Nadir - variation prior to castration resistance

[6357axbz]

Once one reaches their PSA nadir on ADT what is the expected variation in PSA readings while still castration sensitive?

[LearnAll]

It varies,,,it varies...it varies...from individual to individual.

Some general conclusions:

(1) lower the PSA nadir, longer chance of survival . Example: PSA Nadir of less than 0.1 is better than PSA Nadir of 1.0 or 2.0.

(2) Longer the time to PSA Nadir overall longer chance of survival. Example: Nadir achieved in 10 months is better than Nadir achieved in 3 months

Some people linger on for long time on their PSA Nadir...some start moving up...up or down.

It varies by individual too

NOTE: PSA Nadir is the lowest level of PSA one achieves after being on ADT.

[6357axbz in reply to LearnAll]

Thanks LearnAll. I probably should have asked, in general, how does one know when they go CR based on PSA?

[LearnAll in reply to 6357axbz]

Trend is your friend...my friend. Watch the movement of PSA ...if it steadily going u p.. up.. and up...time to worry about castration resistance. Also, need to check total testosterone (should remain less than 20) if you declare yourself castration resistant.

If PSA trends up and down in a narrow range...I do not think you are castration resistant yet. Steady upward movement is needed to consider castration resistance.

And if you have bone mets.. .then.. level of Alkaline Phosphatase have to taken into account.

[6357axbz in reply to LearnAll]

What’s the relationship between bone mets and Alkaline Phosphatase?

[Brbnbrn in reply to 6357axbz]

Yes, I'd like to know that too. My husband's is out of whack.

[6357axbz in reply to Brbnbrn]

See LearnAll’s response below. He answers this very nicely.

[jfoesq in reply to LearnAll]

Hi LearnAll-

Do you have any more info regarding Alk Phos and the meaning of the numbers on lab tests? I have been on treatments (Lupron and Zytiga with a few "vacations) for over 7 years since my dx of metPC. I am now treated with both ADTs continuously.

[Hirsch in reply to LearnAll]

Do you know why a longer journey to nadir is better?

[LearnAll in reply to Hirsch]

I was myself wondering why a long journey to nadir is better. I really don't know..why?

Top researchers have indicated that lowest possible Nadir PSA and longer time to nadir result in longer survival. Famous Dr Maha Hussain's research even showed a graph that showed a Nadir PSA of less than 0.2 results in survival of at least 78 months .

[Hirsch in reply to LearnAll]

thanks for your information

[6357axbz in reply to Hirsch]

Here’s a study:

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

[VictoryPC in reply to LearnAll]

Doubling time of the PSA regarless of the count. I personally know several guys living with stable PSA over 40.

[Hirsch in reply to LearnAll]

can you send a link to Dr Hussains article re nadir and survival

thx

[LearnAll]

Great question !

In normal human beings, the bones are always involved in wear and tear followed by rebuilding.

But this creative destruction of bones remains in a certain limit. This process releases an enzyme which is in amounts proportional to this tear and repair process.

The normal bone activity releases Alkaline phosphatase in range of 20 to 30 units. This is called normal level of bone Alkaline Phosphatase. Now, a normal functioning liver also releases Alkaline Phosphatase....you can call it Liver Alk Phospahtase. The normal level is 30 to 50 units.

So, the total Alkaline Phosphatase in normal man (without bone mets) is in vicinity of 60 -70 units, (half coming from bones and other half coming from liver)

In case of Bone Metastasis, the wear and tear of bones gets faster and consequently the rebuilding of bones also gets faster. Therefore, more and more bone alkaline phosphatase is released...giving higher levels of tot al Alkaline Phosphatase.

Lets take an example:

Mr John developed bone mets and his Alkaline Phosphatase was found to be 250. Now reducing liver generated ALk Phos of about 50...his calculated bone Alk Phos comes out to be 200.

