First post, I am a 70 yr old retired neuroradiologist, trained at MD Anderson, dx'd at age 50, Gleason 6 (graded twice), treated initially with Iridium 192 brachytherapy with adjuvant pelvic RDRx, and subsequently salvage prostatectomy (big mistake) with bone met showing up 8 months later, and subsequently treated with chemotherapy, achieving undetectable PSA. Over the first 10 years treated with hormone ablation, and 5 years ago received IMRT for 7 bone lesions, and cryotherapy for 3 bone lesions 1 year ago. Started Dynamo (Zytiga, prednisone, abiraterone) 30 months ago; PSA stable at 0.6 for last year. Taking about 25 other various misc medications and/or pills all of which have been shown to have some effect on PCA in various animals or humans. Treated at MDA for last 16 years, and quite satisfied with quality, aggressiveness of care and availability of clinical trials.
Of course I cannot prove it, but I am a strong believer that many patients with Gleason 5 or 6 who have delayed mets discovered months to a year after biopsy are related to the rather traumatic prostate biopsy, with prostate RNA in patient's blood after biopsy having been detected in several studies. The prostate is extremely vascular and loaded with lymphatic vessels, and when possible other tumors like such are often removed intact to prevent known tendency for metastasis. However, present standard of care is to prove prostate malignancy with multiple core needle biopsies, as all in this forum have undergone, and grade such prior to any treatment. It is considered malpractice at this time to do otherwise. However, on the horizon are various imaging techniques that might be reliable enough to make a diagnosis, with some sort of grading system. This would be ideal, and I believe for lower grade prostate malignancy we will see fewer cases of delayed metastasis, that presently are classified as "events occurring as a natural course of disease."
Biopsy related metastases are well documented to occur. I have personally biopsied thousands of various tumors with needles similar to those used in prostate biopsy, and have had proven 5-10 or so "tract metastasis" show up later in the soft tissues of the tract on the needle, clearly related to tumor being displaced at the time of biopsy and becoming viable.
I believe it is most unfortunate, but at this time required, that many patients are rendered with metastatic disease during the process of diagnosis and/or treatment. For instance, during brachytherapy, which I had, numerous needles are inserted into the prostate gland, for up to 18 hours, while therapy occurs. Any of these needles could easily result in release of a shower of micrometastasis only to show later on scans or PSA rise. When such occurs, and it almost certainly does, the patient's doctor informs the patient that the disease has spread. It certainly has, but not necessarily as a result of the disease but of the process of diagnosis and treatment. What a shame, and violation of Primum Non Nocere.
It is my sincere hope that men will soon not be treated with such lack of regard to possible silent complications of diagnosis. This disease is being attacked on many fronts, with some success, but until such time as this organ is left untouched by needles or knives, unless absolutely necessary, some men will continue to suffer life long consequences.
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TWTJr
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I have nothing but the greatest respect for TA. Extremely well read, able to process complex data, and articulate solid advice.
I am quite convinced you are aware that the diagnosis of a malignant disease standard of care at this time always requires a fairly gross, bloody cutting needle extraction biopsy or multiple repeat biopsies, often 8-12 cores per biopsy, which shed intravascular DNA/RNA debris(proven). When you follow all patients with a diagnosis of PCA for outcome comparison, there are many independent variables that are not controllable. First, Gleason scoring is highly variable, and only an estimate, and may be under or over estimated, in the tissue sample obtained. As in my case, I was initially graded Gleason 5. Other pathologists graded it 6. Post Prostatectomy specimen was graded 6. (Post excision biopsies more often reveal an upgrade, not a downgrade.) In all likely hood, I was a Gleason 6, but still this is a variable. I had a met proven at 8 months after bx and initial brachytherapy. Was I an extremely rare exception?? I believe not. The problem is that there is not, and at the present time, cannot be a controlled group of patients with whom a diagnosis of malignancy and grade can be been made without invasive biopsy. When such can be made, and perhaps not so distant in the future, accurate comparisons of the natural history (rates of metastatic disease and outcomes) of one group of patients diagnosed and treated non-invasively, versus a second group treated with an invasive diagnosic biopsy ( the present standard of care) can be made. Then, and only then, will the rate of metastatic disease related to invasive biopsy and tumor grade be accurately determined.
