study on 5th generation uPSA assays with interesting recurrence information

[ManuteBol1]

I came across this study from 2011 where Partin et al were researching the reliability of a 5th generation digital immunoassay for PSA using single molecule arrays. This particular test measured to less than 0.1 picograms, so more than 1/1000th more sensitive than the standard testing sensitivity of 0.1 ng/ml.

In addition to proving that the 5th generation test was accurate and effective, a conclusion of the paper was that this 5th generation assay was was able to show bifurcation in eventual BCR likelihood in men from these extremely low levels of PSA. What I found most interesting were the closely followed PSA levels over the first 18 months or so post-surgery and the implications these had for eventual BCR. If I interpreted the information correctly, no one recurred that had a reading of less than 0.003 ng/ml during those first 18mos. Other interesting things I noticed is that there were a number of Gleason 3+2 patients that had surgery and that a Gleason 8 and Gleason 9 were among those that didn't recur (although most of those that recurred, did have unfavorable pathology, staging etc.)

This begs the question: why are these super-super-sensitive assays not widely available? Cost? Something else? It seems like the recurrence fears for many men could be put to rest with a test like this. I, for one, would like to know what my "true" PSA is post surgery. While I'm <0.006 and blessed for now, this data would suggest that knowing if I'm <0.003 has (maybe a lot of) value. This study, while small, is yet another data point that increases my belief in the value of the uPSA.

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

[NanoMRI]

Have not yet seen this - thank you! I have been a strong believer in uPSA testing since my post RP nadir of 0.051 nine years ago next month.

I think the resistance is largely based on the reality docs following common guidelines do not know what to do with very low uPSA, especially as it remains difficult to find the cancer. And, as the medical complex is moving towards treating this disease as a chronic illness with ADT, what is the rush?

As I share, my third treatment, salvage ePLND, confirmed six cancerous pelvic lymph nodes at 0.13, this after successful imaging following failed salvage RT to prostate bed.

[petabyte]

Interesting.

I'm new to PSA testing. So far I have had tests from a private lab and a hospital lab.

Can you know from the quoted figure what type of test they use?

This was from the lab six weeks after RT 0.388 μg/L (I have a prostate)

Latest PSA from the (University) Hospital 0.0452 μg/L 3 months later with one more decimal digit. I'm guessing that based on the precision this is ultra sensitive? (is it 5th gen?)

[ManuteBol1 in reply to petabyte]

The uPSA testing, for the most part, is only useful for those of us w/o prostates!

[petabyte in reply to ManuteBol1]

Because of fluctuations unrelated to BCR? I get that but trends will still be more reliable with more precision. The hospital is a university hospital so I guess they have a good test for research purposes.

from chatgpt

1 Post-Treatment Monitoring in Specific Scenarios:

• After Radiation Therapy (RT): Even with a prostate intact, PSA is expected to decline significantly.

• Ultrasensitive PSA tests can help monitor the effectiveness of treatment or detect early signs of biochemical recurrence (BCR) if the PSA level starts rising consistently.

• Combination Therapy: If you’re receiving additional therapies (e.g., ADT + abiraterone), ultrasensitive PSA tests might help track response to treatment with greater precision.

2. High-Risk or Aggressive Prostate Cancer:

• For patients with high-risk disease, ultrasensitive PSA tests can provide earlier insights into subtle changes that may signal recurrence or progression.

3. Research or Specialized Monitoring:

• In specialized centers or research settings, ultrasensitive tests might be used even with a prostate to monitor PSA trends more precisely.

[petabyte in reply to petabyte]

But I take tall Allen's point that it probably won't impact treatment so is probably not useful in my case, although not knowing causes more anxiety for me.

[Tall_Allen]

They became irrelevant in 2019 when 3 randomized clinical trials proved that salvage radiation when biochemical recurrence was found was non-inferior to adjuvant treatment.

prostatecancer.news/2019/09...

[ManuteBol1 in reply to Tall_Allen]

The Kang 2015 paper would say that a lower threshold (0.03 ng/ml) is better for high risk patients. pmc.ncbi.nlm.nih.gov/articl...