Mr John's Oncologist , Dr. Maha Hussain started him on Lupron inj Q3m and Abiraterone with pred.....Rechecked total Alk Phos after 90 days a. nd found that total Alk Phos is now only 70. That means only 20 coming from bones and 50 coming from Liver

This means the bone mets have shrunken and have become scars (sclerotic lesions) So bone mets are gone as no excessive amount of Alk Phos is being released.

In brief, Alk Phos is a marker of extent of active bone mets and it gives us extent of healing happening. Indeed a very very valuable marker for people who have P CA with bone mets.

[6357axbz in reply to LearnAll]

Great answer! Thank-you LearnAll

[6357axbz in reply to LearnAll]

So my Alk Phos was just measured at 41. I’m also on Lupron and abi/pred. So should I take this to mean that my bone mets (ribs and ilium) are gone?

[LearnAll in reply to 6357axbz]

This is great news...Alk Phos at 41 indicates the bone mets mostly have healed.

Indeed something to celebrate. My Alk Phos is 55 ,hoping to go to 40.

However, in world of metastatic PCA, nothing is permanent. There fore we need to keep monitoring. The attack of PCA on bones leaves them brittle and weaker...so we need to still take precautions. Proper nutrition...dietary calcium (a cup of home made yogurt daily, Vit D (from sun preferably but supplement may work too), strontium, Vit K2, and algae vegan omega DHA (known as COMB protocol) can keep our bones in better shape.

Never forget to get a bone density scan (DEXA) every 6 months.

[6357axbz in reply to LearnAll]

So I looked at first time alk phos was measured after dx with bone mets. It was 42 after one month of Lupron. So either alk phos dropped that rapidly or my bone mets were not elevating alk phos beyond normal levels???!

[LearnAll in reply to 6357axbz]

One month of Lupron, in some lucky people, can knock down Alk Phosphatase quickly. Were you not on casodex before Lupron ?

If there are bone mets, higher Alkaline Phosphatase is the rule.

[6357axbz in reply to LearnAll]

No Casodex

[LearnAll in reply to 6357axbz]

Ok...But I still want to congratulate you as you are having extra ordinary response to current treatment.

You are mostly likely to see dead, scar tissue sticking to your bones on scans due to ALK PHOS level at 40. No activity...dead or unconscious cancer cells. .you are winning.

[westof in reply to LearnAll]

Hmm... Thanks for clarifying some of my misconceptions. I thought that nadir occurred when PSA hit rock bottom during ADT and not after.

Here is my history since dx (8/18): I turn 71 in December. G9, stage 3 and high PSA was 28 (no mets). HDR Brachy (April 26th) and 25 days of IMRT.

PSA has held steady at <0.014 since 4/19 (when I went off Casodex and Lupron and switched to Lupron, Zytiga and prednisone).

My Alkaline Phosphate has held steady (85-100) for the last 4 years and liver enzymes are even better (except for a 2 month spike when I started Zytiga, and they dropped fast since).

Thanks for all of the valuable Info.

Best

[jfoesq in reply to LearnAll]

Thank you, LearnAll for the excellent explanation.

You can disregard my previous email as I just saw this explanation.

[Hidden]

Regardless of fluctuations, if there are 3 doublings over a PSA of 2, you can safely say that you are castrate resistant. The time between doublings gives you a rough assessment of the urgency. In my case the doubling time was very fast (3 weeks) so I really needed to jump on it and start my next treatment.

[6357axbz in reply to Hidden]

Thanks Gregg

[6357axbz in reply to Hidden]

I take it that was Docetaxel?

[Hidden in reply to 6357axbz]

No, I went to Zytiga. PSA is .01 after 16 months on Zytiga. I did do Docetaxel with ADT at the start of treatment. My doctor said he often sees guys who did early chemotherapy have quickly rising PSAs at castrate resistance.

I will probably do Docetaxel again when Zytiga stops being effective, then maybe go back to an androgen blocker such as Xtandi.

[6357axbz in reply to Hidden]

Gregg, r u still CS?

[Hidden in reply to 6357axbz]

No, I'm castrate resistant as of last summer.

