The Case for usPSA

[MrProstate]

Ultra-sensitive PSA (usPSA) testing after radical prostatectomy (RP) allows for the early detection of biochemical recurrence (BCR) at very low PSA levels (typically <0.01 ng/mL). While studies suggest it does not necessarily improve outcomes for salvage radiation therapy (SRT), it may have benefits in emerging treatment approaches such as immunotherapy or radioligand therapy.

Potential Benefits of Ultra-Sensitive PSA Testing

1. Early Detection of Molecular Recurrence

• usPSA testing can detect rising PSA months or even years before conventional PSA tests reach the 0.2 ng/mL threshold for BCR.

• This may allow for closer monitoring and earlier intervention with novel therapies before overt metastases develop.

2. Optimizing Patient Selection for Immunotherapy

• Immunotherapy is more effective when tumor burden is minimal. Early PSA rises may help identify patients who could benefit from checkpoint inhibitors or therapeutic cancer vaccines before macroscopic disease is present.

3. Potential for Early Radioligand Therapy (RLT)

• Radioligand therapies (e.g., PSMA-targeted therapies) work best when disease is still limited to microscopic or oligometastatic levels.

• Detecting very low PSA levels early could guide the use of PSMA PET imaging to identify small-volume disease earlier, potentially improving the efficacy of RLT.

4. Risk Stratification and Individualized Surveillance

• Ultra-sensitive PSA trends (e.g., PSA doubling time) provide insights into disease aggressiveness.

• This can guide decisions on whether to intensify monitoring, initiate early systemic therapies, or defer treatment in slow-rising cases.

Limitations in Salvage Radiation Therapy (SRT)

• Studies suggest no significant improvement in SRT outcomes by initiating treatment at ultra-low PSA levels.

• Radiation efficacy may depend more on PSA kinetics and imaging findings than on absolute PSA levels.

Conclusion

While ultra-sensitive PSA testing may not change the timing of salvage radiation, it could be valuable in identifying candidates for immunotherapy or radioligand treatment at an earlier stage when tumor burden is lower, potentially improving outcomes.

[MelodyCat]

Very interesting ideas here. I think the driver to get this done would indeed be a therapy that has a significant effect on OS (I still am foolish enough to believe in a cure) from super early detection. Going into the weeds, my theory would be to do somatic testing on circulating tumor cells and then do the breakthrough mRNA approach they are starting in Russia and hopefully here. My guess is that there wouldn’t be many variants in the cell lines when the tumor burden is very low. Hey, a girl can dream!

[NanoMRI]

uPSA was my choice post RP, over nine years ago. That decision has served me very well. Post my unsuccessful salvage RT, at 0.093, I had the Ferrotran nanoMRI and then my third treatment, salvage extended pelvic lymph node surgery (not surprised neither is mentioned).

[allie2020 in reply to NanoMRI]

It was also my choice after my RP in 2018. Thankfully, all of mine have been undetectable. Just had my annual uPSA completed last week and it came back <.006. I am grateful and it gives me peace of mind to see it <.006 rather than just <.1.

[NanoMRI in reply to allie2020]

Fabulous!! 7 years - very envouraging!!

[petabyte]

I'm very happy that the hospital I am being treated at does ultra sensitive PSA testing. I have had RT and find it reassuring. Mostly the argument against is related to anxiety and not being able to treat until it gets above .1 anyway.

If PSA starts increasing I'd like to see the trend in as much detail as possible and have time to investigate options even if it ultimately turns out to be a bounce or something else.

For people that can't cope with this information, they should have the hospital/doctor filter it and only report < .1. Admittedly not very feasible with automated reporting and commercial labs.

[street-air]

” Detecting very low PSA levels early could guide the use of PSMA PET imaging to identify small-volume disease earlier,”

not sure how this works since psma is useless below 0.10 and this text talks about 0.01

[kiteND in reply to street-air]

I don't think PSMA is useless when PSA is below 0.10. I've heard that before, but there are many men, like me, who consistently have <0.10 PSA and have mets show on a PSMA. I am receiving Pluvicto, which requires mets revealed by a PSMA, but my PSA has been "undetectable" for nearly three years.

[street-air in reply to kiteND]

that's good that it worked for you however given that, overall, statistics apparently say it rarely works when PSA is very low, it is still unclear to me how you can use a negative result to make any decision. Of course if you have a positive result, that's good. But rare. You might be 1 in 99.

[dans_journey in reply to kiteND]

I've had three 68-Ga PSMA PET scans at PSA levels of 0.23, 0.37, and the most recent a week ago at 0.95. All three "showed no sign of prostate cancer or metastatic disease."

BTW, I had a RP in January 2011 (Gleason 3+4); went just shy of five years of undetectable PSA. Took another six years for PSA to climb to 0.2. Had 35 sessions of SRT (70 Gy) to prostate bed only at 0.36. It failed and my PSA, as stated, is now 0.95.

For me, the PSMA PET scans have been useless in locating any lesions. I meet with my Dr. on 1 April to discuss if I'm one of the 10% for whom PSMA PET scans don't work.

[BOEBOE2]

Thanks, seems we are having very similar thoughts about uspsa I haven't seen much about RLT yet so will be looking into it proactively (so far so good 0.006 ng/ml 4 months after RP , 0.01 ng/ml approx 6.5 months after RP .... next in 3 months from now)

would you have some links to the studies referred to concerning "Limitations in Salvage Radiation Therapy (SRT)" Studies suggest no significant improvement in SRT outcomes by initiating treatment at ultra-low PSA levels." ?

