TO TAKE OR TO WAIT

[GMan-62]

Quick recap.

5/27/2022 - First PSA Test Results since RALP - 8.11

6/1/2022 - Started Bicalutamide one 50mg Tab daily (will stop taking 7/30/22.)

6/14/2022 - Started Eligard 30 mg 4 month dose.

6/15/2022 - Did GA 68 LOCAMETZ PSMA-PET Scan. PET Scan showed an 11m soft tissue nodule in the posterolateral left pelvis and a similar appearing 7mm nodule on the right side. No other hot spots identified.

6/24/2022 - Second PSA Test Results since RALP - 1.67

6/29/2022 - Met with Urology Oncologist Referred to Radiation Oncologist. Next visit will discuss

7/25/2022 - Met with RO to discuss whole pelvic and Lymph Node RT.

7/28/2022 - PSA - 0.01 T - 11.

8/2/2022 - Scheduled for 38-39 IMRT treatments for the whole pelvis and lymph nodes starting 8/15/22.

8/3/2022 -Met with Urology Oncologist to discuss adding enzalutamide to treatment. His thoughts are since the cancer is responding well to Eligard, PSMA PET Scan showed no mets outside the 2 soft nodes, and I'm starting IMRT on the 15th, he would prefer to wait until after IMRT is complete to decide whether or not to start enzalutamide . I'm scheduled to have another PSA and T test 12/8/22 to see how my cancer is responding to treatment and at that time we will reevaluate whether to add enzalutamide or not.

My question is. Is it better to wait to add a 2nd or 3rd level drugs like enzalutamide to my treatment until I'm no longer responding to Eligard or should it be added now. I've read several articles indicating that with Eligard and IMRT I could stay in remission for some time before I need to add another drug to my treatment, but other articles that say hit it hard up front. I don't want to do something that will accelerate when my body stops responding to treatment, but I don't want to wait so long that we are playing catch-up and can't get the cancer back under control if PSA starts rising again.

Does the question make sense?

[tango65]

Discuss doing whole pelvis radiation plus 2 years ADT and abiraterone according to the STAMPEDE protocol

urotoday.com/conference-hig...

[GMan-62 in reply to tango65]

Thanks for your reply tango65,My current plan is whole pelvis and lymph node radiation with a boost to the lymph nodes. That will run from August 15th - October 7th. I'm currently on Eligard and will be for 2 years. Originally the Oncologist was going to start either enzalutamide, or abiraterone + prednisone which are similar drugs except Enzalutamide seems to have better efficacy. My oncologist was leaning toward enzalutamide because of the side effects associated with prednisolone. However since the GA-68 PSMA PET Scan (which was done 6/15/22 when my PSA was at 8.11) only showed tumors in 2 pelvic lymph nodes ( an 11 mm soft node on the left with a SUV of 13.2 and a 7 mm soft node on the right with a SUV of 2.1) he wanted to hold off on the Enzalutamide and see how the cancer responds to the RT.

I have read the STAMPEDE protocol which promotes ADT for 2 years, adding Abiraterone + prednisone or Enzalutamide, and whole pelvic + lymph node RT to the treatment. However, I have also read combining IMRT with Eligard for Oligometastatic PC is a very viable protocol on its own. I know that everyone is different, but I have read several stories on this site where the only treatment men had after Primary treatment of RALP or EBRT and then Eligard or Lupron for 2 years along with 38-40 IMRT sessions to the whole pelvis and lymph nodes and they were in remission for 6+ years and some 10 years or more. Then if their PSA started to rise they would continue using eligard and add the 2nd & 3rd line drugs like enzalutamide to their treatment which would lower their PSA and hold it around .01 to .05. That is why I ask the question add enzalutamide to the eligard and IMRT now or wait.

[TJS-1]

We have very similar Dx and treatment paths, except I was diagnosed younger and have been at this since 2015. See my profile. I believe the Abiraterone + Pred protocol (suppresses T) enhances 1st line ADT, but is a very different mechanism than Enzalutamide (AR antagonist). Since you’re already suppressing T on Eligard; perhaps “hit it hard” by adding Enzalutamide during the IMRT protocol (6+ months?) and decide with your docs how long to continue ADT + the Enza after IMRT is complete? This approach might compromise PCa cells a great deal so the IMRT can be more effective. Your Tx plan might still be curable, and in retrospect this is what I would have done.

I am having to start Enzalutamide or Duralutamide as monotherapy to address rising PSA after having prior ADT and ADT +Abi in connection with the RRP and IMRT. Am probably still hormone sensitive to first line ADT (Firmagon and Lupron in my case), but as others and my MO believe, we are changing the mechanism to deprive PCa of T at this point, rather than continue the Firmagon+ Abi to failure; others call this adaptive therapy.

Best of luck whatever you and your medical team decide!

[GMan-62 in reply to TJS-1]

Thanks for your input. Yes our Dx is very similar. Lots to consider. I will have to have another discussion with my Oncologist and decide what to do. Good luck to you and may you always stay positive.

[London441]

My pathology was similar to both you and TJS-1. If I'd known then what I know now I'd have taken a different treatment path, but sensitive scans weren't accessible to me then (2019).RP 'seemed' like the best plan, as it does to most laymen. 'Get it all out'. Except they didn't tell me it rarely works for anything other than early stage, organ confined disease, and has some particular consequences we all now know about.