I have difficulty getting my head around anyone telling people to abstain from even investigating where the bad cells might be when they start rising from a very low uPSA number. You know where you are eventually headed if you cross these lower (than 0.2) thresholds like 0.03. I feel the advice to wait stems, in part, from the limits of imaging detection. If we had better imaging or a perfect knowledge of where the bad cells were, there would be no advising of 'waiting around' and walking closer to the road of lifelong ADT versus a cure chance.

The PSMA-PET scans have been a big jump in technology and I'm sure more are coming. There are those on this forum who have found the locations of their mets via other imaging technologies that are outside the SoC. There are probabilistic distributions of where cancer is likely remaining with recurrences after surgery. It seems that the patients that are seeing detectable recurrences from uPSA should at least be given probabilistic information on where it might be and what other imaging options are out there, even if it's low chance of detection and then let the patient make their decision on treatment, knowing that it could be over-treatment.

I look at it as there is a binary point during the 'recurrence' process. At some point, one cell tips the scales to recurrence somewhere, be it a local or a distant growth. Best to not give a chance to that one cell.

[Tall_Allen in reply to ManuteBol1]

Ignoring the best evidence is a mistake.

[Hidden in reply to Tall_Allen]

Ultrasensitive PSA has prognostic utility for men post RP. Unfortunately current treatment paradigms mean that the clinical outcome of men will not change with these assays. By way of example if an effective say immunotherapy or other systemic therapy becomes available and is demonstrated to be potentially curative at very low PSA then UPSA would become clinically significant.

Till then all the very best of luck to all of us.

[Tall_Allen in reply to Hidden]

"Ultrasensitive PSA has prognostic utility for men post RP. Unfortunately current treatment paradigms mean that the clinical outcome of men will not change with these assays"

No. it doesn't. You can't just fantasize about medical science - clinical proof is required.

[Hidden in reply to Tall_Allen]

Clinical proof about what exactly?

[Tall_Allen in reply to Hidden]

That uPSA...

1. ...has "prognostic utility for men post-RP." We now have the highest level of evidence that only conventional PSA ≥ 0.2 is needed.

2....has any value for any salvage treatment for men post-RP.

[Hidden in reply to Tall_Allen]

Sorry mate but uPSA does have exceptional prognostic ability when it comes to predicting BCR free survival after prostatectomy independent of other prognostic factors in MVA. This type of information can empower men by reducing anxiety related stress, possibly avoiding over treatment and maybe even reduce follow-up schedules. The importance of the psychological wellbeing of a man diagnosed with this disease cannot be underestimated.

As for your point 2……you won’t get any dissenting views from me.

[NanoMRI in reply to Hidden]

My use of uPSA testing, nine years now, provides me far more than stress reduction and psychological wellbeing. Most importantly, it lead to my decision for salvage ePLND at 0.13.

[ManuteBol1 in reply to Hidden]

Great points. My mindfulness quotient, for lack of a better term, is poor. In my case, knowing my PSA was <0.001 could put the disease out of my mind much more than knowing I was only <0.1.

[TJGuy in reply to ManuteBol1]

So if you had radiation to the prostate, your recurrent PSA value is considered your PSA nadar plus 2.0. so this is very different than after prostatectomy.Now any PSA test I described below is while not on any PC drugs such as hormone drugs.

If you had prostatectomy your PSA 6 weeks after RP is very important and you should have a uPSA test that can measure to less than 0.02

LabCorp Ultra sensitive measures to 0.006.

That is because at 6 weeks post RP, if your PSA is equal to or greater than 0.03 you are likely to have recurring PC. If your uPSA is equal to or less than 0.02 your not likely to have a recurring PC.

[Tall_Allen in reply to Hidden]

Sorry mate, but "prognosis" in oncology refers to the probability of survival.

cancer.gov/about-cancer/dia...

Even if you meant "prediction," youu still missed the point, which is that there is no benefit in predicting a BCR. 3 RCTs have now proven that there is no ad vantage to treating before a BCR.

