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    Old 12-26-2019, 07:23 AM   #1
    Insanus
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    Why do some survive

    Why do some men with Gleason 8+ Stage 4 prostate cancer live 20 years and others live 3?

     
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    Old 12-26-2019, 07:59 AM   #2
    JohnR41
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    Re: Why do some survive

    Most likely, Gleason 8+, Stage 4, spontaneous remissions are so rare that they are difficult to study. I'm not sure how rare they are, perhaps one in 10,000, 1 in 100,000, or 1 in a million? So when you find that one rare person, what do you do? Ask him what he did that was different?

    Maybe there was a drastic change in mental outlook. Maybe the person visualized the cancer going away. Maybe he made a drastic change in his diet and exercise routine. But there's no guarantee it will work again with another person.

    I just remembered that Doctor Dean Ornish has written about elderly men who brought their numbers down by practicing a healthier diet, exercise and stress control. But I don't recall what stage they were in or if it was the aggressive type of cancer. Most likely it was the slow growing type of cancer.

     
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    Old 12-26-2019, 08:07 AM   #3
    Southsider170
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    Re: Why do some survive

    That's the billion dollar question. The short answer is that everyone's disease is different, even when they appear the same at diagnosis.

    Researchers are analyzing the genetics of the cancer cells to try and get an in depth answer to your question which is how to distinguish between different people's disease as well as how to prescribe the exact correct treatment for the exact particular disease that the people have.

     
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    Old 12-26-2019, 09:52 AM   #4
    IADT3since2000
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    Re: Why do some survive

    Hi Insanus and welcome to the Board!

    There has been a lot of progress in understanding and dealing with this kind of cancer, especially over the past decade. Great advances have been made in imaging, in genetic assessment and understanding of genetic impacts on prostate cancer, and in drug development and wise use, for instance, and the pace of useful research continues at a rapid clip.

    One continuing problem area with only a little progress is a kind of very aggressive prostate cancer that does not depend much or at all on androgens (such as testosterone and dihydrotestosterone) for fuel; therefore, the usual tactic that works very well for the vast majority of us - drastically reducing these fuels with androgen deprivation therapy - does not work well if at all. This dangerous kind has subtypes known as "small cell prostate cancer" and "endometrial" (named after resembling female anatomy) prostate cancer. Prognosis is still poor, but there has been some, and, as always, there could be an unexpected breakthrough.

    Certain other genetic factors are also behind shortened survival. While it is now known what some of the problems are, there are solutions for only a portion at this time. But again, a tremendous amount of research is ongoing.

    Personally, I am convinced that diet, nutrition and other lifestyle influences play an important role. I am convinced that the typical Western diet greases the skids for poor survival while, in contrast, a largely plant-based diet, such as the Mediterranean diet, is quite beneficial. It appears that being substantially overweight is dangerous. It appears, on the good side, that being on a statin drug, especially for three years, with five years even better, aids survival. There is promising but not conclusive evidence that the drug metformin - the old diabetes drug - helps substantially against prostate and other cancers. I believe there is substantial evidence that good case assessment and treatment makes a big difference for patients with advanced cancer. As just one example, Dr. Eugene Kwon, MD, director of the prostate cancer clinic at the Mayo Clinic in Rochester, Minnesota, has pioneered the combination of advanced imaging and advanced treatments for patients with challenging cases, achieving some remarkable results.

    There are also some factors that are in the early stages of understanding. For instance, patients who identify as African American do far better on the immune system drug Provenge, despite the fact that African Americans generally have inferior survival for prostate cancer. That suggests to me, as a layman, that African Americans have some adverse genetic factor that involves the immune system and needs to be countered.

    I also believe that attitude makes a difference, and perhaps faith. Some patients go into a "death spiral of despair," as now retired prostate cancer medical oncologist Dr. Charles "Snuffy" Myers, MD, used to put it. We need to find a way to be optimistic and do what we can to fight the disease.

    I hope this helps.

    Good luck!

    Jim

     
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    Old 12-26-2019, 09:56 AM   #5
    DjinTonic
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    Re: Why do some survive

    Some men progress to what is known as the oligometastatic stage (generally defined as 1 to 5 metastases). This can be remaining or recurrent PCa in the prostate bed and, for example, a local and distant lymph node. My uro/surgeon told of a couple of patients he has who, in this stage, respond remarkably well to ADT, and have had stable disease for many years.

