Does anyone know of any studies or MO advice they've gotten regarding use of Dutasteride or Finasteride at very early signs of Biochemical Reccurrence (uPSA in the 0.03 - 0.1 range) prior to Salvage Radiotherapy?
It's obviously going to slow PSA doubling time and thereby probably lengthen the time to when you would pull the trigger on radiation.
I know studies have shown they do not increase Prostate Cancer Specific Mortality (PCSM).
This study, although it is combined with biculutamide, is interesting.
"From the start of PAB, median time to castrate resistance was 49.8 months (IQR 40.9-NR). After starting ADT, median time to castrate resistance was 8.8 months (IQR 4.6-17.7). Our data support the exploration of PAB as a treatment option in carefully selected patients who present with biochemical recurrence after failure of definitive local therapy for prostate cancer."
I've seen previous discussions on this topic, but they are all in the context of later-stage disease. I don't recall discussions on their use at a very early stage of BCR prior salvage therap.
I'm wondering if early use of either of these alone may delay the necessity for ADT and/or delay metastasis in the long-run. I cannot find any long-term studies addressing this.
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Think you got the wrong study link. I found the older thread on this subject but more focused around later stage use. I can't find any long-term, non retrospective, studies on use a chemo preventative agent post PCa diagnosis.
I'm curious what your best guess is on its utility as an early monotherapy to delay the necessity for more aggressive ADT or in Justfor_ 's case delay SRT? It appears retrospective analysis of its usage had no effect on PCSM one way or the other? Seems the risk/reward ratio is attractive from the context of delaying experiencing the side effects of full blown ADT or SRT?
All of our data show the same thing - if required, early, aggressive treatment is the most effective. Anecdotes from single patients should not replace the many patients in the many randomized clinical trials on this subject. I just looked at your profile and don't understand why you think you need any treatment.
This is going to be a bit long and beyond this thread's topic, but since you asked the question, and I highly value your opinion...
I have the personal belief that acting earlier the better in the salvage setting. Acting doesn't necessarily mean solely radiotherapy as a first step in SRT after RARP. There's good data that virtually all patients reaching a PSA of 0.03 and rising are experiencing BCR and data showing a 0.02, 75% of patient went on to BCR. A consultation with Dr. Kishan, UCLA's expert on Radiologic Oncology was of the opinion if the studies had longer follow-up period, 0.02 would have a higher predictability than 75%. However he said he believed there was no data that waiting until at least a 0.1 to do SRT had a decrease in curative potential. Current best practice appears to be before 0.25 with some clinics choosing 0.2 as the cutoff.
Without knowing my future PSA Kinetics, I am investigating not only timing and type of radiotherapy in the context of assuming I get to at least a 0.05, but also what data there is on mitigating BCR before salvage treatment. I believe the highest chance of avoiding PCSM at my relatively young age is being prepared to act early (with higher confirmation of BCR before SRT) and with approaches that may be outside the SOC which is limited to only historical data accumulated thus far. As long as the novel approach has at least some data and that data does not show counterproductive results I think it's worth at least considering as I think the possible reward to risk ratio is high. This is where PCa patients may differ on their perspective. Some may like to "play it safe" in the sense they only base their decisions on large bodies of large well designed trials, and then there are those like me that are willing to take a risk of trying something that there isn't a body of long-term data on. Long term meaning like 15+ years.
This is not to say my approach is pessimistic, just realistic and cautious but with an open mind and a degree of risk tolerance. This article published February 2023 makes some good points, although I personally disagree with the 0.2 cutoff unless I can find a large body of evidence documenting patients that when from undetectable to > 0.05 after RARP that never had a rising PSA exceeded 0.2 for at least 20 years after. That data doesn't exist (yet.) I believe based on basic logic, that if there is a high chance BCR is underway, time is your enemy. In my opinion, the more time, the more chance for distant micrometastases outside the field of treatment for salvage RT. There just isn't a large body of evidence comparing long-term outcomes on early SRT in the 0.15 range. No one wants to risk the side effects of RT especially if they are at an older age within 5 or 10 years o the life expectancy.
