what should next step be? Heads spinning with conflicting and confusing info. and medical advice

[KAgolf]

First I want to apologize for such a long post, but am hoping to give all info. needed for your help.

I have posted a couple of questions before and appreciated your help; again we would VERY much appreciate any clarifications, opinions, insight from you now…also any corrections to what “I think” that could be wrong

History husband is 77 (will be 78 in Aug 2021) other than PCa, is healthy—found out he does have osteoporosis in 1 hip and osteopenia in other (concerning for ADT)

PSA: 3.77 in 9/2019 -- had been in high 2’s to mid 3’s forever 5.15 in 9/2020— uro suggested 3 mo. redo 8.18 in 12/2020—uro advised biopsy (done 1/11/21) 10.43 on 1/28/21 (doubled in 4 months) before Degarelix injection. T=296 2.73 on 2/17/21 T = 41.3 2.52 on 2/25/21 T = 40 1.43 on 4/1/21 0.54 on 5/20/21 T = 41.3

diagnosed by biopsy 1/11/21 with PCa; 1-Original pathology report: GL9: 4+5=9 and 5=4=9, grade 5. Six/12 cores, all left malignant; all right benign. Adenocarcinom w/ intraductal spread, with each core discontinuously involving 50% -70%

2-MDA review of slides: GL9: 4+5=9 and 5=4=9, grade 5. Six/12 cores, all left malignant; all right benign Adenocarcinoma, with each core discontinuously involving 50% -70%

3-Pathologist review for Proton Center graded it 4 + 4=8 GL8 and Grade Grade 4 Adenocarcinoma with Cribriform pattern 4

3-T MRI noted Pi-Rads 4

Started on ADT 1/28: Jan-Degarelix 1 mo. Feb-Eligard 3 mo. May- Eligard 3 mo. Aug- will have 3 mo. Eligard Is tolerating ADT well so far but has had muscle loss and some brain fog which adds to concerns for also having more bone loss with ADT

He has had CT, PET, Axumin PET, and two 3-T MRI's; all show 3-4 “suspicious" lymph nodes (external and internal iliac) which 1 doc says are round, not elliptical so that's what makes them suspicious. NOT biopsied and NOT 1 radiologist will commit to calling them malignant or benign--all say suspicious, so they were treated as positive. bone scan with no bone malignancy was seen.

What his PCa is being called and the confusion!

1-MD Anderson URO oncology surgeon calls his PCa: advanced, (???) very aggressive (GL9 and doubling in 4 mo.) metastatic (???—he calls nodes mets) extremely high risk (primary Gleason pattern 5 and more than 4 cores with grade 4 or 5). stage IVA

2-MDA MO calls it metastatic and wants to do chemo

3-Proton Radiologist calls it IVA, N1, M0

4-2nd MO noted T1c, N1, M0, says NOT metastatic but recommends Zytiga + prednisone

Other terms used by other docs call it "regional", but do not say metastatic.

Hubby finished 39 Pencil Beam Proton sessions with boost almost 4 weeks ago. In addition to prostate, ALL pelvic nodes targeted for 27 sessions and “suspicious” targeted an additional 5 (?) sessions; only prostate treated the last 7 days.

now for my observations and questions:

1-I thought “advanced” meant cancer had spread to bones or distant sites or had recurred; neither is true for Jeff so why calling it advanced? It appears EARLY STAGE to me and NOT advanced

2-I thought chemo was only used for metastatic which Jeff does not have, so why would it be recommended? Agree with Tall Allen that chemo would be of little benefit

3-I thought Zytiga was for mCRPC and nmCRPC and for men with hormone-naïve prostate cancer regardless of metastatic disease status. Jeff does not have hormone-naïve nor CRPC yet—is responding to ADT so far. Would Zytiga benefit him when he doesn’t fall into these categories?

4-I agree with you who call his PCa Regional as opposed to metastatic

5-appears it was caught “early” because his PSA had just started to rise and was starting to take off but stopped by ADT. 10.43 was highest it ever got

6-IF he doesn’t have mets, and is regional, why is it called IVA?

7- AM I being unreasonable when I ask for genetic and genome (bio-marker) testing to be done? I asked for it before he started ADT—not done; I have repeatedly asked for it to be done and it’s ignored saying no benefit until he has metastases.

a-“germline testing is recommended for prostate cancer and with any of the following: …..VERY HIGH RISK, REGIONAL, AGGRESSIVE…”

b-“Genomic testing looks at the DNA of your tumor can find the different types of mutations that may be in your tumor, whether they were inherited or acquired and how they influence the behavior of the tumor, including how rapidly it is likely to grow and spread.”

c-PSMA bio-marker testing??

