"In the current study, we showed that PC progression is possible despite minimal serum PSA elevation. Indeed, 22% of our patients developed metastasis in the presence of an undetectable PSA level."
acsjournals.onlinelibrary.w...
Is it reasonable for all high risk patients to have a PET scan and chemo at the beginning of therapy? Breast cancer is routinely treated with chemo early so why not prostate cancer.
Breast cancer and prostate cancer are different. Here is some info about timing and use of docetaxel:
prostatecancer.news/2019/02...
I agree that ALL high risk patients should have a PSMA PET scan to rule out distant metastases. However PSMA PET scans are very PSA-dependent, so it is unlikely to find such metastases even if they are there when PSA is so low.. They are much more likely to be found with a NaF(18) or FDG PET scan. But neither of those two PET scans are approved for high risk patients, so it would entail an out-of-pocket cost.
Allen:
"The STAMPEDE authors point to their larger trial and that their analysis applies more to newly diagnosed men, whereas the CHAARTED groups had more previously treated men. They advocate early use of docetaxel regardless of metastatic burden."
My understanding is that if you are high risk the Partin tables tell you that chances are over 90% that the cancer is outside the prostate. There is no way of knowing where the micro-metastases are even if you get a negative PET scan and some prostate cancer cells are only amenable to chemotherapy, so why wait? The side effects I would assume are temporary.
Both Dr. Kwon and Dr. Vogelzang stated in the latest PCRI video that breast cancer and prostate cancer are essentially the same.
I had initial PSA of 2.222 five years ago without mets on CT and bone scan, PSMA PET wasn’t available in my country back then. So we decided to start ADT and chemo in 12/2017 followed by RP in 04/2018. Yesterday I just finished me RT (CBCT VMAT, 25 fractions) to prostate bed and PLN. In the meantime I did three PSMA PET and except PLN I have no mets elsewhere. So have trust that early treatment with chemo was successful. As far as I know today this is even online with S3, back then it wasn’t.
They are not the same- only a fool would treat the two cancers as if they were. Maybe that's how they dumb it down for the patient audience they were addressing. It's not what they tell their peers.
Please read that article. All evidence points to no benefit of chemo when there are no detectable metastases.
BTW- CHAARTED and STAMPEDE/docetaxel are irrelevant to this discussion- they dealt with patients already diagnosed with metastases.
Allen:
Your article from 2016 (updated 2018) prostatecancer.news/2016/08...
supports what you are saying. However, I was quoting from the authors of the STAMPEDE trial above that said they advocate the early use of docetaxel regardless of metastatic burden. So, my mistake is in assuming that the probability of metastasis without diagnostic evidence on a scan is a "metastatic burden" even though it is very small. Which begs the question why docetaxel would be of benefit to high metastatic burden and not to small metastatic burden. This does not seems to make sense to my unsophisticated mind.
Thanks for explaining. All people in Stampede who were metastatic (M1) at the start benefitted from chemo. None of the men in STAMPEDE who were non-metastatic (M0) at the start had any benefit from chemo.
The men in STAMPEDE who had a low burden of metastases saw a benefit, but it failed to reach statistical significance in that time frame. They believe a longer time frame and a bigger sample size (called "power") is necessary to show a statistically significant benefit.
The men in the CHAARTED trial who had a low burden of metastases saw no benefit from chemo. But CHAARTED was run for an even shorter amount of time and had even lower power to detect that effect. There was a third RCT called GETUG-15 that showed no benetit for either high or low burden of metastases.
This has led to much confusion. NCCN and ASCO advocate docetaxel for men with only high burden of metastases. AUA/ASTRO/SUO, the Canadian, British and European oncological associations advocate docetaxel for men with any metastases. Adding to the confusion are more sensitive PET scans that can detect more metastases sooner.
Docetaxel only kills rapidly dividing cells (healthy or cancerous). If cells are in a state where they are not rapidly dividing, it is useless and highly toxic. This is why it may not be useful in some circumstances. There is some interesting genomic work being done to help figure out when cells are susceptible.
Allen:
Thank you for explaining this. I am certain that many people will benefit from this information. Perhaps the answer lies in the fact that prostate cancer is heterogeneous and one size does not fit all. But one size may fit some. Then we get into the numbers needed to treat. Some of the people who don't get docetaxel early are going to die and some of those who do will not because of it.