First, considering a PSA value of ≥0.03 ng/ml as BCR is subject to debate. Current guidelines recommend withholding any salvage treatment after surgery before PSA has reached a value of 0.20-0.40 ng/ml [1]. There is great variability in PSA testing kits: [2] as such, PSA velocity or doubling time interpretation at such low values must be cautious. The authors report a median PSA at treatment of 0.08 ng/ml, which is way lower than that supported by the EAU or established in recent RCTs as RADICALS or RAVES trials [3]. Considering that roughly 50% of patients may increase their PSA after surgery, yet never reach the critical value of 0.20 ng/ml [4], triggering treatment before such threshold may determine overtreatment.
When I read that though I think, ya, right. They didn't reach 0.2 because they were 70 when they were diagnosed and died of heart disease before their PSA could go past 0.2.
"Any post-op PSA ≥0.03 captured all failures missed by first post-op value (100% sensitivity) with accuracy (96% specificity). Defining failure at uPSA ≥0.03 yielded a median lead-time advantage of 18 months (mean 24 months) over the conventional PSA ≥0.2 definition."
I'm technically high-risk with a pre-op PSA of 32 and cribriform (small) pattern even though my post-op pathology showed the tumor was contained, no positive margins, no seminal vesicle invasion, 14 negative lymph nodes.
I rather risk some urinary issues from RT sooner than later in exchange for a possibly higher chance to not progress to advanced stage cancer.
But I do admit, aside from the thirst for knowledge about this subject, SRT/ADT would be premature at this point. But I'm going to do anything I possibly can within reason to lower my chances of progressing in the meantime.
The main concern though is using anything very early that lowers PSA without long-term high-powered studies, could have the opposite effect and make you delay SRT too long by masking PSA. I believe a general rule was to double your PSA while taking certain substances (gee ins't that a convenient round number [rolleyes]) This isn't an issue with advanced prostate cancer because you can use PSMA PET scans at that stage to confirm reduction in disease instead of just using PSA alone. Unfortunately, below 0.3 PSA, PSA is all you have to rely high to monitor disease progression.
You quote a lot of old data. I used to believe that SRT at the earliest possible uPSA ≥ 0.03 is a good idea. Since RADICALS-RT etc., the landscape has changed. The 3 RCTs proved that for most men, waiting until PSA reached 0.1 or 0.2 carries no risk (in spite of your unfounded beliefs) and may prevent a lot of overtreatment. There is no reason to assume that your PSA will continue to rise or that treatment before PSA reaches 0.1 or 0.2 (if it ever does) carries any benefit.
Your anxiety comes through in your post. I strongly recommend you deal with it (I did) because it gets in the way of making rational decisions in your best interest.
I was just reviewing this thread to brush up on this subject. I should mention since your reply I consulted with Dr. Kishan at UCLA whom I consider to be one of the world's foremost researchers when it comes to PCa and Radiotherapy. He also confirmed he thought waiting until 0.1 carried no added risk.
On the tangential subject of SRT timing, I think age plays a significant role. A 75-year old would have a more significant negative impact on QOL and has a much higher chance of dying of another cause than a 55-year old. To me if, 0.03 or heck even 0.05 is a reliable indicator of biochemical recurrence post-RARP I think getting SRT at 0.05 instead of 0.1 could only be classified as overtreatment based on being older age or if the data on uPSA levels and biochemical recurrence is unreliable. Otherwise the better term would be early treatment not overtreatment.
Age (neither young nor old) is not a reason to get SRT early or later. There is no reason other than very high risk pathology to have SRT as an adjuvant treatment rather than wait for PSA to reach 0.1. We have level 1a evidence for this, anything else is just a figment of your imagination.
