Understanding PSA after Radiation Therapy

In interviews I did for the Prostate Cancer Foundation’s website, Weill Cornell Medicine urologist Jim C. Hu, M.D., M.P.H. (whose expert opinion also was featured in our book), breaks down what rising or persistent PSA means after treatment for localized prostate cancer, and what you should do next.  Remember the first lesson from Part 1:  Don’t panic!

             How do you know if localized prostate cancer is cured?  That answer to that question is straightforward for men who undergo radical prostatectomy:  in the weeks after surgery, the PSA should become undetectable, falling to less than 0.1.

But for men who undergo radiation therapy, it’s more complicated: there is no definitive PSA cutoff point that signals success or failure of treatment.  That’s because radiation therapy – external-beam or radiation seeds (brachytherapy) – is designed to kill prostate cancer, not normal prostate tissue.  It doesn’t kill the entire prostate – and thus, PSA does not go away completely.

Instead, PSA drops, eventually reaching a rock-bottom level called the PSA nadir.  Note:  there may be a little bump along the way, called the PSA “bounce.”  This doesn’t happen to everyone; it’s more common in younger men.  The PSA bounce does not mean that you are not headed for a low, stable PSA.  It’s just a weird thing that may be related to inflammation of the prostate; it’s temporary and usually happens within the first two years after treatment. Then PSA usually settles down, remaining at a very low level.

It can take anywhere from two to five years after radiation for PSA to bottom out.  If it starts to climb back up, further tests are not indicated until the PSA reaches the nadir value + 2 ng/ml.  “The very term, ‘nadir +2,’ tells you that whole-gland radiation is not expected to kill all the cells within the prostate,” says Jim Hu.  “There are some benign cells left behind that can still make PSA.  But if there are also some remaining cancer cells, those cells will grow over time, and finally produce enough PSA to exceed that nadir + 2 cutoff.”  Thus, if cancer is still present after radiation therapy, it may take months or even years to find out about it.

If Some Cancer is Still There, Where is it?

There are several possibilities as to where the cancer might be lurking, says Hu.  “The cancer could be just within the prostate.  It could be within and outside the prostate, but still in the nearby area.”  Or, it might be further afield – in a lymph node, perhaps.  “It may be that the radiation killed the cancer within the prostate, but there were some microscopic metastases outside the prostate that were not touched by the radiation.”

The first place to look for recurrent cancer after radiation therapy is within the prostate – with an MRI and a biopsy.  What happens next?  Let’s say the cancer is still in the prostate.  “Typically, you can’t do more radiation to the prostate because that part of the body has already tolerated the maximal dosage of radiation,” says Hu.  “But at some centers, they will put some radioactive seeds (this is called brachytherapy) in the area where the cancer is, or within the prostate.”

What about surgery?  Many centers do not offer “salvage” prostatectomy, “because the delay in diagnosing the recurrence means the cancer might have spread.  Some salvage radical prostatectomy series [studies] showed that the likelihood of cure (with surgery after the radiation) was only 20 to 30 percent.”  Hu has performed 20 salvage robotic prostatectomies, but he makes sure his patients know that complications are much more likely when surgery is performed on an area that has undergone radiation therapy.  That’s because the tissue is already damage to start with.  “The incontinence risk, instead of being 1 to 2 percent, is now 50 to 80 percent for stress urinary incontinence (when urine leaks during certain activities, such as exercise), and there is a higher risk of the rectal tissue – which becomes fragile after being irradiated – developing a hole or tear (called a fistula).

Other options:  High-intensity focused ultrasound (HIFU) of the entire prostate is another option, and so is cryotherapy (freezing the tissue inside the prostate).  Both of these options, currently being offered at some centers as focal therapy, have a lower risk of incontinence and ED than salvage prostatectomy, Hu explains – but notes that here again, PSA will most likely not become undetectable after treatment.  Instead, it’s back to waiting for the PSA to reach its nadir.  And if you have a PSMA PET scan or other imaging showing that cancer has spread outside the prostate area, such as to bones, you and your doctor will need to discuss starting ADT, by itself or along with an androgen receptor-targeting drug such as enzalutamide or abiraterone plus prednisone for a combined punch.  These medicines lower testosterone, cutting off the cancer’s “fuel supply,” and can be effective for many years.

In addition to the book, I have written about this story and much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

© Janet Farrar Worthington