Raising PSA after 1st Lupron Shot?

Ken

Welcome to the board.

I am impressed for the long period of 8 years you managed to regulate the levels of the PSA with just an antiandrogen (flutamide) and 5-ARI (Finasteride). Could you tell us what the PSA level was before starting the hormonal treatment and the difference after that?

A reason for the last result of PSA=3.52 could be due to your stopping of Finasteride. This drug is known to halve the level of the PSA which leads doctors to double its value when using it as a marker of progression. In other words, a PSA of two (2) under the influence of Finasteride is considered as four (4) in judging the status of the patient; on the opposite, the PSA in a Patient is expected to be lower when using Finasteride.

The information you shared above is not enough to give you an opinion on refractory and the references are ambiguous. I am not sure if your comment on the increase of the “PSA doubling” (PSADT) means a decrease. Shorter periods in PSADT are worse status. What is the PSADT you are referring to?

Regarding the Lupron shot, which dose are you taking? Is it a monthly shot?

It seems that you took two shots; one for February plus one for March and the last one (last week) was for April. Is it correct or have you missed the shot of March?

I am not aware of Lupron doses for a two months shot. Typically they are administered for: one month (7.5 mg), three months (22.5 mg), four months (30 mg) and six months (45 mg).

These doses are effective for a 30 days monthly period and it should be taken continuously until the end of the treatment. If one misses a shot or spans the period of effectiveness then the outcome is not assured.

http://www.lupronprostatecancer.com/

I also do not understand why your oncologist stopped the Flutamide. In any case, after a long period taking an antiandrogen the bandit manages to “mutate” and start using the antiandrogen as food. This cases are named refractory and typically one experiences androgen withdrawing response (AAWR-PC) represented by a drop in PSA. This seems not to be your case. Here you got a link explaining about the condition;
http://prostate-cancer.org/aawr-the-anti-androgen-withdrawal-response/

The best way to verify refractory is through a testosterone test. Constant increases of PSA in low testosterone environment are bad and may indicate refractory. Can you tell us what your T level is?

I would recommend you to investigate about oligometastases. This is a condition when the cancer is detected at fewer spots that can be radiated, providing still a possibility of killing the cancer. Your case could be such. Read these;

https://ludwigcenter.sites.uchicago.edu/page/ludwig-center-metastasis-research-oligometastasis-curative-subset-metastatic-disease-0

http://www.dattoli.com/publication/PCRI INSIGHTS Oligometastatic.pdf

Let us know more about your past and present status and age, and doubts.

Best wishes,

VGama 

Ken

Looking into the data of the past two years, it seems that your PSADT has been 12 months. This seems to indicate that your cancer is yet of low aggressivity. Worse cases relate to PSADT lower than 9 months. However, by the constant increases we may think of the cancer spreading or increasing in size (bigger tumours/colonies) that now can be detected by a common scan.

The alarming goes to the effect of Finasteride in the PSA values. You have no prostate gland in place so that the theory regarding the effect of 5-ARI drugs in reducing 50% of the PSA value may not be valid. Trials suggesting the decrease have been done with patients with their gland “in place”. But there are no trials to prove the contrary in guys without the prostate too. All what I have read indicates that the effect is done in prostatic tissue to which PCa belong. The question is if Finasteride directly causes the cancer cells to produce less PSA serum instead of lowering DHT absorbed by the cells. In one trial of 1995 they suggest that the PSA effect in finasteride treated patients was not due to the drug, but the trial is not clear about that and still many doctors take the reduction influence of 5-ARI in PSA values.

Here is the trial; http://www.ncbi.nlm.nih.gov/pubmed/7533461

Here is a link to such a controversial;
http://urology.jhu.edu/newsletter/2009/prostate_cancer_2009_10.php

Probably we should not consider the theory but if that is correct, it means that your last PSA before starting Lupron could be 5.06 (2 x 2.53) which is higher than the present PSA of 3.25.

Another aspect from your data goes to the effect of flutamide (Eulexin) that stopped to be effective or still worse it started to be the source of “food” for the cancer. Typically, in similar events of increasing PSA, oncologists increase the dose of the drug (2 pills to 3 pills a day) or substitute it by “analogues” such as replacing Flutamide with Bicalutamide (Casodex). In the event that this does not “work” then they take the case as refractory and stop the antiandrogen because the cancer may have mutated and start feeding on it. Antiandrogens are substances made of similar bio-structures of testosterone so that they easily bind to the androgen receptors (AR) of the cancerous cells, faking the real T. In the long term of the treatment, the bandit learns how to use the antiandrogen in its favour.

Accordingly, your oncologist suggestion may be based on the above so that he decided to stop the flutamide and comments that “…it sometimes takes period of sixty to ninety days…” to clean the drugs from the serum. The antiandrogen could be fuelling the cancer, and if Finasteride was controling the activity of the cancer (not just lowering the PSA), then suppressing it would cause a sudden increase of the value. 

I recommend you to get another PSA test in three months to verify where you stand. The results will provide you a clue on the AAWR-PC status and on the effect of the Finasteride. At the same time you should get a T and DHT tests to check for the effect of Lupron. You should be at castration levels of less than 30 ng/dL.
I also recommend you to check your lipids for any “damage” done by flutamide. This is a drug with toxic effects when taken in long periods of time. Read this link about the side effects of this drug;
http://livertox.nlm.nih.gov/Flutamide.htm

Still another test required is a bone density scan (DEXA) to verify bone loss. PCa likes weak bone and in cases of osteoporosis risk doctors usually add a bisphosphonate to the HT protocol. In advanced PCa status (patients with metastases in bone) they recommend Zometa (zoledronic acid) or more recently a “friendlier” drug named Xgeva (denosumab). Read this;
http://www.medscape.org/viewarticle/444792

http://www.medscape.org/viewarticle/457733_2

http://www.australiandoctor.com.au/news/latest-news/osteoporosis-drug-can-help-cancer-patients-

In case you manage to get back the control on the cancer with Lupron, then you may restart with an antiandrogen but this time take bicalutamide, or still better, take Xtandi (enzalutamide) which substitutes the antiandrogen, being more effective in preventing absorption of androgens. The 5-ARI drugs seems to have “little role” in PCa cases without a prostate gland in place. Most of the inhibition is done at prostatic tissues which are almost none existent in prostatectomies cases.

It will be difficult to return to PSA remission levels when bone metastases are present. You can research about ways to treat such condition with drugs like Xofigo (radium 223) or with spot radiation if it is diagnosed as an oligometastatic case. You will need to get a better reliable image study done with higher resolution equipments and better contrast agents.

Best wishes and luck in your continuing journey.

VGama