Should chemo be used early on in low volume men

[Farn]

Use of chemotherapy in low volume men may not be the best route early on according to these findings

dailymail.co.uk/health/arti...

[LearnAll]

In every prostate tumor, there are 3 different types of cells, (1) Fully androgen sensitive (2) Partially androgen sensitive and (3) Fully Androgen resistant. But the percentage of these 3 types of cells vary from man to man. One man can have 99% Androgen sensitive, 1/2% Partially resistant and 1/2 % Androgen resistant whereas another man can have 50% Androgen Sensitive 25% Partially Androgen sensitive and 25% Androgen resistant cells.How do we find out what ratio one particular man has? A simple clue is Nadir PSA...meaning how low the PSA dropped in the first year of ADT. If it dropped say, 99.5% from top then, that man has most of his cancer cells as Androgen sensitive.

Coming to Chemotherapy...How does Chemo work...Chemo works by killing ALL cells which are growing...Chemo is an equal opportunity killer for all growing cells...whether Androgen sensitive or Androgen resistant.

Based on this , we can say Chemo will work well and needed early on in man wo have high percentage of Androgen Resistant cells. The man with very high Androgen sensitive cells can always wait till way later for Chemo as ADT can keep his PCa controlled for a long time.

The use of early Chemo should be based on individual subtype and degree of Androgen Resistance.

[Farn in reply to LearnAll]

Thanks for the explanation

[Seasid]

I did early chemotherapy and I believe it was a good choice. For some reason early chemotherapy works best. Honestly i can't remember any side effects from the chemo. My biggest concern is an ongoing ADT. If you can avoid adding anything after early chemotherapy than you can only benefit. (Of course you add if you need). At this moment I still didn't add anything. I am still on ADT only.

[DarkEnergy in reply to Seasid]

Me too, did add (early) Taxotere (Docetaxel) chemo, did have side effects, loss of hair, sore mouth cheeks, all foods tasted like metal objects and fatigue.

The strategy at the time was combinational therapies, Lupron, Zytiga, Taxotere and finally PSMA targeted radiation.

So, initial diagnosis of PSA 1000+ with tumor obstructing bladder flow (very painful) to PSA undetectable.

[MateoBeach]

I do agree with the summary and explanation by LearnAll. However it is not completely clear that early docetaxel has no benefit. And adding it has recently been shown to extend PFS and OS in high volume disease.

So also consider that once one goes on to ADT it powerfully suppresses the growth of the androgen sensitive calls. So even they are suppressed and quiescent, possibly for a long time, they would not be as affected by adding docetaxel chemotherapy, only the androgen (deprivation) resistant cells would be actively dividing and therefore most susceptible to the chemotherapy.

So perhaps up-front chemo cycles might be beneficial to some degree.

It is a difficult choice in asymptomatic low volume disease since chemo indeed sucks, to greater or lesser degrees. Regards, Paul

[MateoBeach in reply to MateoBeach]

practiceupdate.com/content/...

[Tall_Allen]

Unfortunately, bad media reports like that one only add to the confusion. For a long time there was conflicting data coming out of the UK (STAMPEDE) and the US (CHAARTED). A recent meta-analysis of all the data is our best data. It showed:

1. For men who initially had metastases when first treated (called "synchronous"), chemo+ADT prevents progression and increases survival. That was true whether they had high volume or low volume of metastases.

More recently, it's been found that adding both docetaxel and a second generation hormonal agent (called "triplet therapy"), significantly delays progression and increases survival:

prostatecancer.news/2021/05...

2. For men who were recurrent after treatment and later developed metastases (called "metachronous"), chemo +ADT prevents progression and increases survival if they had a high volume of metastases but not if they had a low volume of metastases.

Here's the latest data:

meetings.asco.org/abstracts...

[Scout4answers in reply to Tall_Allen]

T_A

Leaves me scratching my head...

I am currently on Lupron + abiraterone and am just starting on EBRT. Is this considered "triplet therapy"?With low volume and LN involvement only will adding Chemo provide any OS or BCR benefit?

I was under the impression that Chemo does not provide any benefit if one is currently on ADTs

I have been contemplating getting Chemo after radiation is complete and after the effects of ADT leave my system. Thinking that while I am still relatively healthy I would try to eradicate all types of cancer cells.

