What is the significance of an ultrasensitive Prostate-Specific Antigen (PSA) level less than 0.006 ng/mL in a patient on Androgen Deprivation Therapy (ADT)?

From the Guidelines

An ultrasensitive PSA level below 0.006 ng/mL while on androgen deprivation therapy (ADT) is a strong indicator of excellent disease control and a favorable prognosis for prostate cancer patients. This extremely low PSA value suggests that the ADT is effectively suppressing testosterone production and controlling cancer growth, as supported by the latest guidelines from the AUA/ASTRO/SUO 1. Patients with such low PSA values typically have a better prognosis and may be candidates for intermittent ADT rather than continuous therapy, depending on their specific clinical situation.

Key Considerations

• The AUA definition of biochemical recurrence (BCR) is a rise in PSA ≥ 0.2 ng/mL, but ultrasensitive PSA assays can detect levels below 0.1 ng/mL, allowing for earlier detection of disease activity 1.
• The decision to modify treatment should not be based solely on this single low PSA value but should consider the overall clinical picture, including the initial disease characteristics, treatment duration, and patient tolerance of ADT side effects.
• Regular PSA testing every 3-6 months is recommended to ensure the treatment remains effective and to monitor for any changes in disease activity.
• Clinicians should engage in a shared decision-making process with patients, using prognostic factors such as PSADT, Gleason Grade Group, and pathologic stage to counsel patients about their risk of clinical progression 1.

Implications for Treatment

• An ultrasensitive PSA below 0.006 ng/mL confirms that very few cancer cells are active enough to produce PSA, indicating good disease control.
• ADT works by reducing testosterone levels, which prostate cancer cells need for growth, and this low PSA value suggests that the treatment is effective in suppressing cancer growth.
• However, continued monitoring is essential as PSA levels can fluctuate, and treatment decisions should be based on the overall clinical picture rather than a single PSA value.

From the Research

Ultrasensitive PSA Levels and ADT

• Ultrasensitive PSA levels less than 0.006 on androgen deprivation therapy (ADT) are not directly addressed in the provided studies 2, 3, 4, 5, 6.
• However, study 4 discusses the prognostic significance of undetectable ultrasensitive PSA nadir after radical prostatectomy, where a nadir of less than 0.001 ng/mL was associated with a lower risk of biochemical recurrence.
• Study 5 examines the ability of ultrasensitive PSA nadir to predict relapse after radical prostatectomy, finding that a nadir of less than 0.01 ng/mL was associated with a low likelihood of early relapse.
• Study 6 mentions that ultrasensitive PSA assays can increase the sensitivity of PSA as a tumor marker after surgical removal of the prostate, but notes that the clinical usefulness of PSA concentrations detected in the ultrasensitive range after radical prostatectomy is unknown.

ADT and PSA Levels

• Study 2 discusses the use of ADT with degarelix, a gonadotropin hormone-releasing hormone (GnRH) antagonist, and its effect on prostate volume and PSA levels 2.
• Study 3 reviews the pharmacological features of Leuprolide, a luteinizing hormone-releasing hormone (LHRH) agonist, and its use in ADT for advanced prostate cancer 3.
• Study 6 notes that the serum PSA level after ADT has prognostic importance, with a decrease to the normal range predicting a prolonged remission in most patients 6.

Monitoring Response to Therapy

• Study 6 discusses the use of PSA levels in monitoring response to therapy, including radical prostatectomy and radiation therapy 6.
• The study notes that an increasing serum PSA concentration after radiation therapy heralds progressive prostate cancer, and that patients who have received ADT must be closely monitored for signs of clinical progression 6.