I am puzzled at the way men seem to have different reactions to prostate cancer. Some people have "more aggressove" and some have less aggressive. Some survive long periods (decades) while others survive just years.
Is there a difference in the actual types prostate cancer? Or is it a difference in their immune systems? Or both?
If it is a difference in the type, how is it different? What is it that makes one more aggressive than the other type?
If it is a difference in the immune system, what is the difference? Racial? Heredity? Diet?
Are there several types? How many? Any clarification will help.
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NecessarilySo
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I think that the answer to your question is YES, indeed all your questions and speculations are players. Something like 10 years ago I recall a speaker at a PC conference stating that there had been 38 specific kinds of Prostate Cancer identified. I don't recall much about what the distinctions and identifications and classifications were and I'm sure that medical science has changed much of that anyway by now. Perhaps it would be better to say "cancers of the prostate". But maybe it is not so important to distinguish them since we seem to have a very limited set of curative tools. OTOH, medical science is evolving rapidly and (hopefully) sooner or later we may discover a tool(s) that will target some of the cancers without all the ancillary destruction.
NecessarilySo....We need to drop this concept of "aggressive vs non aggressive" ...because it is like black and white thinking...in other words..All or None thinking. In real life, this dichotomized thinking does not work,Most life happens in Grey Zone. Prostate Cancer is a spectrum disorder when it comes to degree of aggressiveness and each man falls somewhere on that spectrum.( indolent, mild, moderate, severe and extreme)
Let me give you extreme examples to clarify this spectrum concept:
(1) Mr A has 5+5=10 Gleason Grade, lots of bone and visceral mets, very low PSA along with intraductal and NE cells, physical performance very low.. initial ADT fails within a year or less, Nadir PSA remains above 4.0 and Nadir T remains above 50.
Mr. B has high PSA, GG 3+4=7, Physical performance high, No other type of cells except glandular (acinar) cells in biopsy, initial ADT does not fail for a year or more years, Nadir PSA 0.2 or lower, Nadir T 10 or lower and either no mets or only bone mets.
You can safely say that Mr A's PCa is very aggressive compared to Mr B's PCa which is much less aggressive. Every other man's PCa falls somewhere in between.
The factors which make this aggressiveness depends on several things such as Presence of Germline mutations like BRCA2, family history of PCa or other Cancers, Type of diet such as plant based or mainly animal based, general physical health and other comorbid medical conditions, Gleason Grade, pattern of PSA and ALP rise and fall and so on.
In brief, PCa is one disease BUT it has many shades of Grey. Thats why I keep on saying every man's PCa is unique in itself. And with high quality testing and evaluation, we can almost find out where our PCa stands on that spectrum. That can help with tailored and judicious treatment,,, which I like propagate. No undertreatment and no overtreatment. just the right treatment.
I guess it depends on many factors including how the DNA is disturbed microscopically. Each case is different. But strangely it's all in the prostate, and only there, usually. I mean it's more common there. Maybe it has to do with radiation exposure and/or chemical/pesticide exposure from certain foods and insecticides. Vitamin D. Higher latitudes. Asians have very little, Africans have more. Heredity. So many factors it seems hard to pinpoint anything. Thanks for you input.
Yes, it's very individual. But there are commonalities too. The degree of differentiation (which reflects the underlying genomics) is the prime driver of aggressiveness. Not only does prostate cancer vary across individuals, there is heterogeneity within the same individual. And the genomic profile changes over time, in a process called "genomic breakdown." You can see why cure has been so elusive.
Individual immune systems are as unique as fingerprints, but prostate cancer is immunologically "cold" anyway.
I have no idea what "immunologically cold" means. Can you explain? Does that mean immune systems don't affect it? Not sure I agree. My impression is that immune systems fight it with some affect help such as adt, diet, heat, other things.
It means that, unlike many other cancers, prostate cancer is not very responsive to many kinds of immunotherapy. The only type of immunotherapy that has had some success so far is Provenge. Others are being tested including combinations, BiTEs, CAR-T, antibody-drug-conjugates, peptide vaccines, etc. No one has given up, but, sadly, there have been many failures.
I could be wrong and probably am in some cases. My thinking has been from reading about it is that all cancer "started" due to "something" and then grew as the cancer cells failed to die. For example an exposure to radiation or pesticides. I suppose it could be there at birth, in which case problems would develop at a young age.
Yes, there seems to be a lot of confusion on this....why else would men with 3+3's need to be monitored with PSA and repeated biopsies? This insinuates that the 3's CAN change to 4's, right? For instance, I had a 4+3 Gleason score...does this mean it was always that grade from the start or did it morph into that? It was my understanding that the score was based on the "relative number" of malignant cells to each other, so that in my case, I had more of the worse type than the better type even though they were both considered malignant. I agree that it is not a chronological "age" thing, but maybe it is a progression which changes over time....?
