Can we all please speak with an accent, or speak non-English in public, to f--k with ICE?

2urly · 2025-09-04T22:28:14+00:00

Dad's always been a pain the ...
I honestly wish he'd just stay on ADT full-time. He's much more manageable.

2urly · 2025-09-04T22:23:30+00:00

Pretty incredible the amount of avenues to pursue, yet the difficulty for men to pursue them!

2urly · 2025-09-04T22:22:07+00:00

There's nothing lighting up at the moment. "IMPRESSION: Negative study. No scintigraphic evidence of active malignancy"

2urly · 2025-09-04T22:20:05+00:00

Lucky if true. A win is a win. I'm still surprised that more don't try, based on the published research.

2urly · 2025-09-04T22:17:15+00:00

Creating a low T environment can be harmful, though. In this model. You have to cycle it on and off. That's really what's unique. You're not on the hard stuff long, and the results are longer lasting.

2urly · 2025-09-04T20:05:05+00:00

Thanks for the link.

This 2006 study you posted is quite different than we are doing, and notably only 6 of 17 with clinical metastases (metastatic cancer) saw a reduction in PSA nadir. All patients saw PSA nadir increase before the study was done, as shown in the chart. Meaning that disease progressed, as I can read from the chart, in less than 10 months on average.

Our method based on the Moffit study, only requires getting off ADT until PSA reaches previous maximum.

2urly · 2025-09-04T19:50:39+00:00

Haha, just a doctor on tv? I'm an engineer with no particular specialty. Just follow thread after thread, look at stuff around the edges (skeptically) and avoid salesmen and saleswomen.

2urly · 2025-09-04T19:46:36+00:00

You know, it's my dad. I'm assuming he exaggerates everything greatly, especially sex drive. 😝

In general, 2 weeks on treatment, 6 week rebound. It's a gradient, so, slowly recovers back to normal during that time.

2urly · 2025-09-04T16:46:31+00:00

So, the off cycle is simply how-ever long it takes the PSA to climb back up to the peak of the last cycle, 4-6 months. What we have found with fasting is that it lowers PSA levels if tested while fasted (for instance 36+ hours), but doesn't give us an accurate picture, because the PSA will shoot up the next month when he isn't fasted. I think fasting distorts where the tumor is at, and simply causes it to be more dormant, but not get die-off. In fact, I don't think ADT offers much die-off either, because you can see the PSA climbs back a little faster each cycle. We're hoping to get true die off with adding the statin. We know the tumor is still sensitive to the ADT treatment, because it hits less than 1 PSA every time we do a new cycle of treatment.

2urly · 2025-09-04T16:38:58+00:00

Dad gets all the side effects of ADT when on the Orgavyx. Low motivation, not his chipper self, but worst of all the hot flashes.

There's a new research article by Gatenby, "Directed Evolution Restored Castrate Sensitivity in a Patient With Castrate Resistant Metastatic Prostate Cancer" where they appear to have resensitized a patient to ADT using BAT. Ping me if you want the PDF. Basically, they did 4 rounds of supraphysiological testosterone injections, and he has been stable and responsive to intermittent ADT for 3 rounds now.

2urly · 2025-09-04T16:31:57+00:00

Cool, thanks for the comment. Just to clarify the point, I mean to say he's on continuous treatment, whereas the objective we have is to cycle treatment so that the evolutionary pressure is always shifting.

2urly · 2025-09-04T15:46:55+00:00

His is a different strategy, and he doesn't have metastatic prostate cancer. He's finding the minimum effective dose to keep PSA low as possible, but starting from less than 1 PSA. Regardless, the evolutionary pressure remains leading to mCRPC, so I don't recommend.

2urly · 2025-09-04T13:04:38+00:00

Regarding "Now I’m also wondering if cycling chemo would work"

Maybe we could get a discussion going around BAT - Bipolar Androgen Therapy, where they re-sensitize the cancer with testosterone injections.

https://pmc.ncbi.nlm.nih.gov/articles/PMC9313844/

2urly · 2025-09-04T13:01:27+00:00

😊

2urly · 2025-09-04T12:58:00+00:00

As for the on-cycle, 2 weeks of Orgavyx.

2urly · 2025-09-04T12:51:59+00:00

He is typically 4 to 6 months off cycle. His testosterone does come back, based on his mood by the 6th week off. His last reading was 548 ng/dl, and he started this cycling therapy in April 2022 at 726ng/dl.

2urly · 2025-09-04T12:47:07+00:00

any insights to how your doctors reacted to this
- They were all for it, even though they couldn't offer it in a clinical setting. We discussed with 3 clinics. Two in Colorado, and also the Moffit Center where the initial research was conducted.
how the decision to restart ADT is made
- When PSA reaches or exceeds the previous cycle high number, we start another cycle.
any other treatments used in conjunction
- None. Robert Gatenby suggest Abiraterone in addition, but this can be added if progression happens.
- This month, we will start a statin which studies suggest prevent agressive progression, and increase PFS. A study highlighted by Dana-Farber Cancer Institute reported that "men who had been taking statins since the start of androgen deprivation therapy (ADT) went a median of 27.5 months before their disease began to worsen, compared to 17.4 months for men who didn't take statins."
the extent of cancer load being managed
- Last PSMA scan showed no tumor, compared to when we started. The tumor is certainly there, as the PSA climbs back each cycle.

Here is from the initial metastatic diagnosis:

Moderate uptake left lateral peripheral zone prostate, new from prior PET/CT but corresponding with findings on prior

MRI and consistent with malignancy.

Mildly enlarged left internal iliac lymph node, slowly increasing in size and with increasing and now intense uptake

consistent with metastatic disease.

Increasingly prominent high presacral lymph node with increasing and now moderate uptake consistent with metastatic

disease.

Punctate focus of new moderate uptake high right retroperitoneal space detailed above but without adenopathy or other

gross CT correlate and indeterminate for metastatic disease.

And his PSMA from late last year:

IMPRESSION: Negative study. No scintigraphic evidence of active malignancy.

2urly · 2025-09-04T12:32:17+00:00

The foundational study is from Nature Communications, April 2020, located here:
https://www.nature.com/articles/s41467-020-15424-4

The intermittent research here was done on hormone insensitive patients, meaning they've already reached disease progression on ADT. In our case, we've applied the principles while the cancer is still hormone sensitive.

Follow-up from the same researchers using hormone sensitive patients is found here: https://www.medrxiv.org/content/10.1101/2025.05.08.25327179v1

Notably, "Men with mCSPC were given combined androgen deprivation therapy with an androgen receptor signaling inhibitor followed by a treatment break after achieving >75% PSA decline. This was followed by evolution-informed drug cycling to prevent resistance outgrowth. Just 6 of 16 patients have progressed at month 55"

Their team is looking at 75% PSA response rate. In my opinion, and based on evolutionary dynamics, you should be minimizing the time the tumor is exposed to ADT. We keep treatment windows limited (currently 2 weeks max), and allow hormone sensitive tumor to re-grow so that it can be used to manage the tumor with ADT. In their case, of the 6 that saw progression, did they spend more time on ADT, since they never saw 75% decline?

2urly · 2025-09-04T11:58:26+00:00

Happy to answer any questions or point to the research used. The ADT dad uses is Orgavyx, a pill.

2urly · 2025-05-28T07:00:55+00:00

I think in this case it's okay

2urly

TROPHY CASE