My husband, 67, was Dx with high volume aggressive metastatic PC in April. PSA was 72.8. Started degarelix, had 6 sessions of docetaxel, added abiraterone in August, consolidative SBRT in September. Lowest PSA was 0.99 right after chemo, in August. In September, 1.12, October 1.87, and now in November it is 4.16. His Testosterone levels remain <7. (Switched to Orgovyx 6 weeks ago.) His local MO suggested we recheck PSA in 4 weeks. Is this reasonable? Or with this doubling time, should we act? He is not scheduled to return to Mayo for another PET scan until April, but local MO will consider PSMA next month depending on PSA. His alk phos levels are also rising, which on its own might not be concerning, but in light of the rising PSA might be. Does this rise in PSA mean he is already hormone resistant? Should we consider switching to a different 2nd gen at this point? Or switching from prednisone to dexamethasone to be used adjunctively with the abiraterone? At what point do we consider other treatments? Is there imaging we should get now rather than waiting? He has had no side effects from any of the treatments so far, except for hair loss from the chemo. He feels great, works full time, has a tremendously positive attitude. We will go anywhere and participate in any clinical trials. We would appreciate suggestions, or if we should just stay the course until the next PSA test which is December 10.
Rising PSA after chemo, next steps? - Advanced Prostate...
Rising PSA after chemo, next steps?
Certainly switch to dexamethasone. You don't have to wait for that.
When that fails, a PSMA PET scan and Lu177PSMA617 would be a good move.
Thank you, that is exactly what I was thinking. I thought I recalled that you recommended that course in the past, but was not sure if it was a similar clinical picture. What is the recommended dose of dexamethasone? Is he now considered mCRPC? So much sooner than we had hoped...
0.5 mg/day dexamethasone.
Don't worry about what to call it. There is no sharp dividing line between HSPC and CRPC.
Thank you. Have already texted his MO!
My husband’s PSA was 12.2 on Dec 10, so no benefit on switch to dexamethasone. (PSA tripled in one month.) He had PSMA scan 12/17 (Friday) and we will get results this week. Lu177 not yet approved in US. I have heard of expanded access through Johns Hopkins, and we have a virtual visit scheduled. Are you aware of any clinical trials or other expanded access we should try to tap into? Thank you so much for all your help with this. I would like to have all questions and suggestions in place before we talk to his MO on Wednesday. We are in SE WI, and have been to U of Chicago and Mayo for opinions right after diagnosis April 2021. We are willing to travel domestically.
Here's a list of US trials:
prostatecancer.news/2020/08...
I heard expanded access was no longer recruiting, although that may be site-specific.
Has he tried Xofigo yet?
He has not. Just diagnosed de novo last April. Started degarelix and taxotere, then abiraterone added in August. PSA has gone from 0.99 in August, 1.12 in September, 1.87 in October, 4.16 in November, switched from prednisone to dexamethasone, now December it is 12.2. Alk phos has gone from 65 to 229 in same time period. Testosterone <7 entire time. Switched to Orgovyx for convenience in October, and testosterone has remained <7.
No symptoms; feels great but he always has.
So he really had a very short time frame to resistance, and has not had any other treatments yet.
They look for some pain for Xofigo, but even a complaint of some lower back pain is good enough to qualify
Thank you so much for the tip, and your always helpful response.
My husband was able to get a few more months out of abiraterone when he switched to dexamethasone. Now I have been told the importance to continue taking the drug until progression is seen on scan, not just due to PSA rising. The PSMA would be a great one to have.
Definietely agree with others about trying Dexamethasone. It has worked for me so far.
A relatively short time to castrate resistance generally favors chemotherapy over second-line anti-androgens. I would look at the IHC of the cancer and also do genetic sequencing to see if that helps give some direction for treatment.
Getting a PSMA scan is a good idea to see how PSMA avid he is and that determines whether LU-177 treatment would be effective.
Progression in imaging should be used in addition to rise in PSA to determine when treatments have become ineffective and need to change.
These are things he can discuss with his doctor.
He just finished docetaxel in August. He isn't scheduled for a PET at Mayo until late March, but his local MO plans to get a PSMA in December if his PSA is still going up after the switch to dexamethasone. At what point do we consider Provenge or Xofigo?
Provenge and/or Xofigo would not be my choices at this point.
I would be looking at LU-177 and either a rechallenge of Docetaxel or second-line Cabazitaxel. LU-177 is going to depend on the results of the PSMA PET scan and of course if you can find somewhere to get the treatment.
Would also get a biospy if possible to look at genetic sequencing and IHC. That might effect chemo in terms of possibly adding Carboplatin and also genetic testing might open up other treatment options such as a PARP inhibitor for BRCA or ATM mutations.
