Dutasteride (Advodart) as an Alternative to ADT in Salvage RT Setting?

[jazj]

I know this forum is mainly focused on post-salvage advanced stage but highly respect the knowledge and opinions of the members here.

There's clear evidence in the early stages of recurrence that Dutasteride (Advodart) slows or even stops the progression based on PSA results epecially when started when PSA is very low and with the lack of other negative pathological features (no Gleason 8+, no positive surgical margins, no lymph node involvement post RARP)

However the studies I've found are either not very long-term or the cohort size is small (this study with just 35 patients seems to be the most referenced.)

ncbi.nlm.nih.gov/pmc/articl...

Another issue that commonly comes up with studies showing decrease in PSA is the questioning of whether the treatment is actually slowing/stopping the cancer or simply masking the PSA? This does not seem to be the case with Dutasteride as this study indicates it actually makes PSA reliability for detection of cancer MORE accurate!

nature.com/articles/nrurol....

What I can't seem to find is any studies on effect of progression longer-term (like 5+ years), nor any studies of use of dutasteride during salvage radiation treatment as an alternative to ADT? I've seen studies where ADT has a positive effect when combined with Salvage Radiation, but long-term survival there really isn't that significant of a difference when Salvage RT is undergone without concurrent ADT. The ADT seems to buy a very moderate amount of extra time before metastases occurs but I've yet to find clear data that the addition of ADT significantly increases the probability that SRT is curative.

The side effects of ADT are pretty harsh. So what I'm getting at is, if you had good post RARP pathology (no positive margins or lymph node invlovement, P2 Stage, Gleason < 8) it seems the first step may be to start Dutasteride at say 0.03 PSA and monitor your ultra sensitive PSA score and then elect salvage RT if you see the PSA going up, maybe when it reaches 0.05 or 0.1.

I wish there were studies comparing Dustasteride combined with Salvage RT to ADT combined with Salvage RT because if the long-term outcomes are very similar it sure would be nice to avoid the side effects of ADT in the Salvage RT setting.

[Tall_Allen]

Dutasteride failed to slow progression when used as part of IADT. It has never been used instead of ADT with salvage radiation.

4-6 months of ADT improves results of salvage radiation.

prostatecancer.news/2022/05...

[jazj in reply to Tall_Allen]

I've seen the numbers from this study and I don't find them impressive. I understand in the context of advancing recurrent disease, patients of course want to do anything and everything that will improve their chance of a cure no matter how small. But there can be tradeoffs and/or the law of diminishing returns. ("Androgen deprivation therapy (ADT) is the standard of care for the treatment of advanced prostate cancer (PC). ADT, particularly with GnRH agonists, leads to increased risk of cardiovascular disease, including myocardial infarction, hypertension, and stroke." ncbi.nlm.nih.gov/pmc/articl...

"SPPORT is telling us that if we are willing to put up with 4 months of ADT and some extra short-term toxicity from the wider field of radiation, a cure is likely. "

A cure is likely? What do they define as "likely" a very subjective term? Well looking at the numbers...

"8-year freedom from progression (biochemical or clinical) was 77% for sWPRT+STADT, 72% for PBRT+STADT, and 61% for PBRT" What about 12 or 15 year freedom from progression?

First, recurrence/progression can occur in twice as long as 8 year (16 years) so while 8-years is a sizeable timeframe, other data I've seen shows the addition of ADT made no significant difference in PCSM (the end end result in many cases going beyond 8 years.) Even with that said this is showing a 7.7 out of 10 chance of progression free with whole pelvic versus a 7.2 out of 10. Wow, what a big difference. LOL. What's the statistical differnence in incidence of secondary cancers between those that had pelvic versus no pelvic. "Gee I got myself a 5% more chance of a cure for PC in exchange for a 25% increased chance of bladder cancer and died of the bladder cancer in stead of the prostate cancer." The difference though with and without ADT is more significant, but what's that difference like in additional 7 years out at 15-years instead of 8?

ncbi.nlm.nih.gov/pmc/articl...

"With a median follow-up of 6 years after recurrence and 9 years after prostatectomy, 116 men (18%) died from prostate cancer, including 89 (22%) who received no salvage treatment, 18 (11%) who received salvage radiotherapy alone, and 9 (12%) who received salvage radiotherapy and hormonal therapy."

