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.
Written by
MrProstate
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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!
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).
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.
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.
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.
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.
The decisions are made based on my PSMA or Choline-11 scans, which I get every three months. Unlike dan_journey, below, my scans show evidence of disease.
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.
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." ?
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.
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.
@MBSurfer too. I scheduled my salvage RT to prostate bed at 0.09X, same with subsequent salvage extended pelvic lymph node surgery. Although the RT missed some cancer the ePLND got me to <0.010 - that was seven years ago.
London441 can you cite actual studies that show no benefit below .1?
The ‘Artistic’ meta-analysis details this. However, this is for lower risk men. Adjuvant RT for higher risk ‘seems’ to be indicated, or ‘presumed’ the best option, if you will. ‘Higher risk’ meaning positive lymph nodes, SVI, Gleason 8-10 or especially a combination of these.
In other words (in my case) no one really knows 6 years later at this writing.
I really didn’t mind going for adjuvant since I had 2 of the 3 high risk factors, but again I would have skipped the RP altogether-definitely.
Good chat! I asked for studies because I do not recall that any of them (including Artistic) specify PSA values for timing of adjuvant vs salvage (I have not looked to confirm). My post RP nadir was 0.05 and with perineurial invasion, involved margins and capsular invasion I accepted my cancer was out. I pondered for ten months as my uPSA rose to 0.09 then to 0.113 at start of treatment. As my salvage RT to prostate bed was unsuccessful, nadir 0.075, it seems logical had I had adjuvant it would have been unsuccessful too. It also seems logical had all my remaining cancer been confined to the prostate bed that salvage at 0.113 would have worked as adjuvant at 0.5 would have worked as well.
IMHO what these studies tell us is that if the cancer is confined to the treatment field, success is likely. If the cancer has spread outside the field, well it is obvious.
It’s a complicated disease, but your last paragraph says everything, which is why (predictably) there are basically 2 different recommendations. Scans have improved greatly, so while medicine moves forward too slowly for many, at least there is that.
Surveillance starts early for best results, but typically we are ignorant of our health until it fails. Men, that is. There are many brilliant men on here who have acquired much working knowledge of this disease, and are doing everything they can to extend their life and the quality of it. Some arrived informed, but many of us never had a doctor, never a physical, and only set foot in a Dr office or hospital if they crashed their car etc.
Now we start paying attention of course, hoping it isn’t too late. Often we want nothing to do with any of it sufficiently that a wife or other family member posts on our behalf.
Meanwhile, a regrettable percentage of the rest of the male population behaves the same. Even if they do go to a doctor regularly, they often don’t know what their numbers mean, are in denial about their health in general and get no help from the doctor, who leaves them with the vague ‘you’re doing great’ which they of course run with.
When men start monitoring their health well they reap the benefits of early detection, the best aspect of medicine available. So few do. I didn’t. I am of reasonably high intelligence, which of course is of itself no help at all. I have a doctor in my immediate family and my dumb ass still did not get checkups as I aged. By the time high risk Pca arrived I had finally changed. Maybe that’s why I decided all the adjuvant treatment I could find was the least I could do for myself.
As I always say, the results have been good but not without consequence. The studies indeed indicate adjuvant is perhaps over treatment for lower risk, but good choice for high. Hopefully we know which one we are. Great luck to you!
Artistic demonstrate how difficult it is to know where all the cancer is. It is logical that adjuvant fails to provide benefit when the cancer is already beyond the treatment field.
IMHO the key is individualized/personalized care, which in my experiences, is improved with uPSA testing (OP's topic).
I find insights into general population based studies in comments (highlighted those that grab my attention) "Commenting on the data, Dr Xavier Maldonado, Hospital Universitari Vall d’Hebron, Barcelona, said: “These are the first results to suggest that postoperative radiotherapy for prostate cancer could be omitted or delayed in some patients. This will shorten the duration of treatment for these patients and allow better use of resources since today’s radiotherapy is technically sophisticated and therefore expensive. However, strict follow-up will be needed to identify patients requiring salvage radiotherapy.”