I am responding very well to ADT + abiraterone so it sounds like I have predominantly Hormone sensitive cancer cells.?? does that negate benefit of Chemo to some extent?

I also took a genetic test at UCLA to find out if I would respond well to high dose radiation, I passed but did not get details . I am assuming that I will also respond well to 20 dose radiation as well.

[Tall_Allen in reply to Scout4answers]

No, that is not what is meant by "triplet therapy." Triplet therapy is ADT+chemo+a second line hormonal. It is only known to benefit patients who are newly diagnosed with distant metastases. That has no relevance to your situation. You are pursuing a curative treatment. Chemo has little or no benefit for you.

[MrG68 in reply to Tall_Allen]

Does the data for these trial actually do a prediction of survival due to regressions? If not what is the actual extension of life in years?

[Tall_Allen in reply to MrG68]

I don't know what you mean by "these trials." All trials provide a Hazard Ratio (HR), 1.0- HR is the percent reduction in mortality. So the HR of 0.675 of the triplet used in ARASENS tells us that adding darolutamide reduced the risk of dying by 37.5% vs docetaxel+ADT.

[Tall_Allen in reply to Tall_Allen]

Trials usually end when half of the control group dies. That means we don't usually know how long the median survival of the treatment group is. I say "usually" because sometimes trials have extended follow-up, and sometimes there are subgroups in which the median is reached in both the treatment and the control/standard-of-care group.

To complicate things, the FDA has recently begun to accept "surrogate endpoints" for some therapies. For example, when Nubeqa was approved for non-metastatic castration-resistant PCa, it was approved based on lowering the incidence of metastases by 59% (HR=0.41). That is because there is a very strong correlation between metastasis-free survival (MFS) and overall survival (OS). In that case, the median MFS for Nubeqa + ADT was 40 months, and the median MFS for placebo+ADT was 18 months. At that point, they unblinded the trial and allowed those getting the placebo to get Nubeqa. They planned to keep following the patients until 240 deaths had occurred, which happened a year later. At that point, neither the original Nubeqa group nor the original placebo group reached median survival, but there was 31% fewer deaths in the original Nubega group (HR=0.69), even with the cross-over of the placebo group.

[MarkBC]

My oncologist recommended docetaxel shortly after diagnosis. One argument was that I would be healthier and stronger at that point than if I waited until years later. My body would be better able to cope with it. I followed her advice and didn't find it too difficult.

It has been 3.5 years since I finished. My PSA dropped from 103.0 to 0.17 and has remained low on ADT. My bone mets are no longer visible on scans. My oncologist said that I had such a good response to docetaxel that "we can put that tool back in toolbox and use it again in the future if the need arises". That may be a good reason to use it earlier.

[Farn in reply to MarkBC]

Thanks for sharing your experience delighted you’ve had such a good response

[GummyToad in reply to MarkBC]

I'm in the same boat as you but my oncologist never recommends me to stop ADT...ever. I wonder why yours is ok with hormone therapy vacations but not mine.

[MarkBC in reply to GummyToad]

My oncologist has the same view as yours. I'll be on ADT for the rest of my life. I think there hasn't been enough science done on ADT vacations. A lot of guys hate the side effects so much that they want a break. I don't like the side effects either but I don't want to give the cancer any opportunity to start growing again.

[Hawk56]

After surgery and SRT failed, given my clinical history - only 18 months to BCR, fast PSADT and PSAV, I set about trying to figure out what to do next. I read the STAMPEDE and the CHAARTED results and talked with my urologist, radiologist, consulted with a medical oncologist. The prevailing thought at that time, at least among my medical team was the next step was another monotherapy (having already done two monotherapies, surgery and SRT), ADT. I was not so convinced. I consulted with the Chief of Urology at a NCCN Center who agreed with my medical team, not me. At this point, there had been no real shared decision making between my medical team and I, I was done with that based on "failing" twice.

I know there are different opinions about Dr. Kwon but what struck with me was his approach, why do monotherapy, each destined to fail with death the eventual outcome, why not combine those therapies and bring them forward in treatment where you may overwhelm it and gain longer PFS and perhaps OS? Keep in mind, I had raised the questions with my medical team about adding short term ADT to the SRT based on emerging clinical studies and extending the radiation treatment field to the PLNs based on data Mayo was showing, they said no, there was no long term data supporting it...I reluctantly listened to them, SRT failed and a subsequent C11 Choline scan found the PLNs involved though the scan fortunately did not show any bone or organ involvement. I elected for the triplet therapy and at one point, we were going to add Zytiga but based on the response to the initial ADT and Docetaxel, did not (not my choice, I wanted to add it).

