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Q&A: Rising PSA After Prostate Cancer Treatment

Many questions were submitted before and during PCF’s webinar on rising PSA after treatment for localized prostate cancer. Dr. Paul Nguyen responded to questions during the webinar and Dr. Ashley Ross provided responses to several select questions afterwards. Please note that this information is intended to help guide discussions with your medical provider and is not individual medical advice. We regret that we are unable to answer all questions.

View the webinar recordings here.

1.  How does age play into the treatment decisions?

Age can inform overall survival.  From time to biochemical recurrence to visible metastasis can be several years and from metastasis to death several years more.  Age and overall fitness should factor into the decision to pursue salvage treatments after initial attempts at local control.

2. After prostate removal, does the prostate grow back, just like liver re-generation? If so, will this cause rising PSA scores?

After prostate removal, if benign prostate tissue is left (for example, at the junction with the bladder or at the urethra) this can grow and cause the PSA to rise.  The biggest concern regarding PSA rise after surgery however is the presence of prostate cancer cells (which can also make PSA) and can be growing in the pelvis near where the prostate used to be, in pelvic lymph nodes, or in areas outside of the pelvis (i.e., bone or extra-pelvic nodal tissue).

3. Is there significance in terms of when after surgery the PSA starts kicking up – does a recurrence after, say, two/three years imply a better situation than a recurrence after two/three months?

Yes.  Time to PSA recurrence is important and the longer until recurrence the better.  Other important prognostic factors are PSA doubling time once recurrence occurs, initial Gleason score, and genomic risk (i.e., with Decipher).

4. What is the Decipher test?

Decipher is a genomic test (looks at the genes of the cancer cells) that can be run on routinely fixated and stored pathological tissue (a prostate biopsy or a prostatectomy specimen for example).  It is highly prognostic for disease progression (meaning it is a good indicator of disease risk) that goes beyond what we can understand form histologic (what it looks like under the microscope) and clinical data alone.   Decipher is widely available.

5. At what PSA level can a PSMA PET detect prostate cancer cells in the body?

Detection rates increase with increasing PSA level.  For PSAs of <0.5ng/ml disease can be detected 30-40% of the time, 0.5-1 about 50-60% of the time, and over 1ng/ml about 80% of the time.  Disease is rarely detected when PSA is <0.2ng/ml.

6. How often should one have a PSMA PET when PSA is rising?

There is no guideline for this.  After complete pelvic therapy (i.e., surgery and radiation), I typically will check when a man’s PSA rises to 0.4ng/ml and if the PET PSMA is negative I will check again when the value goes over 1ng/ml.

7. I have had a climbing PSA 6.5 years post-prostatectomy and was sent for radiation consult. My urologist then recommended the PSA with HAMA [human anti-mouse antibodies] and it shows that my PSA is still climbing but my HAMA is still undetectable.  Can I feel confident in the HAMA result and not worry too much about the PSA climb?

Sometimes.  Depending on the assay, HAMA positivity can just indicate that you make higher than normal human anti-mouse antibodies which can interfere with the assay used to measure the PSA.  Presence of Human Anti-Mouse Antibodies does not necessarily mean there is no PSA but rather can indicate that some of the PSA measured is spurious.  There are other assays that can be used to measure the PSA directly (I believe, for example, a goat antibody detection assay exists).

8. If one’s treatment team is recommending delaying radiation until PSA is high enough to more closely guarantee seeing disease on the PSMA PET, what do you do? Do these physicians recommend radiating without seeing disease on a PET (if PSA is rising and pathology reports show several adverse factors)?

Yes.  If someone has had surgery, I would recommend doing salvage radiation when their PSA hits 0.1 or 0.2 and not delay further just to be able to see something on a PSMA PET. I do not wait until the PSA is high enough to see something on a PET PSMA.  This can decrease the chance for cure.  Salvage radiation should be considered when the PSA is low (preferably not higher than 0.4ng/ml with most men undergoing treatment in the 0.05-0.2ng/ml range in my [Dr. Ross’s] practice).  Previous retrospective series demonstrated that the men who benefit most from salvage radiation are those without any detectable findings on PET PSMA.

9. I also had radiation following surgery due to positive margins. Then ADT for a year.  Beginning 2nd cycle of ADT.  PSMA PET shows slight development in seminal vesicles.  Oncologist will consider “pinpoint” radiation.  My question – can seminal vesicles be removed at this point?

They can be removed; that surgery has risks, however, and sometimes side effects can be very serious.  There are false positives in the PET PSMA, particularly in the seminal vesicles or prostate post-radiation, so prior to even considering removal I would suggest a biopsy of the area to confirm viable cancer.

10. If you have had surgery, ADT, and Radiation as treatments [with PSA at <0.008] and PSA begins to rise above 0.03, can you get radiation treatment a second time?

Not usually to the same area.  In these cases, I usually monitor the PSA and when it gets to 0.4ng/ml I get a PET PMSA scan to look for disease that was out of the previous radiation field (many times this is what is going on).

11. PSA rising after hormones, radical prostatectomy (no nerve sparing), 33 days of radiation. PSA in 2020 was 0.008. PSA in 2022 is 0.11. Next steps?

Continue to monitor;  when PSA reaches 0.4ng/ml get a PET PSMA.

12. I am 82, had a radical prostatectomy in 2005. PSA doubling time 2-3 years, now PSA is 1.2. PSMA PET SCAN normal. Do I need treatment?

I would lean away from more treatment particularly if your original Gleason score at prostatectomy was GG1 (3+3=6).  Men like this with PSADT >16mo almost never develop metastatic progression.  I would recommend continued monitoring.

13. My PSA was 0.007 three months post surgery, it is now 0.021 three months later. The value has tripled in three months, what does it mean?

It may not mean anything at these ultrasensitive levels.  It only implies that you should continue to track your PSA at 3mo intervals.  As the PSA rises above 0.03, it is more reliable, and I usually wait until 0.05ng/ml at least before considering more treatment.

14. I have seeds planted in the prostate and have been told I can’t have radiation treatment for rising PSA. Is this true?

This is usually the case.  The seeds were radiation, and getting more radiation in the area can cause serious side effects.

15. I’m 72. I had my prostate removed in early 2014. My PSA started rising two years later. I had a PSMA scan in April 2021 and it found no cancer cells. My PSA keeps rising, doubling in about 17+ months. My doctor and I are monitoring it every 6 months. I’m generally in good health, exercise regularly and I’m within 5 pounds of an ideal weight. Besides losing a bit of weight and staying healthy is there anything else I should do?

It depends.  For men with low Gleason score at prostatectomy (GG1), long time to recurrence and PSADT >16mo, metastasis almost never develops even without radiation therapy.