Failed RP & SRT; Negative PSMA PET

[dans_journey]

Greetings.

I had a radical prostatectomy that failed and then salvage radiation therapy that appears to have failed as well. A recent PSMA PET scan showed no signs of recurrent prostate cancer or metastases. By way of background:

NOV 2010 - Dx at age 52; positive DRE, Gleason 3+3, PSA 5.0; prostate came out cleanly with negative margins, no ECE, SVI, LNI

JAN 2011 - Radical prostatectomy. pathological Gleason upgraded to 3+4

SEP 2015 - PSA became detectable at 0.05 ng/mL

JUL 2021 - PSA hits traditional biochemical recurrence threshold at 0.21 ng/mL

NOV 2021 - PSMA PET scan with PSA at 0.22 ng/mL; no signs of cancer

MAY 2022 - Six-month dose of Eligard in advance of SRT; PSA at 0.36 ng/mL

JUL-AUG 2022 - 35 sessions of IMRT to prostate bed only

MAR 2023 - PSA 0.13 ng/mL

MAY 2023 - PSA 0.11 ng/mL

OCT 2023 - PSA 0.21 ng/mL, nearly doubling from previous test

DEC 2023 - PSA 0.33 ng/mL

JAN 2024 - PSA 0.37 ng/mL, slightly higher than when SRT was started

FEB 2024 - PSMA PET scan; "no signs of recurrent prostate cancer or metastases"

I'm sure that ADT will be the next step in my future, and I meet with the doctors this week to discuss the recent surge in my PSA and inconclusive PSMA PET. My questions to the group would include:

Is it worth letting my PSA continue to increase to the point where a PSMA PET scan would more likely/able to detect where the cancer is located? That would mean delaying the start of ADT. (Both PSMA PET scans used 68-Ga as the tracer.)

Or is there really little value in knowing where the cancer is at this point and just jump into the ADT?

I'd appreciate hearing any thoughts and insights that may help me have better conversations with my urologist and radiation oncologist.

Thanks!

[Tall_Allen]

3 options:

1. Radiation to pelvic LN area with 2 years of ADT

2. One year of ADT+apalutamide as in the PRESTO trial:

prostatecancer.news/2022/09...

3. Intermittent ADT+enzalutamide as in the EMBARK trial:

prostatecancer.news/2023/05...

[dans_journey in reply to Tall_Allen]

Thanks, Allen! I'll print those off and read them before my appointment this week.

[NanoMRI]

As you have asked for any thoughts and insights. My focus since diagnosis nine years ago has been to not give this beast time and obscurity, and to avoid/delay ADT and thereby castration resistance for as many years as possible. Six years ago, after my salvage RT to prostate bed, no ADT, failed to get all the remaining cancer, and before my next treatment decision, at usPSA 0.10, I went to Europe for both Ga68 PSMA and Ferrotran nanoparticle MRI. The Ga68 was clear however the nanoMRI identified five suspicious pelvic lymph nodes. Instead of ADT and/or pelvic region radiation I went for extended pelvic lymph node surgery. My nadir after the ePLND was <0.010 which held for two years. Then it slowly crept up through 0.01X, 0.02X and for past two years 0.03X range, no ADT. Rather than doing nothing I am taking supplements with other measures to combat cancer stem cells (yes somewhat theoretical and out in front of common clinical practices). Also, my Ga68 and Pylarify PSMAs, done in 2022, at 0.031, were clear. I am considering choline and fluciclovine for further investigation and comparison. It is interesting that the often cited Dr Kwon of Mayo Clinic recommends not ranking imaging methods because different results are realized on an individual basis. Hope this helps. All the best!

[dans_journey in reply to NanoMRI]

Thanks for sharing your experiences. I can understand the reluctance to rush into ADT. I seemed to tolerate the six month dose of Eligard that was done concurrently with the SRT pretty well—minor to moderate fatigue and more fragile emotions, but no hot flashes or weight gain. But that was just the Eligard not in combination with any anti-androgens.