[jfoesq in reply to Hidden]

I thought I once read on this forum info about some individuals "fortunate" enough to be able to "bounce back" and use ADTs (such as Lupron or Zytiga) AGAIN after getting chemo (docetaxel). Somehow, the ADT treatments that had stopped working, became responsive again after the chemo.

That sounds like something you are thinking of trying with Xtandi. I am assuming from your post that you had Xtandi before. Wondering why you're thinking about Xtandi instead of Lupron and/or Zytiga.

[Hidden in reply to jfoesq]

I'm on Zytiga now, never had Xtandi. Many doctors will not put you back on the same treatment again once it stops being effective. I've asked and mine told me he wouldn't put me back on Zytiga, but I could try Xtandi. So that's my plan, but after chemo to give myself a better chance of success. Who knows what will work.

My plan for down the road is:

Continue on Zytiga. When it starts to become ineffective, switch steroids to Dexamethasone. Then when PSA continues to rise, start imaging to determine if there is progression. Once there is progression, biopsy the met(s) and do molecular profiling to look for treatable varaints. Then possibly go to chemo or targeted treatments.

[jfoesq in reply to Hidden]

Thanks, Greg. Perhaps other docs try the meds that previously failed- perhaps not. I just thought I read that on this site before.I could be wrong and what your doc suggests seems to make sense. Anyway- I am now curious about the molecular profiling. I really don't know anything about it. How could that be helpful in deciding what step to take next?

[Hidden in reply to jfoesq]

If you go to Foundation One's website, you can get a better understanding. They are one of the companies that offer it.

To sum it up, our cancer mutates as it progresses. Some of those mutations have weaknesses that can be exploited. For example, there are mutations known as Homologous Repair Defects. These make it more difficult for the cancer to repair DNA.

An example of that would be BRCA2. If you have this mutation, you can take what is called a PARP inhibitor. These block the other method of DNA repair and the cancer cells accumulate DNA defects until they eventually die.

[jfoesq in reply to Hidden]

Thanks, Greg

I will check out Foundation One.

[LearnAll in reply to Hidden]

Gregg...do you mean we do not need to worry about resistance as long as PSA is less than 2.0 ?

[Hidden in reply to LearnAll]

For those that have stage 4 and currently on ADT, a PSA over 2 is generally where you start watching for castrate resistance. My PSA nadir was at .19 and when it went to .4 they said "Yes, it's doubled but these kind of doublings we are not concerned about." If the PSA never goes below 2, then you are just looking for when it starts rising afther the nadir. It's not an exact science. The most important thing to determine is the trend.

[Tall_Allen]

There is nothing in your profile. I can't answer without your diagnosis and treatment history. The answer depends on why you were using ADT and for how long.

[6357axbz in reply to Tall_Allen]

Dx July 2, 2018 by a urologist. PSA 8.2. Prostate biopsy showed 11 of 12 sectors filled the cancer the worst being G8. Scans (CT and bone) at the time showed pelvis and rib mets. That “doc” said he gave me a 6 month Eligard (Lupron) injection. That occurred late July. Went to MD Anderson late August. PSA down to 6.4. , T 37.

Returned to MDA end October. PSA 10.3, T 147. We determined that urologist, since referred to by me as “fuckhead”, screwed up and gave me a one month Eligard injection instead of a 6 month. MDA MO gave me degaralix and After 6 months transitioned to Lupron which I’ve been on ever since, adding abiraterone/p in late April 2019, recommended by the way by yourself and Schwah (thank-you).

IMRT to prostate, completing 30 sessions June 21.

My PSA went down steadily to a low of 0.02 in September 2019 until my last PSA test on November 18 was 0.028. T has remained at castrate level.

I think that covers the basics. Now that I’ve recorded it I’ll past this into my profile.

Thanks TA

[Tall_Allen]

Thanks - I know you've told me before, but I forgot.

