Prostate cancer develops when cells in the prostate gland grow abnormally, forming a tumor. The Prostate-Specific Antigen (PSA) blood test is a common screening tool that measures a protein produced by prostate cells. While elevated PSA levels often raise suspicion, a low PSA does not always exclude its presence. Understanding other diagnostic approaches is important for a comprehensive assessment of prostate health.
Why PSA Can Be Low with Cancer
While higher PSA levels generally correlate with more extensive disease, several factors can influence PSA readings, making a low PSA level an unreliable indicator on its own. Some aggressive forms of prostate cancer may not produce significant amounts of PSA, leading to a low or even normal reading despite advanced disease. This phenomenon, known as PSA-negative prostate cancer, occurs in a small percentage of cases, estimated to be less than 1% for metastatic prostate cancer.
Very small or localized tumors might not elevate PSA levels significantly, as the amount of PSA produced is often related to the cancer’s volume. Certain medications, like 5-alpha reductase inhibitors (e.g., dutasteride and finasteride), can also lower serum PSA levels, potentially masking prostate cancer.
Individual variations in PSA production and metabolism exist, influenced by factors such as age, race, weight, and smoking status. For example, younger men and those who are overweight may naturally have lower free PSA levels.
These variables contribute to a “false negative” PSA result, where prostate cancer is present despite a normal PSA reading. Around 15% of individuals with a normal PSA may still have prostate cancer. This highlights the limitation of relying solely on a PSA test for detection, underscoring the need for a broader diagnostic approach.
Other Ways Doctors Detect Prostate Cancer
Given the limitations of the PSA test alone, doctors employ several other methods to detect prostate cancer, often in combination.
Digital Rectal Exam (DRE)
A doctor manually feels the prostate through the rectum for any lumps, enlargements, or hard areas. While it cannot detect all cancers due to its inability to reach the entire prostate, it can sometimes identify abnormalities in men with normal PSA levels.
Multiparametric MRI (mpMRI)
This tool provides detailed images of the prostate gland using magnetism and radio waves. This advanced imaging technique helps identify suspicious areas within the prostate, guiding decisions about whether a biopsy is needed and where to take tissue samples. MpMRI can also help determine if suspected cancer is confined to the prostate or has spread beyond it.
Prostate Biopsy
A prostate biopsy remains the definitive method for diagnosing prostate cancer. Small tissue samples are removed from the prostate using a thin needle, often guided by ultrasound or MRI, and then examined under a microscope for cancer cells. If cancer is found, the biopsy results provide information about its aggressiveness, including the Gleason score.
Advanced Blood and Urine Tests
Newer blood or urine tests offer further insights beyond total PSA. These include:
Prostate Health Index (PHI): Combines total PSA, free PSA, and proPSA to provide a single score indicating the likelihood of clinically significant prostate cancer.
4Kscore: Assesses the probability of aggressive prostate cancer by incorporating four kallikrein proteins, along with age and DRE findings.
PCA3: A urine test that detects a gene overexpressed in prostate cancer cells, offering high specificity for cancer detection.
When Further Testing is Needed
Even with a low PSA level, several clinical scenarios and patient factors can prompt further investigation for prostate cancer.
Persistent or concerning urinary symptoms, such as frequent urination, a weak urine flow, or difficulty starting urination, warrant attention, as these can sometimes indicate prostate issues, including cancer. An abnormal finding during a Digital Rectal Exam (DRE), such as a nodule or firmness, irrespective of the PSA level, is also a clear reason for additional tests.
A strong family history of prostate cancer significantly increases an individual’s risk. If a close relative, such as a father or brother, has been diagnosed with prostate cancer, particularly at a younger age, further screening may be recommended, potentially starting earlier than general guidelines suggest. Belonging to a higher-risk ethnic group, such as African American men, also increases the likelihood of prostate cancer, including more aggressive forms, and may prompt earlier or more frequent testing.
A rising trend in PSA levels over time, even if individual readings remain within a “low” range, can also be a cause for concern. This “PSA velocity” or “PSA density” (PSA level divided by prostate volume) can indicate a more aggressive disease course. A comprehensive patient assessment, considering all these factors, guides a doctor’s decision to pursue further diagnostic steps, ensuring that potential prostate cancer is not overlooked based solely on a low PSA reading.