Rather than "empowering" and reducing anxiety, as you imagine, a uPSA only ser ves to increase anxiety. What lessens anxiety is a conventional PSA test with reports of <0.1. It is uPSA that creates unnecessary anxiety and overtreatment. To see the harm, you only have to read all the threads on this forum that begin "I got a uPSA of 0.03 --should I be worried?"

[Hidden in reply to Tall_Allen]

This from the National Cancer Institute

prognosis

(prog-NO-sis)

The likely outcome or course of a disease; the chance of recovery or recurrence.

We can play semantics all you like but my understanding of it’s meaning is sound. To state that prognosis only refers to survival is deliberately using a very narrow definition, but if you’re so inclined don’t let me stop you.

Numerous studies and publications unambiguously demonstrate that uPSA after a RP is an excellent prognosticator of the chance of BCR. Some conclusions made by several authors indicate that men with an undetectable uPSA <0.01 at 3 years post surgery have an excellent prognosis of 100% BCR free survival for 15 years. Others conclude that a uPSA <0.04 at 3 years confers an excellent long term BCR free survival. Both of these conclusions confer an excellent long term Metastasis free and Cancer specific survival. In one particular paper the authors acknowledged that benign uPSA fluctuations can occur in the range of 0.01 to 0.02 and that a definite increasing gradient of values above 0.03 on serial draws might be used as a definition of BCR.

I agree with you that fixating on minute fluctuations can be a source of anxiety for some. That’s purely a symptom of not understanding the use of these assays. That’s why I believe that proper counseling is imperative.

With proper counseling from knowledgeable doctors the information in the above mentioned scientific conclusions can be a source of immeasurable reassurance to a patient. That can only be a good thing.

Agreed that earlier intervention using currently available therapy may not translate to a better clinical outcome.

I maintain however, that with more effective interventions,that should become available in future,the paradigm of very early intervention will become valid. However that’s a discussion for another time perhaps.

[Tall_Allen in reply to Hidden]

You don't seem to understand "levels of evidence." Medical science is not predicated on your beliefs (or mine), it is based on evidence. We now have Level 1a evidence that uPSA is not necessary. This may help you understand how modern medicine is practiced:

prostatecancer.news/2022/07...

[Hidden in reply to Tall_Allen]

I think some clarification is needed.

I understand that the so called Level 1a evidence is that uPSA does not change the management of recurrent prostate cancer. I’ve stated that I agree with you that the clinical outcomes of BCR will not change with uPSA.

I GET IT.

This isn’t about what I believe or some personal opinion. Nor is it about what you perceive to be a true picture of my level of understanding.

UPSA is a valid prognostic tool that in the right context with proper counseling by a knowledgeable professional can serve to alleviate a man’s anxiety about recurrence. This can only be a good thing. The science behind this assertion is real. It is not just my opinion.

[Tall_Allen in reply to Hidden]

It is a relic of the past whose only purpose is to cause unnecessary anxiety. There is no science backing it up.

[Hidden in reply to Tall_Allen]

Your assertion that there is no science backing it up is incorrect. I stand by the science that is easily available to anyone with an interest on the subject.

UPSA has clear and meaningful prognostic relevance to men post prostatectomy. When readings are undetectable or low and stable this is a very good sign. This can serve to allay fears of recurrence any time soon if ever. That is a good thing. When readings are detectable and unstable they are not specific enough to indicate recurrence. So the consensus cut off of 0.2 is used as a trigger for salvage treatment.

Ultimately I don’t need to convince you of anything mate. That’s not what this is about.

All the very best.

[gsun in reply to Tall_Allen]

That’s exactly what i was thinking. It will increase stress in more people than it will decrease. And probably not affect treatment.

[NanoMRI in reply to Tall_Allen]

I am most grateful I did not wait until my PSA reached 0.2 post RP. Nine years in and uPSA continues to provide me prognostic utility.

[Tall_Allen in reply to NanoMRI]

What would have happened had you waited, and how could you possibly know?