    As we now know, the propensity to metastasize ranges from low to high and cuts across all Gleason scores, from G6 to G10. Given, say, a G8 that can metastasize, but with difficulty and/or slowly, and a PCa genetic profile that responds well to treatment, esp. ADT, you have a very different scenario from other mPCA.

    Djin
    __________________
    69 yr at Dx, BPH x 20 yr, 9 (!) neg. Bx, PCA3-
    7-05-13 TURP for BPH (90→30 g) path neg. for PCa, then 6-mo. checks
    6-06-17 Nodule on R + PSA rise on finasteride: 3.6→4.3
    6-28-17 Bx #10: 2/14 cores: G10 (5+5) 50% RB, G9 (4+5) 3% RLM
    Nodule negative for PCa. Bone scan, CTs, X-rays: neg.
    8-7-17 Open RP, neg. frozen sections, Duke Regional Hosp.
    SM EPE BNI LVI SVI LNI(5L, 11R): negative, PNI+, nerves spared
    pT2c pN0 pMX, G9 (4+5) 5% of prostate (4.5x5x4 cm, 64 g)
    Dry; ED OK with sildenafil
    11-10-17 Decipher 0.37 Low Risk; 5-yr met risk 2.4%, 10-yr PCa mortality 3.3%
    LabCorp uPSA: 0.010 (3 mo.)…0.015 (1 yr. 6 mo.)…0.015 (2 yr. 4 mo.)

     
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    Old 12-27-2019, 06:36 AM   #6
    IADT3since2000
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    Re: Why do some survive

    Hi again,

    You might be interested in the series of annual reports on progress against all kinds of cancer that is published by the American Association for Cancer Research, the premier organization for cancer researchers from all over the world. It's reports are available free online at www.cancerprogressreport.org ; the electronic version is highly searchable. The 2015 report, the fifth in the series, is a little different because it took a look at progress over the previous five years combined. The latest report is for 2019.

    I've been at this now for 20 years, and back when I was diagnosed the pace of progress against cancer was slow. Some even wondered if the enormous investment was worth it. However, the pace began to pick up, and now substantial progress is being made against many cancers, with especially rapid progress for prostate cancer. (That said, as most of us know, a diagnosis of prostate cancer is far from being like a cake walk and around 30,000 of us in the US will die of the disease each year. ) There are a number of reasons why more progress is being made, but two that are at the forefront are understanding of the human genome and enormous advances in computing power.

    But it takes time for research at leading centers to reach the doctors that many of us will see, and some doctors are not as good as others at incorporating advances into their practice, even when encouraged by their associations and other guideline groups. I believe that finding a really good doctor/medical team makes a big difference in survival for those of us with challenging cases.

    Jim

    --------------------------------------
    Diagnosis Dec 1999 PSA 113.6 (first ever), age 56
    Gleason 4+3=7 (J. Epstein, JHU), all cores +, most 100%; "rock hard" prostate with ECE - stage 3, PNI, PSADT determined later 3-4 months; prognosis 5 years.
    ADT Lupron as first therapy, then + Casodex in March 2000, then + Proscar and Fosamax in Sep 2000. Rejected for surgery January 2000; offered radiation but told success odds were low; switched to ADT only vice radiation in May 2000; PSA gradual decline to <0.01 May 2002. Commenced intermittent ADT3 (IADT3) with first vacation from Lupron & Casodex.
    With improved technology, tried TomoTherapy RT, 39 sessions, in early 2013, plus ADT 3 in support for 18 months (fourth round of IADT3), ended April 2014. Continuing with Avodart as anti-recurrence shield. Current PSA remarkably low at <0.01; apparently cured.. Supportive diet/nutrition, exercise, supportive medications during this journey, as well as switches in antiandrogen, 5-ARI, and bone drugs.

     
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    Old 12-31-2019, 03:57 AM   #7
    SubDenis
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    Re: Why do some survive

    Quote:
    Originally Posted by DjinTonic View Post
    Some men progress to what is known as the oligometastatic stage (generally defined as 1 to 5 metastases). This can be remaining or recurrent PCa in the prostate bed and, for example, a local and distant lymph node. My uro/surgeon told of a couple of patients he has who, in this stage, respond remarkably well to ADT, and have had stable disease for many years.

    As we now know, the propensity to metastasize ranges from low to high and cuts across all Gleason scores, from G6 to G10. Given, say, a G8 that can metastasize, but with difficulty and/or slowly, and a PCa genetic profile that responds well to treatment, esp. ADT, you have a very different scenario from other mPCA.