On know you MO here is basically do what has been proven to work. Based on the pre-existing data, I actually agree with you. You can use the term 'figment of your imagination' and would choose the phrase 'unproven theory.' If you can find me any studies that have a large cohort of patients receiving post-RARP SRT at PSA > 0.02 and 0.1 and < 0.2 I would love to take a look. I've not found any to date because the outdated standard for BCR has been 0.2 and therefore the cohort of possible subjects that are far enough post-surgery to be in suitable physical condition for SRT and received it at PSA < 0.1 where there was at least 10 years of follow-up are probably non-existent?
Excuse my typos. It's strange, I've lost all options in the More dropdown to edit my typos (it's now blank. ) Anyone else? Just started happening today and I tried a different browser too.
So let's try this again...
I know your MO here is basically do what has been proven to work your input is extremely valuable. Based on the pre-existing data, I actually agree with you. You can use the term 'figment of your imagination' and would choose the phrase 'unproven theory.' If you can find me any studies that have a large cohort of patients receiving post-RARP SRT at PSA > 0.02 0.1 and < 0.2 I would love to take a look. I've not found any to date because the outdated standard for BCR has been 0.2 and therefore the cohort of possible subjects that are far enough post-surgery to be in suitable physical condition for SRT and received it at PSA < 0.1 where there was at least 10 years of follow-up are probably non-existent?
Interesting, I see part of the problem. Equal sign followed by a greater than sign is filtered out. I was trying to type basically cohort A is greater than 0.02 and less then 0.1 and cohort B is equal to or greater than 0.1 and less then 0.2.
Level 1a Evidence means that it has been established as true. Three large RCTs proved that there is no advantage in treating before PSA reaches 0.1 or 0.2, in any but high-risk men. Anything else is just a reflection of your anxiety, and psychotherapy may be useful (I highly recommend it - it worked for me!)
I stand corrected and probably read this and other studies before. Most of the men in this study had PSA < 0.1 and the benefit with RT at that low of PSA was in the men with adverse pathology which I personally would not fall into that group.
It still begs the question if 0.03 PSA is confirmation of BCR excluding having to go through RT earlier rather than later, what would be the harm in getting SRT at 0.05 as opposed to 0.1? Surely no one's PSA post primary treatment has risen to 0.05 and not continued to have progressed? So why let the cancer grow further at 0.05?
Thanks. That's sort of what I'm looking for. But ya, still no long-term studies out there and yet this study states:
"If dutasteride was provided before the PSA value increased to 0.195 ng/ml after RARP, it would reduce the probability of acquirement of RT/ADT."
My question to that statement is FOR HOW LONG? And more, such as, does it increase time to castration resistance later with more aggresive ADT? Does it reduce the chance or delay metastasis? All we know in general is retrospectively, it doesn't increase PCSM. I guess one could argue, if it doesn't increase PCSM, then what do you have to lose initiating it as a very early monotherapy and first sign of BCR?
Eh, in reading the full article, it eventually doesn't provide the clarity I'd like to see but there's no evidence of negative outcomes. The large study that showed higher grade cancer when 5-Aris were used prior to diagnosis was later debunked apparently on the theory the 5-Aris lowered the PSA so the diagnosis was made later than had they not taken them allowing the cancer to progress.
For this study the sentence bolded and underlined is what concerns me...
"Our study, however, has some limitations. This was a single-arm study, and the results of this study cannot be compared with the results of those who did not take dutasteride. Moreover, this study was a single institutional study, which did not include a large population. A large and randomized prospective study is required to confirm these findings. To date, the adverse side effects of 5-ARIs on sexual function have received minimal attention and were deemed clinically less important [16]. However, in patients who have undergone RP, these sexual side effects could be an important issue. Another potential concern is that 5-ARI treatment for PCa may shorten the time for development of resistance to androgen deprivation therapy, despite 5-ARIs being the subject of long-term follow-up (7 years) clinical trials and in clinical use for more than 10 years [17]. However, 5-ARI may have utility as less aggressive treatment options for patients who have rising PSA after RP, and in patients with PSA progression having resistance to androgen deprivation therapy."
