My PSA lows tend to be around 3.3, and it occurs to me that some might think it odd that I don't drive it lower.
I think it is very common for men on ADT to draw too much comfort from a significant PSA reduction, if not a near-zero PSA. I have witnessed men misinterpret a dramatic drop in PSA as a possibility that ADT might actually be curative. In a paper from 2019:
"A large proportion of patients with metastatic prostate cancer reported beliefs inconsistent with understanding that treatment was not curative." [1]
Following my failed prostatectomy in March 2004, it seemed inevitable that Lupron would be in my near future. I had read dozens of papers with boilerplate introductions where ADT was described as a therapy that was usually effective at first, but for only 18-24 months in most men. So why rush into it? I decided to ignore the advice to "hit it hard and hit it early" and save palliative therapy for when palliation was required.
I started out with continuous testosterone on the basis that untreated men have 'wild type' androgen receptors. They also already have a decline in the beta estrogen receptor [ER] and an increase in the alpha ER.
While testosterone will convert to dihydrotestosterone [DHT] in the absence of Avodart, say, DHT is one's friend - until it isn't, imo. As with the vitamin D conversion of 25-D to 1,25-D, the presence of the strong hormone triggers its decay in prostatic cells. A metabolite of DHT - 3beta-diol - is the natural ligand of ERbeta (a growth inhibitor.) [2] As long as there is ERbeta, the narrow window of opportunity that DHT has, is followed by a sustained period of growth inhibition.
When my PSA doubling time began to shorten, I knew that I was losing ERbeta, so I switched to 3 months of ADT followed by 3 months of high-normal testosterone.
PCa begins to adapt to therapy from day one. What do those cells look like after 3 months of ADT - versus 6 months, 12 or 24?
For whatever reason, 3 months of ADT worked for me. Enough cells able to return to their "normal" pre-ADT state to crowd out the advanced cells that are suddenly at a disadvatage with restored testosterone levels.
Of note: I began ADT & the testosterone reset at the same time. Rapid androgen cycling, however defined, is not something one saves for later imo.
Incidentally, that phrase - rapid androgen cycling - brings to mind the work of Howard Scher [3] (2006)
When Abiraterone and Enzalutamide were approved, I was briefly tempted. But however efficient they were at controlling PSA, the effects were transient for most men.
In addition, I was wary of the new adaptations to Abi & Enza. Would testosterone be as effective after 3 months?
In the end, I decided to skip Abi, Enza & Lupron and go back in time to DES (diethylstilbestrol). It's a synthetic estrogen that maintains bone health even while estradiol falls to zero. And it has anti-PCa properties.
The reason why DES was phased out is that oral estrogens increase the risk of life-threatening blood clots. I take a very high dose of nattokinase to keep D-dimer low.
My approach is quite simple: as long as there is no upward PSA trend at the end of each 3 months, I am content. I don't worry that the PSA is not driven down to zero. I don't believe that a near-zero PSA is necessarily a good thing?
My approach is sometimes confused with BAT, but I originally used daily transdermal testosterone patches. Enough of a dose to create high-normal levels - not supraphysiological levels. With Denmeade's BAT, testosterone levels are modulated - and there is no castration-only phase. In my original protocol, there was an abrupt shift from high-normal to castrate testosterone.
More recently, I moved to something closer to BAT, with a single dose of testosterone cypionate at the start of the cycle (as with BAT) and two months of pure ADT at the end of the 28-day BAT phase. This is basically because insurance would no longer pay for the expensive testosterone patches. (I do not use daily DES during the first week of the 3 month cycle.)
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I don't make any changes to my supplement usage before a PSA test.
For men with intact prostates, the advice is to avoid stimulation of the prostate before a test. The aim is to avoid a "false positive", i.e. a result higher than the arbitrary cut-off for biopsy.
An example of a "false-negative", is failure to use a lower cut-off when taking a drug that targets BPH but not PCa. The old 4.0 PSA cut-off for biopsy takes into account the fact that BPH is common in screened populations. Take away BPH noise and a significantly lower cut-off must be used.
For men diagnosed with PCa who have had their prostates removed (as I have), PSA results are compared to historic results, rather than an external number. This is what the PSA was intended to be used for - a post-treatment tool. Importantly, the conditions should be similar during each test. The actual PSA number lacks significance imo.
During my 3-month cycle, my PSA might be 7.5 at the end of month-1 and 3.5 at the end of month-3. I don't usually check the former. All that concerns me is that there is no upward trend for month-3 results.