It would be of interest to know of all men participating in this forum what their Gleason score was, how many have at this time metastatic disease, (or a positive PSA in the situation of post-prostatecomy) and how long after initial biopsy or treatment their recurrent disease became evident. Quite a few participants have had surgical resection, with or without adjuvant radiation, and have non-zero PSA. All of these have either residual local disease or metastatic disease, whether visualized on images or not. How many of these patients disease could be related to multicore biopsy, which penetrates the anterior rectal wall and often slices into the prostatic bed and seminal vesicles?
It cannot be determined, at the present time, what the expected outcomes for treatment of Gleason 6 PCA diagnosed non-invasively. We simply do not have such a group.
Lastly, certainly lower Gleason scored patients do seem to do better than higher Gleason score patients, although this may change somewhat if immunologic treatment improves. But I for one, am a Gleason 5/6 with early onset metastatic disease.
Cancer cells MUST undergo epithelial-mesenchymal transition (EMT) before they can remain viable outside of the prostatic environment and clump to form metastases. GS6 is incapable of doing that. It is not enough that the cancer cells escape - they do all the time, in fact, even without a biopsy (e.g., via prostate massage, bike riding, orgasm).
It is extremely difficult to ascertain a real Gleason score from salvage prostatectomy tissue - the radiation screws up the architecture.
In doing my regular CME for licensure, I take tests daily. Questions often use the word "must". The answers to any question involving the word MUST or ALWAYS are almost always false. But with due respect, I am not informed on the EMT, and necessity of such for metastasis. As for release of cells during regular daily activities, yes, cells are released, and may very well be one of the etiologies of delayed silent metastasis.
Yes, it is most difficult to grade post prostatectomy specimens, but MDA and Methodist pathologists are pretty good at it, despite the limitations.
Thanks TA, I briefly read a little about EMT, and 3 types, so called Type 3 needed for metastasis. I unfortunately do not have the time to read extensively on the subject, but must draw on my experience and clinical observations. Track metastasis are without question, and occur after surgical or needle biopsy of many cancers. The incidence is always in question simply because many of these patients die long before tract metastasis can be demonstrated.
Metastasis from breast cancer, or melanoma, as you know, can become apparent many years after primary resection. 10-15 years is not at all rare. Where did these come from? Natural course of disease, cells released secondary to a needle, surgical or vacuum extraction biopsy, or from primary tumor resection? I am no expert on the subject, but I have not heard that there is a consensus or proof that all of these cases must have had at the time of original diagnoses type 3 EMT that was disseminated, and lay dormant for 15 years. Does not make sense to me. I am sure it is far more complex than I recognize, but all I know is that there are strange events that occur when dealing with malignancy, as I have had occur in my 40 year career, and my course certainly was one of them.
My intuition suspects that the process of diagnosis and or treatment may account for an unknown incidence of metastatic disease, substantially greater than recognized, particularly prostate malignancy, due to its location, with the prostate intrinsically very vascular and loaded with draining lymphatic vessels, surrounded by an extensive pelvic vascular network, draining into Batson's plexus. I know for a fact that the medical profession as a whole does not want to discuss this subject with the patient for fear of liability. The standard answer from MD's is "yes, it may occur, but is very rare." When it does occur, the answer is "I am so sorry for you, PCA is a wicked disease." When you get the bone met a year later after biopsy, you never hear "Maybe it was the biopsy". The fact is they do NOT KNOW the incidence of post BX or treatment related metastatic disease that can be proven related to such without a comparison group treated without invasive techniques. Discussions of EMT do not really prove, or disprove the etiology of metastatic disease.