"Results: We included 9 eligible studies for analyses from 2011 to 2017. We found that 5-ARIs group may have fewer progression (OR = 0.48 95%CI: 0.37-0.61 P < 0.00001, I2=4% p = 0.39) and lower pathological progression (OR = 0.46; 95%CI: 0.29-0.73; p = 0.001, I2=0% p = 0.45), compared with control groups. However, the OS did not show significant difference between two groups (OR=1.10; 95%CI:0.90-1.35; P = 0.35, I2 = 93% P < .00001 ).
Conclusion: The use of 5-ARIs could prevent progression in PCA patients both clinical and pathological."
I started taking Avodart 3 months after RP (PSA at 0.02) as I had reviewed 4 papers, from every corner on this planet, claiming that it delays BCR. Can't tell if it actually did, but 2.5 years later at PSA 0.17 started an adaptive dosing of Bicalutamide. 26 months in now, I intentionally maintain my PSA at the limits of detectability (0.010-0.016) to prolong effectiveness.
Adaptive dose of Bicalutamide? Is this a strategy you came up with or is there clinical data on it somewhere? So did your PSA go above 0.02 at some point to confirm BCR or have you essentially phased Bicalutamide when you hit 0.02 to keep your PSA from every going above 0.02? So you actually wouldn't know 100% certain if you had BCR yet? (0.03 seems to be currently the reliable level to indicate BCR after RP.)
It was my own idea but it was later found out that it wasn't just me following that trail. Dr Bob Gatenby of Moffitt center in Tampa is the lead of a group that has been doing research/clinical trials since more than 5 years back. My plan is different, but the underlying idea is the same. You may check my bio for detailed information.
In 2.5 years, my PSA rose from 0.02 to 0.17, PSADT was 9.5 months. So, BCR was confirmed. Just wanted to delay sRT, thing that I have managed thus far.
Oops. When I read your reply I accidentally read 0.17 as .017.
I like the strategy though. I think the decision on at what PSA to initiate SRT involves many factors, mainly your post-surgery pathology but also your age and current urinary function.
I'm at 0.02 now and contemplating going on Avodart but balancing that with the fact I'm 55 with 95% the same urinary continence I had before surgery so I'm not very concerned about dealyed toxicity on the SRT in my health at my age. I just can't decide if the Avodart is just masking PSA versus truly slowing the cancer down. There's no long-term studies on use of Avodart and time to metastasis and/or castration resistance when started early.
Spare your time and research efforts on red herrings of the kind of "PSA masking" and redirect it to learn about irradiation late toxicities and second cancers. You have, on average, 3 decades in front of you, being 55 y.o. today. Radiation is known to be a slow killer, but a killer none the less.
I had one doctor tell me that when he put patients on dut or finasteride that none came back w adv pca, so right it’s just an educated guess on whether to go on it or not… good luck
Catching up on this interesting conversation - you post some questions/approaches I am not familiar with - thanks! This question of when and how to treat remain with me - fortunatley I am quite calm about it all. Although I have posted my single patient anecdotes quite a bit, thought I would share a summary of my PSA post treatments. Post RP nadir 0.050. Waited until 0.11 to do salvage RT - no ADT; nadir 0.075. When back up to 0.11 went for imaging abroad that identified suspicious pelvic mets. When for salvage ePLDN - 6 of 31 nodes confined for cancer including common iliac and para-aortic. Post ePLND nadir <0.010. That was six years ago this month. After two years at <0.010 the < dropped and very slow rise began - been holding very low stable 0.03X range last two years. I have done Ga 68 and Pylarify and blood biopsy in past two years. I have learned to not give this beast time and obscurity. All the best to all of us!
My surgical margin was "involved by invasive cancer, focally at the left apex". There was no indication of seminal vesicle invasion; but then there are discussions about the meaning and threat of seminal vesicle invasion - i.e. muscular wall or ejaculatory duct? My first biopsy path was 3+3, second and third opinions 3+4, final 4+3 (had two opinions). I see pathology reports as variable opinions, and if one has only one, isn't it just a single doctor anecdote (albeit not amusing!)? I only had a few pelvic nodes removed at surgery - saw no reason to risk lymph node chasing without probable cause; they were 'clear' or at least that is what the pathologists thought. If I could do it all over I would have the nanoMRI prior to RP and if it showed suspicious nodes, would as done for my ePLND, have frozen section of common iliac nodes at the start of the RP.