[NanoMRI in reply to dans_journey]

My reluctance to ADT is just not the side-effects, it is the start of clock to castration resistance. I know this may be inevitable for me, but I will do all I can to reduce tumor burden before then. As 0.05 was my post RP nadir, and with cancer confirmed in my para aortic nodes at 0.10, 0.03 is my new actionable number. Why I test nearly bi-monthly, began imaging at 0.03. I will look again to targeted surgery or radiation if/when get targets. I do ponder RT to pelvic region, even without successful imaging - but still not willing to radiate this area blind.

[2babeliever]

Dan,

You never mention your testosterone level at the time of your recent PSA measurements (I have been told that these should always be done at the same time). When I look at your PSADT since your SRT - I wonder if your testosterone is merely coming back after your ADT usage causing your shorter PSADT (...it appears your PSA is about what it was before SRT...perhaps it is not growing as fast as you think). This is just my thought...but I am no expert.

[dans_journey in reply to 2babeliever]

Thanks for sharing. It's interesting. I've been getting my care through the VA and they have not yet tested testosterone levels at any point through this. It's a point that I plan on discussing with the doctor this week. If nothing else, establish a baseline for future reference.

[2babeliever in reply to dans_journey]

Dan...I have followed your case closely for about 3 years on your blog (I live about 2 miles from you)...my hopes and prayers are with you! FYI - the UCSD Medical Oncology Department is who told me to always get the testosterone checked with a PSA measurement...

[Fortran1958]

6 years after radical prostatectomy my PSA hit 0.2 triggering a PSMA Pet scan. Over the course of the next 12 months I had 4 (maybe 5) PSMA scans including one with an experimental isotope. Nothing definitive PSA was 0.33 at last scan.

Urologist said let’s wait until 0.5 for next scan. PSA slowed to hit 0.44 at which time urologist changed the targe to be 0.6 before next scan. It had already been 18 months since last PSMA.

No other treatment other than 6 monthly PSA test.

[NanoMRI in reply to Fortran1958]

Interesting how different approaches can be. I am also six years out since treatment and my last two PSMA scans, Ga68 and Pylarify for comparison were also clear. Differences are I have had three treatments, RP, salvage RT at 0.1 then six years ago salvage extended pelvic lymph node surgery when my usPSA was back up to 0.1 and Ferrotran nanoparticle MRI identified suspicious pelvic lymoh nodes; cancer confirmed at paraaortic nodes. I will next scan if/when back up to 0.050, now considering (older) choline and fluciclovine agents and going back to Europe for Ferrotran nanoMRI.

[dans_journey in reply to Fortran1958]

Thanks for sharing. I'm of a similar mindset to let my PSA increase a little more (but definitely <1.0) until we can determine what's really going on. Obviously, there's some risk in that and it's something I'll discuss with the doctor.

[ron_bucher]

When I reached a very similar situation in 2016, I added Mark Scholz to my medical team. I told him my inclination was to treat aggressively. He suggested triplet therapy of 18 months of Lupron + docetaxel + prophylactic radiation of abdominal lymph nodes outside the local area. I stopped Lupron at 9 months due to side effects, but that triplet therapy gave me another 4-5 years of undetectable PSA. My side effects from the chemo and radiation were not bad.

Dr. Scholz and my local oncologist say they have a lot of patients who are having success (i.e. "remission") with the "radiate what shows on a PSMA scan" approach. Probabilities of seeing a tumor with PSA 0.20 is ~ 20%, PSA 0.40 is ~40%, PSA 0.60 is ~60%, etc. One or two tumors is typical in cases like this, and they are usually in lymph nodes or bones.

[dans_journey in reply to ron_bucher]

Thanks, Ron.

Yeah, I knew going into the PSMA PET scan at my PSA level there was only about a 40% chance of it finding something.