The toxicity is too high to give without some indication of success.
If you cannot see the cancer on a scan so that it can be removed by surgery or hit locally by radiotherapy but it is growing fast, as indicated by a short PSA doubling time, why not use chemo? Providing the individual is healthy enough to take the chemo of course.
Would chemo be any less toxic than radiotherapy to the whole pelvis?
Has this scenario been subject to a clinical trial?
Good thoughts. Short PSADT should indicate more likely benefit from chemo, one would think.
All of what follows is solely my understanding, which could very well be breathtakingly misguided. I don’t want to hijack this thread, so apologies if this is a bit off-topic; but I would like to paraphrase what my MO tells me, and see what folks on this forum think of it:
Short PSADT does not necessarily indicate a cancer that is growing quickly; it could represent the activity level of established mets…i.e. for whatever biochemical reason, they are producing more PSA in a short time frame. However, if this is the case, it means these mets are more likely to metastasize and thus the cancer is more likely to “grow”. So when DT gets low enough, someone on an off-cycle is motivated to get back on treatment.
However, a short PSADT could of course represent new PSA coming from additional mets due to cell division, i.e. “growth”….if that’s what we mean by “growing”. I suppose we could also mean the existing mets grow in size, vs in number. Here I assume a 1.5cm met would produce more PSA in a given time frame than that same met when it was 6mm.
Bottom line, PSADT is only about how much does PSA increase over a given time frame. It is a “clue” and likely a “warning flag” but not a direct indication of “growth”.
As always, I could have this wrong. I welcome informed corrections to this.
Let's clarify what we are talking about. If a man is only N1 but M0 - cancer only in pelvic lymph nodes but no other metastases, STAMPEDE showed no benefit to docetaxel, but there was a benefit to abiraterone and whole pelvic radiation.
If a man has any distant metastases (M1), STAMPEDE proved there was a benefit to docetaxel.
That's what they did to a guy I met at radiation therapy. They had him on ADT and abiraterone but no docetaxel. He had a couple of nodes but no metastases outside the pelvis.
I have looked at the STAMPEDE reports. There seems to be no analysis of PSADT against the effectiveness of Docetaxel for either M0 or M1. The comparisons seem to be mainly SOC versus SOC + DOC and I guess a short doubling time would not be expected once you start using SOC. I think an interesting analysis would be DOC only against PSADT.
How many different types of PET scans now exist for PCa? I get quite confused on that point.
The insurance companies dictate our health again.
They practice medicine without a license.
In fact, several cutting edge trials for high risk prostate cancer are doing something similar. Since, as you say, if you have a high risk Gleason score it is likely out of the barn, the trials are 6 months of “intensive adt” (not chemo but similar idea) to deal with the escapees followed by surgery to deal with the mother load. I had Gleason 9 about 3 years ago. I participated in such a trial (at NIH). Did the intensive adt (adt+enzelutimide+abiraterone) and then surgery. When they dissected my removed prostate, no cancer found! Now, almost 2 years later, psa still undetectable. It’s not yet SOC but I suspect it will be when the trials are concluded.
Congratulations. You found the right path for you. 👍👍🙏
When I was treated with IMRT ADT and Brachy, I was given the statistics about likelihood of metastasis due to Gleason 9 5/4 I sort of missed it but not sure if there were any alternatives 8 or so years ago. Sure would have liked it to have the mets killed then instead of dealing with stage 4 now.
Even now no one is interested in anything other than ADT until the cancer becomes castration resistant. This makes little sense to me and I hope others think so too.
So I’m semi confused. What is the min PSA lab required to qualify fo 68Ga-PSMA-11 PET??And two I was told Feb MO visit I would PSMA qualify if i developed significant clinical body symptoms. Ok
Which is it?
My view is that any man with APC and a PSA above 0.2 should try to get at least a baseline PSMA PET scan. The information will be useful even if negative. Does not depend on symptoms so don’t wait for that.
I am a ‘non metastatic (sort of) early chemo guy’.
I had RP in 2019 at Johns Hopkins. Post op pathology revealed seminal vesicle invasion and a positive pelvic node out of 15. Gleason 4+3, negative margins.
My surgeon said at that time in my case he expected the first post op PSA to be undetectable (it was), and would tend to advise no further treatment until any recurrence.
However, he then added that he was also referring me to a MO to discuss adjuvant therapy. One who would probably, in his words, ‘take a much more aggressive approach’.
