Adding Abiraterone to ADT for node negative, non-metastatic disease?

[petabyte]

Please see my bio for my situation.

One arm of the Stampede trial compared ADT alone to ADT+Abiraterone for high risk PCa.

This resulted in a "Strong" recommendation in the European Prostate Cancer guidleines:

"Offer IMRT/VMAT plus IGRT to the prostate in combination with long-term ADT and two years of abiraterone to cN0M0 patients with ≥ 2 high-risk factors (cT3-4, Gleason ≥ 8 or PSA ≥ 40 ng/mL)."

I attached an excerpt.

This is the list of points I presented to my RO (we had already discussed this trial).

These are the reasons I'd like to try adding Abiraterone

▪️ Stampede trial, for ABI + ADT thelancet.com/journals/lanc... (also attached)

▪️ ESTRO/EAU guidelines, Section 6.3.4.4: uroweb.org/guidelines/prost...

▪️ I have two high risk factors T3b, GS 4+4, but additionally intraductal with cribriform

▪️ US guidelines suggest it: nccn.org/guidelines/guideli...

▪️ I have limited Adverse Effects from Orgovyx (no fatigue, no weight changes)

▪️ Recent ECG was OK: QTc interval normal. BP readings good, Liver/Kidney Function good (recent tests). Potassium OK

He referred me to an MO who agreed with what I suggested but could not answer my main question (I knew the answer before I asked it)

Given the trial was with Abi given together with RT, have I missed out on the positive effects of the treatment?

He replied, and I tend to agree: Nobody can answer that but I woud certainly be excluded from joining the trial (obviously 😉)

I started it anyway. I've been taking it 10 days now and have a blood test Friday.

My PSA at 6 weeks post RT was 0.388 and then measured at the hospital (a different lab) was 0.400, which is essentially unchanged (which bothered me a bit - I had wanted to see a steady decrease).

What is your opinion? Am I wasting my time? (I suppose I will at least get the PSA down).

Will using ABI early mean I risk early castrate resistance or resistance to Abiraterone or other ARIs?

Any insight would be appreciated, especially links to studies or reliable sources.

❤️ petabyte

[Tall_Allen]

Almost everyone in the STAMPEDE trial had positive LNs on a CT scan. This clinical trial will tell us if a high Decipher score can differentiate those high risk men who would benefit from 2 years of apalutamide:

clinicaltrials.gov/study/NC...

[petabyte in reply to Tall_Allen]

Hi Tall_Allen . Thanks for the response

Indeed most of the Stampede was node positive but in this arm of the Stampede trial they were specifically using cM0 patients (with roughly 50% cN0 and cN1) but I don't know how this was determined - they don't mention PET scans so it is possible the cN1 figure was higher.

Nice to know about the other trial though, thanks for that.

[Tall_Allen in reply to petabyte]

You misunderstand theHigh Risk trial. It can be confusing because STAMPEDE recruited patients for several trials at the same time. STAMPEDE defined "high risk" patients as any of:

• Node-Positive (N1)

• ≥2 of:

Stage T3 or T4

PSA≥40ng/ml

Gleason 8, 9 or 10

(There were also a few relapsed patients). Almost everyone in the High-Risk Trial was N1.

The "High Risk" trial randomly assigned these patients to abi (or abi+enza) or to ADT only (which was SOC). It found that 3 years of ADT +2 years of abi improved outcomes in N1 M0 patients. N1 was determined by conventional imaging only.

In another STAMPEDE trial, N0 M1 patients were randomly assigned to abi (or abi+enza) or to ADT only. The purpose of that STAMPEDE trial was to determine whether abi improved results in metastatic patients ( it did).

[ulfhbg]

Hi !

I personally think you did a good choice to add Abiraterone. You may still have a lot of radiated cancer cells that perhaps is weakend but have not died of yet. Anyway by adding Abiraterone you increase the hostile environment for the cancer cells to survive in and adds to the curative intent by starving and weakening any possible survivors and the better the hostile environment the better the possibilities are.

With prostate cancer my personal opinion is, hit it hard with everything possible so, instead of thinking if it promotes any resistance in the future, if you can add some possible benefit upfront then, use the possibility.

Best wishes - Ulf

[petabyte in reply to ulfhbg]

I share your opinion ulfhbg . Thanks for taking the time to reply.

[ulfhbg in reply to petabyte]

Hi !

I also had Abiraterone added adjuvant 2 weeks after my 20 fractions of IMRT (and before that 3 cycles of Lutetium 177 and I also started Firmagon (which I then changed to Orgovyx)). Anyway, two weeks after my IMRT my PSA ( in April 2024) had decreased to 0.55 and then I added Abiraterone. In July 2024, 3 months after radiation, my PSA was < 0.1 and then in October 2024, 6 months after radiation, my PSA was < 0.1 ( we don’t measure ultra sensitive PSA in Sweden by the way)

So my believe is that by adding Abiraterone to the mix of treatments this added to a very hostile environment for the weakend and radiation damaged cancer cell that died off or have gone dormant and if I’m lucky then my 2-3 years of Orgovyx and 2 years keeps me in remission and who knows what the future will be.

Best wishes - Ulf

[CancerConcierge]

We decided to add abiraterone to my husband's treatment plan in 2023, based on the Stampede trial protocols for high risk prostate cancer. His oncologist was not urging him to add abiraterone, though discussed it with us and agreed to prescribe it. It was his RO who initially recommended the addition of abiraterone. He was already on Orgovyx and had completed Proton radiation to the prostate when he started the abiraterone.

