(This new thread stems from the following thread to give a more detailed reply to the question quoted. I hope others will contribute if they know more about this question. Jim)
Re: how many biopsies are taken before discovery of prostate cancer

Jim - have you any figures on how much PCa is triggererd by DRE and biopsies?

I think a lot of us wonder about this, especially as we have biopsies performed.

My impression is that it is not a problem with DREs, though some procedures like the PCA3 Plus test and its predecessor the uPM3 test use a vigorous DRE to deliberately cause shedding of some prostate cells into the urine. Perhaps some go to the blood as well, but it is probably an extremely small risk, and I can't find any research linking DREs to spread.

There have been studies done about whether biopsy causes any spread of prostate cancer cells, and I've heard several audience questions to experts about this at conferences. My impression is that biopsy does cause some spread of prostate cancer cells, though it is not typcial, but that adverse impact is quite rare. In other words, even if there is spread of some cells, they are rarely viable and rarely cause any trouble.

"Iatrogenic" is a strange word that I never knew until I got into this world of prostate cancer. It basically means "doctor caused." I just went to the free Government web site www.pubmed.gov and used this search string to check on relevant studies: " iatrogenic prostate cancer AND biopsy ". Here are some key facts from hit #14 (many of the rest looked irrelevant); it is highly technical, but the abstract excerpts quoted below are pretty clear:

Urology. 1997 Apr;49(4):515-20."Transrectal ultrasound -guided biopsy causes hematogenous dissemination [meaning spread in the blood] of prostate cells as determined by RT-PCR [RT-PCR: Reverse Transcription-Polymerase Chain Reaction, which is a valuable research tool; I can explain if desired.]." Moreno JG, O'Hara SM, Long JP, Veltri RW, Ning X, Alexander AA, Gomella LG. Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. "... OBJECTIVES: To determine if transrectal ultrasound-guided (TRUS) prostate biopsy causes dissemination of prostate cells into the circulation... RESULTS: Among the 47 TRUS cases, 43 specimens were evaluable. Forty-two cases were negative before biopsy; among these patients, 4 cases (9.5%) converted to a positive RT-PCR PSA result. Both benign and malignant TRUS biopsies were capable of producing a positive RT-PCR PSA signal implicating iatrogenic dissemination of cells. All three TURP cases converted from a negative to a highly intense positive signal. CONCLUSIONS: We conclude that a positive RT-PCR PSA signal may result from release of prostate cells into the peripheral circulation after a TRUS biopsy and TURP. TURP causes greater dissemination than TRUS.... This may be an important mechanism of prostate cancer dissemination meriting further investigations."

Here's another, later reference that PubMed highlighted as a paper related to hit #14:

Urology. 1998 Aug;52(2):261-6; discussion 266-7.Detection and clearance of prostate cells subsequent to ultrasound-guided needle biopsy as determined by multiplex nested reverse transcription polymerase chain reaction assay.Price DK, Clontz DR, Woodard WL 3rd, Kaufman JS, Daniels JM, Stolzenberg SJ, Teigland CM.
Molecular Biology Laboratory, Cannon Research Center, Carolinas Medical Center, Charlotte, North Carolina 28232-2861, USA.
OBJECTIVES: To determine if circulating prostate cells are detectable subsequent to transrectal ultrasound (TRUS)-guided biopsy, and if so, whether cells remain in circulation for up to 4 weeks.... RESULTS: Of 45 patients with biopsy-proven adenocarcinoma, 22 were RT-PCR positive prebiopsy and all remained positive 30 minutes postbiopsy. Of 23 patients with adenocarcinoma who were RT-PCR negative prebiopsy, 5 (22%) converted to positive 30 minutes postbiopsy (P < 0.001). Four of these 5 patients returned to negative after 1 week or 1 month. Of 45 patients without cancer at biopsy, 32 were RT-PCR negative prebiopsy and 6 (19%) converted to positive 30 minutes postbiopsy (P < 0.001). Although four of six available samples were still positive at 1 week, all four samples available 1 month postbiopsy were negative. CONCLUSIONS: Detection of circulating prostate cells subsequent to biopsy occurred in 11 of 55 (20%) previously RT-PCR negative patients, a proportion twice that reported in the literature. We attribute this higher proportion to the simultaneous detection of PSA and PSM mRNA in our multiplex assay. Conversion rates were similar in patients regardless of biopsy result. Testing of serial postbiopsy blood demonstrates clearing of these cells by 4 weeks in most patients."

The last sentence is very important. It is hard for cancer cells to take hold and establish themselves even if they have made it into the blood. :) That means that spreading cancer due to a biopsy is apparently a rare event. :) It does make you wonder if saturation biopsies, which can involve, say, 40 to even more than 100 needle sticks, might increase the odds, and whether many repeated biopsies would increase the odds.

By the way, I substituted "DRE" and "digital rectal exam" separately in the above PubMed search and got no hits; to me that indicates that no such published research has been done, though my search string may have not covered all the instances. Also, poster studies are presented at medical and medical research conventions that typically do not get picked up by PubMed, and it is possible that this question has been explored in a poster study.

Jim

Thanks for all this Jim - though as far as I can understand it, it seems to cover the spreading of existing cells, which I hadn't thought about. By "triggering" I meant irritating a healthy prostate into turning cancerous.

Thanks for all this Jim - though as far as I can understand it, it seems to cover the spreading of existing cells, which I hadn't thought about. By "triggering" I meant irritating a healthy prostate into turning cancerous.

In all that I've ever heard, read, or understood, prostate cancer is not created initially by DRE or biopsy procedures. I meant to mention that in the previous post. Thanks for bringing it up.

It does not make sense to me that this could happen. As I understand it, PC begins when a normal cell mutates or is triggered to grow abnormally by a biological event or accumulation of events (such as oxidative stress), but not by physical events, such as a DRE or biopsy.

Just as a probe to see if I was missing something, I just tried a PubMed search at www.pubmed.gov for " physical cause AND etiology AND prostate cancer ", and none of the 28 resulting hits looked pertinent. I also tried "physical cause AND tumorigenesis AND prostate cancer " and got no hits.

However, there has been a lot of research on what causes ("etiology") prostate cancer. There is a strong genetic component that affects a small proportion of patients, and a weaker genetic component that apparently affects a larger proportion, though still a minority. Accumulated oxidative stress seems to be a likely causal candidate. Nutritional deficiencies and excesses appear to play a role. Interestingly, testosterone and its derivative DHT do not seem to actually cause prostate cancer, though they certainly serve as fuels in some circumstances. Race appears to be associated with cause, though I doubt it is itself a cause. For instance, African American men have a much higher incidence of prostate cancer, but African men have a low incidence; differences in vitamin D may in part explain this.

There are probably several or even many causes, with a combination of factors the likely answer as I see it. I'm also convinced that we can counteract some of these causes or interrupt the sequence that leads to significant cancer and achieve prevention in many instances. That's already been proven with the drug finasteride, and there is some faily persuasive evidence involving nutritional tactics, exercise and stress reduction.

I tried this PubMed search for information about cause and got 531 hits, many of them highly technical and based on animal and lab studies (that is, not human studies), judging from the first page: " tumorigenesis AND prostate cancer ". I flipped on the limits feature and checked "studies with abstracts" and "human" studies, reducing the hits to 435. A lot of terrific research is being done, as reflected in these hits, but the information is highly technical and hard to interpret for laymen. You can do the same search and read the abstracts by clicking on the authors lists. Usually the introductions and conclusions are fairly easy to understand.

Jim