For many years now, people have asked whether specific PSA levels after initiation of androgen deprivation therapy (ADT, also known as “hormone therapy”) have significant predictive impact on long-term survival.
Finally, we seem to have an answer to this question — at least for men newly diagnosed with metastatic, hormone-sensitive prostate cancer.
In a newly published paper in the Journal of Clinical Oncology, Harshman et al. have used data from the original CHAARTED trial to assess how patients’ PSA levels at 7 months after the initiation of treatment were related to their long-term survival. Regular readers will remember that the CHAARTED trial randomized men with newly diagnosed, metastatic prostate cancer to treatment with either standard ADT alone + a placebo or to standard ADT + docetaxel chemotherapy.
Their findings are really very straightforward:
- Patients were more likely to have a 7-month PSA level of ≤ 0.2 ng/dl (P ≤ 0.01) if they had one or more of the following:
- Treatment in the docetaxel arm of the trial
- Low-volume metastatic disease at time of trial enrollment
- Prior therapy for localized prostate cancer
- Lower baseline PSA levels at time of trial enrollment
- Average (median) overall survival of all patients in the trial was
- 60.4 months if their 7-month PSA level was < 0.2 ng/dl
- 22.2 months if their 7-month PSA level was > 4.0 ng/dl
- On multivariable analysis, two clinical criteria were prognostic (P < 0.01) for longer overall survival:
- A 7-month PSA level of ≤ 0.2 ng/dl
- Low volume disease at time of trial enrollment
- Compared to treatment with standard ADT alone, the addition of docetaxel increased the likelihood of achieving a PSA level of ≤ 0.2 ng/dl at 7 months
- 28.8 percent of patients on ADT alone
- 45.3 percent of patients on ADT + docetaxel
- Patients on ADT alone who achieved a 7-month PSA ≤ 0.2 ng/dl had the best survival and were more likely to have low-volume disease (56.7 percent).
PSA ≤ 0.2 ng/dL at 7 months is prognostic for longer overall survival with ADT for metastatic hormone-sensitive prostate cancer irrespective of docetaxel administration. Adding docetaxel increased the likelihood of a lower PSA and improved survival.
Many physicians and patients have long believed that men who had a high-quality initial response to ADT (characterized by a low PSA level) were the ones who were most likely to have a significantly longer survival after initiation of treatment. We appear, finally, to have data from a large, well-conducted clinical trial that confirms that belief — at least in the types of patients enrolled in the CHAARTED trial.
Filed under: Living with Prostate Cancer, Management, Treatment | Tagged: ADT, androgen, CHAARTED, deprivation, hormone-sensitive, metastatic, PSA, survival |
THE "NEW" PROSTATE CANCER INFOLINK 
One caveat here … and I wonder if it was taken into consideration. What was PSA prior to any treatment?
Some men with aggressive disease make very little PSA and they may have adenocarcinoma, not neuroendocrine or small cell disease — AnCan supports a few. I am aware of men with extensive disease whose PSAs were never higher than 3.0 or 4.0. Such cases could see a drop to < 0.2 but for them it may not augur longer overall survival.
As we know, prostate cancer is so heterogeneous, so we should be aware of exceptions when reading results like this.
Dear Rick:
Yes, there are going to be exceptions to every general rule in the treatment of prostate cancer — and most other diseases too. But general rules are still very valuable.
I had a prostectomy and radiotherapy but my disease progressed. I began to have affected a rib and a lymph node. Then I began on the CHAARTED treatment protocol. Thirteen (13) months after beginning treatment with docetaxel + ADT I now have a PSA level of 0.046; at 6 month months I had a PSA level of 0.15.
It seems that I am, statistically speaking, inside this group.
What does “P < 0.01″ mean?
Josep:
The P level of < 0.01 (in this case) is a measure of probability, and so (in this particular case) it is just a statistical way of saying that the likelihood of extended survival was much better than average for the men whose PSA levels fell to < 0.2 ng/ml within 7 months of starting treatment (like you).
I did ADT with radiation (started with a PSA over 250) — PSA dropped to undetectable during entire 18 months of ADT, and for a while after that. Four years after diagnosis PSA is hovering around 0.18 (so reading this gives me a lot of hope for the future).
I had ADT treatment of four injections over a year. PSA was < 0.008 and testosterone undetectable. Injections have stopped and there has been no rise in PSA over 18 months and testosterone levels have only increased to 65 ng/dL. What’s the reason for the slow recovery in testosterone levels.
Dear Stephen:
That is a question you are going to need to discuss with your urologist. There are all sorts of possible reasons for this, of which the most important may be what your normal serum testosterone levels were prior to the application of the ADT.