A characteristic of good mystery stories is the use of clues designed to mislead the reader. These literary devices are called red herrings, and they are meant to throw the reader off track. Most prostate cancer (PCa) patients who are treated with beam radiation or brachytherapy (seed implants) can expect they are on the road to a successful treatment. Then, like a red herring, something called a PSA bounce throws them off track. Months after their treatment, their PSA suddenly begins to rise—and they fear their PCa is back.

In fact, a 2021 paper specifically noted that the bounce can cause “significant patient and provider anxiety out of concern for a recurrence.”^[i] As it turns out, this reaction is unfounded. Statistics vary, but it appears that up to 31% of post-radiation patients experience a brief rise in PSA. It happens more frequently in younger men, and those with less aggressive disease. It can occur as soon as 6 months following treatment, or even closer to 2 years later. A new blood test after a short waiting period will reveal that no further rise is happening, or that PSA has dropped back to its previous lowest point.

Surprisingly, research suggests that radiation patients who go through a bounce actually have better long-term outcomes than those who don’t.

What causes the bounce?

Scientists are still trying to pin down exactly what the bounce is all about. In an August, 2019 blog about a PSA bounce after brachytherapy, I cited a 2016 paper which theorized that “a strong anti-tumor immune response coupled with the therapeutic effect of radiation on the tumor is responsible for the PSA bounce.”^[ii] According to that theory, radiation initially delivers a setback to immune system cells already present at the tumor. However, radiation causes corruptions in the DNA of PCa cells, so they cannot reproduce and begin to die off. As they start dying in numbers, months after the treatment has ended, their biochemical fragments are released into the bloodstream, catalyzing the immune system to recognize and tackle the invader. This inflammatory response may be the source of the PSA bounce, serving to reinforce the lethal activity of the radiation. Thus, the bounce is a good sign.

If this is correct, it might help explain why younger patients are more likely to have a bounce, since their immune systems are more robust. It would also account for better radiation success with low-risk PCa cell lines, which seem to be less radiation-resistant than aggressive cell lines.

Is it a bounce or biochemical recurrence?

The problem is, how can one be sure it’s a bounce and not a sign of PCa recurrence? PSA is a biochemical marker of prostate activity, including PCa. As I said earlier, a post-radiation patient whose PSA is now starting to rise is justified in worrying over biochemical recurrence (BCR). It’s anxiety provoking to have to wait for one or more repeat blood tests to find out if PSA is coming back down.

Thankfully, a presentation by Monaco, et al.^[iii] at the 2022 annual meeting of the American Urological Association offers some real clues—not red herrings—to help tell whether a rising PSA is more likely a bounce than biochemical recurrence (BCR) as indicated by a rising PSA.

The team researchers studied 170 PCa patients who were treated with stereotactic body radiation therapy (SBRT). They compared the factors associated with PSA bounce vs. BCR. Here’s a comparison table:

PSA bounce	BCR
Defined as a rise of greater than 0.2 ng/mL over the pre-rise nadir (lowest point after treatment) followed by a decline without intervention	Defined according to Phoenix criteria as PSA nadir (lowest point after treatment) plus PSA 2ng/mL.
Patients tend to be younger	Patients have no bounce or tend to be older
Significantly lower PSA doubling time	Shorter PSA doubling time
Took significantly longer to reach nadir	Reached nadir sooner
Lower PSA nadir (avg. 0.30)	Higher PSA nadir (avg. 0.90 ng/mL)
Bounce occurred at average 16 months	BCR detected at average 33 months

Thus, post-radiation patients whose are worried about a rising PSA can consult the above factors to find out whether it’s something of concern, or simply a red herring they can ignore.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Kishan AU. PSA bounce, prognosis, and clues to the radiation response. Prostate Cancer Prostatic Dis. 2021 Dec;24(4):937-938.
[ii] Yamamoto Y, Offord CP, Kumura G, Kuribayashi S et al. Tumour and immune cell dynamics explain the PSA bounce after prostate cancer brachytherapy. Br J Cancer. 2016 Jul 12;115(2):195-202.
[iii] Charnow, J. PSA Bounce vs Biochemical Recurrence After Prostate Cancer SBRT Probed. Renal & Urology News, May 14, 2022. https://www.renalandurologynews.com/home/conference-highlights/american-urological association-annual-meeting/aua-2022-annual-meeting/psa-bounce-vs-biochemical-recurrence-after-prostate cancer-radiation-therapy/