Maldonado noted that longer follow-up is needed for the main endpoint of RADICALS-RT, which is freedom from distant metastases at ten years, and to comprehensively report on toxicities."
Perhaps adjuvant is over treatment for some, but how can we really know what one's cancer would have done? Did my ten month delay to "salvage" RT provide sufficient time for my cancer to move beyond the bed? I had six cancerous pelvic lymph nodes confirmed by salvage ePLND - I ponder might they have been cancerous at the time of my RP two years prior? If the Ferrotran nano-MRI had been available to me I might have known. But then, as Maldonado says, technically sophisticated and therefore expensive.
It’s all expensive except for the PSA tests, so you may as well get them as often as you like.
Yes there is so much unknown about the specific disease path in each individual that even hindsight can’t serve us particularly well. Funny how frequent uPSA can make one more or less comfortable, depending. I wouldn’t touch the stuff, but I do understand.
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. 🕵🏻️
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".
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.
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.
Mgtd, (Is your user name reminiscent of Morris Garage's 1950s? I myself owned a 1957 MGA. A fellow fan, here.)
I did check out LabCorp for a test that could differentiate different PSA levels below 0.014 ng/mL. Cost is $109 (U.S.) but no one could tell me for certain that the test could (read down to 0.006 ng/mL). I am not willing to plunk down $109 ust to (maybe) find out.
In other words, a lab that cannot tell me how sensitive their test is does not fill me with trust and confidence.
I have used LabCorp for years. Most report to <0.010, a few I have used <0.006. Other members and other men also report <0.006. Not sure why the variances - I will take <0.010 as I settled on this nine years ago.
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.
Thank you. Makes me feel better about testing at this level as I always have since my 3-4 diagnosis and RP almost 7 years ago. I checked every 6 month and don’t dwell on results. Perhaps it gives me a heads up.
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?
Yes, I did not address PSA Anxiety. I should probably have a disclaimer on all my posts about that very real danger. I do not allow myself to suffer from that affliction. Small variations do not alarm me. I wonder at them, but pay attention only to overall trends. Frequent testing (I figure) will let me see such a trend more definitively than 3-month testing, and sooner, too.
My doubling rate 5 months after prostatectomy was two moths. 4.67 ng/mL when I started ADT, so (rather than panic-prone), I am vigilant. (At least in my own mind.)
Dan, thanks for sharing your story and for reading my post(s) critically. Readings such as yours help improve my thinking and my posting.
DJ - I see "psa anxiety" as a lack of understanding of uPSA and it's clinical use, significance and value.
Just like the "psa testing anxiety" in screening for prostate cancer. That has been used as a mitigation tool by the healthcare policy oligarchs to steer men from screening. What if you're 47 and have a psa of 9.7? Or .63? Educating men on the use and value of psa testing is key whether screening for prostate cancer or monitoring treatment efficacy.
I use uPSA because I believed the "anxiety lie" with my urologist. The anxiety hit in a short 8 months after RP when I was feeling more and more confident because I was "undetectable". This is another BS word used for clinical purposes but has made its way into the patient population. So many men and doctors use this like they have been cured and have NO disease left. I lacked understanding of what "undetectable" really meant.
PSA is nothing more than a biomarker. It shows changes and abnormalities in the prostate. One of the abnormalities could be prostate cancer.
Post treatment PSA is still just a biomarker to monitor treatment efficacy in somewhat of a blind fashion. There is no empirical evidence that I have seen that shows what an "undetectable" or < .1 amount of prostate cancer cells really is or what grade of cells are present.
This is where I see a huge value in imaging in the coming years. Blood biopsies are up and coming too.
I manage any potential PSA anxiety by testing on my frequency; similar to how I manage all other health concerns. I do not let health care policy and guidelines drive my healthcare.
My situation is similar to yours as I was undetectable for 4 years after RALP. I’ve now gone a year with quarterly usPSA tests ranging .02 - .03 —- I’m now in a holding pattern as my MO recommends waiting until a PSA of .20 before PSMA scanning with salvage RT and ADT. It’s been tough mentally but hoping new research & treatments are developed. Thanks for sharing your journey.
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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)
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