use PSA as the first screening test. (Strong Recommendation; Evidence Level: Grade A)

    3. For people with a newly elevated PSA, clinicians should repeat the PSA prior to a secondary biomarker, imaging, or biopsy. (Expert Opinion)

    4. Clinicians may begin prostate cancer screening and offer a baseline PSA test to people between ages 45 to 50 years. (Conditional Recommendation; Evidence Level: Grade B)

    5. Clinicians should offer prostate cancer screening beginning at age 40 to 45 years for people at increased risk of developing prostate cancer based on the following factors: Black ancestry, germline mutations, strong family history of prostate cancer. (Strong Recommendation; Evidence Level: Grade B)

    6. Clinicians should offer regular prostate cancer screening every 2 to 4 years to people aged 50 to 69 years. (Strong Recommendation; Evidence Level: Grade A)

    7. Clinicians may personalize the re-screening interval, or decide to discontinue screening, based on patient preference, age, PSA, prostate cancer risk, life expectancy, and general health following SDM. (Conditional Recommendation; Evidence Level: Grade B)

    8. Clinicians may use digital rectal exam (DRE) alongside PSA to establish risk of clinically significant prostate cancer. (Conditional Recommendation; Evidence Level: Grade C)

    9. For people undergoing prostate cancer screening, clinicians should not use PSA velocity as the sole indication for a secondary biomarker, imaging, or biopsy. (Strong Recommendation; Evidence Level: Grade B)

    10. Clinicians and patients may use validated risk calculators to inform the SDM process regarding prostate biopsy. (Conditional Recommendation; Evidence Level: Grade B)

    11. When the risk of clinically significant prostate cancer is sufficiently low based on available clinical, laboratory, and imaging data, clinicians and patients may forgo near-term prostate biopsy. (Clinical Principle)

    Initial Biopsy

    1. Clinicians should inform patients undergoing a prostate biopsy that there is a risk of identifying a cancer with a sufficiently low risk of mortality that could safely be monitored with active surveillance (AS) rather than treated. (Clinical Principle)

    2. Clinicians may use magnetic resonance imaging (MRI) prior to initial biopsy to increase the detection of Grade Group (GG) 2+ prostate cancer. (Conditional Recommendation; Evidence Level: Grade B)

    3. Radiologists should utilize PI-RADS in the reporting of multi-parametric MRI (mpMRI) imaging. (Moderate Recommendation; Evidence Level: Grade C)

    4. For biopsy-naïve patients who have a suspicious lesion on MRI, clinicians should perform targeted biopsies of the suspicious lesion and may also perform a systematic template biopsy. (Moderate Recommendation [targeted biopsies]/Conditional Recommendation [systematic template biopsy]; Evidence Level: Grade C)

    5. For patients with both an absence of suspicious findings on MRI and an elevated risk for GG2+ prostate cancer, clinicians should proceed with a systematic biopsy. (Moderate Recommendation; Evidence Level: Grade C)

    6. Clinicians may use adjunctive urine or serum markers when further risk stratification would influence the decision regarding whether to proceed with biopsy. (Conditional Recommendation; Evidence Level: Grade C)

    7. For patients with a PSA > 50 ng/mL and no clinical concerns for infection or other cause for increased PSA (e.g., recent prostate instrumentation), clinicians may omit a prostate biopsy in cases where biopsy poses significant risk or where the need for prostate cancer treatment is urgent (e.g., impending spinal cord compression). (Expert Opinion)

    Repeat Biopsy

    1. Clinicians should communicate with patients following biopsy to review biopsy results, reassess risk of undetected or future development of GG2+ disease, and mutually decide whether to discontinue screening, continue screening, or perform adjunctive testing for early reassessment of risk. (Clinical Principle)

    2. Clinicians should not discontinue prostate cancer screening based solely on a negative prostate biopsy. (Strong Recommendation; Evidence Level: Grade C)

    3. After a negative biopsy, clinicians should not solely use a PSA threshold to decide whether to repeat the biopsy. (Strong Recommendation; Evidence Level: Grade B)

    4. If the clinician and patient decide to continue screening after a negative biopsy, clinicians should re-evaluate the patient within the normal screening interval (two to four years) or sooner, depending on risk of clinically significant prostate cancer and life expectancy. (Clinical Principle)

    5. At the time of re-evaluation after negative biopsy, clinicians should use a risk assessment tool that incorporates the protective effect of prior negative biopsy. (Strong Recommendation; Evidence Level: Grade B)

    6. After a negative initial biopsy in patients with low probability for harboring GG2+ prostate cancer, clinicians should not reflexively perform biomarker testing. (Clinical Principle)

    7. After a negative biopsy, clinicians may use blood, urine, or tissue-based biomarkers selectively for further risk stratification if results are likely to influence the decision regarding repeat biopsy or otherwise substantively change the patient’s management. (Conditional Recommendation; Evidence Level: Grade C)

    8. In patients with focal (one core) high-grade prostatic intraepithelial neoplasia (HGPIN) on biopsy, clinicians should not perform immediate repeat biopsy. (Moderate Recommendation; Evidence Level: Grade C)

    9. In patients with multifocal HGPIN, clinicians may proceed with additional risk evaluation, guided by PSA/DRE and mpMRI findings. (Expert Opinion)

    10. In patients with atypical small acinar proliferation (ASAP), clinicians should perform additional testing. (Expert Opinion)

    11. In patients with atypical intraductal proliferation (AIP), clinicians should perform additional testing. (Expert Opinion)

    12. In patients undergoing repeat biopsy with no prior prostate MRI, clinicians should obtain a prostate MRI prior to biopsy. (Strong Recommendation; Evidence Level: Grade C)

    13. In patients with indications for a repeat biopsy who do not have a suspicious lesion on MRI, clinicians may proceed with a systematic biopsy. (Conditional Recommendation; Evidence Level: Grade B)

    14. In patients undergoing repeat biopsy and who have a suspicious lesion on MRI, clinicians should perform targeted biopsies of the suspicious lesion and may also perform a systematic template biopsy. (Moderate Recommendation [targeted biopsies]/Conditional Recommendation [systematic template biopsy]; Evidence Level: Grade C)

    Biopsy Technique

    1. Clinicians may use software registration of MRI and ultrasound images during fusion biopsy, when available. (Expert Opinion)

    2. Clinicians should obtain at least two needle biopsy cores per target in patients with suspicious prostate lesion(s) on MRI. (Moderate Recommendation; Evidence Level: Grade C)

    3. Clinicians may use either a transrectal or transperineal biopsy route when performing a biopsy. (Conditional Recommendation; Evidence Level: Grade C)