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rising psa after radical prostatectomy

Billybumps
Posts: 18
Joined: Aug 2003

I had RP in June 2003. My post surgery pathology was: Gleason 7 (4+3), margins clear, cancer on both sides of prostate. All of my PSA readings since then have been less than .04. The last blood test with that result was in June 2005. My most recent PSA taken on 11/9/05 was .6. I saw my doctor the day before yesterday and he didn't think it was something to be concerned about. He told me to come back in 6 months and he would do another blood test at that time. I am worried. To me, going from less than .04 to .6 is a significant increase. Do you think I am worrying for nothing? Should I seek a second opinion? Is it normal to wait another 6 months after there has been some increase in the PSA? I appreciate any information you can provide to me . Thank you. Bill

bdhilton
Posts: 756
Joined: Jan 2010

Larry...wishing you the best and I hate this waiting game as much as but I am sure it will ease as more time passes on...God bless-B

hopeful and opt...
Posts: 2218
Joined: Apr 2009

there is a urban legend that the biopsy causes the cancer to spread, but this is not true.........tis has been dcoumented...one doc, Dr. Scholtz, in his book "Invasion of the Prostate Snachers" wrote about this.

Kongo's picture
Kongo
Posts: 1167
Joined: Mar 2010

Ira, while many doctors do not subscribe to the notion that biopsies or surgery contribute to the spread of cancer, there is a rather large body of evidence easily found on the web that suggests that indeed, biopsies can contribute to metastasis of many cancers, including prostate cancer. Even though the idea of cancer spreading as a result of a biopsy is not generally accepted (otherwise, why are they continuing to do biopsies?) there is enough out there that I would not classify it in the “urban legend category.” Instead, I would classify this as “maybe in some cases.” But in general, I don't think we yet know enough about this do be able to state definitively that it isn't a factor with any more conviction that when the "experts" dismissed Rachel Carson when she suggested that the chemicals we were putting into the environment was causing cancer.

The phenomena known as needle tracking where cancer is observed growing along the path of a prostate needle is fairly common in post RP pathologies, and other soft tumor cancers where surgery is involved following a biopsy. Women who have had a biopsy for breast cancer have a 50% higher risk of seeing their cancer spread than those women who have their tumors removed through a radical mastectomy or lumpectomy.

A recent study done at UCSD indicated that damage to the tumor during a needle biopsy may cause inflammation which is correlated to cancer metastasis. See http://ucsdnews.ucsd.edu/newsrel/health/03-07prostate.asp

Generally doctors will state that “there is no evidence that a biopsy can spread cancer” but it seems to me that that this is a plausible statement because they simply haven’t done any studies to determine if this is the case. Biopsies are such an integral part of the way cancer is diagnosed today that few physicians would ever challenge it. Without a biopsy they can’t give a definite diagnosis and none of the treatments that flow from that diagnosis could be undertaken. In the case of prostate cancer, 25% of needle biopsies show some level of prostate cancer and frequently these lead to follow on treatments that also make a great deal of money for the doctors. For all cancers, biopsies are not only a very large money making operation for doctors and pathologists, they lead to further treatments which also make a lot of money. Doctors have a vested interest in conducting biopsies.

Cancer can spread in many ways, such as through the lymphatic system called "embolization". The lymph system has its own channels that circulate throughout the body, similar to the veins and arteries of the bloodstream. These channels are very small and carry a tissue fluid called lymph throughout the body. Cancer also metastasizes when cells break off from the original tumor and travel through the blood stream to other parts of the body. Cancer can also spread directly to adjoining healthy cells such as occurs in skin cancer. For prostate cancer to metastasize to a distant organ such as the bone, lung, liver or whatever, it is probably traveling by the bloodstream. While cancer needs blood like any other cell, sometimes cells slough off and enter the bloodstream naturally and eventually find someplace that provides a home for a new colony.

My personal feeling is that when the tumor is pierced with a needle that some of the cancer cells also enter the bloodstream. Another way intervention can cause a spread is when surgery cuts across a margin where cancer is present and cells can then enter the bloodstream. The study I cited earlier suggests that the inflammation caused by a biopsy creates a chemical condition that accelerates the shedding of cancer cells that can spread through lymphatic action or by the bloodstream. The frequent manifestation of “needle tracking” suggests that SOMETHING abnormal is going on along the path that the needle takes during a biopsy. The needles in a biopsy gun that are used today (18 gauge) are much smaller than those used years ago, and may reduce the likelihood of cancer spreading as a result, but needle tracks still occur, and to in my opinion, the fairly frequent recurrence of cancer years after initial treatment when it was originally considered to be “contained within the prostate” makes sense if you consider that the original biopsy and treatment caused cancer cells to enter the bloodstream.