For curcumin, I use Longvida - sold by NOW Foods as CurcuBrain. It has been shown to cross the brain barrier, which is a good (if not scary) indicator of bioavailability.
I use curcumin because of the >150 PubMed hits for , not to mention the >250 hits for or ~500 for .
Within those papers there is ample evidence that curcumin has properties that are helpful against PCa. For example, as with a wide range of polyphenols, it can inhibit NF-kB activation and reduce pro-growth inflammation triggered by the cancer. If I am keeping markers of inflammation in check, why would I stop using any polyphenol or other anti-inflammatory agent before a PSA test?
To those who claim that curcumin, say, is masking the "real" PSA number, I would say that there is no "real" number. All that we have are numbers for comparison. For those who stop taking some or all of their supplements before a test, the important thing is consistency - but I doubt that there is any benefit.
Always enjoy your posts. In my conversation with Denmeade last year at John's Hopkins, he referenced a steady PSA trend as fine. Maybe something along your thoughts.
PCA - Much appreciated perspective on your n=1 treatment history and it's well-considered rationale.Your long successful out-of-the-SOCbox protocol, while not exactly similar to current BAT protocols, has always seemed to me to anticipate it. Embedded within your post are some insights that should be very helpful to others.
Several that I have come to also embrace are:
1. "3 months of ADT worked for me". Similarly, I only did 3 mos of Lupron after my BCR#1 (PSA ~ 25). Three months after that initial treatment, my T rebounded above to near 600 and my PSA remained <0.1. That condition existed (with a progressively rising T!) for about four years. The cause(s) for that stable durable response ending and BCR#2 are speculative on my part and not relevant here. Note: I've always wondered why durable response to ADT is not "tested" after an initial short induction period (for a significantly sustainable durable response) vs the longer SOC induction period, saving the bulk of ADT for "palliative therapy", if needed later.
2. Obsession "for men on ADT to draw too much comfort from a significant PSA reduction". With my current self-directed treatment program, I seem to have settled into a 0.2 PSA level over the last year. (My original target PSA had been 0.05, but I have embraced the higher level due to its current stability.)
3. Supplements mask "real" PSA lab results. I used to stop all supplements several days before lab blood draws. I no longer do that, as it seem to me that a suppression of PSA might in some cases correlate with a similar suppression of the source of PSA; i.e., prostate cancer.
4. "PCa begins to adapt to therapy from day one". With metastatic disease, sticking with the same treatment program (waiting for its failure) is not a good long-term strategy for most. Gatenby's group at Moffitt argues that maintaining competitive diversity is a better treatment strategy; i.e., Adaptive/Evolutionary Theory. I am anticipating a partial or total break in the three drug treatment I am currently using later this year. The Moffitt approach would be to let my PSA double and then resume/restore the full treatment regime until the previous PSA level is restored. While different in particulars, BAT seems similar in its cyclical framework.
5. Curcumin has been a near constant supplement since my diagnosis with my CLL 17 years ago. I mostly still use the C3 formulation and typically vary the dosage quite a bit over the year. Much of the initial appeal for its use (for CLL) was for your noted inhibition of NF-kB. (MateoBeach recently suggested the use of the Longvida/CurcuBrain formulations for cognitive health due to its ability to cross the blood-brain barrier. I have no reason to think I am at increased risk for dementia/Alzheimer, so sticking with the C3 formulation for the time being.)
Finally, your insights into inflammation as providing the major fuel for the development and later progression of PCa has been prescient, insulin resistance being the #1 source for PCa patients to control with diet, lifestyle, supplements, and pharma.
Thanks for the insightful post and best wishes to you and your family for a happy, healthy 2024!
I am a hard believer in establishing equilibria. This is how everything in nature functions. As an electrical engineer I very well undestand that if any fool were to implement a Maximum Tolerable Dose equivalent mode to the electrical Grid, an end-to-end black-out would have occured in a matter of minutes. My latest 4 monthly tests PSA have hovered between 0.010 and 0.016 by dosaging half a 50mg Bicalutamide tablet every 5 days. My PSA target is a bit higher, around 0.025 and have been tempted to reduce dosage to get it there, but 5 day periods are easy to remember/follow. Next increment (every 6 days half a tablet) will take something to remind me to follow. Last year, I tried half a tablet every week, the easiest schedule to remember, but proved sub critical and PSA rose above my 0.050 comfort zone limit.
