What does a low Prostate-Specific Antigen (PSA) level mean in a patient with prostate cancer?

From the Guidelines

A low Prostate-Specific Antigen (PSA) level in a patient with confirmed prostate cancer typically indicates a smaller tumor burden or less aggressive disease, but it does not necessarily mean the cancer is insignificant. PSA is a protein produced by both normal and cancerous prostate cells, with higher levels generally correlating with more extensive disease. However, a low PSA in a diagnosed prostate cancer patient doesn't necessarily mean the cancer is insignificant. Some aggressive prostate cancers, particularly those that are poorly differentiated, may produce little PSA despite being advanced. This phenomenon, known as PSA-negative prostate cancer, occurs in approximately 5-10% of cases. For patients with low PSA and confirmed cancer, treatment decisions should still be based on multiple factors including Gleason score, clinical stage, imaging results, and overall health status, as suggested by the guidelines from the National Comprehensive Cancer Network 1. Regular monitoring is essential even with low PSA levels, as some cancers can progress despite minimal PSA elevation. PSA velocity (rate of change over time) may provide more valuable information than absolute values in these cases, as indicated by studies on PSA doubling time 1. Patients should understand that while a low PSA is generally favorable, it must be interpreted within the context of their specific cancer characteristics and comprehensive clinical evaluation, considering the latest recommendations for post-treatment follow-up prostate cancer 1. Some key points to consider include:

• The risk of prostate cancer increases with increasing PSA, but there is no level of PSA below which the risk of prostate cancer can be eliminated 1.
• Approximately 15% of men with a PSA level of 4.0 ng/mL or less and a normal DRE had prostate cancer, as diagnosed using end-of-study biopsies 1.
• Total PSA (tPSA) levels greater than 10 ng/mL confer a greater than 67% likelihood of biopsy-detectable prostate cancer 1.
• A PSADT <3 months has been found to be a useful surrogate marker for prostate cancer–specific and overall survival in patients with relapse after RP or RT 1.
• MRI can identify isolated local recurrences very early, with PSA levels < 1 ng/mL 1. It is essential to consider these factors and the latest evidence when interpreting low PSA levels in patients with confirmed prostate cancer.

From the FDA Drug Label

In clinical trials, dutasteride reduced serum PSA concentration by approximately 50% within 3 to 6 months of treatment. This decrease was predictable over the entire range of PSA values in subjects with symptomatic BPH, although it may vary in individuals. Dutasteride may also cause decreases in serum PSA in the presence of prostate cancer.

A low Prostate-Specific Antigen (PSA) level in a patient with prostate cancer may not necessarily indicate a lower risk of cancer, as 5 alpha-reductase inhibitors such as dutasteride and finasteride can decrease serum PSA levels.

• Key points:
  • A low PSA level may be due to the effect of the medication rather than the absence of cancer.
  • Any confirmed increase from the lowest PSA value while on dutasteride or finasteride may signal the presence of prostate cancer and should be evaluated.
  • To interpret an isolated PSA value in a man treated with dutasteride or finasteride for 3-6 months or more, the PSA value should be doubled for comparison with normal values in untreated men. 2 3 3

From the Research

Low PSA Levels in Prostate Cancer

A low Prostate-Specific Antigen (PSA) level in a patient with prostate cancer can have various implications.

• It may indicate that the cancer is not aggressive or is still in its early stages 4, 5.
• However, it is essential to note that low PSA levels do not always rule out the presence of prostate cancer, as some types of prostate cancer may not produce much PSA 6, 5.
• In some cases, prostate cancer can progress despite low or undetectable PSA levels, especially in patients with high-grade, locally advanced tumors or atypical histologic variants 6.

Implications of Low PSA Levels

• A low PSA level after treatment can be a sign of a good response to therapy 4, 7.
• However, it is crucial to continue monitoring PSA levels and performing regular check-ups, as low PSA levels do not guarantee that the cancer will not progress 6, 5.
• The presence of low PSA levels can also make it challenging to determine the stage of the disease or predict the prognosis of the patient 5.

Treatment and Surveillance

• Patients with low PSA levels and prostate cancer may still require treatment, such as radical prostatectomy, radiation therapy, or hormone therapy 6, 7, 8.
• Surveillance and regular monitoring are crucial in these patients to detect any changes in PSA levels or disease progression 6, 5.
• The use of imaging studies and physical evaluations can help detect metastasis or disease progression, even in patients with low PSA levels 6.