8-I have asked about use of low-dose Estrogen patches to offset the brain fog, possible bone loss, and muscle loss—response has been underwhelming. SO FAR Jeff doesn’t have hot flashes so the theory is not to use Estrogen…

9- I hate that everything to do with PCa seems to be re-active—“when it comes back”; we’d rather be pro-active to try and prevent it from coming back, but not sure anything really is other than the ADT.

10- He can get a PSMA imaging—the new MSK one—but advised to wait at least 3 months after the Proton ended before doing that—sounds reasonable a-Would this be a good pro-active move? To see IF there are any lurking cancer cells not shown on other imaging and perhaps zap them before they cause trouble?b-Is the PSMA targeted therapy that’s waiting to be approved going to be able to eliminate these cancer cells early? Is it worth waiting for?

THANK all of you for your help and continued prayers for you and for beating this thing

[LearnAll]

It is common for different sub specialists to look at someone's cancer from the tubular vision of their area of specialization. ...hence the confusion. At age 78, it becomes even more important to balance benefits and toxicity of aggressive treatments. In Japan, Doctors are reverting back to simpler, less toxic treatments in older men.. taking into consideration the fact that toxic treatments can cause more harm than good . Personally, I would be cautious and not be too afraid of labels such as "advanced", "very aggressive" etc.PSMA PET CT scan can help in assessing the current state of his cancer and can guide type and extent of treatment required.

[KAgolf in reply to LearnAll]

thanks--guess I am a bit OCD about the labels since treatments seem to be based on those labels

[Dachshundlove in reply to KAgolf]

The irony of the “labels” with regards to prostate cancer, is a person with a very ominous “label” (cribiform, Gleason 10) can have a spectacular response to treatment and die from something other than PC. While a person with a benign label (Gleason 6) can die from PC. How one responds to treatments becomes the determining factor in life expectancy. In the world of medical insurance “labels” help people access potentially helpful medical treatments.

[KAgolf in reply to Dachshundlove]

thank you--very good points

[Dachshundlove]

Hi KAgolf

Sorry to hear about your husband. The “metastatic/ non-metastatic” designation related to lymph nodes becomes like hair splitting.

The most educated minds on this site would likely agree that even a Gleason 8 (which is the low grade Of the High Grade) is likely to metastasize.

Lymph nodes are not technically metastasis for treatment/ insurance purposes. BUT, what oncologists have conjectured about prostate cancer, is that it produces “micro metastatic disease” early on in the disease process. So before a man is remotely symptomatic or experiences exponential growth in PSA, his prostate tumor is likely shedding cancer cells, which MAY or MAY not become tumors later on.

Micro metastatic disease is common with many types of cancer. Even the most advanced scans cannot see or predict it, but oncologists know it is a reality, as a person can have surgery to what appears to be a localized cancer (prostate, breast, kidney) and think they are cured and then, 10 years later, have a metastasis from the primary cancer tumor they thought they had completely removed.

If your husband is referred to as being “metastatic” by MD Anderson. This gives him access to early chemo. Early chemo with a secondary anti-androgen gives an enormous survival benefit. If your husband is 77 with a high performance status, your oncologist may consider this approach.

Keep asking questions here. There are so many brilliant people who generously take their time to educate and enlighten all of those lucky enough to have found this mutual aid community!

[tallguy2 in reply to Dachshundlove]

I agree 100%.

[KAgolf in reply to tallguy2]

thank you

[KAgolf in reply to Dachshundlove]

thanks very much; as mentioned to LearnAll, I am a bit OCD about the labels since treatments seem to be based on those labels; while I certainly want him to have any an all treatments that will/could benefit him and provide longer OS, I also am am a believer of "why put someone thru a treatment that probably won't be beneficial and probably will be toxic?" I agree with the "one size doesn't fit all" when it comes to prostate cancer; hence my wanting the genetic and genome testing for guidanceI WISH I could find an MO who specializes in prostate cancer only--see there's a group in Marina del Ray CA, cut we're on east coast in GA, just above Jacksonville, FL; MSK would be a good place but seems they are booked for months.

another question: does Zytiga need to be done ASAP or could he wait 3-4 months to start that?

[Dachshundlove in reply to KAgolf]

If your Dr is recommending he start Zytiga, I would do it sooner rather than later, although a few months wait should not make a difference.