[lhall2 in reply to Tall_Allen]

Here you go again. We all know your bias against uPSA. But you are right that no one really knows what would happen if we waited. For me, I am a believer in uPSA. My post RP standard PSA was <0.1 or undetectable. “Maybe they got it all or maybe they didn”t”. Switch to uPSA and recorded 0.028 & 0.026 all with the same lab. Decided on 40 rounds of whole pelvic radiation followed by 3 years of lupron, abiraterone and prednisone. Post radiation recorded 12 rounds of uPSA at a basic level of 0.014. 2 rounds of uPSA since stopping all treatment in May 2034 remains at 0.014. So post radiation uPSA about 1/2 pre radiation uPSA. Will reoccurrence happen? No one really knows , but I doesn’t make sense to me to let cancer grow in me until it become “detectable” if there is a question “did they get it all”. uPSA helps in early treatment decision and creates less anxiety not more

[Wgly in reply to lhall2]

Trial results are an averaging of the group response to treatment. It would be good to know if uPSA can identify those individuals who will be on the long tail of drug effectiveness. I've been a stable 0.008 for about 18 months, and it would also be nice to know if my treatment is holding or reaching its end of life, i.e. no surprises SVP

[Tall_Allen in reply to lhall2]

My bias, if you call it that, is toward science. I once believed, as you do, that it was important to treat as early as possible. Three RCTs convinced me to change my mind. That's how science works: we hold onto provisional hypotheses until we get better data. For 228 years, we believed that gravity was a force. Then, Eddington proved it wasn't.

What "makes sense" to you is immaterial. All that matters is what the data say.. You were overtreated because the uPSA caused anxiety in you.

[lhall2 in reply to Tall_Allen]

What causes me anxiety is a standard PSA of <0.1 or “undetectable “ but having a mildly aggressive Gleason (4+3) and 1 lump node with cancer. Maybe they got it all (<0.1 undetectable) or maybe they didn’t (one lump node with cancer). Thank goodness uPSA exist to help me decide my treatment. Maybe I was overtreated, but rather than that vs undertreated. Clearly my aggressive treatment approach produced 14 uPSA’s of 0.014 or nearly 1/2 of the 0.026/0.028 prior to aggressive treatment. Interesting all these readings would show up as <0.1 or undetectable. Will reoccurrence happen. No one knows for sure but I am comfortable with the decision I made with my medical team. The role of this community is to share our own cancer experiences so others can use those experiences in discussions with their medical team. I see many members of our community find value in using uPSA in their treatment. You do not. Maybe it is time for “science” to take another look at the value of uPSA

[Tall_Allen in reply to lhall2]

Men who have a cancerous lymph node, should have innediate (adjuvant) whole pelvic radiation. Your doctors were wrong to wait for any PSA test. You should have been spared the anxiety of waiting at all:

prostatecancer.news/2021/10...

Again, this proves that there is no need ever for a uPSA test -- either one is a candidate for a conventional PSA test (min PSA 0.1) or no PSA test - nothing in between.

[lhall2 in reply to Tall_Allen]

But they may have gotten it all as my standard PSA was <0.1 as defined by the medical community as “undetectable “

[Tall_Allen in reply to lhall2]

No, they could not have "gotten it all" with surgery. You had cancer in a lymph node. There are over a hundred lymph nodes in the pelvic region, and the just sample a few when you had a prostatectomy. Lymph is a fluid that carries metastatic cancer cells from one node to every other regional node. If there is cancer in one node, there is cancer in many.ALL of them have to be irradiated and simultaneous hormone therapy must be given if there is to be any hope of a cure. You should have received that treatment immediately, not waiting for any PSA tests of any kind.

[lhall2 in reply to Tall_Allen]

Escaping the prostate is always scary. But it all starts with one lymph node infected but like you said there is probably more. One person’s medical team might say the same thing you said about likelyhood of many infected lymph nodes needing radiation and ADT. However the patient after understanding the risk and potential adverse effects of further treatment, might go against their medical teams advice especially with a standard PSA of <0.1 or undetectable. Fortunately, for me the uPSA eliminated any possibility of not pursuing aggressive treatment. You need to understand patients might make the wrong decision on further treatment and should use “every tool in their tool box” to make the best decision possible. uPSA can be one of those “tools”

[Tall_Allen in reply to lhall2]

It only confused what should hav e been a straightforward decision for you.

