Prostate-Specific Antigen (PSA) is a protein produced by prostate cells. Its level in the blood is the primary indicator used to monitor prostate cancer activity, particularly during and after treatment. Hormone Therapy (HT), also known as Androgen Deprivation Therapy (ADT), is a standard treatment that works by dramatically lowering male hormones, primarily testosterone. Since prostate cancer cells rely on testosterone for growth, blocking this hormone signal causes PSA levels to fall sharply. Monitoring this decline and the subsequent suppressed level assesses whether the treatment is working.
The Goal: Achieving the PSA Nadir
The initial objective of hormone therapy is to achieve the PSA nadir, which is the lowest point the PSA level reaches during treatment. This nadir indicates the treatment’s effectiveness and is associated with a better long-term outcome. The target for the PSA nadir is typically very low, often below 0.1 ng/mL or 0.2 ng/mL, depending on the disease context.
Achieving a low nadir, especially an undetectable level, is strongly associated with a reduced risk of the disease returning. For men with non-metastatic disease, a nadir slightly above the undetectable range can indicate a greater risk of progression. The PSA decline is usually rapid initially, often dropping by 90% within the first month of therapy. The lowest point is generally reached within three to twelve months after starting treatment.
Interpreting Stable PSA Levels During Hormone Therapy
Once the PSA nadir is reached, the goal shifts to maintaining a stable, suppressed level throughout the hormone therapy. A consistently low PSA confirms that the treatment is successfully depriving the cancer cells of hormones. This stable suppression suggests the cancer is under control and responding well to ADT.
Regular PSA testing, typically performed every three to six months, tracks this stability and looks for concerning trends. Clinicians understand that minor, transient fluctuations can occur and do not necessarily signal treatment failure. The pattern over time is important, not a single test result.
If the PSA remains low and stable, it indicates the therapy is continuing to suppress the cancer. Maintaining a suppressed PSA is the ideal scenario, and any sustained change warrants closer attention. Any change must be evaluated to distinguish between insignificant variations and true signs of resistance.
Defining Biochemical Recurrence on Hormone Therapy
A rise in PSA while on hormone therapy may signal the development of Castration-Resistant Prostate Cancer (CRPC). This occurs when prostate cancer cells grow even when testosterone levels are suppressed to castrate levels. Biochemical recurrence relies on a confirmed, sustained rise above the established nadir.
Recurrence is generally not confirmed by a single, slight elevation, though the exact threshold varies by guidelines. A common indicator is a sustained rise, often defined as a series of three consecutive increases from the nadir. Some settings consider a rise above a specific absolute value, such as 1.0 ng/mL or 2.0 ng/mL, as a threshold for intervention.
Any confirmed, unremitting rise in PSA after the nadir suggests the cancer is becoming resistant to the current hormone therapy. This necessitates an immediate clinical evaluation, often including a review of symptoms and advanced imaging studies. Detecting this recurrence prompts a discussion about changing the treatment strategy, such as adding new hormone agents or chemotherapy.
PSA Changes After Stopping Hormone Therapy
For patients who stop hormone therapy, the PSA level is expected to increase. This rise is often called a PSA “rebound” or “recovery” following the return of testosterone production. Once ADT is stopped, natural testosterone levels gradually recover, stimulating remaining prostate cells to produce more PSA.
This expected rise does not automatically signify a return of the cancer, but rather a recovery of hormone-sensitive tissue. Clinicians carefully monitor the rate and extent of this PSA increase. A slow, stabilizing rise that remains at a safe level is the desired outcome, showing that remaining cancer cells are still hormone-dependent.
Monitoring tracks the PSA for any subsequent, sustained, or rapid rise that goes beyond the expected recovery level, which would indicate true cancer progression. The decision to restart hormone therapy in an intermittent schedule is often based on the PSA reaching a pre-determined trigger point. This trigger point is generally set much higher than the nadir, such as 4 ng/mL or higher, depending on the patient’s health and prior response.