PSA in my opinion indicates the growth of cancer cells, which is or can be doubling or increasing progressively (x times 2)) over time at a rate roughly once every 45 days. As the time passes, without treatment. PSA grows. With treatment, PSA goes down.
PSA grows, but it seems that Gleason doesn't really reflect any of that. I met a man in my surgeon's office had a PSA of 1 (yes, ONE); turns out he had something like a Gleason 10 and very aggressive at that. The surgeon told him that they've found the most aggressive cancers do not produce high PSA - I think the radio personality John Tesh had a similar situation, which showed low PSA but metastases to his spine at his first scan....just too scary for words!!
Just wondering, where do source the idea of a general doubling time of 45 days? I would think this varies greatly, and wouldn't Gleason score perhaps have something to do with it?
I have read that the Gleason 6 has a very long cell doubling-time at 400-500 days so that from mutation to a growth of about one cm takes some 40 years.
Of course, once you are far along in that doubling, the curve gets really steep really fast. (Easy to see when you carry out 2+2, 4+4, 8+8, etc.)
I'm going by online studies and my own PSA. It may be abnormal. I took a four year vacation from adt from 2016 to 2020. But all four rises were similar, doubling approximately every 45 days.
Uncontrolled cell proliferation, leading to an increased proliferation rate, or a failure of cells to arrest their proliferation at the normal time, is a cause of cancer.
PSA chart over lifespan from discovery in 2008 to present.
Thanks. Here is a link to an article referencing the typically long doubling time... have not read the full article, but have read Anthony Horan's book (The Big Scare)that has a chapter on this:goldjournal.net/article/S00...
Yup, agree....so do you think your high scores started out like that and then the tumors simply got larger? Or did they begin as 3's and become more irregular and higher in score as time went on? Haven't gotten a clear answer on this from many different sites - including Hopkins, Mayo, etc...
I posted about this issue a while back. Asking how age affects our overall severity. If I correctly remember a conversation I had with my MO when I was initially diagnosed, he stated that my bulky Gleason 8 tumor was likely growing for a decade or so- I was 52 at the time. So, will a younger "8" see a longer overall survival than an older "8", or do we both get about the same amount of time no matter what we throw at it?
Well, you've certainly had your fill of treatment - that's for sure! But you seem to be doing very well after all that - and still retain a great attitude! So far I've only had RP and hope to keep it that way but my surgeon (Dr Samadi in NYC) said that even with his best efforts a 4+3 could give me problems down the road. Everything was negative pathologically, but all you need is one cell to get away, right? Best of luck in your continued recovery.
Yep. My PSA never has gone above 18.6 and lower than 4.5. Does not respond like my oncologist thinks it should treatment seems to be 2 steps forward 3 steps back. SOC is killing me. Sitting here getting taxol now. Chemo has shrunk abdominal lymp nodes which super surprised the med onc. Tumor board meets on my case this afternoon to see what course to take. I hope some radiation to get rid of the bilateral nephrostomy tubes. If so Belize and snorkeling here I come!
ME TOO! I keep my expectations very low and I'm not disappointed all that much when things go south; in fact, much to my wife's aggravation, I keep telling her that I'm not done with this thing by a long shot. She says that negative thinking will make it happen....I could probably use some Lexapro myself!
I have been a VERY LOW EXPECTATIONS GUY for decades, a die hard pessimist expecting the worse and that way I am always right or pleasantly surprised. SIX YEARS AGO next week will be my diagnosis confirmation r.e. PCa that I knew was bad and guess what >>> hit the jackpot with 5+5. Went with CASTRATION immediately then OUTSIDE THE BOX with cryoablation, an immunotherapy injection and then a prescription for TESTOSTERONE INJECTIONS that allows me to maintain a level of performance though much lower than before but none the less acceptable. Today's 45.54 mile bicycle ride was much slower than BC (Before Castration) but I guess being almost 71 also plays into the equation. Have a 100+ mile bike ride planned for the FULL MOON this SUNDAY. 👍 👍
I saw an OS graph that showed the differences in the types of PCa. Mucinous is the best. Followed by nonvariant, by far the biggest number, then Ductal, Signet Ring, and then a huge drop in OS for Adenosquamous, Sarcomatoid, and worst, Neuroendocrine. But almost all are Nonvariant.
This is not where I saw that, but it is similar. I wish I could post the screenshot I took. auajournals.org/doi/abs/10....
Estimated 10-year overall survival was highest in mucinous (78.0%), followed by nonvariant (71.1%), signet ring cell (56.8%), ductal (56.3%), adenosquamous (20.5%), sarcomatoid (14.6%) and neuroendocrine (9.1%)
May be mixing apples and oranges though. These types are rare. Maybe 3,000 out of a 1,000,000 patients
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