Justfor_ - Very glad to hear that your low dosing levels are continuing to work for you. I had hoped to run along side you in a race to a PSA 0.00 bottom, but even at 50 mg bical per day (+ dutasteride QOD & 1/2 tab tamox QD), I've settled in at 0.2. Considering the tiny untreated(able) lymph nodes ID'd in my PSA scan, I'm OK for the time being with 0.2 as a still respectably low and seemingly stable PSA - all things considered. I have super-high T and enjoying a fine QOL now that I have been back in the gym for almost a year.
Are you getting any feedback from the group at Moffitt? You may well be the world's PCa poster patient for the study of bical dosing. I have a hard time keeping track of daily and every-other-day dosing. Not sure I'd ever be able to keep up with once every 5 days.🙄
HNY cujoe. The key is to keep PSA flat, not the actual value. You may try the following test to see your body's reaction. Select a day of the week, for example Sunday, skip taking Bicalutamide on that day for a month and have your PSA counted the next day, in our example Monday, when the Bicalutamide blood concentration deeps. Everything else as usual.
Justfor_ Thanks for the suggestion. I just got blood draws today, so barring any wacky results, I will give it a try. I'm thinking you are suggesting a method to test gradual dosage reduction; i.e ~ one-day-at-a-time x one-month-at-a-time.
Based on half-lives of most meds, skipping a day here and there should not have much negative effect (esp with dutasteride*). . . and possibly even be positive in an adaptive sense? I definitely would like to get as much mileage out of my current program as I can - while doing some dosage adjustments and cycling to keep the adaptive processes working to my advantage.
In the end, it's all n=1 testing trial and error, but nothing ventured, nothing gained. My current QOL is superb, so it's hard to consider making a major change right now. I'll share this year's journey with you, as you are the resident King of the Bical Road.
* Due to a change in Drug Plans, I will have to switch from dutasteride to finasteride when my current supply runs out. Friedman prefers finasteride, esp. for those using it for cycled treatments, due to its drastically shorter half-life, so the change should be long-term beneficial for me. Γεια σας, cuJoe
I run some numbers for you. I assumed that you have been taking one tablet daily for at least 60 days now and thus your blood concentration has already plateaued.
Now, the first time you skipped taking it, your next day's blood concentration (before taking this day's tablet) will be lowered by 89%.
Second week in succession, this further dips down to 85%.
Third week and onward 83% and that's as low as it can get by skipping one tablet per week.
Thanks for taking the time to do the analytics for a stage 1 reduction in bical. If today's PSA is near the 0.2 of the last three labs, I'll drop the one day per week and test again in a month. If I'm able to do it, you'll be the first to know the 30-day result.
My urologist put me on finesteride but as I indicated in a recent posting I had to stop taking it after it caused nasty dental problems. He suggested dutasteride but I refused that too, thinking that with the same mechanism of operation it would cause dental problems too. Weird situation.
Thanks for the detailed review of your treatment and decision making, Patrick.
I think the 3 month cycling of a modified BAT has merit. Though the single injection of T-cypionate is not ideal as it falls from supraphysiologic into high normal after just one week. And probably takes 6 weeks to fully clear to castrate level. Though having 2 months of ADT will provide leeway for that. I do not know what the optimal timing and cycle lengths are. Though it has become more clear that dropping AR activity and number, along with lowering MYC expression is part of what happens during the high-T phase. This has now been shown to be underway at day 7 on SPT and is near maximal by 28 days.
Conversely, during ADT with castrate T the low AR expression is reversed and returns to supra-normal levels within one month. So that seems sufficient to "prime" the system to respond to the next SPT phase. That is why I have chosen to have 4 weeks of ADT (Orgovyx) and adding Nubequa at half dosing for the firest 2-3 weeks of ADT. Enough to cover any remaining T-cypionate effect. I stop weekly T-cypionate 5 weeks before my ADT phase and replace it with T-propionate (inexpensive and available online for "laboratory use") for the final 4 weeks of my SPT cycles. (Total period of High-T (SPT) is currently 12 weeks.) So 3 months on SPT and one month castrate. My PSA remains undetectable during the last week which is the only time I test it currently.
As for the other supplements, I too take lots of polyphenols and other antioxidants and anti-inflammatories. My curcumin is currently Theracurmin which also crosses the BB-Barrier. Though I may consider switching to Longvida/Curcubrain when I reorder.
