The paradox of testosterone and ADT

Posted by hans_casteels @hanscasteels, Mar 29 11:07am

It’s a curious thing, really — this blind devotion to testosterone as the prime mover in prostate cancer’s twisted little drama. One might imagine that a tumor emerging in an environment already barren of testosterone — my personal endocrine wasteland — might, out of sheer metabolic necessity, learn to dine elsewhere. Glucose, glutamine, maybe even sheer spite. In other words, it may never have been dependent on testosterone in the first place, rendering castration-based therapies about as effective as removing the steering wheel from a horse.

And yet, when I dared to suggest this — that perhaps my tumor was an evolutionary overachiever, already adapted to scarcity and thus indifferent to the standard hormonal starvation diet — I was met not with curiosity, but catechism. The gold standard, they said. Tried and true. As if medicine were a medieval guild and I, an unruly apprentice questioning the sacred text.

Now, don’t get me wrong — gold standards exist for a reason. They work. Mostly. But I’m not "mostly." I’m me. And my concern is not the statistical majority. It’s whether this doctrinal adherence overlooked a tumor that, by virtue of its very origin, had already found a detour around the testosterone toll booth.

So here we are: therapy proceeding with grim determination, and me quietly wondering if we’re starving a tumor that was never hungry in that way to begin with. And if that’s true, what then? Will the outcome reflect biology’s stubborn individuality, or medicine’s one-size-fits-all optimism?

Either way, it seems I’m not just fighting cancer — I’m also in a polite but pointed disagreement with protocol.

Interested in more discussions like this? Go to the Prostate Cancer Support Group.

@dpfbanks

The ‘Art’ of the science? I am not sure I could give an exact why, to be honest, other than the suspicion of a ‘sneaky’ cancer presenting very oddly. The ‘plan’ is coming from a CCOE and was modified by our local MO from what we are calling ‘quad’ therapy (triple therapy + the carboplatin) to double chemo, following by double ADT (+ ARPI) at the end of chemo. I guess we have to trust the unconventional for the win. Living with uncertainty may not be a fool’s errand.

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A couple of things about carboplatin

When combined with docetaxel, carboplatin has shown improved response rates and overall survival compared to single-agent chemotherapy in hard to treat cases

Patients with mutations in DNA repair genes (BRCA1/2 or other recombination repair HRR pathway genes) may respond better to carboplatin, as these tumors are more sensitive to platinum-based chemotherapy

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Thank you @jeffmarc - You wisened comments are helpful. The only mutation showing in liquid biopsy is NF1- another rabbit hole I’ve been down. I am getting more comfortable with seeing that there are some ‘clear contributing facts’ and then it’s the ‘intuitive notions’ that become ‘the Art’ for the practitioners. “Something is amiss…and isn’t revealing itself…yet”

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