Making Sense of PSA After Treatment, Part 2

Let’s say a prostatectomy patient’s first PSA after surgery was less than 0.02 at three months, but at one year is 0.1.  “If that patient is high-risk (see Box) to begin with, that’s a pretty clear signal that this particular patient is probably going to have a recurrence,” says Hu.  “On the other hand, if that patient were Grade Group 2 (Gleason 3+4=7), had negative margins, had low-volume disease confined to the prostate, and then had a 0.1 PSA, there’s more of a comfort level in having a higher threshold, in waiting to let it declare itself further.”  The advice here would be to wait another three or six months, and check it again.  “You want to give it long enough to see if anything has changed.”

Is there a magic number that signals further action is needed?  The American Urological Association and the Society of Urologic Oncology recommend a cutoff of 0.2.  “Some literature and research have suggested you could even hold off until 0.4,” notes Hu.  “The new guidelines say that for detectable PSA after radical prostatectomy, when radiation therapy is considered, clinicians should provide salvage radiation when PSA is less than or equal to 0.5.  At 0.4, there is still debate among radical prostatectomy surgeons that you could wait longer to let the cancer declare itself.”  (A genomic test may help; see below.)

Here’s a big question:  is it actual prostate cancer causing the rise in PSA, or just some leftover prostate cells?  “Everyone does this surgery a little differently,” says Hu.  “It could be that a little bit of benign prostate tissue was left behind, especially if the surgeon did aggressive nerve sparing.”  The nerves responsible for erection sit in two neurovascular bundles outside the prostate, and are left intact in the “nerve-sparing” prostatectomy – if there is no cancer nearby.  (If cancer is too close, one or both neurovascular bundles may be removed.)  But it is possible, if a surgeon is really trying to stay away from those nerves, that some prostate cancer cells may be missed.

Thus, this prostate tissue could very well be benign – but because these are prostate cells, and prostate cells make PSA, that PSA could become detectable over time.  Or, there could be cancer in this prostate tissue.  “This comes back to the risk,” says Hu, “and there needs to be shared decision-making, or patient involvement, in the decision of what to do next.”

Can PSMA-PET imaging help?  Yes, but not when the PSA is very low.  “PSMA-PET is unlikely to show anything until the PSA gets to 0.4 or higher,” Hu explains.  “Many patients get a PSMA-PET scan before surgery if they have high-risk disease, but we often do a repeat PSMA-PET if their insurance allows it,” because their next step is salvage radiation.  “The radiation oncologist may want that imaging study, as well, to determine whether to extend the radiation field.  But at PSA below 0.4, it’s unlikely that anything is going to light up” to show whether there is residual cancer, and where it is.

What Happens Next?

Let’s say a man has a prostatectomy and one of his PSA follow-up tests shows the PSA has gone from being undetectable to being 0.1 ng/ml.  What should he do?  Wait until the next test, and see what happens.  “To be concordant with guidelines, you wait until the PSA reaches 0.2 before you see a radiation oncologist.”

Could a genomic test provide helpful information here?  Decipher^® and other genomic tests examine prostate tissue (either from a biopsy or from the prostate specimen after prostatectomy), looking look for genes that are known to be involved in aggressive prostate cancer.  If you did not get a genomic test at diagnosis, getting one now may help determine your next steps.  For example, using the Decipher score, cancer that is less aggressive shows up as less than 0.45; intermediate risk cancer is less than 0.6, and high-risk cancer is from 0.6 to 1.0.

How might this help you and your doctor decide what to do next?  Do you need “salvage” radiation (radiation given after prostatectomy)?  And do you need a temporary course of ADT, as well?  Hu gives an example:  “’The PSA is 0.2 or higher.  Let’s send off the Decipher, see if it is favorable, and then we can just do the radiation without androgen deprivation therapy (ADT).’  That’s where shared decision-making comes into play, because of the undesirable side effects of ADT.   There are many reasons, ranging from masculinity concerns to worries about bone fracture, why the individual may want to avoid ADT – and a low or intermediate Decipher score may reinforce their desire to avoid it.”  But the stakes are higher this time, he cautions.  “If it were me, I would take the short course, four to six months of ADT, along with the radiation to make sure that we get the cancer.   We’ve already missed one chance to get a cure.”

Treatment Options

The standard of care treatment for a rising PSA after prostatectomy is salvage radiation therapy to the prostate bed (where the prostate was) and potentially to the entire pelvis.   The National Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) guidelines recommend that if a patient has high-risk features (see above) after prostatectomy, and if there is a short PSA doubling time (if it doubles in less than 6 months), he should also get four to six months of ADT in addition to salvage radiation therapy.  “This maximizes your chance at a cure,” says Hu.

Note:  If salvage radiation therapy is the next step for you, sooner is better than later, and this is why early PSA monitoring is so important.  “There is strong evidence that for a detectable PSA after radical prostatectomy, salvage radiation is more effective when the PSA is at 0.5 or lower,” says Hu.  However, if you are at high risk for clinical progression, and you have a detectable PSA, your doctor may recommend starting salvage radiation when the PSA is at 0.2.  “Here again, shared decision-making is really important,” because salvage radiation is going to an area that has already gone through the upheaval of surgery.  This means that the risk of side effects, including problems with urinary control, ED, and bowel function, is inherently higher.

To Recap:  

If this feels confusing….that’s understandable.  These decisions are complex, and because each patient’s situation is unique, there’s no one-size-fits-all answer.  In general, consider the following thresholds, and consult your doctor:

• Do not skip your PSA monitoring appointments.
• PSA rises to 0.1: Recheck in 3 months. Patients who had high-risk disease features at surgery may need to act sooner
• PSA rises to 0.2: See a radiation oncologist and consider a genomic test of prostate tissue to better understand your risk of aggressive, recurrent prostate cancer
• PSA rises to 0.4: Consider a PSMA PET scan to look for small amounts of cancer in the pelvic region or elsewhere in the body.  Consider starting salvage radiation therapy with or without ADT