Persistent psa

[Bkln77]

I’m wondering if anyone has had experience with benign prostatic tissue left behind after RP. My husband was diagnosed in 2019 with psa 16 and gleason 3+4. He had RP in August 2019 and his post surgery psa was .644. An mri showed a nodule at the bladder neck and a cystoscopy confirmed it was benign prostatic tissue. Since then psa has bounced up and down ranging between .31 and .64 with no way of knowing if the psa is from the benign prostatic tissue or cancer or both . He had the 18Fpyl psma scan at Columbia in Nov. 2019 with no uptake and the Ga68 psma scan at UCLA in Jan. 2021 with no uptake. Radiation has been suggested but with a less than 50% chance that cancer would be in the prostate bed and the side effects/morbidity associated with radiation he is not anxious to radiate without a target. The medical oncologist said this is a very unusual case and he is ok monitoring psa as long as it does not spike up. Any similar experience or advice is greatly appreciated!

[Tall_Allen]

PSA from benign tissue vanishes quickly, while PSA from cancerous tissue persists.

goldjournal.net/article/S00...

ncbi.nlm.nih.gov/pmc/articl...

ncbi.nlm.nih.gov/pmc/articl...

It is worth understanding what serum PSA actually measures.

Benign prostate tissue that is not damaged by cutting, handling, BPH or prostatitis contributes no PSA to serum PSA levels. All men with healthy prostates express lots of PSA on their prostate cells, but it only gets into the serum if the prostate cells are damaged in some way. When such cells are cut, irradiated, or physically handled, their PSA leaks out into the blood. However, PSA half-life in the blood is about 2-3 days, so within a month, their PSA is no longer detectable.

Cancerous prostate tissue, on the other hand, develops its own blood supply. The blood vessels generated are "leaky" so the PSA leaks out at an increasing rate into the serum. Some days more leaks out, some days less. But as the tumor grows there will be more PSA detected over time.

PSMA scans are not good for detecting cancer at or near the prostate because the currently approved PSMA scans (Ga-68 and Pyl) are excreted via the urinary tract. It also can't detect low grade PCa - PSMA expression increases with grade. Even if there were a "target," there are size detection limits - tumors less than 5 mm are not detected - so the entire prostate bed must be treated.

[Bkln77 in reply to Tall_Allen]

Thank you!

[Justfor_]

The signature of PCa is an exponential PSA rise. Frequent PSA tests is the only available tool for descerning any underlaying consistent trend masked by overlaid random components. If you have at least 10 time samples I can do the number crunching and offer a personal opinion. FYI, I had my RP two months earlier than your husband and next week I will have my 27th PSA test.

[Bkln77 in reply to Justfor_]

Thanks! Here are his twenty post prostatectomy PSA’s: 10/7/19 .614; 10/09/19 .644; 11/15/19 .527; 11/21/19 .552; 12/30/19 .553; 2/24/20 .412; 3/17/20 .41; 4/16/20 .399; 6/3/20 .306; 7/20/20 .32; 8/24/20 .308; 10/7/20 .434; 10/29/20 .434; 11/20/20 .489; 12/28/20 .452; 1/19/21 .414; 3/30/21 .638; 4/28/21 .438; 6/1/21 .448; 7/28/21 .5

[Justfor_ in reply to Bkln77]

On a first glance I detect two phases:

a) A smooth and consistent decline up until mid 2019 and

b) A gradual rise since then.

The second is the important part to analyze.

There are two samples though that look quite suspicious:

1st) 3/30/21 .638, probably erroneous.

2nd) 7/28/21 .5, probably originating from another lab reporting to a single decimal point.

There is also this sample 7/20/20 .32 that may originate from a different lab reporting to two decimal points.

1. Worst case analysis comprising all 12 samples starting and including nadir of 6/3/20 .306

1.1. Linear regression coefficient R = 0.698, log regression coefficient R = 0.736 indicating a weak correlation (less than 0.85 for a strong one) but giving a tiny likelihood of a log prevalence.

