PSA results on Lupron alone before Zytiga.

[Doug47]

My PSA was checked before my Zytiga, so Lupron only, it went from 50.0 to 3.3. Now I don’t know a lot about all of this but, I think that is good news for now? Of course I’m now taking the pred and Zytiga and I will continue this cocktail until it doesn’t work anymore. I just wanted to share this to those of you who know about all of this. Question, is that good news?????

[Tall_Allen]

Yes - very good news indeed! Hopefully, the Zytiga will knock it back even lower within the next couple of months.

[Hawk56]

So, bear with me...

First, good news, the drop in your PSA...

Adding Zytiga, definitely, it assists in eliminating testosterone production from the adrenal glands and the PCa cells from using any testosterone.

There is a piece missing from your post, is your medical team monitoring your testosterone level? Here's why:

In the setting of hormone naïve M1 metastatic PCA, is achieving a low testosterone (T) level really important? Up until several years ago, any answers to this question were completely unknown as T levels were rarely measured in the setting of follow-up of advanced PCA patients. In men that undergo bilateral simple orchiectomy, the mean T level was approximately 20 ng dL However, the traditional T level to define a castrate state has been 50 ng dL−1 . In fact, all contemporary clinical trials related to PCA have used the level of 50 to define castrate-resistant disease. In 2007, Morotefurther reported patients that failed to achieve T levels below 20 had a more rapid progression toward castrate-resistant disease Examined another way Morote et al. found that patients who had a T level above 32 ng dL − 1 had a more rapid course toward castrate-resistant disease. In contrast, patients who achieved a T level < 32 enjoyed an additional 4 years on average until castrate-resistant progression. In 2010, Perachino et al. reported similar findings which the T level measured after 6 months of hormone therapy was a strong predictor of progression to castrate-resistant disease. More recently, Pickles et al. studied 2196 patients treated with LH-RH agonist during and after radiation therapy. Five to 8% of patients experienced breakthrough T levels above 50 ng dL − 1 . Importantly, young age < 70 predicted higher risk for T breakthrough above 50. Pickles also demonstrated patients that experienced no T breakthrough levels above 50 enjoyed a better disease free survival after external beam therapy treatment. Finally, and most recently, Klotz studied 626 patients on the continuous hormonal therapy arm of PR-7. The PR-7 trial was a Canadian study of intermittent versus continuous hormonal therapy in M1 metastatic hormone naïve PCA. These authors looked at serum T levels and time to the development of CRPC and studied patients after a median follow-up of 8 years. For those men who had T levels that measured > 50 the hazard ratio for CRPC was 1.91 compared to a control group of men who maintained T levels < 20. For the group who had T levels that measured between 20 and 50 the hazard ration for CRPC was 1.41. In summary, these multiple lines of investigation suggest that the level of T suppression during the initiation and early course of ADT for hormone naïve metastatic PCa is a powerful prognostic factor.

In the setting of traditional metastatic PCa, a number of key questions arise with regard to the use of hormone therapy in hormone naïve disease. The first key question: is the PSA response to initial ADT important to predict response and survival? The second question: does the type of ADT matter for maximal response? And the third question: is achieving a very low T level really important in the setting of M1 metastatic PCa?

As early as 1990, it was shown in a small study that PSA declined after the initiation of hormone therapy predicted survival in patients with metastatic PCa. Patients who enjoyed a > 80% PSA decrease in the first month of ADT enjoyed a significantly longer progression-free survival compared to those patients who had a < 80% PSA decrease in the first month.

In a study published by Fowler in 1995, PSA nadir was a very significant predictor of response to hormone therapy. In this study, after patient exclusions, 245 patients with localized and 78 patients with newly diagnosed metastatic PCa were treated with ADT in the form of orchiectomy or LH-RH agonist. PSA regression, nadir and doubling times were calculated for the patient cohorts. For the metastatic patients who reached a PSA nadir < 1.0 ng ml − 1 , they experienced a statistically significant longer time to BCR. These authors further stratified PSA nadir on initial ADT from 1 to 1.9, 2 to 3.9, and a PSA nadir of > 4. Patients whose nadir was < 1 enjoyed a much greater disease-free interval compared to patients who experienced a PSA nadir > 4.

The largest and most noteworthy study to look at PSA levels after initiation of ADT for new M1 PCA was published by Hussain et al. in 2006. Specifically in this large Southwest Oncology Group (SWOG) trial, the authors showed that initial PSA nadir 7 months after initiation of LH-RH agonist was a strong predictor of median overall survival . Specifically, patients who enjoyed a PSA nadir ≤ 0.2 at 7 months after the initiation of therapy had a median overall survival of 75 months. In contrast, patients who had a PSA nadir of > 0.2 but < 4.0 had median overall survival of 44 months. Finally, the patients who experienced a PSA nadir at 7 months that were > 4.0 ng ml − 1 had a median overall survival of only 13 months. In my practice, I use these publication data to help counsel patients who I initiate on ADT for traditional M1 prostate cancer. I attempt to defer discussion regarding prognosis with these patients until I have been able to examine a 7-month PSA level. Once the patient and I have the 7-month PSA nadir value in hand, we will use the aforementioned survival data to counsel them on prognosis and future treatment strategies. In fact, many of those patients who have suboptimal PSA nadir > 4 at the 7 months interval after starting ADT will have impending CRPC and may benefit from early novel therapeutic agents. Unfortunately, from this SWOG study in 2006 by Hussain et al., we do not have the serum T levels at the 7-month point. It is possible that a combination of PSA response as well as T response at 7 months or even an earlier interval may provide additional prognostic information to help guide future treat strategies for these patients.

[CalBear74 in reply to Hawk56]

Thank you Hawk56 for your thoughtful, evidence-based post.

CalBear74

[Doug47 in reply to Hawk56]

I’m not there yet with the meaning of everything that you are saying but, thank you for the information.

[Hawk56 in reply to Doug47]

my medical team has learned that I am a very informed patient...who challenged them to think differently about treatment.

I spend a fair amount of time researching and educating myself. It is the reason I am still here, the standard of care would not have worked for me.

[Doug47 in reply to Hawk56]

I believe that! I hope I didn’t come off rude, not my intention! Your knowledge on our state is impressive to say the least. I’m spanking brand new to all of this. Thank you for your inspiration and hard work!!!!

[Hawk56 in reply to Doug47]

No worries, I was diagnosed in Jan 14, looking back I realize how little I knew, it’s been a journey to learn, the major thing is you must be your own advocate in this journey, the decision making must be shared between you and your medical team.

These forums allow us to share what we have learned so that we can make the best possible decisions.

Hang in there, there have been many advances in treatment, imaging...I like to think it’s analogous to the early days of AIDS, once the medical community brought its brainpower to the fight and began combining therapies, well, in many ways it has become a chronic disease.

My urologist and I call it the whack a mole theory. I stopped thinking 10-15 years and asked “will this get me through the next five years...?” If the odds are yes then I know something else will be available to treat...

I have not met anyone on this forum who is not willing to share, explain...

Kevin

[Doug47 in reply to Hawk56]

Very well said

[David2703 in reply to Hawk56]

I am seen in a group practice and all the doctors follow the same protocol. They will not follow the recommendations of the STAMPEDE trials.

Hopefully, I can find a smaller group practice.

[Bab63]

Big thanks