2nd pBAT cycle results: AR upregulation? Double strand breaks? Darolutamide?

[Ichthus316]

Started 2nd pBAT cycle on 4-22-24 with a PSA of 0.62 measured 2 days earlier. All 6 injections were 50 mg eod of T propionate with .625 mg letrozole every 5th day as an aromatase inhibitor.

The hiT cycle was cut short by 2 injections because of a plan to SBRT treat a pelvic lymph node chain that lit up on January’s PSMA scan. But my RO cancelled it after reviewing my 5-6-24 MRI and failing to see anything warranting treatment. He said the chain had "melted away."

Here are my blood test results during the cycle:

5-2-24, drawn 7 hrs after the last of 6 T injections

T = 2557

E2 = 6, will continue to reduce frequency of letrozole dose until E2 is > 10

PSA = 2.14, exactly the same as peak PSA at end of 1st hiT cycle (after 8 injections)

5-25-24, results at end of 2nd loT cycle, 23 days after last T injection:

PSA = 0.74, not close enough to original 0.5 baseline, so extended loT for 9 days

E2 = 35, upper end of ref range is 29 pg/mL; will reduce # of days on low dose E2 patch

6-3-24, results at end of 2nd full BAT cycle, 32 days after last T injection:

PSA = 0.58 (Started hiT phase of 3rd BAT cycle 6-4-24)

Questions:

1. A respected fellow BAT-man wrote that "a 4 week castrate period following a 1 week washout of the T-prop...is how long it takes for the androgen receptors (AR) to up-level in number and activity in preparation for the next high-t BAT cycle." Is that independent of hiT cycle length? True for everyone? Are there any studies?

2. Is it common for a PCa affected lymph node chain to “melt away” strictly due to ADT? If not, did the supra-physiological T part of the cycle destroy PCa (including stem cells) via double-strand DNA breaks, as the theory goes?

3. Next week, my MO plans to send Medicare a request to approve darolutamide in order to initiate a double blockade of T. How should that be worked into my next low T cycle?

[Ramp7]

You may wish to review Russ's book on Amazon. He provides links to ll the studies. amazon.com/Adaptive-Bipolar...

[Ramp7]

I think length of cycles is an excellent topic. Some are doing a much longer high T cycle. Maybe PSA length of response may also be considered.

[OsloN]

I have been on BAT + ARSi for 15 months: My findings being G9, no chemo:

1. In order to downregulate AR I know that 3 cycles works excellent, 1 is not enough. Next time I will perform 2 like in the STEP-UP trial.

2. In the AR upregulate phase with Daro PSA rises after 6 weeks, meaning resistance again.

3. During BAT I add 50% Olaparib, keeps PSA constant.

So, 2 Cycles with BAT + PARPi during 60 days, then ARSi with Daro for 6 weeks. I add Indomethacin to avoid AR-V7 by neutralizing AKR1C3.

[Ichthus316 in reply to OsloN]

Thanks for the info. Just to be clear on what you are doing, "2 cycles" means 2 injections of supra-physiological T cypionate 28-30 days apart without any ADT in the background, then switching to Daro for 6 weeks?

My initial 30 day cycles of 15 hiT & 15 loT were designed by Russ, presumably to see if I was a responder, and I am already at 30 days of loT. But it would seem that I may need to work toward extending both loT and hiT phases of the BAT cycle to at least 30-35 days each in order to re-sensitize the ARs to the next phase.

Since I am clearly hormone sensitive and still early in the BAT game, what do you think about this strategy: Extend each hiT cycle by 2 days (by a single Tp shot) and check PSA on the last day of hiT. In 6 months or less I should arrive at a 60 day cycle. If/when PSA begins to progress too rapidly, add a PARP inhibitor.

I know that PSA is overexpressed by T and is more important to monitor during loT, but I still worry about high PSA during any part of the BAT cycle.

[OsloN in reply to Ichthus316]

Answer is yes.

Got a PSA result yesterday, PSA 0.9 from 4.1 in 14 days using Daro. Expect 0.2 in the next month.

I am a no responder to BAT in the sense that PSA rises, BUT it obviously resensitize the cells extremely well, AR back to normal.

I am using Olaparib in 50 dose + Indomethacin.

[NPfisherman]

Great post.... Thanks for your case presentation....

I did my 2nd SBRT while T was higher, before starting abiraterone ... using eligard 2 days before my first session which causes T to rise initially.. and fall by the end of SBRT...

As for question 2--maybe... There are patients that start out with multiple mets, and they resolve with treatment over time....or they have a few left...(I call that resistance) and likely should be eliminated with SBRT or MDT... IMHO...

DD