TA I have skim read both articles, and am aware of most. But as importantly, I am also aware of what is a fact, and what is study, and independent variables not evaluated in studies. I have read tens of thousands of medical articles in my life, published some, and have lived long enough to see a number of well established facts proven totally wrong, due to lack of control groups. I would have failed my surgical rotation had I not discussed the surgical treatment of peptic ulcer disease as a method to control acid, and therefore control gastric ulceration related to such. It was completely wrong, despite 50 yrs of surgical research proving such. Almost all peptic ulcers are due to infection, as we know now. I am very skeptical about medical research, not because of authors being deliberately misleading, but because of the uncontrolled nature of so many other variables, known or unknown that may impact outcomes.
I am very restrictive when I use the term KNOWN FACTS. Known facts may not be facts. Yes, I harbor my intuitions, and make no mistake in stating that they are my intuitions only. My anecdotal observations prove nothing.
Lastly, I would like to commend you on your outstanding work. It is most beneficial to many men suffering from this unpredictable disease.
Dr Michael Modic classified degenerative disc disease (DDD) into 3 types, Type I, Type II, and Type III, based on MRI findings, about 30 years ago and tens of thousands of papers have been published on such, including a study my me. These 3 types were all related to degenerative disease, as Modic cultured disc materials on many cases and nothing was found. You were considered a heretic if you questioned the etiology of degenerative disc disease. Surgeons would not believe anything else.
However about 15 years ago, and more recently about 7 years ago, other physicians tried harder to culture disc material, and found that a number of cases indeed did show positive cultures for Propionibacterium acnes, a common skin bacterium, which is very hard to culture. This dramatic finding is slowly but progressively changing treatment for Type I degenerative disk disease, from a surgical treatment to a simple course of antibiotics.
Tens of thousands of studies were published using the original description of Type I as being caused by degeneration. The studies were wrong, and the so-called facts were wrong. Many cases of Type I are caused by infection.
Published studies or FACTS are not necessarily facts. They are merely published studies. I remained a skeptic 15 years ago about Modic Type I DDD, and recommended antibiotic treatment rather than surgery on many patients that I was convinced had infections. While I was fairly heavily criticized by both orthopedic surgeons, who lost a surgical case, and administration, who lost an admission, the patients did very well. But I was correct. Published facts were wrong.
Dr. Herb Fred, an internationally known internist's favorite saying is: "If it has a tail and barks, do not call it a cat. It likely is a dog." In the situation of metastatic disease that occurs in close proximity to an invasive procedure, be it biopsy or invasive treatment, treatment related spread should be considered as a possibility. This is about the only fact I know on this disease.
I have been requested for a list of my medications. They have changed from time to time over the past 18 years, but I will list my present medications . Please understand I do not recommend any of these for anyone without advice and consent from your physician. I am a physician, cognizant of my metabolic functions, cardiovascular status, body mass and accepting of significant side effects.
Those starred are recommended by my MDA oncologist:
Very interesting. A lot people aren't aware of this. What would you say the best way to avoid metastasis during diagnosis or treatment. And if left untreated it might get worst too. Also does Robotic Surgery have good prognosis?
Unfortunately, present standards of care require biopsy prior to treatment. Getting the best surgeon you can is your best option. I do not have data on long term outcomes data from robotic surgery resection vs open prostatectomy. Perhaps Tall Allen might. He is most informed.
I am told, but am not recommending, that there are treatment centers in Mexico that will treat prostate cancer based on data that is convincing, but lacking a tissue diagnosis. This is being done to avoid the issue being discussed.
Quite possibly, but dependent on many factors and Gleason score. Make sure your MD is very up to date. Almost all urologists are not. Get the best oncologist you can, and get consult from best RDRX you can.
TWTjr, for what it is worth, I concur. 2003, Brachytherapy with Palladium and 25 sessions of IMRT by a treating RO at Methodist and professor at BCM as primary treatment on a Gleason 7(4+3). Within a year, two mets and PSA 34.2. Started a chemo-hormone clinical trial at Methodist - treating MO, a researcher and professor at BCM.
Mets resolved. But I was struck by a comment during the first meeting with the MO. I asked should we biopsy the met to be sure and his response was, no, too much of a chance for the needle to spread the cancer. Further, I got here because no matter by primary treatment, because micro-metastates. Minute cancer cells released and traveling through my lymphatic and vascular system.