That's what I would likely be doing, but talk it over with the doctor.
He did have his original biopsy sent for all the generic testing and there were no high value targets. My understanding, from studies I have read, that there would be additional value in doing a biopsy on a mets if possible. Is this correct? Thank you for your time. With luck, the switch to dexamethasone will do the trick for a while.
He tolerated chemo so well that he would not object to more, but we are also willing to travel for Lu-177. We have plenty of vacation and travel has been Covid curtailed!
I hope things work out with the Dexamethasone, it has for me so far. My concern is again the short time to resistance for hormone-based treatments. It's good that you are working on a "Plan B". It also sounds like you aren't considering switching to another anti-androgen like Xtandi and I would agree that's unlikely to work.
You would want to have the biopsy on some new mets because of the somatic mutations that occur.
I'm glad to hear he has tolerated chemo well. I would try to make a determination about how effective Docetaxel was the first time around so you can "see if you can go back to the well" as my doctor says.
Otherwise Cabazitaxel is an option and has easier side effects for many. LU-177 should be approved in the US soon so maybe you won't have to travel, although what I've been hearing is the price may be high enough that it's cheaper outside the US.
When you say “try to make a determination about how effective docetaxel was the first time around” do you mean anything beyond PSA and PET scans? The PSA fell from 72.8 to 3.4 after first two treatments, and continued to fall until it reached 0.99 after all 6 doses.
Scans in August after 3 and 6 treatments showed treated, sclerotic metastases with only residual activity in right lobe of prostate. SBRT after that, but PSA rising in October and November. So, I believe it was pretty effective, right?
Agreed that I see little value in switching to Xtandi, even though it costs us nothing with my insurance through my employer. (Pfizer) Perhaps after chemo whenever the next course occurs.
And yes, we had hoped to get a lot longer before hormone resistance! Years or months rather than weeks. Scary. Hard to wait for next PSA but now that he has made the switch to dexamethasone we know we need to give it a few weeks.
When you do Docetaxel upfront with ADT, it's difficult to determine how much of the PSA drop is the chemo and how much is the ADT although the ADT generally has a bigger effect.
I think you should discuss his response to Docetaxel with his doctor since I don't feel qualified to make a determination. I have to say, I was suprised when my doctor said he felt my response to Docetaxel was not good enough to go back. He felt my PSA started rising too fast after I stopped Docetaxel.
I agree that you might get some more time out of Xtandi later on after chemo and/or LU-177. Do keep in mind that imaging is important in addition to PSA in determining progression. We often focus on the PSA since it's easy to measure and compare.
I agree about imaging, but Mayo said we needed to wait until March. Our local MO is willing to order a PSMA in December if the PSA is still high.
Good thoughts about ADT vs docetaxel response. He always teased them that they forgot to put the meds in, because he felt so good. 😊 If he hadn’t lost his hair, we would seriously have wondered.
Consider checking testosterone level to verify Orgovix plus abiraterone are doing the job of keeping castrate at total T less than 20. If that is okay then he can be considered castrate resistant, mCRPC, which means Provenge will be covered. Request referral for Provenge and put it on his side. No reason not to. He should also be on a bone protective regimen as early as possible, either denosumab (Xgeva) or Zometa infusions. These are tolerated better before there are painful bone mets. I agree with the PSMA PET scan at this point. Hope the switch to dexamethasone helps. Also, most clinical trials are for mCRPC patients. Need a top tier urologic MO to sort out and advise, one who is plugged-in to the most promising trials and emerging therapies.
Thank you. Yes, his testosterone has been <7, and remains so. I appreciate your thoughts on Provenge. I did see one trial where Provenge and Xofigo are being given together that looked very promising. Not sure if they are still enrolling.
He is being followed at Mayo with Dr Kwon, but he isn’t scheduled to be seen there again until late March.
We have also consulted with R Szmulewitz at U of Chicago, and keep those communication lines open. (He is the guy who did the study on abiraterone 250 mg with food.)
We are in Southeastern WI, so it’s easy to travel anywhere in the Midwest, but are open to traveling anywhere if there are appropriate MOs he should be seeing. Our community MO is a good friend, Johns Hopkins trained, and will facilitate anything we suggest.
He starts the dexamethasone tomorrow, so will recheck his PSA in a few weeks.
I insist you to discuss your husband's issue with Dr. Ishita Sen (MBBS, DRM, DNB (Nuclear Medicine)) at dr.ishitasen@nuclearmedicinetherapy.in. She is currently the Director & HOD of Nuclear Medicine & Molecular Imaging at FMRI Gurgaon, India and available for a free second opinion.
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