So in this case, in the end, the patients who had ADT with their SRT did slightly worse.

In addition the latest studies are showing an ultra-sensitive PSA result of 0.03 or greater as being a reliable indicator of biochemical recurrence. In that context, many of the previous studies are outdated, as they are examining results of patients that initiated salvage therapy at much higher PSA levels. So for all we know, if salvage RT is started below 0.1, that may be a more significant factor in the outcome than either width of field or addition of ADT.

In fact, using 0.03 instead of 0.2 as a cutoff was shown on average to provide 18 months additional lead time for SRT. I think the 18 months additional lead time may have a higher potential of increasing the odds of SRT being curative than adding ADT or including the pelvic area.

ncbi.nlm.nih.gov/pmc/articl...

"uPSA ≥0.03 is an independent factor, identifies BCR more accurately than any traditional risk factors, and confers a significant lead-time advantage."

"A meta-analysis quantified the success of salvage RT to decrease by 2.5% with every 0.1 PSA increment [10]. Thus, detecting failure at the lowest possible PSA concentration would be valuable to establish a greater ‘lead time’ to identify recurrences early while it is most likely to be confined to the prostate bed."

pubmed.ncbi.nlm.nih.gov/231...

"Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease."

So the way I look at it is ADT delays biochemical progression of PCa. So does Dustasteride. So I hypothesize starting Dutasteride and SRT when PSA reaches a much lower threshold of 0.03 could have at least the same if not higher chance of being curative than initiating SRT with ADT at higher PSA levels (> 0.1) as has been the tradtional approach.

But as you point out, there are no studies (yet) validating this hypothesis and of course Oncologists have to base their current recommendations on pre-existing data.

[ElRanchoDePoisonIvy in reply to jazj]

I’m wondering if the early SRT guys would potentially include a lot of men whose PSA numbers would decline on their own, making the survival rates for early SRT appear better than they are.

[FlyJ]

See my profile. I had robotic RP with lymph node dissection 7/2019. Path report T3A No Mo. Gleason 9 (4/5) Two areas of ECE. I had BCR (BCR PSA .21 ) Last year and then interesting a drop in PSA from .21 to .18 to .15 . Discussed with R.O. and decided to go ahead with Salvage Radiation(to prostate bed and pelvis) if PSA rose- which it did to .17. PSMA gallium scan done and negative. Because of high Gleason score and High decipher test we chose ADT (4 month lupron injection.) Also doing casodex 50mg/day similar to Spport study which I will do for 6 mos. I have decided to also take avodart .5mg day for anticipated 2years. I see little down side and "possible" help from this. You have probably seen ARTS- Avodart study. clinicaltrials.gov/ct2/show...

[larry_dammit]

beware of Avadart, this drug just masks the PSA results while the cancer is still growing. I was on Avadart while under a urologist care, seeing him every 6 months. By the time the PSA started rising slowly , I already had stage 4 with Mets. To each there own but Avadart has managed to ruin and shorten my life span.

[Balsam01 in reply to larry_dammit]

I completely agree. I had the same thing happen to me. Wound up with Gleason 9, migrated to lymph nodes. After I stopped Avodart my psa increased and I went to a urologist and the rest is history.

[maggiedrum]

If you have the same experience I had, you have to have demonstrated castration resistance before you can get the dutasteride. It would not be SOC per the FDA and most (if not all) insurance providers, which I have been led to believe includes Medicare itself regardless of your Advantage or Supplement plan.

[MateoBeach]

I applaud your careful research and critical analysis Jazj. However, I am unclear if you are actually BCR after your RP, or just trying to plan for future contingencies? What are your PSA results?

[SpencerBoy11]

My new urologist I just saw took me off of it, but kept me on alfuzosin.

[maggiedrum]

Thanks for the info. If I were to do that I would want to change my doc to one who knows that I am taking the med (perhaps the one who gave me a script). I wouldn't feel comfortable taking a med like this on my own without someone who is paid to constantly monitor my health, and, who is also keeping track of the information concerning the med. For something like this, I (just my personable preference) don't want to self-medicate.