Recently I did a personal trial of low dose colchicine (0.3 mg/day). It is a unique and interesting anti-inflammatory. Look at the rather amazing CV protective benefits in the LoDoCo2 Trial. However I did not tolerate it due to diarrhea so had to stop.
I also recently started Magnesium-l-Threonate supplementation (Mag-T) as it also gets into the brain and the limited research is pretty positive. Discussed in the recent Peter Attia podcast on Magnesium supplementation.
Then, just when I think my supplement regimen is already out of control, along comes Spermidine! I am going to write a post about it in FPC. It has been under the radar too much.
Yes, if I waved Patrick's discussion in front of my urologist his eyes would glaze over. I already know that he won't budge from the SOC lane. He doesn't like "fringe" treatments and has said so when I mentioned BAT.
janebob - For reasons still unclear to anyone here, Patrick continues to be unable to post or reply here at FPC. Here is the email I received from him overnight, along with the reply to your question he WOULD have posted, were he able to:
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Odd that even in exile I should be notified of responses.
I posted on "PSA suppression" 4 months ago & janebob99 has just responded (see below).
I would like Bob to know that I can't answer.
My response to Bob would have been:
I have known several men who have done well on 1 mg DES. And back in the day there were men getting Honvan (Fosfestrol - DES diphosphate) from Mexico & cutting the pills into tiny pieces. So I was expecting to be on 1 mg. I actually needed 3 mg, which is considered to be an effective dose for almost all men.
In the past, I had been using a product thought to be "contaminated" with DES, and doing well on it. I was quite unprepared for the effect of 3 mg DES. For the first time, I felt profoundly castrate.
The men on 1 mg DES were of the opinion that the dose is not a risk factor for blood clots. While it does not add much to the risk, cancer itself is a clotting risk factor. Everyone with PCa should be testing D-dimer and taking nattokinase to keep it controlled. At 3 mg DES I need a very large dose of nattokinase to achieve that.
I can't remember when I began using Dutasteride (Avodart). I avoided it while my PSA doubling time was under control, but it became essential when the PSADT shortened dramatically.
When I moved to a 3-month cycle, where testosterone is high for only a week or so, I stopped using it. Dutasteride has a very long half-life. It takes a long time, at the regular dose, to attain the target blood level. It isn't something one can take only during the days of high testosterone.
But recently, I have returned to it.
Note that Denmeade (Mr. BAT) allows patients to have been on a 5-alpha reductase inhibitor in the past, but requires a 6 month washout period for inclusion in a BAT trial.
It seems that Denmeade wants T to be converted to DHT. Makes sense to me, which is why I stopped using it. Not sure what is best.
-Patrick
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It is a major disservice to our community that Patrick continues to be blocked from participation. I suggest you and others contact SUPPORT and request that he have his privileges at FPC restored.
Bob - In response to Patrick's comments on the EXTREMELY long half-life of dutasteride (1), that is why Ed Friedman instead recommends finasteride (2) for anyone using it with BAT. (Due to it's very short half-life.) It is also one of the appeals of using darolutamide (3) in a BAT routine, if $$$ are not an issue. However, for long-term use of finasteride, there is some chatter about what has been referred to a "post-finasteride syndrome". Peter Attia discussed it in detail in his podcast with Dr. Ed Schaeffer. (available on YouTube)
Good Luck - Ciao cj
(1) The terminal elimination half-life of dutasteride is approximately 5 weeks at steady state. This long half-life accounts for the serum concentrations remaining detectable for up to 4 to 6 months after discontinuation of treatment.
(2) In healthy young subjects receiving finasteride, the mean elimination half-life in plasma was 6 hours ranging from 3 to 16 hours. In elderly patients over the age of 70 years, the half-life is prolonged to 8 hours.
(3) The half-life of darolutamide and its active metabolite, keto-darolutamide is about 20 hours. A phase 1 study determined a terminal half life ranging between 10-15 hours.
Note: the above half-life info comes from the DRUGBANK Online website. (go.drugbank.com/drugs)Emphasis was added.
Bob - Patrick should read your reply (HU has not prevented him from doing that . . . yet.), but I will pass a link to it via email just to make sure.
BTW, the most likely reason for Denmeade not wanting anyone to use dutasteride is due to it's extremely long half-life; i.e., it persists at significant levels through both castrate and high-T phases of the BAT sequence.
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My Recent and Temporary BAT failure and it's relation to High Uric Acid (Kidney Stone and Gout)
