What Happens to PSA After Radiation Therapy?

This is probably the question I hear most often during follow-up visits after treatment has been completed.

Many patients expect their PSA to drop to zero immediately. When that does not happen, they often assume that the radiation therapy did not work or that the cancer is still present.

In most cases, neither of those conclusions is correct.

PSA behaves differently after radiation therapy than it does after surgery.

When a radical prostatectomy is performed, the prostate is removed, and PSA levels usually fall to nearly undetectable levels within a few weeks.

After radiation therapy, the situation is different. The prostate remains in place, and some normal prostate tissue continues to produce small amounts of PSA. For that reason, we do not necessarily expect the PSA to reach zero.

In addition, radiation therapy does not eliminate cancer cells overnight. Its effects occur gradually, and PSA levels may continue to decline for months or even years after treatment has been completed.

As a result, a detectable PSA after radiation therapy does not automatically mean that active cancer is present.

One of the most important concepts during follow-up is the PSA nadir.

The nadir is the lowest PSA level reached after treatment. This value matters because multiple studies have shown that it is associated with long-term cancer outcomes.

Some patients reach their nadir within a few months. Others may take several years.

That is why we do not usually interpret PSA results based on a single measurement.

It is also relatively common to see small PSA fluctuations during follow-up.

Some patients experience a temporary rise in PSA followed by a subsequent decline. This phenomenon is known as a PSA bounce and has been described in multiple studies, particularly after brachytherapy, although it can also occur after external beam radiation therapy.

When interpreted without proper context, a PSA bounce can cause unnecessary concern.

For that reason, during follow-up visits we pay much more attention to the overall PSA trend than to any single PSA value.

Another important aspect is understanding how recurrence is defined after radiation therapy.

Today, the most widely accepted definition is the Phoenix definition, which is recommended by ASTRO, NCCN, and other international professional societies.

According to this definition, biochemical recurrence is diagnosed when the PSA rises by 2 ng/mL or more above the lowest PSA level (nadir) reached after treatment.

This definition was developed because small PSA fluctuations are common and do not necessarily indicate that the cancer has returned.

What does all of this mean for someone who has just completed radiation therapy?

It means that follow-up requires patience.

A detectable PSA does not necessarily mean that treatment has failed.

A small increase does not automatically mean that the cancer has come back.

The most useful way to interpret PSA results is to look at how they change over time.

If I had to summarize this entire discussion in one sentence, it would be this:

After radiation therapy, we do not expect PSA to reach zero, and we do not interpret each PSA result in isolation.

What matters most is the overall trend.

Before worrying about a specific PSA value, it is worth reviewing the complete PSA history with your radiation oncologist or urologist.

References

Hamdy FC, Donovan JL, Lane JA, et al. 15-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. New England Journal of Medicine. 2023;388(8):718–732. doi:10.1056/NEJMoa2214122

Roach M 3rd, Hanks G, Thames H Jr, et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer. International Journal of Radiation Oncology Biology Physics. 2006;65(4):965–974. doi:10.1016/j.ijrobp.2006.04.029

Zumsteg ZS, Spratt DE, Romesser PB, et al. The natural history and predictors of PSA bounce following dose-escalated external beam radiation therapy for prostate cancer. International Journal of Radiation Oncology Biology Physics. 2015;91(4):729–736. doi:10.1016/j.ijrobp.2014.11.016