Short version (bio has more detail): omHSPC, started ADT (Lupron + Darolutamide - ARASEC Trial) in September 2022. MO has me scheduled for a consultation with RO for a planned debulking IMRT/IGRT to the prostrate and pelvis in Nov/Dec.
My question for this group - is IMRT/IGRT the best option here, (or maybe the one that matches the equipment that Northwestern has)? Other literature treatment references include SBRT, hypofractionated, proton beam, brachytherapy, etc. Do any of these other techniques show improved outcomes for debulking w/ confirmed distant metastic disease?
Hard to keep track of the various options here, matched to the disease status . . . .
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Heykm01
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You should be starting docetaxel immediately (triplet therapy). It is now the standard of care for men in your situation. Unless there is a compelling reason not to:
As I read the literature, there is consensus on the benefits to triplet therapy for high volume disease. I am low volume, and there has not yet been a demonstration of benefit for triplet over doublet therapies. And debate and the expressed need in the uro community for studies on this (hence the ARASEC trial). When I asked my MO about triplet, he said "at this point I think docetaxel would do more harm than good". I can press him on this.
I am curious as to your "now or never" comment. Are you saying that my current treatment plan will take any future chemo treatment off the table? I understand the disease mutates, but are you saying that ADT+ ARI or ADT+ARI+Radiation will result in mutations that escape chemo?
I. Both ARASENS and PEACE1 showed that the benefit of triplet was significant in ALL patients newly diagnosed with metastases, whether high volume or low volume. One has to be careful about relying on subgroups when there is insufficient follow-up and sample size.
In ARASENS: "The significant OS benefit was consistent across prespecified subgroups." They did not stratify by volume.
In PEACE1: "By analysing the ADT with docetaxel population according to the disease burden, we observed that compared with SOC (including docetaxel) without abiraterone, the addition of abiraterone decreased the number of radiographic progression events or deaths from 55 to 41 and from 156 to 97, and reduced the relative risk of radiographic progression or death by 42% and 53%, in patients with low metastatic burden and patients with high metastatic burden, respectively (low-volume burden median not reached vs 2·7 years; adjusted HR 0·58, 99·9% CI 0·29–1·15; p=0·0061; high-volume burden median 4·1 years vs 1·6 years; adjusted HR 0·47, 99·9% CI 0·30–0·72; p<0·0001; appendix p 10, table 2)...As the data were not mature, no conclusive response in overall survival could be shown for patients with low metastatic burden "
2. I agree that we do not yet have the RCT that proves that adding docetaxel to an ARSi increases survival over ARSi alone. But if you look at Fizazi's bar chart in the article, you immediately see that the triplet (Docetaxel+ARSi) seems to afford a survival advantage over the doublet (ARSi). No evidence of effect is not the same as evidence of no effect.
3. Your MO opines "more harm than good." But chemo side effects are worse with age and with disease progression. You will never do better and get more benefit from chemo than you will right now. I don't minimize that potential side effects for 5 months, but after that, by delaying progression, you will probably have an improvement of quality of life over if you had not done it.
Also, see discussion in my article: "Does docetaxel only benefit mHSPC patients with a high-volume of metastases?"
4. "Now or never" There is a synergy in using the triplet early. Darolutamide will probably work for at least 3 years. During that time, your cancer cells are dormant and chemo cannot be used. Chemo is only useful against rapidly growing cells. And taking the drugs sequentially does not have the same impact as taking them together.
Hey, while our situations are similar, they differ in that my primary treatment was 118 seeds with 24 sessions of IMRT in 2003, my PSA never really came down and with a PSA explodingti 32.4 and two Mets to the spine, I entered a six month clinical trial of chemotherapy with Lupron/Eligard. One of the hypothesis’ from my Professor, Researcher, Medical Oncologist was, Is it not better to attack metastatic lesions and micro-metastasis with chemotherapy while the body is strong and the tumor burden minimal? The answer for me was a resounding, Yes......
Subsequent trials that Allen wrote about reinforce Dr Amato’s hypothesis. My guy told me that in 1978, the cure was found through chemotherapy. The only problem was the dosage required, killed the patient quicker than the cancer. At the time most people tried chemotherapy as a last ditch effort when the body was weak and the tumor burden massive; yielding poor results. Unfortunately last ditch chemotherapy attitudes still exists today; especially with co-morbidity issues at hand.
At age 75, I would not change a thing in my treatment path. I am close to 20 years in the fight. I have been undetectable since 2005. Stepped hormone injections in 2010. Some say my personal experiences are antidotal. I say from Stage 4 Prostate Cancer and a poor life expectancy prognosis in 2004, I’ll take it!
I say kill the little bastards early. I wish you the best.
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