[lhall2 in reply to Tall_Allen]

Not confusion but clarity.

[NanoMRI in reply to Tall_Allen]

*die from something else; the outcome for most of us, or so they say

*be one of the millions progressing to ADT

*be one of the avoidable deaths from this beast

A few of the what might happen - I know because these happen.

Alan, your flippant reply is one more example I continue to believe the dropping of the guideline to speak from experience degrades this forum.

[Tall_Allen in reply to NanoMRI]

It wasn't flippant. The reason we have randomized clinical trials is the only way to know what would have happened. What probablly would have happened to you is what did in fact happen to thousands of men in your situation.

There never was such a guideline to "drop."

[NanoMRI in reply to Tall_Allen]

and what would that have been?

BTW!

[j-o-h-n in reply to Hidden]

Greetings Olda,

Would you please be kind enough to update your bio with a some more of your personal and Pca history (age? location? meds? doctor(s)? treatment center(s). and etc.) All info is voluntary but it helps you and helps us too. Thank You!!!

Good Luck, Good Health and good Humor.

j-o-h-n

[j-o-h-n]

Gentlemen (and of course Ladies), I know you don't really care but this post has made me very very anxious............ (and on the day of infamy)...

Good Luck, Good Health and Good Humor.

j-o-h-n

[RMontana]

The standard assay uPSA available to most men in laboratories and the one you took providing uPSA readings <0.006, can also be used to predict BCR. Here is a post that I made sometime back. Based on this and other research that I did I asked for uPSA testing from the beginning of my PCa journey. My Dr's were not supportive but I insisted. I have also posted that for some men they may not want to know in advance, or may not benefit from knowing the 'train is coming down the tracks,' but if you are the type that wants to know then this article may be of use...the use of the conventional assay and cutoff (PSA ≥0.2 ng/mL) is flawed and in my opinion should not be used. But there is peace of mind not knowing your are going to fail, until you do...its our choice. Rick

From the article;

Any post-op PSA ≥0.03 captured all failures missed by first post-op value (100% sensitivity) with accuracy (96% specificity).

Defining failure at uPSA ≥0.03 yielded a median lead-time advantage of 18 months (mean 24 months) over the conventional PSA ≥0.2 definition.

uPSA ≥0.03 is an independent factor, identifies BCR more accurately than any traditional risk factors, and confers a significant lead-time advantage.

healthunlocked.com/active-s...

[Hidden in reply to RMontana]

Absolutely correct.

Some of us would like to have an idea of when BCR is likely to occur. While we can use scientific evidence that apparently shows no clinical benefit in very early salvage radiation, we must not assume that other forms of very early treatment fall into the same category. I for one would like to have that option. To bury my head in the sand is simply unappealing. Following standard treatment protocols may be alright for some but having the option to try different treatment alternatives at least for me, is very important.

A very high profile melanoma professor by the name of Richard Scolyer apparently thinks the same way. He was diagnosed with very aggressive glioblastoma and opted for a non standard treatment using immunotherapy and surgery. 18 months later he has no evidence of disease.

He is about to publish his paper on his treatment and clinical trials are now being planned. You can follow his story on Instagram.

[TJGuy]

So I went once to UNC medical center chapel Hill NC and spoke with a doctor there that had developed a uPSA test to 0.000. They no longer used the test because it was more expensive and few used it, so it wasn't economically successful.

They did offer a <0.01 test which at that time was the most sensitive available that I could find.

Later LabCorp reintroduced their <0.006 becoming the most sensitive test available to me.

[ManuteBol1]

At the risk of unleashing the hounds again, I did come across a very interesting Japanese study tonight with respect to a uPSA threshold of 0.008 and BCR probabilities. What I found most interesting in this particular study is that there seems to me a large subset of men that are initially <0.008 uPSA after surgery and then climb above that level, but then manage to stay <0.05 for a very long period of time (perhaps indefinitely), or even go above 0.008 and then back below it. There are other conclusions brought forth in the paper as well.

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