PSA After Treatment

If you’ve started your prostate cancer treatment, the next question on your mind might be – how do I know if it’s working? Notably, nearly one-third of those with prostate cancer experience disease recurrence after the first round of treatment, although baseline risk factors (Gleason score, size of tumor, T stage or prostate-specific antigen (PSA)) significantly affect the risk of recurrence.

While the PSA test is not a particularly good diagnostic test for determining who does and does not have prostate cancer, it is very good for monitoring response to treatment and is so sensitive that it makes routine imaging unnecessary.

After prostate cancer surgery, you can expect your PSA level to drop quite quickly. However, it may take some time for the old PSA to be cleared from your system, and so the first post-surgery PSA is typically drawn at least 6 to 8 weeks after treatment.

After removal of the prostate, there should be no detectable PSA, in contrast to after radiation therapy (as discussed below). Recurrence of prostate cancer in this case can be defined as a PSA above 0.2 ng/mL on two tests. However, ultrasensitive PSA tests can pick up detectable levels below this threshold and need to be interpreted carefully in the context of your original risk factors and how they change over time. Repeating this test allows your doctor to confirm the PSA rise while estimating your PSA doubling time to check how aggressive the cancer return may be.

After radiotherapy, PSA may continue to drop for months to years. The PSA nadir is the lowest PSA value recorded, and levels below 0.1 ng/mL within 6 months of radiation connote an excellent long-term outcome (although nadirs above this certainly do not equate to guaranteed recurrence). Unfortunately, this uncertainty can cause some stress and anxiety for you and your doctor. You may need to wait up to one to three years before finally seeing your PSA nadir.

Recurrence after radiotherapy is most commonly defined as an increase from the PSA nadir by over 2.0 ng/mL. Importantly, for patients who received concurrent androgen deprivation therapy, PSA may rise slightly after nadir as testosterone recovers; as long as this stabilizes, it is not of concern. In addition, PSA can transiently rise approximately 12-18 months after radiation, followed by a fall back to prior baseline (“PSA bounce”).

In the STOMP and ORIOLE trials on stereotactic ablative radiation therapy for oligometastatic prostate cancer, a new and rapidly emerging therapy, treatment responses showed significant improvement. Over 15% experienced progression-free survival of over four years, with progression defined as an increase in PSA from nadir by at least 25% and 2 ng/mL.

For patients who meet criteria for recurrence described above, a rising PSA is almost always asymptomatic and typically precedes development of metastatic disease by many years. Low-risk biochemical recurrence may never progress to metastatic disease within a patient’s lifetime. Thus, it is very important to stratify risk based on:

• PSA doubling time

PSA doubling time is the amount of time taken for your PSA level to increase to two times its previous level. This is important as it measures the speed at which your PSA level increases. The highest risk PSA doubling times are <3 months, whereas PSA doubling times of a year or more are typically much lower risk.

• Original Gleason score

• Time to recurrence

Imaging studies such as PSMA PET scan may detect the earliest signs of recurrent cancer, which can then sometimes be targeted using local therapies such as radiation or ablation. However, it is important to remember that very early metastatic disease seen on PSMA PET is almost always asymptomatic and is not equivalent to having widespread disease on conventional imaging (CT, MRI, bone scan).

Hormonal therapies such as androgen deprivation therapy and/or enzalutamide can be used to treat patients with biochemical recurrence and fast PSA doubling times. Recently, the EMBARK trial reported that those who experienced biochemical recurrence and had a high risk of prostate cancer progression (e.g. PSA doubling time of 9 months or lower) were found to benefit more from enzalutamide, with or without leuprolide. However, these treatments merely suppress cancer cells and do not eradicate them, and it is unclear whether starting hormonal therapy to treat a rising PSA is better than waiting to start if/when more widely metastatic disease emerges.

It's crucial for those who have undergone treatment and are monitoring their PSA levels to maintain regular follow-up appointments with your healthcare provider. These check-ups allow your healthcare team to closely monitor your health, discuss any concerns, and make informed decisions about further treatment or adjustments to the ongoing care plan. Regular communication with healthcare professionals is key to managing post-treatment care and maintaining your overall well-being.