[MBSurfer]

The important and real questions are whether earlier ‘detection’ leads to improved progression free survival/cancer specific survival and the number of patients ‘salvaged’ unnecessarily.

[London441 in reply to MBSurfer]

Studies show no benefit treating recurrence below .1. USPSA is great for assisting worry about recurrence though so there’s that.

I had truly ‘adjuvant’ treatment post RP 5 years ago (RT, abiraterone, chemo) with undetectable PSA in a clinical trial. I was definitely high risk, and so far it has produced the desired result.

However, the cumulative effect and consequences are ongoing and have been permanently life changing. If I had it to do again I would look for hard evidence it would make a difference. None exists now, much less 5 years ago. Such trials were essentially based on wishing and hoping, and not enough has been revealed to change that.

How I would proceed today? As I have. The elements in my control, particularly exercise, are better choices to bet my life on.. I certainly wouldn’t be wasting my time getting USPSA’s at near undetectable levels.

[Papa1]

Source???

[street-air in reply to Papa1]

if OP says an AI then I will bang my head on the keyboard.

[petabyte in reply to street-air]

Based on the style I assumed the text was from an AI but I don't have a problem with that although I think posters should identify the AI and model used.

I asked chatgpt (o3-mini reasoning with web search) to factcheck and supply references. 🕵🏻️

chatgpt.com/share/67e0ddf9-...

Remember. Just because there are published studies with conclusions or conference presentations does not make it true. The quality of the study and level of evidence matters.

BTW, I did not bother to check those links since this topic is not relevant to my case. Sometimes links from chatgpt don't pan out. Perplexity is better for this. If you are interested try that using "Deep Research".

[EdBar]

When I was undetectable I always got a usPSA per Snuffy Myers. It gives you an early alert that something is brewing.

Ed

[j-o-h-n]

Thanks for clearing that up.......... all this time I always thought the "us" stood for "us" in the "united states".

Good Luck, Good Health and Good Humor.

j-o-h-n

[Lost_Sheep]

MrProstate, this is EXACTLY what I need to convince my medical team (especially the Laboratory head) to let me have ultrasensitive testing (usPSA).

But I need supporting documentation. Clinical studies, peer-reviewed medical journal articles, approved "best practices" protocols, etc to put forth my case.

I had such support for me enrolling myself in my "clinical trial of one" use of estradiol to suppress my rapidly rising post-prostatectomy PSAs. I had partial success - my oncologist promised not to "fire" me if I used E2, but would not prescribe it themselves. So, I got another practitioner to write the script. My PSA is now below the standard test's ability to detect/report (0.014 ng/mL).

To get to where I am, I assembled a 13-page presentation "Proposal for Androgen Deprivation Therapy (ADT) using off-label Trans-Dermal Estradiol (TDE) for suppression of Prostate Cancer (PCa)”. This (and my face) was enough to get me this far.

To get my oncologist and laboratory to go along with usPSA testing, I would need substantial support (such as you apparently have researched). Can you share titles and/or links?

Thank you. You may be saving a life or two.

edited to add: I have weekly PSA and hormone testing and monthly CBC and CMP as well for an abundance of caution over unintended consequences to organ function. I do not worry at all about minor variations (varying from below 0.014 to 0.17 over the past 5 months). My immediate goal is to get as early a warning of castrate resistance developing.

[Justfor_ in reply to Lost_Sheep]

With your weekly PSA testing you gain an additional decimal place in precision compared to someone else testing quarterly at the same lab. Oversampling reduces random measurement errors.

[dans_journey]

One aspect that you fail to address is PSA Anxiety.

In my 14+ years of dealing with this disease and hanging out in forums like this, I've seen a number of men go into panic mode when their PSA goes from 0.003 to 0.005. IMHO, usPSA tests amplify that anxiety, and the patient's mental health needs to be fed into consideration as well.

As you say, it could lead to earlier treatment, but is that treatment really necessary?

I had an RP (3+4, no LNI, ECE, SVI) and it took nearly five years for my PSA to become detectable at 0.05 ng/mL (my provider uses an assay that calls anything less than 0.03 undetectable). For 18 months, my PSA bounced around between 0.04 (went down slightly) to 0.08 before it started a true upward climb.

My PSA doubling time was measured in years, so we agreed to just monitor it. It took another six years (without any intervention) for the PSA to reach 0.2 ng/mL. A year later, it was at 0.36 when we started 35 sessions of SRT to the prostate bed with a six-month dose of concurrent ADT.

Sadly, the SRT/ADT failed, too, and now nearly 3 years after completing it, my PSA is 0.95 ng/mL. The SRT has slightly worsened my incontinence issues and I also had a very mild case of radiation proctitis that was addressed during a recent colonoscopy.

The point of sharing all this is that I believe using usPSA tests may pressure patients to acting when they can afford to wait without incurring additional side effects from treatment. I had 8 or 9 good, quality years without the side effects of additional treatment.

My decision to delay was right for ME.

Lastly, I've had three PSMA PET scans at 0.23, 0.37, and 0.95, and all three showed "no sign of prostate cancer or metastases."

Of course, every case is unique and my circumstances may be more the exception than the rule.