I would trust the oncologist at MD Anderson to offer advice based on reporting from the most recent clinical trial data. Any good Dr/ Scientist will integrate new information/ data from large scale well designed trials and let that information guide the evolution of the care they offer to their patients. Although we all wish they were, Anecdotes are NOT Evidence.

[pjoshea13]

Hi,

[1] "Prostate cancer is usually called "advanced" if it has spread outside of the prostate gland. It may have moved to the tissues nearby, which doctors call “locally advanced.” It also could have spread to the lymph nodes, bones, or other parts of the body. Then it’s called metastatic prostate cancer." [1]

[8] You "found out he does have osteoporosis in 1 hip and osteopenia in other".

For an otherwse healthy person, I would say that he should start taking vitamin K2. Vitamin K is required for the transport of minerals to bone. The knee-jerk reaction is to suggest calcium and vitamin D, but other essential minerals are neglected (magnesium, boron, etc). There are studies suggesting that high doses of calcium should be avoided by men with PCa. Excess calcium may inhibit the conversion of inactive vitamin D (calcidiol) to the active hormonal form (calcitriol). Here is a bone supplement that he might try: [2].

For someone with a castrate level of testosterone (which he will have on ADT), I would suggest an estradiol [E2] test. For bone health it should not be below 12 pg/mL. A low-dose E2 patch can be used to get E2 into the safe 20-30 pg/mL range. I would aim for 20 pg/mL.

I hope that others will answer your other questions.

Best, -Patrick

[1] webmd.com/prostate-cancer/a...

[2] swansonvitamins.com/swanson...

[KAgolf in reply to pjoshea13]

thank you--I have asked for the E2 test but reply was "we don't normally do that". %&%@$# will see if primary will do that

[pjoshea13 in reply to KAgolf]

If you are in the U.S. you can get an E2 test from Life Extension. The test is actually done at your nearest LabCorp office. The annual sale on blood tests is over, but the cost is only $33. [1]

Armed with a low number & one or two E2 studies (specifically for men), I don't see how a request for a low-dose E2 patch can be refused.

& there other doctors who are happy to work with an educated patient/partner.

Best, -Patrick

[1] lifeextension.com/search#q=...

[KAgolf in reply to pjoshea13]

THANK YOU!

[Justfor_]

He should had done the PSMA scan before RT for planning guidance and as a baseline for future use. Now the first reason is past and gone but the second is still there. I wouldn't wait for 3 months.

[KAgolf in reply to Justfor_]

PSMA scan wasn't available then--just FDA approved 5/27; he did have an Axumin scan prior

[Hidden]

I was 53 when diagnosed with a similar pathology as your husband. Biopsy a mix of 4 and 5 but mostly 4. So I'm G9. Cribiform is an aggressive tumor architecture and tends to spread. Its similar to ductal but there must be some differences because apparently its hard to delineate where ductal is not. Nearly 70% of gleason 4 are cribiform.

Anyway, my treatment to date has been RP followed by IMRT along with eligard and zytiga. My psa is < 0.01 and T < 1.

For nearly 20 months.

[KAgolf in reply to Hidden]

thanks-glad this is working for you; do you have SE from Eligard and from Zytiga too? did you start Zytiga right away? we've also been told, it may be too late to start that????

[Hidden in reply to KAgolf]

After the June 2019 RP didn't get me to undetectable, I received my first eligard shot in July 2019 and started on Casodex at the same time. IMRT commenced 0ct 3 2019 and zytiga was added in early Nov 2019 and stopped Casodex simultaneously.

I have a recent post about starting an ADT holiday soon. I received my last eligard shot last week and stopped zytiga. I'm now weaning off prednisone. Some SEs from zytiga...but all gone now...mostly a blanket of fatigue that requires exercise to breakout from.

So basically, yes zytiga from nearly the beginning.

[Tall_Allen]

(1) Some understanding of the terminology may help:N1= pelvic lymph nodes have metastases

M1a= non-pelvic lymph nodes have metastases

M1b= metastases in bones anywhere - pelvis, ribs, femur, etc.

M1c= metastases in visceral organs - liver, lungs, etc.

M1= M1a and/or M1b and/or M1c

Regional= N1 but M0

"Metastatic"= N0 or N1, and M1. So what is normally meant by the word "metastatic" is M1, even though there may or may not be metastases in pelvic lymph nodes.