He was right about that. The MO said as an oligometastatic I was virtually certain to die within 10 years if I did nothing more. With radiation and ADT I could expect either no evidence of pca at the same 10 year mark or that I would alive but fighting it with drugs. 50/50.
He then offered a clinical trial which added chemo and abiraterone to the upfront ADT followed by radiation. He said this would improve my odds of complete remission in 10 years by more than the aforementioned 50%, but couldn’t say how much more.
I asked if he was confident it was worth it and said absolutely.
This is of course now 2 1/2 years ago. As we see, we are barely can’t closer to knowing if early chemo adds to the efficacy of treatment in cases such as mine or not. And there obviously a lot of men in the boat I was in (and am now) that would like to know.
Being a physiologically young 64 year old athlete
with no other health issues made the decision to do the trial easier; my team was confident I could withstand this ‘kitchen sink’ well and that side effects would not be an issue if I maintained my lifestyle. Fortunately that was correct.
The treatment portion of the trial ended in September 2020 after the last 3 month Lupron shot. 18 months since full return of testosterone my PSA remains undetectable, as it has been throughout.
And yet, after all this, I may still never know if the early chemo made any difference, regardless of the outcome. In fact, I won’t ever really know for sure if any of the additional treatment did, although it’s obviously likely.
If I had to do it over again I would never have gotten the RP in the first place. ED has been a constant issue despite purported sparing of the nerves, and relentless incontinence resulted in a artificial urinary sphincter for me.
And yet I have absolutely zero complaints. I am grateful that the arc of medicine is becoming ever shorter nowadays. Only 30-40 years ago things would have been very different for so many guys. The advances are coming faster than ever, and this should be a great source of hope to all of us.
Shit.... now I have to go out and buy a pet......
Good Luck, Good Health and Good Humor.
j-o-h-n Friday 04/01/2022 7:37 PM DST
My impression is we are now at a point where if no pet scan is available when you are presented with a diagnosis of prostate cancer you need to be sent, or on your own go, elsewhere for treatment. There are 4 PET/CT targeting prostate cancer at this time is my understanding: Axumin, Choline C-11, Pylarify, and Ga 68 PSMA 11. FDG has at best a 20% detection rate based on my review of the literature and discussion with my 2 RO's and my MO as well as two academic second opinion MO's who all felt it was extremely low yield in prostate cancer. FDG may have more of role in the presence of progression to neuroendocrine prostate cancer. Also if somatostatic receptors are present in neuroendocrine prostate cancer 68 Ga Dotate PET/CT may have role but doubt you could ever get that in the US.
In my opinion getting a proper scan at the outset is so important that we should pay for it if we have to. But, if we do and it is positive then the insurance company should pay for it. If you can afford it and don't, you have to live literally, with the consequences. We already know that in a significant number of cases (is it 40% ?) that clinical decisions are modified because of it.
ADTMan, I have written on this many times. I was most fortunate to be included in a six month chemotherapy and hormone therapy trial. My primary treatment started in April 2003 and within a year, I had metastatic lesions. During this short period, I had eight PSA tests and four nuclear bone abandon soft tissue CT Scans. In other words, I was closely monitored. I immediately enrolled into the clinical trial.
“Trial of chemotherapy plus hormonal therapy as initial treatment for unresectable or metastatic adenocarcinoma of the prostate
Robert Amato and Haby Henary
DOI: Published May 2005
Proc Amer Assoc Cancer Res, Volume 46, 2005
Abstract
5748
Background: The delivery of chemotherapy in a setting of hormone refractory prostate cancer has shown palliative benefit, with substantial PSA decline, strongly suggesting that disease modifying potential exists. Recently, chemotherapy is being reported to show a survival advantage. The stage is set for chemotherapy to be given earlier in men’s with prostate cancer. As a working hypothesis, transformation from an androgen-dependent to an androgen-independent phenotype is mediated by the expansion of an androgen-independent clone already present at the time of androgen deprivation. If this model is correct, then it would be desirable to bring treatment to bear on the androgen-independent component when the corresponding tumor burden is minimal. We view the androgen-independent component as analogous to “microscopic residual” or micro-metastatic disease for which adjuvant chemotherapy has shown to be effective in other contexts. ...”