    Djin
    G6 metastasis? I have not heard that before, can you point me to a study discussing that? Denis

     
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    Old 01-05-2020, 04:18 PM   #8
    Steve135
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    Re: Why do some survive

    Insanus, really a tough question? Been hunting these forums going on 4 1/2 years and see each react differently then the next with very simlar conditions. I did learn early on that whats good for one isn't always good for you! I do my reading to be ahead of the doctors so I can ask question the day they say whats next so I don't have to research till next appt.
    steve d

    ________
    Diag. 56 DOB 2/59 PSA 01/14 2.0 6/15 2.4
    Biopsy 6/15 5 Gleason Score 8
    RP 10/15 Path 54g 5x4.2x2.8cm 4+3=7 Tumor location quadrants Bilateral
    Extra-capsular extensions present,SV no invasion
    Vascular invasion none, PNI ,Multicentricity multifocal
    Margins NP lN's 5 neg pT3a,N0
    PSA 10/16 0.1 1yr 02/7/17 0.4 02/15/17 0.5
    Pet Scan 2/17 Neg PSA 03/17 0.6 Axumin trial 17.4mm BCR rt. SVB Casodex + Trelstar
    04/17 SRT (42)
    08/17 PSA 0.1 Last 6 uPSA 0.006 uPSA 2/19 0.030 2nd BCR 5/19 0.235 5/19 03.2 6/19 0.34 7/19 0.06 8/19 0.08 9/19 0.056
    10/190 0.08 11/19 0.07 12/19 0.07
    7/19 Trelstar, Xtandi, Zoledronic Acid
    12/19 (3) SBRT Iliac bone liasion

     
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    Old 01-06-2020, 06:29 AM   #9
    IADT3since2000
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    Re: Why do some survive

    Whether Gleason Score 6 Prostate Cancer Metastasizes

    The discussion of who survives triggered this question:

    Quote:
    G6 metastasis? I have not heard that before, can you point me to a study discussing that? Denis
    My impression is that medical consensus is that the potential of true Gleason 6 cancer to metastasize is at least very low, if not virtually non-existent. That said, fairly often the biopsy will state that the score is Gleason 6, but a higher grade of cancer is found in the biopsy from the removed specimen, and sometimes pathologists get it wrong, especially if they do not have a lot of expertise with prostate cancer biopsy specimens.

    One leader in active surveillance for more than two decades now, Dr. Laurence Klotz of the U. of Toronto, Sunnybrook, has watched this carefully in his very long, very large series of patients on active surveillance, about which he publishes many research papers. He is therefore in a position to know this territory very well. You can check this by going to www.pubmed.gov, a US government web site under our National Library of Medicine, and using a search string such as - klotz l [au] AND prostate cancer AND active surveillance AND Gleason 6 AND metastasis . If you select this 2016 report from the list - https://pubmed.ncbi.nlm.nih.gov/26707510 , you will see that only 2 of his hundreds of Gleason 6 patients (probably about 769 as of paper submission) metastasized. In some papers he discusses this in detail.

    Jim

     
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    Old 01-06-2020, 06:43 AM   #10
    DjinTonic
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    Re: Why do some survive

    I didn't mean to say G6 metastasizes when I said G6 disease has the propensity to progress and lead to metastatic PCa, i.e., higher-grade lesions can arise and they can metastasize.

    There are a couple of separate issues regarding G6 status and metastases.

    1) As mentioned, even though a biopsy finds nothing higher than G6, there could well be higher G lesions present. Those could metastasize.

    2) G6 itself does not metastasize. In every case where a man with a G6 post-op grade went on to metastatic PCa, when they went back and re-examined the prostate, they found higher-grade lesions that were missed.

    AFAIK there has been one very instructive case of confirmed G6 metastasis! That is, all the metastases themselves were found to be G6. However, when they investigated the genetics of the mets, they found that the patient had pattern 3 adjacent to pattern 4 or 5 (I don't remember) in his prostate and a G6 cell(s) picked up the genetic material from the higher-grade that allows it to "go metastatic." So highly exceptional case it was just a fluke that the G4 or 5 present didn't metastasize, but that this "weaponized" G6 did.

    Genetic studies have found that in the majority of cases all of one's metastases originate from a single lesion!
    https://www.nature.com/articles/nm.1944

    3) We know PCa is a heterogeneous disease. We see this all the time in biopsy reports. It it not known conclusively how higher-grade lesions form. One theory is that there are precursor cells, which give rise to a lesion with a certain G profile. There could be a change in these precursors that cause them to form higher-grade lesions.

