Is my cancer still hormone sensitive?

[dac500]

I had my last Eligard 3 month shot on March 2, 2021, when I started a ADT break. By beginning of September my PSA was 0.10 with T <20. On December 2021, my PSA rose to 0.18 with T = 28. I had another PSA and T test today, six weeks later. My PSA has risen to 0.34 and my T = 54. Since my testosterone is still very low (just above castrate level), PSA increasing with PSADT < 2 months might indicate that my cancer is pointing towards becoming castrate resistant. I personally feel that some of my cancer is already castrate resistant. Am I wrong to think that way?

[dac500]

December PSA was on December 2, 2021

[tango65]

I do not think the cancer is castration resistant. If you reduce the testosterone below 20 using Lupron or similar the PSA will go down, showing the cancer still responds to castration.

[Hidden]

The only way to know if you are castrate resistant, is to be at a castrate level of testosterone and still have rising PSA (generally accepted as rising and > 2).

I've had small blips in my testosterone level that correspond to small increases in PSA. That's normal. Prostate cancer never completely loses hormone sensitivity, it just becomes less sensitive.

[Tall_Allen]

Your PSA is tracking with your testosterone increase. Seems very hormone sensitive to me.

[dac500 in reply to Tall_Allen]

Even when testosterone in very low? I know my cancer is still hormone sensitive. But the number of castrate resistant cells is increasing. I think it is time to end the ADT break. Do you agree with these?

[Tall_Allen in reply to dac500]

As the cancer mutates it gets even more sensitive to ever smaller amounts of testosterone. The value of a vacation is only if you actually feel better on the vacation. It really depends on whether you feel better.

[Chadsdad in reply to Tall_Allen]

TA, is it your opinion that as long as 2nd generation adt is keeping your PSA undetectable, scans clear, to continue meds longer than 5 years or more? I haven’t read of any trials that reported longer use of stuff like Erleada and Xtandi. Thank you for the time you spend researching and answering our questions.

[Tall_Allen in reply to Chadsdad]

There are two different uses for hormone therapy (both ADT and advanced):

(1) Adjuvant hormone therapy, which is given for a limited time together with radiation for men getting primary radiation or for salvage radiation. The intent is curative. Like antibiotics, adjuvant HT is never stopped and restarted - you just take it for the prescribed duration.

(2) Lifelong hormone therapy, which is given permanently for men with distant metastases, or after all curative attempts have failed, as part of their maintenance therapy. ADT (e.g., Lupron, Firmagon, Orchiectomy) always works and is never stopped completely (some men take vacations). Advanced hormone therapy (e.g., Zytiga, Xtandi, Erleada, or Nubeqa) is used until failure.

[Hidden in reply to dac500]

I sometimes wonder sbout the value of these ADT "vacations".

It seems to me that by the time your testosterone goes up enough to feel better, the cancer is feeling better too. And then it looks like in meantime, you end up stressing out over watching your PSA rise and that also effects the quality of life. Makes me wonder if it's worth it. I guess it is for some.

[dac500 in reply to Hidden]

In my case, the quality of life doesn't improve during ADT break. Since my testosterone remains in castrate level for over six months during the break, the break can save some money for medicare. May be a break for nine months for me is beneficial for that. Also my MO thinks the break reduces my cardiovascular risk.

[Hidden]

My primary doctor said he has several guys that go a year or more off ADT until it gets too high and then go through the cycle again. Forgot to ask what that number was. I think 5. If it were me I would want to see what the PSA was when my T was 250 or above. My personal opinion

[dac500 in reply to Hidden]

Every case is different. In my case, for my T to reach 250 will take several years of break from ADT. By that time with a PSADT of about 2 months my cancer would spread all over my body. Nine months after last Eligard shot my PSA barely reached 54.

[CAMPSOUPS in reply to dac500]

Everyone is different is true.You said: "nine months after last Eligard shot my PSA "barely reached 54".

I don't know if it is because of the head to toe mets I had at dx but at a PSA of 54 I would be one hurting son of a gun.

When the benefit of chemo began to wane last spring and my PSA went to 40 I was in bone pain and even debilitation to some degree.

None of that once Zytiga brought the PSA back down.

[dac500 in reply to CAMPSOUPS]

Sorry mistake it is T reached 54 not PSA.

[CAMPSOUPS in reply to dac500]

Oh. OK. Funny ha, ha.

[Hidden in reply to dac500]

you might try the clomid and hgc. works for some

[MateoBeach]

Your thinking seems very sound to me. Castrate resistance develops in different sub populations of cancer cells. It is the evolutionary drive and genetic mutations selecting for the androgen negative and androgen independent sub populations that can thrive in very low T conditions. So you are moving towards “castrate resistance” even if you don’t fully me the criteria yet.

Some very excellent MOs favor testosterone replacement on IADT off cycles if it doesn’t recover quickly on its own. This is the underpinning of BAT and other cyclic testosterone therapies. (Such as what I am on.) staying castrate or very near castrate will continue to favor cells that do not require much androgen AR-, or that can make their own, androgen independent. It is the Catch 22 of PC.

Your PSA is still very low, as mine was, and I felt terrible from ADT sarcopenia effects. My MO finally agreed to let me try modified BAT, 8 weeks of very high testosterone followed by 4 weeks of none with Firmagon to get castrate very quickly, just one 80 mg shot. My PSA has behaved staying at or under 0.10 for over a year on this. You have the wiggle room to try something like this to see if it works for you or not. I can say it feels really good in every way.

See my previous posts and others with peer reviewed research links on BAT, intermittent testosterone cycling and “evolutionary dynamics” in PC. ADT “vacation” without testosterone recovery or replacement makes no sense to me.

[dac500 in reply to MateoBeach]

Thank you for a very sensible reply. I have an appointment with my MO in March. I may bring it up at that appointment.

[ADTMan in reply to MateoBeach]

A very good explanation. From my understanding, prostate cancer is heterogeneous. It consists of three types of cells: 1) testosterone sensitive cells that require testosterone from the testicles; testosterone sensitive cells that are able to produce their own testosterone and do not require testosterone from the testicles; and 3) cells that do not require testosterone. Prostate cancer cells do not mutate from hormone sensitive to hormone insensitive, but rather there is competition between the cells to grow. Since there are much greater numbers of testosterone sensitive cells, ADT renders them inactive or kills them (haven't really gotten a good explanation of this phenomenon). The reduction of the hormone sensitive cells reduces the competitive pressure on type 2 and 3 cells so they grow. The theory behind intermittent high testosterone cycling is to allow the testosterone sensitive cells to grow again thereby putting pressure back on type 2 and 3. This is repeated until it is no longer effective. (Please note that type two cells are 2nd generation anti-androgens which target the testosterone receptor.)

It appears to me that the most significant prognostic factor would be how many of these type 3 cells you have to begin with. This is why low psa disease is associated with greater aggressiveness. Hormone therapy does not directly treat type 3 cells but chemotherapy, radiation and immunotherapy do to some extent.

[MateoBeach in reply to ADTMan]

That’s why you’re the ADT man, man. 😆👍🏼

[Magnus1964]

If eligard is the only ADT drug you were given, you are not castrate resistant. You can still benefit from other ADT drugs. Next time skip the ADT vacation.