I was one of nine with a complete response. I believe the reason was that I started chemotherapy when my body was strong and the tumor burden minimal. Through 2016, I had a total of 25 nuclear bone scans paired with CT scans. To date, I have had 101 PSA tests always paired with Testosterone tests. Ninety-seven PSA tests were standard tests. My last four tests were ultra sensitive PSA tests. The only reason is that after twelve years without Hormone Therapy and no evidence of disease, I began in inject 0.4 ml of Testosterone Cypionate twice a week. This was on the heels of using Androgel for eleven years.
A comment on Breast Cancer. First, my MO who spent a career in PCa Research and Professor at several major medical schools, told me that Prostate Cancer and Breast Cancer are closely related; more than most realize.” Second, my 1st Cousin was DX’d with metastatic breast cancer, her treatment was exactly what I received in 2004. In fairness, Dr Amato did the research at the medical school where she was treated.
Soap Box Time...... did you know that dollars raised for Breast Cancer Research totals $6 Billion every year; while dollars raised for Prostate Cancer Research totals, $2 Million. Apparently people are relying on government dollars and NCI Budget for research. In 2019, the numbers were $545.4 Billion for Breast Cancer and $244.8 Billion for Prostate Cancer.
One day.....
Gourd Dancer
Gourd:
Thank you for your response which is consistent with my thoughts: "As a working hypothesis, transformation from an androgen-dependent to an androgen-independent phenotype is mediated by the expansion of an androgen-independent clone already present at the time of androgen deprivation. If this model is correct, then it would be desirable to bring treatment to bear on the androgen-independent component when the corresponding tumor burden is minimal."
Its really not a transformation but an expansion of the androgen-independent phenotype which only chemotherapy can address. If people are worried about side-effects, then perhaps they could use a milder drug or limit the number of treatments.
Another issue I have is that the studies which have been cited do not give enough information about the patients. There must be a difference in the patient population that is not considered when determining the efficacy of early use of chemotherapy. Just using PSA, Gleason score, etc. is not enough. More research on the basic biology of the androgen-independent phenotype must be done. Yet, everyone seems to most concerned about which treatment is better or worse than another, yet they are all inadequate when addressing what kills people.
Never worried about side effects as they are easily managed. Keeping the eye on the ball, metastatic prostate cancer is a terrible disease with a poor prognosis. I took heart with every infusion and injection, I was killing the little bastards.....
ADTMan, published in 2013:
“A phase II trial of androgen deprivation therapy (ADT) plus chemotherapy as initial treatment for local failures or advanced prostate cancer
Robert Amato, Mika Stepankiw, Patricia Gonzales
Published in Cancer Chemotherapy and… 2013
Medicine
Purpose: Long-term hormonal ablation in prostate cancer is associated with decreased overall health and quality of life. Few reports emphasized the role of chemotherapy in the management of early stage prostate cancer. This study analyzed the safety and efficacy of androgen deprivation therapy (ADT) plus chemotherapy as initial treatment for patients identified as local failures or not eligible for prostatectomy or radiation therapy due to advanced disease presentation.
Methods: Enrolled patients received ADT in the form of leuprolide every 12 weeks for 24 months with bicalutamide initiating after the completion of chemotherapy. Chemotherapy consisted of ketoconazole and doxorubicin for weeks 1, 3, and 5 and estramustine and docetaxel and for weeks 2, 4 and 6. During weeks 7 and 8, no treatment was received.
Results: Forty-six patients were enrolled, and forty-five patients were evaluable. Median progression-free survival (PFS) was 23.4 months. Median overall survival (OS) was 53.7 months. Out of 45 patients with measurable disease,c 22 patients had an objective response: 9 patients achieved a complete response; 2 patients achieved a partial response; 10 patients achieved stable disease. Frequent grade 3 adverse events included elevated ALT (17 %), hypokalemia (13 %), and hypophosphatemia (13 %). Grade 4 adverse events were rare and included low bicarbonate (2 %), hypokalemia (2 %), leukocytopenia (2 %), and neutropenia (2 %).
Conclusions: The treatment demonstrated clinical benefit in all patient subsets with minimal reversible treatment-related adverse events. Subgroup analysis suggests that having prior local therapy resulted in greater PFS and OS. LESS”
Gourd Dancer
18F-DCFPyL PSMA PET/CT Scan Result
PSMA PET scan results 
bone scan following chemo
do we need scans after chemo completed
Accuracy of PSMA PET scan?