Advanced= T4 or N1 or M1 (cancer is in extraprostate organs, bones or lymph nodes

(2) I agree - there is no evidence that chemo is useful for M0

(3) Zytiga is only approved for metastatic (M1) HSPC or metastatic (M1) CRPC. There are some suggestions that it may be useful also adjuvant to primary or salvage RT, or with recurrences. But it is considered experimental in those situations.

(6) IVA is an AJCC prognostic stage group. It means N1M0 (Regional)

(7) He can certainly have germline testing, as with Color Genome Dx. As for somatic testing, you are much more likely to find something useful if there are M1 metastases to sample. Genomics change over time, and the more actionable mutations are more likely to occur later.

(9) It's a bummer that it isn't more predictable. The upside is that there is no advantage to starting a treatment too early.

(10) PSMA expression occurs later

[KAgolf in reply to Tall_Allen]

THANK YOU--don't know where you find the time to answer all our questions and help us so much-thanks again for your insights and thank all of you others too...

[KAgolf in reply to Tall_Allen]

wondering why an MO would prescribe Zytiga for T2b N1 M0. NOW after proton treatment there are no signs of the 3-4 "suspicious" iliac lymph nodes. Everything I read says:

Zytiga is used to treat prostate cancer that has spread to other parts of the body.

Zytiga is used for prostate cancer that cannot be treated with surgery or other medicines.

Zytiga is used for mHSPC and nmCRPC and mCRPC

Husband is NOT metastatic and NOT CRPC

the kicker is we couldn't afford $2000/mo. per medicare + supplement even if he met the criteria.

[Tall_Allen in reply to KAgolf]

If cancer was only in the lymph nodes (N1), you are right that he is not "metastatic" in the sense that Zytiga was approved for. Generic Zytiga (abiraterone) costs about $260/mo on GoodRx

[KAgolf in reply to Tall_Allen]

Thanks, Tall_Allen--Goodrx is a go-to for a couple of his other RX'sI checked on GoodRx the other day--in our zip code, it's $2,863.00 for 500mg 60 tabs which is his RX; HOWEVER, the 250mg and 120 tabs is $260--crazy!!

another question for you, if you don't mind--I feel like I am imposing asking you so much but you are so very knowledgeable.

EVEN though we agree that Zytiga wasn't approved for him if non-metastatic AND not CRPC, would it benefit him? That's what I am all about--if no benefit, why do it; IF benefit, at least try it.

However, I am wondering if at this point it is too late to start? "thought" I read it needs to be started close to ADT starting

1st ADT 1/28/21

proton 4/29-6/25

[Tall_Allen in reply to KAgolf]

It is off-label, as you say. I don't know of any data on its use along with ADT+whole pelvic radiation for N1. It sounds good to me - maybe it can help make the ADT duration shorter.

[KAgolf in reply to Tall_Allen]

as always, THANK YOU

[treedown]

I match all your husbands "labels" but have a lower Gleason and had considerably higher PSA at dx. I am younger and was diagnosed at 56 with a PSA of 156 (dropped to 110 mat start or treatment). I have had radiation , Lupron and Zytiga/Pred. I will be at my 2 year mark in mid Sept when should things remain as they are today I will go on vacation to see if my treatment which was with curative intent was in fact curative. Learning labels and wrapping your head around it all won't take that long and pretty sure TA wrapped it all up for you above. Best wishes to you both.

[KAgolf in reply to treedown]

thank you and best of luck and praying your treatments ARE curative. just still so confused about Zytiga and if it will benefit or be a burden of S.E.'s

[treedown in reply to KAgolf]

Its different for everybody and if started it can always be stopped. I had a issue when I started radiation and my lymphocytes dropped. I was off it about 6 weeks and came back on at 750mg per day, which is what I am taking still. It may be both beneficial and have side effects so you won't know unless you try. If the Dr does not agree with adding than there must be a reason. I often overlooked some small variable for one thing or another when trying to educate myself online. I have learned a lot since the beginning of this ride but and have a good idea what's in store for myself but we all have different cancers and yet all PC. What works for one may not work for another. I am certainly lucky in having tolerated the side effects very well as for the benefit of taking the drug I won't ever know for sure. I read about and implemented a decision early on. I won't second guess my treatment decisions dafter the decision has ben made. I will accept they are what I decided on and take the good and the bad. That does not mean I won't alter them if necessary but I won't beat myself up over making them. Best of luck to you both.

[KAgolf in reply to treedown]

thank you--good words of wisdom!!