1.2. Estimated doubling time for linear / log DT = 17.9 / 18.8 months, the exact opposite of what anticipated according to the regression coefficients, i.e. if log prevailed a shorter log DT should had been noticed.

2. Improving things by dropping the 3/30/21 .638 sample.

2.1. Linear regression coefficient R =0.767, log regression coefficient R = 0.765.

Both regressions got tighter, though not to a high confidence level, but at least there is no more the anomaly with the estimated DT which now becomes:

2.2. Estimated doubling time for linear / log DT = 20.7 / 22.0 months.

My conclusions: No indication of an exponential PSA rise. On the contrary if all 20 samples were analyzed the conclusion would had been that 5 years after RP your husband would had reached the undetectable level. Check if there has been any systemic reason for the nadir during mid 2019. The worst case scenarios that I analyzed do NOT support any additional treatment at this point in time. This comes in agreement with your doc's advice. In your husband's shoes I would just continue close monitoring the PSA, nothing more. Best of luck.

[LearnAll]

There is no certain way to tell whether PSA is coming from cancerous cells or benign cells...BUT there are some clues to know....If PSA is fluctuating from one reading to another ..it usually means that either Benign hyperplasia or prostatitis is causing the rise.When the PSA rise comes from prostate cancer cells, it rises in steady fashion and only has upward trajectory. Absence of uptake on Ga68 PSMA PET indicates that whatever little rise in PSA is NOT coming from cancer cells.

Agree with MO ..that PSA needs to be monitored closely and not to get alarmed as long as there is no abrupt ,significant spike.

[Bkln77 in reply to LearnAll]

Thanks!

[tango65]

A PSA of 0.6 seems high to me to be residual tissue. A value of 0.6 is the mean PSA value for men in the 40s and 50s with a median prostate volume of a least 20 ml.

hopkinsmedicine.org/health/...

ncbi.nlm.nih.gov/pmc/articl...

If they did not do a biopsy during the cystoscopy and one wants to have more certainty there is a Ga68 PSMA 1007 PET/CT developed in Germany which is not excreted in the urine like the Ga 68 PSMA 11 PET/CT or the DCFPyl PET/CT used in the USA. This technique perhaps may help to identify if the nodule is PC. If consider a possibility you could contact : [e-mail] and find out if this technique may be of any help.

jnm.snmjournals.org/content...

You could also inquiry with the radiologists if a mpMRI (multi parametric MRI) of the pelvis may help to identify if the nodule is a benign or a cancerous lesion.

[Bkln77 in reply to tango65]

Thanks. They did do biopsy during the cystoscopy and when they pathology said benign prostatic gland we were hopeful the psa would go way down with some of the nodule removed but it has just continued to bounce around.

[LearnAll]

"PSA continues to bounce around" That's good. It could have been worrisome if it was rising continuously in straight, upward slope .

[luis85715]

SORRY WHAT HAPPENS, MY PROSTATE WAS REMOVED IN 2012 AND MY PSA WAS ZERO FOR TWO YEARS, AFTER THAT START GOINF UP SLOWLY DIFERENT MEDICATION TO KEEP PSA UNDER CONTROL, THEY WORK FOR A WHILE UNTIL YOUR BODY RESISTED THE MED. THE SOONER YOU ATTACK WHATEVER IS LEFT FROM CANCER IS BETTER. I AM STILL FIGTING THESE UP AND DOWN OF PSA, I RECEIVED INMUNITHERAPY, RADIATION, NOW LOOKING TO GET PSMA CT SCAN IN SAN FRANCISCO TO FIND OUT IF I CAN GET THE PSMA THERAPY WHICH IS NOT YET APPROVED BY FDA. KEEP IT UP I AM STILL DOING NORMAL LIFE I AM 64 YEARS OLD.