Does Prostate Cancer turn agressive at some point in time

One Doctor's Opinion
I asked my doctor this very question when I was diagnosed 12 years ago. H e said that if it was aggressive, it was so from the start.

caseyh said:

One Doctor's Opinion
I asked my doctor this very question when I was diagnosed 12 years ago. H e said that if it was aggressive, it was so from the start.

Progressive status
David

I think that your question refers to a progressive status of the cancerous cells not to the status of the disease. While there are many theories on both matters, doctors have different opinions and there is no prove to the contrary. As they say; "it is difficult to separate the wheat from the chaff".

One thing they all agree is that Cancer begins from a deformation of the prostate stem cells. Some scientists believe that prostate cancer is derived from a luminal cell progenitor that has acquired self-renewal activity through mutation. This equals to the progressive theory.

In folks language it is to say that from PIN it develops into well then poorly differentiated (Gleason grades from 1 to 5). However this action takes time to be accomplished and one may find equal types of cells (same Gr) being constantly produced (doubling) and causing a tumor formed with the same DNA characteristics.
In other words, if at initiation the Pca is formed by say only two types, these will progress without altering their aggressivity. Late metastases (after a treatment) have been found to be of the same grade.

In any case, there have been proved that cells may alter their grade after treatments that affect or damage their DNA (such as radiation and chemo). Hormonal treatment cases with 5-ARI (Avodart, etc.) become controversial after comments that doctors found a more aggressive grade of cancer after years on the drugs.
My take on the matter is that 5-ARI drugs “clean” the serum from low grade cells (killing them) and such leave behind the aggressive ones (that usually are not hormonal dependent) which will increase the initial findings (Gleason scale from 3+3 to 4+3 or 4+5). This is also seen as a progression of the disease.
Equally, in treatments one will try to catch the “bandit” with radicals and at each failure we have accomplished a “clean up” of many cancerous cells that could be composed of the higher aggressive ones. Such would lead to a continuous grade supporting the theory that “cancer does not turn aggressive at some point in time”.

In this detailed article researches say this;

“……..Interestingly, several aspects of this disease are remarkably similar to CML. CML is most frequently diagnosed in adults and the elderly and first presents as a chronic myelogenous hyperplasia that eventually progresses to acute immature blast crisis following the accumulation of genetic and epigenetic alterations in addition to BCR-ABL. Prostate cancer is similarly a disease of aging that is thought to begin with the chronic accumulation of prostatic intraepithelial neoplasia (PIN) lesions that may eventually develop into adenocarcinoma, although no experimental evidence for this has yet been provided. Many adenocarcinomas also progress to a poorly differentiated, hormone-refractory prostate cancer (HRPC) consisting mostly of immature blast-like cells. Arul Chinnaiyan and colleagues have recently identified a class of translocations that, like BCR-ABL, are present in the majority of prostate cancers (16). These translocations result in fusion of the androgen-regulated promoter for TMPRSS2 with the coding regions of ETS family TFs that are associated with Ewing sarcoma and several types of human leukemia (17, 18). In light of these findings, a major goal of our laboratory is application of the fundamental concepts learned about stem cells in CML to elucidate prostate cancer etiology. This Review will focus on current concepts of stem cells in prostate cancer initiation and progression as well as the implication of these concepts in prostate cancer research and therapeutic development. We hope that understanding the cellular basis of prostate cancer will yield insight critical for the development of more efficacious therapeutics to fight the disease.”

Here is the full text;
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934594/

I believe that the Gleason of tumours at diagnosis will kept it status along our journey. You should care in having due pathological analysis at the beginning to make it sure that the highest grade is found and not left occult in the tissues.

I admire your confidence in AS. The twelve years living with the bandit is worring you but the results of your last tests does not support the theory of "progressive aggressivity of cells". The disease may be expected to progress because cancer do not "die" but multiply. Your type though is sort of indolent.
The grade 4 is the baddy but you could get a DNA profile to verify if such cells are prone to become androgen independent. That could cause trouble in future metastases.

Regards.
VGama

My experience
I'll share my experience with you.

I had an elevated PSA & subsequent biopsy in July 2011 that came back with no signs of cancer in any of the 12 cores taken. Had another PSA in May 2012 that was 8.1 and a digital exam that showed enlargement and nothing he could feel so he put on 3 weeks of antibiotics in case it may have been due to prostatitis. Went back in June after the antiobiotics & had another PSA with a result of 9.2
Had biopsy in July that came back with positive cores on right side of prostate a Gleason score of 9. My local urologist said I had a very "angry" and aggressive cancer to go from no signs to a Gleason 9 in a year.

Exactly one month to the day of my diagnosis we were at my first appointment aft MD Anderson. They drew labs for another PSA and it was now 12. Had an endorectal MRI on day 4 that showed cancer in the right as expected and in the left side as well. I started my treatment on day 5.

So in my experience prostate cancer can be quite aggressive.

VascodaGama said:

Thirteen years on the run
David

I was diagnosed at the age of 50 in 2000. I am now 63 and probably of the same age as you. My cancer was diagnosed as being a well differentiated type (Gleason 2+3) which tends to be indolent. However, my wife and I decided to get rid of it the soonest because of the high PSA of 22.4 ng/ml.