Thank goodness, the trial worked for me. Able to stop Lupron in February 2010 and still maintain undetectable PSA. Started 4 mg of Androgen twice a week in 2012 and T ranges between 350-750 depending and day of blood draw. I am still a guinea pig in the study.
You are very lucky, and have been well cared for. My initial care was also at Methodist, and the IMRT was by Dr. Butler at Methodist. He did a great job at treating the evident oligometastatic disease. Unfortunately for me, there are a number of other sites that have become evident. When they occurred is unknown. Studies are showing individuals should aggressively treat with local therapy scattered osseous disease. Years ago the recommendation was "3 or fewer sites". That is non-sense. Treat as many as you can within limitations of number, marrow response and funds. Insurance may not pay for RDRX other than pallative treatment.
I chuckled. In 2003 I went to Dr. Brad Prestidge in San Antonio as he had done over 2000 and SA had a lot of retired military who would develop Prostate Cancer. His plan was to do the Brachy and then send me to his Air Force best bud at Lackland, Dr Brian Butler for the IMRT.
When I developed mets on an exploding PSA, Brad shot me up with Lupron and told me that anyone could give me future injections or I could drive 400 miles round trip stick with him. I looked him in the eye and told him that was not my question..... The question was simple, if you were in my shoes, what would you do? He thought a minute and gave me an answer. My followup question was do you know one?
The next week at Brian's office, I asked him the same question. He told me that Brad called him and told him that I would ask. Brian gave the same answer and on the followup question, he said, Yes, I do. I sit on a SPORE committee with him. I don't know if I can get you in, but I will call Dr. Amato. Fifteen minutes after I got back home in Spring, Dr Amato's Office called and told me that he wanted to see me the next day. Further that he had already seen my scans.
Dr. Amato spent two and half hours with me explaining the trial and I enrolled and had a port put in and started the trial. Heck, you probably did my scans.....
Anyway, Doctor Butler or his right hand Dr. Bin Teh call me every five years to check on my progress. I saw Doctor Teh last year. I took a friend with a different cancer. Teh spent about 15 minutes getting an update. I really like the people at Methodist.
I know Dr. Amato well, he is an excellent oncologist, trained at MDA, went to Methodist about 2001, presently at Memorial Hermann Houston. You are in excellent hands. Stick with them. Houston is very fortunate to have several great institutions providing state of the art care, but always be curious about your treatment and alternatives.
I have long suspected my delayed metastasis was due to cancer cells released into the blood stream in 1999 upon biopsy and subsequent radical prostatectomy. However, I suppose cancer cells could just as easily have entered my blood stream from the blood flowing through my prostate and the tumor prior to the biopsy and prostatectomy. Who can say whether the biopsy and prostatectomy speeded up or delayed the eventual metastasis that has occurred. Oh well, I suppose what will be, will be. A summary of my progress and treatments since diagnosis is in my profile. From 2006 to 2011 I was treated at MD Anderson Houston.
You will never know. Until we can diagnose, grade and treat this highly variable disease with non-invasive techniques, we must rely on present standard of care, which includes invasive needles, and a crude visual technique of grading (Gleason score).
We have known for many years not to needle biopsy ovarian cancer, which will result in peritoneal metastasis easily seen at surgery. As you can tell, I believe many cases (not all) of prostate cancer are spread (in very complex ways) during both diagnosis and during invasive treatments.
When I had 14 core samples instead of 12 during my biopsy I was thinking wow I got a perfectionist here. Already metastasized so probably didn't make any difference at all. Except to convince me that I will never have another prostate biopsy. Do admit I was stunned by all of the meds/drugs you are taking. Maybe I should look into some of them closer. I was thinking the less the better. You have obviously decided the more the better. And I surely ain't no doctor. Best of luck.
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PSA Recurrence - confused on next steps?
Now 6 years in Lupron alone failed my Gleason 9 nmpca
6 years post Diagnosis!!
I am a newbie on this site...
Radiation or operation with mets and beginning ADT only once symptoms arise?