    Lesions seem to put out filament or tendril-like outgrowths that can lead to separate lesions. Perhaps pattern 3 can further mutate on division to a higher-grade, giving rise to pattern 4 or 5 clones elsewhere.

    The statement "G6 doesn't metastasize" can lead to a false sense of security, in that there is no guarantee that higher-grade lesions won't form, by whatever mechanism. These higher-grade lesions may have or develop the ability to metastasize. This is reflected in the fairly large percentages of G6 men whose Decipher met-risk score comes back intermediate or high.

    Back to AS. The figures I've seen show that although many men have to abandon AS because their G6 status has changed to G7, the number who slip through programs and actually have metastatic PCa at the time they abandon AS is extremely small.

    Djin

     
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    Old 01-19-2020, 08:34 PM   #11
    Insanus
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    Re: Why do some survive

    Quote:
    Originally Posted by SubDenis View Post
    G6 metastasis? I have not heard that before, can you point me to a study discussing that? Denis
    It’s misinformation on various forums that you can’t die of G6. While few die of G6, there are those that do.


    https://www.renalandurologynews.com/home/news/urology/prostate-cancer/gleason-6-prostate-cancer-more-lethal-in-black-men/

     
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    Old 01-20-2020, 06:08 AM   #12
    DjinTonic
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    Re: Why do some survive

    Quote:
    Originally Posted by Insanus View Post
    It’s misinformation on various forums that you can’t die of G6. While few die of G6, there are those that do.

    https://www.renalandurologynews.com/home/news/urology/prostate-cancer/gleason-6-prostate-cancer-more-lethal-in-black-men/
    If you read the journal paper that this news story references, and especially the references it cites, they are talking about men and AA men with G6 at diagnosis who progress. It is known that AA men need close supervision because their PCa tends statistically to be more aggressive (and, BTW, they have more serious disease at lower PSA levels).

    But these deaths are not from G6, but rather from higher-grade disease that arises. All men on AS have to be monitored for disease progression.

    Death from PCa occurs because of the metabolic decline from metastatic prostate cancer. You can die from PCa, but it's not the G6 that kills you.

    You can read more about Epstein's view of Gleason 6 and progression here:

    Should Gleason 6 be labeled as cancer? [2015]

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878816/

    Epstein argues Yes because mainly because (1) G6 can sometimes grow through the capsule and can invade adjacent structures, like the bladder neck, and (2) men with G6 can progress and develop higher-grade lesions.

    (see quote from Dr. Epstein below)

    Djin

     
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    Old 01-20-2020, 06:36 AM   #13
    IADT3since2000
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    Re: Why do some survive

    Quote:
    Originally Posted by DjinTonic View Post
    If you read the journal paper that this news story references, and especially the references it cites, they are talking about men and AA men with G6 at diagnosis who progress. ...

    But the deaths are not from G6, but rather from higher-grade disease that arises. All men on AS have to be monitored for disease progression.
    Dr. Laurence Klotz, MD, the great urologist from Toronto and arguably greatest guru for active surveillance, agrees with this.

    His team's active surveillance series now includes 1,500 patients, the earliest from 1995, with 500 now deceased, the vast majority not from prostate cancer, and his data show that true GS-6 prostate cancer metastasizes extremely rarely. Patients with advancing cancer who were considered GS-6, he says, usually harbored undetected higher-grade cancer or developed higher-grade cancer later, but not from the earlier GS-6 cancer except in those extremely rare instances. He has addressed this issue in a number of his published research papers. (He has also discussed the issue with Dr. Epstein, who convinced him that GS-6 really does need to be considered cancer despite its virtual lack of ability to metastasize. Source: his talk at the September 2019 Prostate Cancer Conference in Los Angeles.)

    Jim

     
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    Old 01-20-2020, 06:46 AM   #14
    DjinTonic
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    Re: Why do some survive

    Further to my Post #12,

    "Dr. Epstein: Because a pure Gleason 6 score determined at radical prostatectomy—where you can examine the entire tumor—has no risk of metastasizing and no risk of leading to the patient’s death, some people question whether we should call Gleason 6 an indolent lesion of epithelial origin (or IDLE) rather than cancer. But morphologically, Gleason 6 is cancer."

    From https://www.ascopost.com/issues/july-25-2018/when-can-patients-with-gleason-6-prostate-cancer-safely-undergo-active-surveillance/ [2018]

     
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