Castration Resistance

Posted by glabelle @glabelle, Jun 4 4:01pm

For all of us that are having success with ADT, I’m sure there is the dread of hearing the words that our prostate cancer has become castration resistant. I am on month three of Orgovyx and Nubeqa. I asked my oncologist if he could give me some kind of estimate as to when hormone sensitive PCa becomes castration resistant and his reply was that he couldn’t. It’s different with everyone, he said. That being said I’d love to hear stories of your journey from hormone sensitive to castration resistant. Things like timelines, treatments, etc…anything that you might find helpful to share. Thank you all in advance. This forum has been a wealth of fantastic info for me!

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

glabelle | @glabelle | Jun 6 1:46pm

In reply to @wooldridgec "I stage 4 denovo and I am thankfully still castrate/hormone sensitive at 3 years." + (show)

Thanks for posting…and congrats on where you are!

glabelle | @glabelle | Jun 6 1:57pm

In reply to @jime51 "I think you're in good shape! Nubeqa is to stop the process by which cancer cells..." + (show)

For me, the first 8 weeks on Orgovyx caused the worse side effects. Fatigue in the afternoon, low libido and brain fog. Occasional hot flash. These side effects have gotten much less bothersome in my third month of Orgovyx. Better energy (I’m exercising 6x/week), and less brain fog. Low libido still an issue. Maybe I’m getting used to the “new” normal or maybe the exercise is really kicking in. Anyway, I wish you great luck as you navigate these waters.

smc24 | @smc24 | Jun 7 7:58am

In reply to @wdene "On ADT for 2 1/2 years when PSA started climbing. Bone metastasis now. On Xtandi and..." + (show)

Ask your medical team about starting on Pluvicto. I've been through it all...a very long story, and Pluvicto worked and it working extremely well, better than anything I've done with very few, and mild side effects. I'm a patient and no direct connection to the pharmaceutical company, but for me, it is working great.

proftom2 | @proftom2 | Jun 7 9:44am

I am a stage 4 guy. 4.6 years on this journey. Diagnosis 11/20, Became resistant in July 2023 starting a slow upward trajectory PSA which brings us to now. My PSA is at 12.4. Interesting twist. My oncologist put me on Pluvicto January. PSA continued its slow pace upward. Whoops, last month my PSA jumped from 7.5 to 12.4 and just like that oncologist viewed we decided to stop/paise Pluvicto and right to Xtandi. Yikes, current plan is one more Pluvicto shot, PSA still rising we stop. Either way we set the appointment to go to the big Cancer Research Center and start searching trials.

My boats not sinking, its navigating heavy seas. All journeys in life deal with heavy seas now and then.

jeff Marchi | @jeffmarc | Jun 7 10:28am

In reply to @proftom2 "I am a stage 4 guy. 4.6 years on this journey. Diagnosis 11/20, Became resistant in..." + (show)

Your experience with Pluvicto is not unusual.
It works really well in 1/3 of cases OK in 1/3 of cases and not at all in 1/3 of cases.

It is not uncommon for the PSA to rise until the third or fourth session, It may go down it may not.

If you are on Xtandi You should also be taking ADT, You don’t mention that. Even if castrate resistant ADT does help because not all of your cancer is castrate resistant. Good to hear you were going to another place for treatment advice, They should never have let your PSA get so high, sounds like You should’ve been on an ARSI like Xtandi before Pluvicto.

If the side effects of Xtandi (Enzalutamide) are too much, you should ask your doctor to switch you to Nubeqa (Darolutamide). It works the same, but has a lot fewer side effects.

One important thing to do before Pluvicto Is to get a somatic genetic test. That’s because some genetic changes that occur due to your cancer can either make Pluvicto worse or better.

Pluvicto genetic issues
RB1, PTen, TP53 are Pluvicto resistant
ATM & BRCA work better with Pluvicto

This is assuming you’ve already had a hereditary, genetic test, If not, I can tell you where to get one done for free.

ajpernsteiner | @ajpernsteiner | Jun 7 3:17pm

In reply to @wdene "On ADT for 2 1/2 years when PSA started climbing. Bone metastasis now. On Xtandi and..." + (show)

Similar here. Are you taking 160MG Xtandi? I take 80MG. Wondering about your side effects.

wdene | @wdene | Jun 7 4:36pm

160 mg. On it for 4 months now. Major fatigue is only discernible side effect.

chippydoo | @chippydoo | Jun 8 9:16am

In reply to @glabelle "For me, the first 8 weeks on Orgovyx caused the worse side effects. Fatigue in the..." + (show)

At 5 months of doing the slow grind to the bottom on Ogorvyx. The fatigue is real and slowly losing the exercise battle from it. Thankfully only 1 grade 1 hot flash and the drug is doing what it should be doing so there is that. I refuse to project on the "what ifs". I choose to focus on today and enjoy the peace and strive to get the most out of it. We can drive ourselves crazy worrying about the future. We all gonna die of something eventually.

wooldridgec | @wooldridgec | Jun 9 8:06am

I have a friend that has been on Xandi for almost 5 years now. Xandi breaks the blood brain barrier. I noticed that he loses a lot of words when we talk. Darolutamide does not break the blood brain barrier so you may feel much sharper mentally on this drug. I take Darolutamide and I work as a software engineer and heavily depend on my brain. It has not slowed me down one bit. However, I cannot speak to the hot flashes. They are steady and awful at times. There is also fatigue that I push through every day.

phil89 | @phil89 | Jun 9 9:59am

Hi there, I am happy to share my father's journey from castrate sensitive to castrate resistance. He was diagnosed de novo in June 2023 at 67 y/o, and started Triplet Therapy shortly thereafter (6 cycles of Docetaxel Chemotherapy, Lupron/ADT and Nubeqa/Darolutamide). Everything went well and his PSA went from 800+ right down to 0.1. In February 2025 (around 18 months after starting triplet therapy), his PSA went up to 3.43, then up to 8.54 by April 1, 2025, when he started Cabazitaxel (Jevtana) and Prednisone. He also continues to receive Lupron every three months. Currently after 4 cycles of Cabazitaxel, his PSA is down to 4.02. We are hoping it goes down even further. Best of luck to you and I hope you stay hormone sensitive as long as possible.