Gat’s hypothesis for the cause of most prostate cancers


Nearly 3 months ago, we reported on the publication of a paper by Gat et al. that describes a completely normal way by which very high levels of testosterone could “flood” through the prostate and potentially stimulate the development of prostate cancer.

In the full text of their original paper, Gat and his colleagues describe how, in a very high proportion of men diagnosed with prostate cancer, testosterone may reach the prostate directly from the testes as a consequence of an age-associated malfunction of the testicular and the prostatic venous drainage systems, allowing testosterone to bypass the normal systemic circulation and massively over-stimulate the androgen receptors in the prostate. They go on to describe two different procedures (using either microsurgery or an invasive radiological procedure) that can be used to stop these high levels of testosterone from reaching the prostate, and the effects of one of these techniques in a small set of patients.

The actual paper describes two experiments. In the first experiment, Gat et al. examined 72 randomly selected patients with localized prostate cancer for varicocele  — an abnormal enlargement of one or both of the internal spermatic veins in the scrotum that drain the testes. They showed that all 72 patients had malfunctioning one-way valves of the internal spermatic veins (bilateral varicocele). They postulate that this type of malfunction of these valves could have led to massive overstimulation of the prostate by testosterone.

In their second experiment, Gat et al. describe the use of “percutaneous selective sclerotherapy” to seal off the flow of high levels of testosterone from the testes to the prostate that had resulted from this malfunction of the internal spermatic veins. This procedure was carried out on 6 patients, all of whom had Gleason 3 + 3 = 6 disease and were being managed on an active surveillance protocol. The results of this second experiment were as follows:

  • Before the procedure, the patients’ average prostate volume was 65.3 ml (range 41.7–114 ml), and their average PSA level was 8.89 ng/ml (range 3.69–14.5 ng/ml).
  • At 6 months after the procedure
    • The patients’ average prostate volume had decreased to 36 ml (range 26.2–71.4 ml), and their average PSA level had decreased to 5.95 ng/ml (range 2.24–9.5 ng/ml).
    • In 5/6 patients (83.3 percent) there were no prostate cancer cells observed on post-treatment follow-up biopsies.
    • In 1/6 patients (16.7 percent) the post-treatment follow-up biopsy showed persistence of localized prostate cancer.

Why are we re-commenting on this paper? Two reasons. (1) Because the first time we wrote about it, there was surprisingly deathly silence, but yesterday a respected regional support group leader, who had not seen our original report, brought this paper to our attention again. (2) Because this may prove to be the most important paper on prostate cancer published in 2009 — which would make it a good gift to pass out on Christmas Day!

The hypothesis proposed by Gat and his colleagues may seem completely “off the wall” to many. However, The “New” Prostate Cancer InfoLink thinks that their hypothesis makes some sound physiological sense — and their hypothesis appears to receive confirmation from their initial experiments. We believe that someone at a major prostate cancer center (in the US or elsewhere) needs to repeat these experiments in an attempt to confirm or disprove the findings published by Gat and his colleagues. This group of investigators won’t have their careers shattered if their hypothesis is shown to be unsound. However, if they are correct in their hypothesis, then we need to know this soon!

Radically new theories that propose “off the wall” causes for common disorders take time to filter their way into the medical mainstream — even when those theories are right and are supported by relatively compelling data. One of the best, and relatively recent, examples of this was Marshall and Warren’s “outrageous” suggestion (in 1982) that most gastric ulcers might be caused by a very common bacterium found in the gastrointestinal tract of half the people on the planet. In took Marshall and his colleagues the best part of 10-15 years to convince the medical establishment that this was, in fact, true. In the end, however, Marshall and Warren were awarded a Nobel Prize for this work in 2005. Even if Dr. Gat and his colleagues are correct in their hypothesis, it may take a similar effort over a similar time period to convince people that the cause for most prostate cancers is physiological in nature. But if they are, another Nobel Prize may well be in order.

37 Responses

  1. I missed the original post in October. Interesting hypothesis as it is well known that excess androgens can generate DNA damaging ROS (reactive oxidative species) and be an initial step in the carcinogenic process in prostate tissue.

    It would be interesting to know if there is an excess of androgen in the prostates of young men who died of an accidental death and shown to harvest occult prostate cancer at autopsy.

    The corrective procedure proposed by Gat et al., if proven true, would be a major step in eradicating PCa and BPH.

    Something well worth following.

  2. Ralph:

    Chuck can give you a copy of the actual paper with some notes on it from Steve Strum.

    Maybe every Us TOO group leader should be handing this paper out to their urology advisors. (Somehow I don’t think most prostate cancer specialists read the journal Andrologia.)

  3. I did read the abstract in its first go around. ‘Fraid I just shrugged; there is/was little I could do — even if I had more than the cryptic info of the abstract: “… testicular and prostate venous drainage systems, [wha's that?] …” and “early results of an interventional radiological procedure, super-selective intraprostatic androgen deprivation therapy …” [more wha's that?]

    Chuck and Ralph add considerable info, maybe moving this into a more exciting arena. However, since it’s NIH (not invented here), the likelihood of it being pursued (read: funded) decreases. And, as noted, the journal, Andrologia, is not a widely read one; why did the authors choose this?

