Aggressive Prostate Cancer Subtype More Common Than Expected

[GranPaSmurf]

cancer.gov/news-events/canc...

[LearnAll]

I am confused. For last few years, they were pushing people to take Zytiga with Lupron and now, suddenly they came up with this study that treatment with Zytiga or Enzulatamide makes PCA more aggressive. Whats going on ?

[pjoshea13]

There was a thread on "Treatment-emergent small cell neuroendocrine prostate cancer." last July:

healthunlocked.com/advanced....

The more sophisticated the treatment, the more sophisticated will be the form of resistance.

Which is why I believe that one should delay initiating such treatments, if possible, as long as possible.

-Patrick

[tom67inMA in reply to pjoshea13]

Not sure I agree. Studies have been showing that overall survival is longer when abiraterone is used earlier. While it may make individual cancer cells more likely to mutate into NEPC, the longer survival would suggest that is offset by having fewer cancer cells. Of course, when treatment does eventually fail, watch out!

[tango65 in reply to pjoshea13]

I agree. The problem is that many therapies, such as immunotherapy (Provenge and others), Lu 177 PSMA, xofigo etc, are not available unless ADT and chemo or ADT and new anti-androgens were used.

[Tall_Allen]

This was 17% of men who were (1) mCRPC and (2) were already resistant to Zytiga and Xtandi. It is a rare finding.

[LearnAll in reply to Tall_Allen]

Thanks for the clarification. So this does not apply to hormone sensitive pCAs.

[Hidden in reply to LearnAll]

Neuroendocrine PCa rarely occurs at diagnosis or in the hormone sensitive stage. When it does occur at diagnosis, it's a pure form whereas the treatment -related variety is mixed with other PCa cells.

Anything you do to successfully treat PCa will inevitably lead to a more aggressive and harder to treat strain due to the natural selection process of a fast growing disease.

[GP24]

In this review the authors point out:

nature.com/articles/nrurol....

Following treatment with AR pathway inhibitors, ∼20–25% of patients with prostate cancer relapse with tumours that have shed their dependence on the AR and have neuroendocrine features; these cancers are termed neuroendocrine prostate cancer (NEPC)

AR pathway inhibitors are abiraterone and enzalutamide.

As Patrick wrote: "The more sophisticated the treatment, the more sophisticated will be the form of resistance." Many patients in this forum mention that they failed Zytiga or Xtandi. Testing for neuroendocrine PCa could make sense for these.

[DenDoc]

This study supports my clinical course completely. The importance of getting a biopsy of one of the mets is key and also getting a full genetic profile of the tumors. I am not surprised to have NEPC after 24 years of treatment starting at a time when none of this genetics was known.

My other lesson has been that not all of the cancer converts to NEPC. Once we treated that my PSA rose to all-time highs and so I am now on Enzalutamide with a PSA drop to 2 and my tumors appear to be static or smaller on PET scan.

The importance of having a good medical oncologist who keeps current on the literature is apparent to me.

[GranPaSmurf]

The followup discussion begs another question for me. At diagnosis, the biopsy report showed only Adenocarcinoma in the primary tumor. I have 2 small METS, spine and tibia. I'm wondering now if the METS, when they grow, might be/become neuroendocrine PCa.

[immunity1]

Thanks for article, as it adds to the story on the development of NEPC that has been described over a number of years. However, here they distinguish it here from de novo NEPC that affects few people (<1%). Like you, most of us start off with adenocarcinoma, and seemingly 17% of us may end up with this 'type' following second generation ADT which I personally think should be used earlier rather than later. Sadly the molecular evidence is that the genotype of these induce NEPC types does not include BRCA1/2 variants that are being treated, at least in trials, with PARP I inhibitors.