That's all in the past, but I can also say if I had had a post op PSA of 8.11 (or 10 in TJS-1's case) I would have wanted to set the urologist's car on fire and then have a talk with him. Detectable PSA post RP is not a good prognostic indicator, and 10 or close to it is very high.

However, I've also learned that RP is a difficult surgery to do well, and multiple factors can be responsible for less than optimal results. Attempted nerve sparing can leave cancer behind. Lymph node dissection approach varies, is not uniform. Placement of the individual patient's surrounding organs, his body composition and age matter. In addition, location and size of the tumor (and the prostate itself), and of course the skill of the surgeon (regardless of experience) are all potential factors.

I like to think having my RP done at a center of excellence (Johns Hopkins) contributed to my undetectable PSA post op, despite the negative features of seminal vesicle invasion and a positive node, but that is pure speculation. I also speculate that my subsequent care there compares favorably to many, but I have only what I've learned about SOC to go on.

For instance, if I were you I would not be concerning myself with the side effects of the accompanying prednisone (with aberaterone) vs enzalutamide. Abi is known to have less side effects than enza, and Eligard's side effects generally take precedent anyway. The important thing is to drive the testosterone as low as possible to enhance the efficacy of the coming radiation. Abi assists the Eligard to lower T, and the low T assists the IMRT. Trials comparing adding abi vs enza are still early in their results, and I'm not a doctor. But I do know you want to lower your T as much as you can as part of the plan.

Old SOC regarded anything under 50ng/Dl as 'castrate level' but it is now clear that for setting up radiation, lower is better. I was given abi with Eligard and T was <10ng/dl for the entire time I was on it.

As you probably know, the old SOC for oligometastatic pca was to treat it the same as metastatic-LHRH drugs until they stop working, followed by chemo and palliative care, see ya. This is now many years ago of course. As radiation advanced and 2nd line anti androgens arrived, things changed. But even today oligometastatic guys have to know how to advocate for themselves and weigh risk and benefit. Taking QOL now or later is a huge consideration for many.

We need to keep up on the treatment approaches! Case in point is salvage radiation of the prostate bed only for oligo. The entire pelvic girdle must be radiated for optimal result. This is subject to change of course, but for now it is essential. Yet many RO's still don't do it.

Another: Many MO's will still let post-op PSA rise to 5, 10 or beyond before recommending further intervention. On one hand it seems crazy, but if the patient is older, or in poor health, or is basically refusing (or delaying) any additional treatment that might impede on QOL, this is what they do.

So in TJS-1 case, from reading his profile it seems clear he was taking a very conservative, QOL priority approach. No radiation until 3 years after surgery despite PSA of 10 post op might seem unwise to me, but look how it's working for him more than 6 years later! Of course, if you've read any of my posts and replies you can guess how much I think his exercise habits are influencing this.

😀

For you, curative (or whatever you wish to call it) intent is still completely realistic. If it were me I'd take the abi with the Eligard for sure and set those juvenile delinquent vandal pca cells up for total eradication while you can. That's what I did. Other than early docetaxel chemo (which has not been proven to help in this setting) it was the essence of my clinical trial at JH.

Remember, 'combining IMRT with Eligard for Oligometastatic PC is a very viable protocol on it's own' is something you read. The STAMPEDE trial showing the effectiveness of adding abi is likely orders of magnitude more substantial than that.

All opinions expressed are my own, as if I have to say it.

I had RP in June '19, started the trial of Eligard/abi/taxotere in September '19, followed by IMRT in Feb-March '20. Last Eligard shot Sept '20. Full return of testosterone by April '21. As of 7/22, PSA has been undetectable throughout and T is 730. We'll see. Today is all that matters. Great luck to you!

[Nusch in reply to London441]

Very interesting arguments. May I just ask a question, please? I’ve had it all: RP, chemo and full blooded RT - please see my bio in the profile. Now I‘m lower than 10 ng/dl Testosterone with Lupron only and PSA is undetectable. I have ERLEADA at home for three months, but didn’t start up to now. Still considering 🤔… What would you do?

I wish you on-going success, you are doing extremely well!

[London441 in reply to Nusch]

What is 'full blooded RT'? Did you have lymph node metastasis directed radiation only, or to the entire pelvic region?

With a PSA of <0.03 I wouldn't be adding anything, but that's what you get for asking me.

You are now in the realm of adaptive therapy, intermittent ADT, ducking and dodging, shaking, baking etc. It's hard to know what to do, I get that.

The 2 basic philosophies have pretty much been hit it as hard as you can vs don't empty all your bullets too soon. Timing is everything though. There are other options too. Gather all the info you can is the best I can suggest.

[Nusch in reply to London441]

Many thx - I think like you.

I had first RT in 09/2020 to two PLN - that was all PSMA PET CT found at this time.

Second RT started 03/2022 to prostate bed, two PLN spots and to whole PLN area after findings of PSMA PET CT showed possible biochemical recurrence plus 2-3 small PLN spots. PSA at this time was 1.4 with normal level of testosterone. Restarted Lupron 01/2022 and since 7/2022 down to PSA undetectable and Testosterone less 10 ng/dl.