The difference in our cases after 12 years is that you did "nothing" and I did it all (RP+RT+HT). Interestingly we both did not manage to get "free" from the bandit, but I have been affected by the side effects from treatments whether you have not.

You probably have realized on the advancements done in medicines to combat PCa since 1999. Newer drugs have come out and others are on the drawing board (trials), particularly in the field of genetic "engineering". Improvements in image studies and treatments have also had a big step forward and they are now friendlier of the patient.

Consideration on Quality over Quantity may help you guys in confronting a decision.

Wishing you continuous "normal" way of living.

VGama

Not a one size fits all disease.
VG
Your PCa history points out how complex and individualized this disease can be. With a Gleason 2+3, by current thinking, you should have walked away from PCa after your surgery. The fact that micro metastasis had already taken place suggests to me that regardless of the Gleason score, your cancer was anything but indolent. That raises the question, “Where would you be today had you not taken a very aggressive approach to the disease?” I suspect that the the odds are pretty good that you would not be here. In hindsight, AS was probably not an option. Your already high PSA most likely would have continued to rise and within a short time required aggressive treatment. Who knows how much your cancer would have progressed while on AS? There is a lesson here for all of us. Seek the BEST medical care that you can afford. This is definitely not a one size fits all disease.

VascodaGama said:

Progressive status
David

I think that your question refers to a progressive status of the cancerous cells not to the status of the disease. While there are many theories on both matters, doctors have different opinions and there is no prove to the contrary. As they say; "it is difficult to separate the wheat from the chaff".

One thing they all agree is that Cancer begins from a deformation of the prostate stem cells. Some scientists believe that prostate cancer is derived from a luminal cell progenitor that has acquired self-renewal activity through mutation. This equals to the progressive theory.

In folks language it is to say that from PIN it develops into well then poorly differentiated (Gleason grades from 1 to 5). However this action takes time to be accomplished and one may find equal types of cells (same Gr) being constantly produced (doubling) and causing a tumor formed with the same DNA characteristics.
In other words, if at initiation the Pca is formed by say only two types, these will progress without altering their aggressivity. Late metastases (after a treatment) have been found to be of the same grade.

In any case, there have been proved that cells may alter their grade after treatments that affect or damage their DNA (such as radiation and chemo). Hormonal treatment cases with 5-ARI (Avodart, etc.) become controversial after comments that doctors found a more aggressive grade of cancer after years on the drugs.
My take on the matter is that 5-ARI drugs “clean” the serum from low grade cells (killing them) and such leave behind the aggressive ones (that usually are not hormonal dependent) which will increase the initial findings (Gleason scale from 3+3 to 4+3 or 4+5). This is also seen as a progression of the disease.
Equally, in treatments one will try to catch the “bandit” with radicals and at each failure we have accomplished a “clean up” of many cancerous cells that could be composed of the higher aggressive ones. Such would lead to a continuous grade supporting the theory that “cancer does not turn aggressive at some point in time”.

In this detailed article researches say this;

“……..Interestingly, several aspects of this disease are remarkably similar to CML. CML is most frequently diagnosed in adults and the elderly and first presents as a chronic myelogenous hyperplasia that eventually progresses to acute immature blast crisis following the accumulation of genetic and epigenetic alterations in addition to BCR-ABL. Prostate cancer is similarly a disease of aging that is thought to begin with the chronic accumulation of prostatic intraepithelial neoplasia (PIN) lesions that may eventually develop into adenocarcinoma, although no experimental evidence for this has yet been provided. Many adenocarcinomas also progress to a poorly differentiated, hormone-refractory prostate cancer (HRPC) consisting mostly of immature blast-like cells. Arul Chinnaiyan and colleagues have recently identified a class of translocations that, like BCR-ABL, are present in the majority of prostate cancers (16). These translocations result in fusion of the androgen-regulated promoter for TMPRSS2 with the coding regions of ETS family TFs that are associated with Ewing sarcoma and several types of human leukemia (17, 18). In light of these findings, a major goal of our laboratory is application of the fundamental concepts learned about stem cells in CML to elucidate prostate cancer etiology. This Review will focus on current concepts of stem cells in prostate cancer initiation and progression as well as the implication of these concepts in prostate cancer research and therapeutic development. We hope that understanding the cellular basis of prostate cancer will yield insight critical for the development of more efficacious therapeutics to fight the disease.”

Here is the full text;
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934594/

I believe that the Gleason of tumours at diagnosis will kept it status along our journey. You should care in having due pathological analysis at the beginning to make it sure that the highest grade is found and not left occult in the tissues.

I admire your confidence in AS. The twelve years living with the bandit is worring you but the results of your last tests does not support the theory of "progressive aggressivity of cells". The disease may be expected to progress because cancer do not "die" but multiply. Your type though is sort of indolent.
The grade 4 is the baddy but you could get a DNA profile to verify if such cells are prone to become androgen independent. That could cause trouble in future metastases.

Regards.
VGama

Similar historiries at 12+
VG
Your disease history is very much like mine with the exception of my 4+3. My disease is also nowhere to be seen although my PSA is almost the same as it was in January. I am also a former MSK patient. Dr. Michael Morris treated me immediately after my recurrence.