Here I am, roughly four years later, no additional treatment. I know it's not a "cure," but four years off treatment has been extremely enjoyable.

I do remember reading about the heterogeneity of the PCa cells but did not have the opportunity to determine that by being on ADT for a year and having clinical data about the response. I started AT and chemotherapy simultaneously.

So, not possible to say in my specific case about the mix of PCa cells I had but I believe that triplet therapy with chemotherapy (for those who can do it physically and health wise) as one of the three may make sense given the description of the types of PCa cells.

Kevin

Clinical History

[Hidden]

Farn, I can not answer your query with medical fact, however, I will say that I am an adherent of the research of Robert J. Amato. I was one of nine in his clinical trial in 2004 and which he told me in 2010, "I can not find any cancer in your body. You are cured." If you would review my treatment, readily seen is that I took more that Taxotere - alternated with Adriamycin with Ketoconazole and Estramustine paired and Lupron, plus 50 mg of Prednisone daily for 6 months. All of this was very early.

Background Statement in the Research Project: "Chemotherapy is a setting of hormone refractory prostate cancer has shown palliative benefit especially with substantial PSA decline strongly suggesting that disease modifying potential exists. Recently, chemotherapy is beginning to show a survival advantage. The stage is set for chemotherapy given earlier in a disease course. As a working hypothesis, we suspect that the 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. Thus, 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."

Method Statement: "Each course of chemotherapy lasts for 8 weeks. Patients were treated in weeks 1, 3, and 5 with doxorubicin 20 mg/m2 as a 24-hour intravenous infusion on the first day of every week in combination with ketoconazole 400 mg orally 3 times a day daily for 7 days. In weeks 2, 4, and 6, treatment consisted of docetaxel 100 mg/m2 intravenously on the first day of every week in combination with estramustine 280 mg orally 3 times a day for 7 days. After completion of 3 courses of chemotherapy, hormone management [medical castration plus casodex (at the completion of chemotherapy)] is initiated at the start of chemotherapy and for a total of 24 months. " I stopped Casodex 8 months after completion of chemo and Lupron/Eligard 5 years later.

With this said, my current medical oncologist has told me that she is very conservative and that Dr. A was very risky.... Yet, she is baffled about my results. Especially after starting with Testosterone Cypionate injections in January. She is concerned, but willing to observe. She asked me last week, what would I do if PSA rose from undetectable. I told her that I would follow Dr A's advice, stop the testosterone and re-start Lupron. Its been a great run.... Anyway, its the reason that I have frequent PSA and T testing and physically see her quarterly.

My results after starting T Cyp injections: Lost - 6" in the waist; 10 " in the abdomen; 3 " in the thighs. Gain - back to normal member size.

Farn, I accept the risks of being a guinea pig and was most fortunate to jump on my Stage 4 very early. However, I can not recommend to anyone that they follow my path; even if you could find a world class Researcher and Professor. They just do not fit the conservative mold of todays oncologists...... Beside's there is not enough money available for research. Almost all research dollars are poured into increasing life with palliative treatment and not curative treatment. And that is not a bad thing.

I wish you the best in killing the little bastards,

Gourd Dancer

I'll post new number in the first week of July.

[Farn in reply to Hidden]

Thank you for your response glad to hear your in a good place with your treatment

[MrG68]

If you are considering chemo, I would recommend you look into using fasting as an adjunct therapy to go with it. Apparently it helps with the side effects.

[Mascouche in reply to MrG68]

I have read this also. The recommendation was to start the fast 2 days before chemo and to end it one day after. The idea is that fasting will slow down your normal cells but not your cancer cells. Since chemo attacks fast dividing cells (hence why people sometimes lose their hair and nails under chemo), your normal cells get some protection while the cancer cells get the brunt of the chemo.

[Mascouche in reply to MrG68]

Here is another testimony of someone saying that fasting helped him during chemo. I think it is at around the 9th minute or so of the video: youtube.com/watch?v=YzPrxku...(Not working as expected?)