    Finally, even if it were the breakthrough of the century. it will take 10 years PLUS for it to get into mainstream US. Clinical trial, stage 1, 2, 3, back to FDA, opposition by drug companies (no patentable stuff here!) Do I sound negative?

    Herb

  4. Herb: Go and ask your urologist to check you for varicocele!

  5. Herb,

    I think that Mike’s point has value for those with viable prostate glands. Treating a varicocele could be important in disease control.

  6. I have varicoceles and was diagnosed at 48. What an intriguing hypothesis.

  7. Interesting! I have a unilateral varicocele, and was “treated” in about 1969 (when I lived in Jamaica) by cutting the cremaster muscle and thus lowering the testicle to keep it cooler. The purpose at the time was to improve my sperm count because my wife and I were having problems getting pregnant. The “joke” was that at the time I was on the surgery table she was actaully pregnant! I still have the varicocele, but no prostate!

    Hugh

  8. I absolutely agree with Gat´s hypothesis, and since his first paper published in October 2008 about BPH and varicocele I have begun checking for it on all my patients.

    I do have not definitive figures, but clinical bilateral spermatic vein reflux is present in more than 75% of men 60 years old or more.

    I’m now working on prostate cancer patients and whenever I have further results I’ll be glad to send first results.

    Fernando Premoli, MD, PhD
    Clinical Urologist Specializing in Prostate Cancer
    http://www.doctorprostata.com
    fernandopremoli@argentina.com

  9. Pleased to note that Fernando is monitoring the InfoLink. For those who do not know him, Dr. Premoli serves a medically disadvantaged area of Argentina, providing his services to those less fortunate. He is a proponent of transdermal estradiol (TDE) therapy and those interested in this treatment option should exchange e-mails with him.

  10. I gave a copy of this article to the urologic oncologist I’d chosen to complete my biopsy, which was scheduled after we investigated a 200% spike in my PSA in 2 years (still under 4.0). The doctor said, “Well it’s not in a peer review journal.” I have also been on testosterone replacement for 7 years, which Gat et al noted is the primary reason for their investigation. My doctor is at a major research facility.

    The notable thing is that fixing a varicocele is not that difficult so why not do it before radiotherapy/chemo/prostatectomy? I believe the wall we’re banging our heads against is an entrenched profession (and don’t get me started on what a government supervised medical system would do to that wall) and so spreading the word, advocacy and peer (that would be you, dear reader) support and research are key to getting these types of ideas put into the mainstream practice MUCH faster than H. pylori took. (By the way, I had gastritis in 1990 and was finally given a strong antibiotic after I insisted. Voila! No more symptoms.)

  11. I would love to hear from others who share the Gat article with their urologists — what reactions do they get, what may be a persuasive way to get the medical practitioner to consider varicocele repair first, etc.

  12. I am mildly puzzled by the suggestion that Andrologia isn’t a peer-reviewed journal. Certainly it is not a “society-sponsored” journal. I think your urologic oncologist may have been implying that (in his opinion) ist isn’t a journal that most urologists would read, which is true, but I am as sure as I can be that all papers accepted for publication in Andrologia undergo peer review priopr to acceptance and publication. Whether your doctor would consider the opinions of the reviewers to be acceptable to him is a quite other question!

  13. I had bi-lateral varicoceles surgically repaired about 14 years before I was diagnosed with T2b PC at aged 53. Mind you, I had precisely no clue what my PSA was at the time nor did I even know it at 53 but that’s another story entirely.

    Plan on sharing this with my urologist and Dr. Laudone at Sloan-Kettering.

  14. I have had a varicocele for at least 20 years. I now (at age 51) have rising PSA and 2 negative biopsies. My older brother had prostate cancer.

    I asked my urologist and he pointed out that all Gat and his colleagues have shown is that they can lower PSA. There are also studies that show large doses of antibiotics will lower PSA, but not lower the chances of finding prostate cancer.

    I have approached Gat and he has advised me to treat my case as simple enlargement of the prostate.

    I am concerned about treating the symptom (PSA) but not the cause.

  15. Dear Shimon:

    Dr. Gat and his colleagues have proposed an interesting hypothesis. At present that hypothesis is unproven. You would be wise at this time to follow the doctors’ guidance, and continue to monitor your PSA over time. We do not know what causes prostate cancer today. There are many different hypotheses out there.

  16. I am proceeding with caution. I am wary of a treatment that lowers my PSA but does not monitor any tumors that might be found.

    From my layman’s understanding, the PSA is a symptom. I want to deal with the cause.

    If I meet with Dr. Gat, I will report further.

  17. Here it is almost a year later and Gat’s idea has resurfaced for me during a web search. I did have my urologist look at the abstract. He was not impressed but/and would not check me for a variocele, commenting “what difference would it make?” Can they be detected easily?

    I subsequently sent a more complete paper and Dr. Gat’s credentials to my MD. We’ll see what he says next time I’m there. Stay tuned.

  18. My understanding from Gat’s original paper and an e-mail from him is that identifying the presence of a variocele is not difficult at all.