Interesting information. Thanks for the follow-up.
I've always pondered, at what PSA, post-surgery, is the cancer most likely metastatic. Your nadir was still in the detectable range at 0.05 which probably indicates it had already "escaped" but unfortunately PSMA PET has limits on its sensitivity. My initial PSA was 32 but I was negative on PSMA PET and in all 14 or whatever lymph nodes they took out with no positive margins. The initial PSA puts me technically in the clinical high-risk category while my pathology was good so my may concern is the longer I wait for SRT the higher the chance it gets outside the field of radiation now that my PSA went from undectable to detectable.
The latest data seems to indicate there is a significant increased risk waiting until 0.25 or above to do SRT. And those getting adjuvant RT at PSA < 0.1 after surgery didn't show any benefit then those that got it at <= 0.2.
I now there are inherent risks and side effects in radiotherapy, but I think where the technology is now keeps those a lot lower than many years ago. My thinking is that if 0.03 is being considered a reliable BCR value based on latest studies, then if maximizing chance of cure regardless of SRT side effects is the primary goal, getting SRT at 0.05 can only have a better (albeit maybe negligble) chance of being curative then at 0.1. In a nutshell, if you have reliable confirmation of BCR, then that's not going to reverse on its own so time is only a friend to the cancer. But again, that's me personally downplaying factoring in the downside of SRT side effects.
What's most interesting about your case is although there are no studies to back up my theory SRT at 0.05 has a higher potential for cure than at 0.1, the fact it appears you had lymph node involvement probably both before and definitely after SRT at a PSA of only 0.11 shows cancer can have gone outside the prostate bed VERY early. Maybe the argument then why the studies don't show a benefit of ultra-early SRT at 0.05 over 0.1 is because even a 0.05 either you have micrometastaic disease outside your prostate bed or you don't so the SRT isn't going to get it even at PSA of 0.05 (except maybe if you did whole pelvic with your SRT.) If that's the case then ya, I'd want to maximize my pre-SRT time as long as possible without being irresponsible.
jazj, Excellent chat - an example of why I am finding this platform useful. Sharing further thoughts based on my experiences and consultations with fine list of international pedigree docs. Given:
RP nadir of 0.05.
11 months later salvage RT to bed, done at 0.11, yields nadir of 0.075.
12 months later salvage EPLND, done at 0.13, confirms cancer at common iliac and one para-aortic, yields nadir of <0.010.
Raises the question, just how far had my cancer spread at the time of my RP? Seems to me and the doc's I dive into this with, clearly my cancer was out of the bed at the time of RP, maybe already to common iliac and perhaps para-aortic? (certainly well ahead of common guidelines).
One can only speculate, but had I had the nanoparticle MRI prior to my RP, it likely would have shown pelvic mets, still leading to my choice for RP but with frozen section biopsy of common iliacs first. That may well have led to the taking of as many pelvic lymph nodes as possible, possibly yielding a nadir of <0.010 with my first treatment; not my third.
My experiences are why I believe 0.2 for CR post RP is wrong, deadly wrong, and why I feel 0.03-0.05 post RP is the PSA value to begin imaging and blood biopsy testing. Even if clear, IMO a man has a better understanding for Earlier treatment decision making.
Further IMO, studies are lacking and lagging behind - which is why I did and still am generally out in front of them and common clinical guidelines, with intent, if it comes to it, to defer ADT/chemo/CR as long as possible.
As I am fond of saying, all the best to all of us facing this beast.
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Low T could hasten time to post-RP biochemical recurrence.
Hi folks, are the Metastatic Hormone Sensitive Prostate Cancer (mHSPC) patients here, which, treatments are at least ADT2, taken Docetaxel?
PTEN loss is not a determinant of time to castration-resistance following androgen-deprivation therapy in prostate cancer
