In interviews I conducted for the Prostate Cancer Foundation, Weill Cornell Medicine urologist Jim C. Hu, MD, MPH (whose expert opinion was also featured in book)discusses what a rising or persistent PSA means after treatment for localized prostate cancer and what to do next. Remember the first lesson from Part 1: Don’t Panic!
Suppose a prostatectomy patient’s first PSA after surgery was less than 0.02 in three months, but in one year it is 0.1. “If this patient is high risk (see below) first of all, this is a pretty clear signal that this particular patient is it will probably have a repeatHu says. “On the other hand, if this patient was Grade 2 Group (Gleason 3+4=7), had negative margins, had low-volume disease confined to the prostate, and subsequently had a PSA of 0.1; there is more comfort level to have a higher limit, to wait to let it state further.’ The advice here would be to wait another three or six months and check again. “You want to leave it long enough to see if anything has changed.”
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Do you have high-risk cancer?
Features that indicate aggressive cancer and a higher risk of recurrence:
*Positive surgical margins
OR
*Seminal vesicle invasion
OR
*N1 lymph node involvement
OR
*High grade cancer (Group 4 or 5, Gleason 8, 9 or 10)
OR
*Pathological stage T3b
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Is there a magic number that signals further action is needed? The American Urological Association and the Society of Urological Oncology recommend limiting it 0.2. “Some literature and research has suggested that you could even stop as low as 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 the 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 manifest itself.” (A genomic test can help, see below.)
A big question arises here: is it the actual prostate cancer that is causing the PSA to rise, or just some leftover prostate cells? “Everyone does this surgery a little differently,” says Hu. “It could be that some benign prostate tissue is left behind, especially if the surgeon did aggressive nerve sparing.” The nerves responsible for erection sit in two neurovascular bundles outside the prostate and remain intact in the nerve-sparing prostatectomy – if there is no cancer nearby. (If the cancer is very close, one or both neurovascular bundles may be removed.) But it’s possible that if a surgeon really tries to stay away from these nerves, some prostate cancer cells may be missed.
So, this prostate tissue could very well be benign – but because these are prostate cells and prostate cells produce PSA, this PSA could become detectable over time. Or, there may be cancer in this prostate tissue. “This goes back to risk,” says Hu, “and there needs to be shared decision-making or patient involvement in deciding 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 reaches 0.4 or higher,” explains Hu. “Many patients have a PSMA-PET scan before surgery if they have high-risk disease, but we often do a repeat PSMA-PET if their safety allows,” because their next step is salvage radiation. “The radiation oncologist may want this imaging study, too, to determine whether to expand the radiation field. But at a PSA below 0.4, it’s unlikely to light up anything’ to show if there is residual cancer and where it is.
What will happen next?
Let’s say a man has had a prostatectomy and one of his follow-up PSA tests shows that the PSA has gone from undetectable to 0.1 ng/ml. What should he do? Wait until the next test and see what happens. “To be in line with the guidelines, wait until the PSA reaches 0.2 before seeing a radiation oncologist.”
Could a genomic test provide useful information here? Decryption and other genomic tests look at prostate tissue (either from a biopsy or a prostate sample after a prostatectomy), they are looking for genes known to be involved in aggressive prostate cancer. If you didn’t have a genomic test at diagnosis, getting one now can help you determine your next steps. For example, using the Decipher score, cancer that is less aggressive is shown as less than 0.45. Intermediate risk cancer is less than 0.6 and high risk cancer is between 0.6 and 1.0.
How can this help you and your doctor decide what to do next? Do you need “salvage” radiation (radiation after prostatectomy)? And do you also need a temporary ADT course? Hu gives an example: “The PSA is 0.2 or higher. Let’s send Decipher, see if it’s favorable, and then we can just do the radiation without androgen deprivation therapy (ADT).’ That’s where shared decision making comes in, because of the unwanted side effects of ADT. There are many reasons, ranging from masculinity concerns to bone fracture concerns, why a person 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 timewarns. “If it were me, I would do the short course, four to six months of ADT, along with the radiation to make sure we get the cancer. We’ve already lost an opportunity to find a cure.”
Treatment options
The standard of care treatment for a rising PSA after prostatectomy is salvage radiation therapy at prostate bed(where the prostate was located) and possibly at the entire basin. The National Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) guidelines recommend that if a patient has high-risk characteristics (see above) after prostatectomy and if there is a short PSA doubling time (if doubled in less than 6 months), he should also receive an additional four to six months of ADT for salvage radiotherapy. “This maximizes the chance of a cure,” says Hu.
Note: If salvage radiation therapy is the next step for you, sooner rather 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 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 been through the turmoil of surgery. This means that the risk of side effects, including problems with urinary control, DM and bowel function, is inherently higher.
Summing up:
If this feels confusing… understandably so. These decisions are complex, and because each patient’s situation is unique, there is no one-size-fits-all answer. In general, consider the following limits and consult your doctor:
- Don’t miss your PSA follow-up appointments.
- PSA rises to 0.1: Recheck in 3 months. Patients who had high-risk disease characteristics at the time of surgery may need to act earlier
- PSA rises to 0.2: See a radiation oncologist and consider genomic testing 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 area or elsewhere in the body. Consider starting salvage radiation therapy with or without ADT
Next: Part 3: What if PSA When does it become undetectable after prostatectomy?
In addition to book, I have written about this story and many more about prostate cancer on the Prostate Cancer Foundation website, pcf.org. The stories I have written are in the “Understanding Prostate Cancer” and “For Patients” categories. As Patrick Walsh and I have said for years in ours books, Knowledge is power: Saving your life can start with going to the doctor and knowing the right questions to ask. I hope all men put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s and if you are of African descent or have a family history of cancer and/or prostate cancer, you should be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask.
© Janet Farrar Worthington