  19. Hello.

    Identifying a variocele is not difficult from my experience. It is a varicose vein on the testicle. Mine was identified with a hand examination. So was my son’s.

    I am a half an hour from Gat, so I contacted him. He was not very helpful via email. He did want me to come in for a consult. However, he is not recognized by my health insurance to treat these things. From what I understand he is a gynecologist by training. My urologist dismissed his work as not well structured and treated it as one of the many not-real cures. So I dropped it.

  20. Has anyone found a doc willing to provide the procedure? If so, who and where, please.

    Where is Dr. Gat’s office?

    Are variocele’s treated routinely for purposes other than prostate shrinkage or prostate cancer treatment?

    Thanks very much for any and all information, suggestions, and links to more!

  21. Dear Terry:

    As far as I am aware, no US-based urologist has yet taken Gat’s hypothesis seriously, and varicoceles are not treated routinely in the US with any intent to affect risk for prostate cancer. Dr. Gat works in Israel.

    For more information on varicoceles and their management, I suggest you see the information on about varioceles on the Wikipedi web site.

  22. Terry,

    As far as I know Dr. Gat has not published any progress in over a year. When I spoke to two urologists in Israel, they dismissed Gat’s hypothesis.

    If you hear any breakthroughs, please let us know.

  23. Might Michael Milken pursue this? At one time I understand he funded research without some of the bureaucratic and time-consuming analysis involved by governmental sponsors.

  24. The Prostate Cancer Foundation (PCF) — of which Mr. Milken is the chairman — still funds enormous amounts of prostate cancer-specific research each year. I have no idea whether PCF would fund this research, but the process of applying for funding is still very simple by comparison with other types of grant request.

  25. Why not ask Dr. Gat and Dr. Goren? If you Google “Gat Goren clinic”, you will find it. There is an English version of most pages.

    From reading their pages now, they are saying that this treatment will relieve benign prostate enlargement, not tumors, etc.

    Have you spoken with your doctor to get his/her opinion on the procedure?

  26. I have repeatedly emailed the Rabin Medical asking for more information, but have received no responses.

    Shimon, if you live near Dr. Gat in Israel, I hope you may be able to visit with Dr. Gat or someone at the facility and learn how an American or anyone, really, can get appointments to undergo the procedure.

    And whether he is still doing it, or whether anyone else is. This is all much too promising to just fade away. Perhaps in Belgium or Holland someone has begun treating patients with the procedure?

  27. Message to Terry,

    Hello,

    I live in Israel and I plan to undergo this procedure for BPH. I was there yesterday and just witnessed a visit by a US guy who will probably be treated today.
    I spoke with few Israelis who have had this procedure and they are very pleased with the results.

    Let me know if I could be of any further assistance.

    Yoav (yoav.benshalom at gmail.com)

  28. Would be very interested to learn more about the Gat-Goren clinic and its methodology.

  29. Mitch,

    I dropped contact with the Gat-Goren clinic, but I am sure that you can call them to speak with them about it. Since the treatment is for benign prostate enlargement, it did not seem very pertinent to me.

    Their research was published 2.5 years ago. Since then I have not heard anything. Wouldn’t some of the establishment be talking about it if they had some fantastic results in that time.

  30. Shimon,

    I guess you live in Israel, if so may I call you (please leave a phone number). I’m planning to undergo Gat procedure and did talk with some patients who had it but would like to obtain some more information.

    I’ve noticed that urologists tend to question this procedure but this is a natural response. I bet you most did not even read the description by Dr Goren.

    My email: yoav.benshalom@gmail.com

  31. Hi. I have tried to e-mail this clinic several times for more information on the procedures. I believe they could help me. It would help if the clinic released further updates. After all, it would of course be in their interest to do so. Perhaps if someone from the clinic would like to update us? Perhaps if a urologist or two could give an opinion this would be helpful.

  32. Dear Fred:

    We have previously sought additional information from Drs. Gat and Goren on this topic. To date, we are not aware of any further study data available from this clinic, and no American urologist with whom we have discussed this form of management seems to find it compelling. We are in no position to be able to pursue this matter further.

  33. Hi,

    Try Dr Robert Jay Second Opinion (US) of May 2011

  34. They didn’t believe Semelweis either.

  35. Sure, but that does not reflect on this situation, either way.

    Drs Gat and Goren published an interesting paper 3 years ago. I think that everyone who reads this blog are anxious to find a cure for prostate cancer. If Gat and Goren have a solution, that would be fantastic. That said, what has been done in 3 years? If they believe that they have the cure, have they done a full-scale study with all the trimmings? Has anyone else picked up the mantle? Proving the cure would be an easy way to wide recognition and fame. No takers?

    I spoke with a gentleman who underwent the procedure. He said that it increased his free testosterone level, and he is satisfied at this point.

  36. Anything new on this?

    I just saw this article about varicocele and hypogonadism.Might make sense if testosterone was being diverted out of the blood stream into the prostate.

  37. Ho Doug. Yes … I had seen this too, but I haven’t seen anything meaningful on Gat’s hypothesis in years.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

Follow

Get every new post delivered to your Inbox.

Join 1,132 other followers