My husband's PSA was 46.6 the week before his biopsy that showed Gleason 9 cancer ( Hopkins downgraded to G8) His cancer was localized to the prostate.

We asked the oncology NP for the Decipher test, but she dropped the ball, and was replaced by two more NPs. We meet with the MO in early December, and will request Decipher again.

In December he will have been on Abiraterone for a year and Orgovyx for 15 months.

Adding abiraterone caused his blood pressure to rise for a period of time, but has since stabilized , and he has stopped his BP meds.

He does have a dilated aortic root (4.6 cm) which increased from 4.0 cm 15 months previous to his most recent ECHO and CT.

He will have a follow up ECHO in December. If it's further enlarged he may need surgery, so that would be concerning in regards to continuing his cancer treatment...all to be discussed with his MO and Cardiologist.

It was a big decision for my husband to add the Abiraterone...We hope it was the right one.

He already had chronic fatigue symptoms prior to starting treatment for his prostate cancer. He was also treated for bladder cancer in 2020, and has a chronic Kliebesella Pneumoniae UTI infection and has been on antibiotics for over a year and a half (when he takes a break from the antibiotics it comes back quickly)

[petabyte in reply to CancerConcierge]

Thanks for the reply CancerConcierge it is reassuring that others took this path but we can never know if it was the right one. We can just try to stack the odds in our favour.

Sorry to hear about your husbands side effects, you know I think this disease is at least as difficult for the partner, I think it is worse for my wife. So far I've been OK but am getting a blood test and seeing a cardiologist for an echo this Friday as well (3 appointments in one day!) so we'll see after that...

Annoying they don't do the decipher for your husband. I asked about genetic sequencing as well (it is not a big thing here in Belgium like in the US) but they don't even have a biopsy sample saved 🙁 and if they did I'd need to pay for it myself (not covered by insurance unless it impacts treatment decisions). So I am just assuming it is aggressive.

I am also paying for the Abiraterone myself (also not covered for cN0M0).

❤️ petabyte

[CancerConcierge in reply to petabyte]

Yes! Hard for the wives too

The MO did order a genetic blood test at the beginning of his treatment.( there were no inherited genes relevant to treating his PCa)

He had previously had a test on a lower grade Gleason 6 lesion , but it wasn’t Decipher. We will ask again at our next appointment for the Decipher test.

My stepmother who lives in Paris was recently diagnosed with breast cancer, with spread to a lymph node. She didn’t have any genetic testing, and doesn’t think it’s something they do there routinely…

That’s concerning that they didn’t save your biopsy sample! That prevents you from getting a second opinion on the Gleason Grade too.

We too, have assumed that my husband’s cancer is aggressive , given his G9 and high PSA. In one year he went from all cores benign on biopsy to 8 cores positive for cancer.

Where are you living in Belgium? I was in Brussels for eight years when I was young.

You sound very proactive and well researched in your approach to treatment!

Best of luck with your treatment!

[vintage42 in reply to CancerConcierge]

"... In December he will have been on Abiraterone for a year and Orgovyx for 15 months.It was a big decision for my husband to add the Abiraterone...We hope it was the right one."

Why was adding the Abiraterone controversial? Doublet therapy is better than ADT alone, and Abiraterone is a very effective and popular inhibitor. For that and other reasons, I chose Abiraterone over the 'lutamides. I have been on Abiraterone for 8 months and Orgovyx for 11 months, and like this doublet. Castrate resistance happens with all hormone therapy, but it seems better to use medicatio early to control the spread, than save it for later after the spread.

[CancerConcierge]

Adding Abiraterone is not controversial at all for metastatic PC.

My husband’s cancer is localized.

And adding Abiraterone, based on the Stampede trial, can be a treatment for high risk localized cancer too. We are hoping that his treatment protocol will be curative.

What we don’t know is if it has worsened his heart issue. The dilated aortic root can dissect and rupture.

Your decision to add Abiraterone makes perfect sense.

Our decision made sense too.

We’ll know more next month after his next Echo.

[Gatodd]

I had a similar diagnosis Oct 2021- Gleason 8, tb3 and cribriform morphology. I started adt and Abi in December 2021. HDR in Feb 2022, EBRT in March 2022.

Did Abi for 2 years. Final ADT shot (hopefully) later this week. Yea! Blood pressure went haywire high for a month getting on and off Abi/prednisone. Probably the prednisone

MO suggested to throw what we could early while reasonably healthy. Another respected doctor did not recommend Abi, but wasn’t opposed to it either. I decided to add Abi and watch liver and kidney numbers closely. The numbers got a little high, but nothing alarming.

Good luck.

[lowT163]

sounds like you were same as me. I had proton instead of imrt. All treatment was complete Feb 2020. Lupron and zytiga and 40 rounds of radiation. My tumor was outside the prostate against my rectum. Also in the nerve bundle. I was misdiagnosed in 2017 and then in 2018 it was out of the prostate. Started Zytiga 8 months in advance of radiation. My psa 3 months ago was .10. Testosterone was at 150. It moved up from <3 to .10 as the testosterone returned. It has stopped returning. Was at 350 1 year ago and dropped back to 150 for unknown reasons.

So holding pretty good and maybe my cancer was a lot worse than yours. Best of luck.