I actually tolerated the Eligard injection better than most, with minimal to moderate fatigue and hair-triggered emotions, but no weight gain or hot flashes. The salvage radiation kicked my butt in terms of fatigue the last 2-3 weeks of zapping plus 3-4 weeks after. But 18 months out, the longer term side effects are minimal (slightly increased stress incontinence and slightly worse ED).

I follow Dr. Scholz's PCRI channel on YouTube and he presents a lot of good information. I'm in San Diego and I've thought of contacting his office to get a second opinion on my situation.

Thanks again for taking time to respond.

[NanoMRI in reply to dans_journey]

I consulted with Scholz six years ago after I had the Ferrotran nanoparticle MRI, done at 0.10. He recommended ADT and against ePLND-the treatment route I took. We face so many disparities in diagnostic and treatment approaches.

[MateoBeach]

My suggestion is to go for the full pelvic LN field radiation up to the aortic bifrucation. Prostate bed only SRT is no longer the standard and you are the perfect demonstration of this (as was I). Some duration of ADT improves outcomes from extended field SRT, but the duration necessary is not so clear cut The two years seems most clearly best for those with high pretreatment PSA and those who tolerate it well. For others 6 months may be sufficient. It is an individual assessment made with your team.

ADT alone without the RT should be combined with an ARSI. Clearly better. But it does not lead to a cure. Will eventually fail and lead to castrate resistance. So that is why I favor the pelvic RT as a chance (at least) for a cure.

[j-o-h-n]

"I had a radical prostatectomy that failed and then salvage radiation therapy that appears to have failed as well."

What do you mean by failed? Do you mean cured?

Good Luck, Good Health and Good Humor.

j-o-h-n

[Hope422PC]

it is totally an individual decision. There is no magic bullet. We waited anxiously for years for the Lu 177 treatment. PSMA scan was very encouraging and only showed slight pelvic lymph node involvement. However, we went to Mayo clinic and saw Eugene Kwon who did the Choline Pet scan which found extensive spread of the non-PSA cancer cells. My caution is to not let the findings of the PSMA scan hold too much weight. I feel like a sucker punch when we found out that he had extensive cancer spread, despite the good results from the PSMA scan.

However, my husband was already castration resistant when he got the Lu177. He is similar to you in age and diagnosed in 2009. If you have been able to avoid ADT until this point, it seems like it might be a good time to do it. You have had a great success thus far. You can try the intermittent ADT and will still be eligible for the androgen uptake inhibitors e.g. Zytiga, down the road. Best wishes.

[dans_journey in reply to Hope422PC]

Thanks for sharing your experiences. I've wondered about using different tracers for the PET scan (both of the ones that I've had were Gallium-68). Do you recall what your PSA was when you had the Choline PET scan? As I understand it, the Choline scan doesn't pick much up until the PSA is at least 1.0 ng/mL.

[Hope422PC in reply to dans_journey]

It was 50

[ManuteBol1]

Hi Dan. Thanks for your posts and your information. You’ve had a long road, which I suppose is both a good and a bad thing! Keep the faith!

I saw you were 54 months undetectable and then had your PSA start to climb. You just had 0.00 on the graphs, but I found in your synopsis that your PSA tests were apparently using a threshold of <0.03. Is that right?

I’m six months post prostatectomy with post-op pathology a little worse than yours, so I’m very curious about both good and bad outcomes from folks that might’ve been undetectable (at various thresholds of undetectability.) I’m particularly interested in what “undetectable” really means because I’m not a believer one can discount tests with lower thresholds, based on a preponderance of the research I’ve seen so far, which strongly leads me to believe that an undetectable on a test with a <0.1 threshold isn’t at all the same as an undetectable under, say 0.006. You could be one such case if you were really, say, 0.02 to begin with.

I am fully aware that many knowledgeable people think that <0.1 is all you need to worry about but I’m not so sure because of studies like the link below (as well as the ones talking about the 0.03 threshold for salvage radiation treatment)

ncbi.nlm.nih.gov/pmc/articl...

I welcome any input