When Docetaxel Isn't Working

[julyturqsee]

After 4 Docetaxel infusions out of 9 planned & bone & pelvic scans, the cancer is spreading on the spine (new & enlarged metastases) & pelvis. PSA remains low (less than 4). Side effects of the Docetaxel has impacted quality of life (extreme fatigue, listlessness, depression). We fear the neuroendocrine variant? Recommendations for the next steps?

[Tall_Allen]

Neuroendocrine is one of several possible low PSA variants. I think it is a good idea to investigate exactly which type it is, because it may suggest more effective therapies or clinical trials. The next step is a biopsy of the metastatic tissue (the most recent, largest, and most accessible metastases are best for this purpose). Analysis of the tissue should entail all of the following:

(1) cell histology

(2) IHC analysis including AR (androgen receptor), PSA, PSMA, MSH2, MSH6, PD-L1,chromogranin A (CGA), neuron-specific enolase (NSE), synaptophysin (SYP), DLL-3, CD56, Somatostatin (SST). Hospital labs are unlikely to have all of those stains, but may have some. The Wang Lab at Duke may have them all. Tissue size may be a limiting factor.

(3) Genomic analysis with Foundation One, Claris, or similar

[julyturqsee in reply to Tall_Allen]

thank you so much for your detailed reply. I've copied & pasted so as to discuss/request at our PO session tomorrow. None of this was ever brought up. HealthUnlocked members are truly generous.

[j-o-h-n in reply to Tall_Allen]

You're an Ace.............

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 11/30/2021 7:16 PM EST

[Chugach]

Have you had genetic testing done on your prostate cancer? Certain mutations can open up other therapies. Such as immunotherapy

[tango65]

This is a review of the complex issue of neuroendocrine prostate.

tau.amegroups.com/article/v...

"Histologically, immunohistochemistry (IHC) with

synaptophysin (SYP), chromogranin A (CgA), and CD56

may be useful for confirmation of NE differentiation,

and ERG FISH assay may be useful to confirm prostatic

lineage. In the case of mixed adenocarcinoma and NEPC,

prostate- specific markers such as prostate specific antigen

(PSA) and NKX3.1 could also be used to confirm the

origin of cancer. Other potentially useful IHC markers

for the diagnosis of NEPC are positive staining for CD56,

p53, thyroid transcription factor-1 (TTF-1), CD44, and

forkhead box A2 (FOXA2), and negative staining for Rb and

cyclin D1 (4)."

It seems that histology is the gold standard for the diagnosis. Direct biopsy with an adequate yield is the best way to get to a correct diagnosis.. Generic studies may help with the prognosis and treatment,

[j-o-h-n in reply to tango65]

You're an Ace too.....

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 11/30/2021 7:17 PM EST

[julyturqsee in reply to j-o-h-n]

thank you John. Had our appointment w/ PO yesterday. PO suggests he might have a combination PC: adenopathy and neuroendrocrine. It seems very little is known about this cancer variant. Actions to be taken: Biopsy from pelvic node fluid; he'll return to Chemo with addition of Carboplatin next week with scans done after 3 more infusions to determine efficacy; Chromogranin A blood test done to also determine neuroendocrine variant. We'll be consulting with Dr Kelly re future trials applicable to his cancer and as well Dr Beltran @ Dana Farber, an Oncologist researching the neuroendocrine variant. Will keep HU posted as our world turns.