So to your question --

(1) you should not be using an ultrasensitive PSA test

(2) as long as you are continuously taking Lupron and Zytiga, your PSA should remain below 0.1 ng/ml while you are hormone sensitive

(3) According to some oncologists, a confirmed 25% rise in PSA and nadir + 2 during therapy or if there is evidence of metastatic progression (larger or more mets), it will be time to abandon Zytiga and move onto the next therapy (while staying on Lupron). This is not set in stone, and you and your oncologist may decide to, say, stick with Zytiga but switch from prednisone to dexamethasone at an earlier point.

On another site, I put forth a recommendation that oncologists "stage" prostate cancer with a new designation that reflects the patient's status with respect to multiple hormone therapies:

— H0 = hormone therapy-naive or -sensitive (to GnRH agonist/antagonist, orchiectomy, mild anti-androgen (e.g., bicalutamide, flutamide, nilutamide), estrogen patch, or combination of those.

— H1 = first-line hormone therapy-resistant (to any of the above)

— H2 = second-line hormone therapy-resistant (to abiraterone, enzalutamide, apalutamide, darolutamide, etc.)

— H3 = third-line hormone therapy-resistant (to any two of the above)

There would be a definition of resistance at each "stage" (it's not really stage, but it uses staging-type nomenclature).

[6357axbz in reply to Tall_Allen]

Thanks. So at each stage would you propose treatment options?

[Tall_Allen in reply to 6357axbz]

Yes, options and eligibility for clinical trials may change depending on "H-stage," and N/M-stage.

[6357axbz in reply to Tall_Allen]

A better road map

[johnscats in reply to Tall_Allen]

Hi tall Alan would I be correct in saying that zytiga blocks all methods of testosterone production including the testes which lupron blocks

[Tall_Allen in reply to johnscats]

There were two small studies that suggested Zytiga alone could stop T production, but they have to be confirmed in a larger study.

urotoday.com/conference-hig...

urotoday.com/conference-hig...

[johnscats in reply to Tall_Allen]

Ok thanks

[6357axbz]

Can anyone interpret the following?

Pathology of biopsy specimen:

Immunohistochemical staining reveals tumor cells are reactive for PSA, PAP, NIOC3 (not sure of the second character due to fuzzy photocopy) and AR while negative for COX2 support the diagnosis metastatic prostetic adenocarcinoma

[LearnAll]

95% prostate cancers are Adenocarcinomas ...which means the cancer cells originated from the glandular tissue of the prostate.

Remaining 5% are a mix of Ductal cell carcinoma, small cell carcinoma and Neuroendocrine types.

As a general rule, Adenocarcinomas have a relatively better outcome compared to the second group which are uncommon and harder to treat.

[6357axbz in reply to LearnAll]

Thanks again LearnAll!

[GeorgesCalvez]

Unless you have a doctor with the wisdom of Solomon then interpreting PSA nadirs can be a dodgy business.

I had a PSA of 133 at diagnosis with all scans clear and what seemed to be a substantial but localised tumour, this fell to 2.07 five weeks after my prostatectomy. I then began Firmagon and it was 0.27 after another two weeks after. It was below the limit of detection < 0.03 after three months on Firmagon and 66 Gy of radiation and it has stayed there for fifteen months.

So my PSA fell to a very low nadir, good, but it fell really quickly, bad.

One of my doctors has been predicting that I will have recurred by the next time I see him since the beginning, but I remain stubbornly below the limit of detection, the other is not so sure and is fence sitting.

On verra, I could still be on the right side of the daisies in five, ten, fifteen years, etc or maybe not!

[6357axbz in reply to GeorgesCalvez]

Thank-you for your reply George. Very informative. Given yours was localized on dx it seems your prognosis is good. I’m not sure if those time to nadir studies apply to localized PCa. Hopeful for you! Keeps us informed.

[j-o-h-n]

Quote: referred to by me as “fuckhead”.....Hey man, tell that dickhead doctor, that's reserved for my ex-wife's user ID...

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 11/24/2019 6:27 PM EST

[VictoryPC]

Stability in the PSA regarless of the count is the goal. I personally know several guys that have developed CRPC and through the right means are maintaining stable PSA's out 6 years now.