I wish there was a better, non-invasive way to determine prostate cancer without a biopsy and I am sure that our generation will see such a development given the pace of modern research. In the meantime we must take our chances as the only way to confirm a suspected cancer is to conduct a biopsy.

hopeful and opt...
Posts: 2218
Joined: Apr 2009

Actually, since I guess that I waved a red flag for you, I'm surprised that it took you so long to respond......

My view is that it is current establisted practice by the medical profession to do biopsies...it is up to nay sayers to provide concrete information to validate problems caused by biopsies, other than possible infections...I have not seen any information that does this....I believe that you are presenting a well thought out hypothesis, but the facts are lacking.....anyway my opinion.

I looked at the article that you referenced......as I read the article published in 2007, where mice were the subjects, it suggests...( I wonder if there has been any follow up in response to this study) more needs to be done to investigate the hyposthesis...(that's what I get from it, however others may see differently, so I pasted the article below.

You wrote "

"I wish there was a better, non-invasive way to determine prostate cancer without a biopsy and I am sure that our generation will see such a development given the pace of modern research. In the meantime we must take our chances as the only way to confirm a suspected cancer is to conduct a biopsy."

I agree, by the way a few weeks ago there was something on TV about colon cancer, and examining stools to determine cancer, I think looking at genes instead of a colonoscopy.So I'm thinking that a colonoscopy may go by the wayside

Anyway that's my take.

> News Releases > Health Sciences
Inflammation May Play Role
in Metastasis of Prostate Cancer

March 19,2007

By Debra Kain

Many would assume that “mounting an immune response” or “having your body fight the cancer” is a good thing. Now, research at the University of California, San Diego (UCSD) School of Medicine strongly suggests that inflammation associated with the progression of tumors actually plays a key role in the metastasis of prostate cancer.

The research, appearing online March 19 in advance of publication in the journal Nature, identifies a mechanism which triggers metastasis, which is the spread of cancer in late stages of prostate cancer development. The findings by Michael Karin, Ph.D., professor of pharmacology in UCSD’s Laboratory of Gene Regulation and Signal Transduction, and colleagues may help solve the puzzle of why it takes so long for cancer to metastasize, as well as what causes it to do so. Furthermore, this new work may lead to development of anti-metastatic therapies.

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A major hypothesis in cancer research has been that whether the cancer metastisizes or not is determined by genetic changes within the cancer cell itself. But this hypothesis didn’t explain why metastases appear many years after the initial tumor.

“Our findings suggest that promoting inflammation of the cancerous tissue – for instance, by performing prostate biopsies – may, ironically, hasten progression of metastasis,” said Karin. “We have shown that proteins produced by inflammatory cells are the ‘smoking gun’ behind prostate cancer metastasis. The next step is to completely indict one of them.”

More than 200,000 men are diagnosed with prostate cancer in the United States every year. As many as 25,000 men will probably die of prostate cancer in 2007, most as a result of metastatic disease.

Early tumors confined to the prostate can be treated, but no effective treatments are available for metastatic disease, according to Steven L. Gonias, M.D., Ph.D., professor and chair of the UCSD Department of Pathology, a study investigator.

“This study helps explain the paradox that, in certain types of malignancy, inflammation within a cancer may be counterproductive,” said Gonias.

In research using mouse models and confirmed in human tissue, the scientists observed that a protein kinase called IkB kinase α (IKKα) turns down the expression of a single gene called Maspin, which has well-established anti-metastatic activity in breast and prostate cancers. They found that the production of Maspin is repressed by a series of events triggered by tumor inflammatory cells, with the result that prostate cancer cells spread.

“An excellent inverse correlation between IKKα activation and Maspin production was detected, such that advanced prostate cancer cells contain high amounts of activated IKKα in their nuclei and express little or no Maspin,” said Karin. He noted that a perfect correlation between nuclear accumulation of activated IKKα and reduced maspin expression was also seen in human prostate cancer, and both correlated with the clinical stage of the disease.

Karin and his colleagues discovered a signaling pathway that increased metastases in a mouse model of prostate cancer. The pathway is activated by a ligand that binds to a Receptor that Activates Nuclear factor Kappa-B (RANK). RANK ligand has been shown in previous studies to be an important inflammatory protein (cytokine) that can lead to bone loss through activation of bone resorbing cells.

RANK ligand, produced by inflammatory cells that invade advanced prostate tumors, triggers a chain reaction in which IKKα is activated, allowing it to enter the nucleus of the cancer cell, repressing Maspin. IKKα is a key linchpin in the pathway that turns off the Maspin gene and activates the metastatic program. The new results also support the view that RANK ligand is a general promoter of prostate, and possibly breast, cancer metastasis.

“Maspin is a very potent inhibitor of metastasis; in a patient with metastasis, cells have found a way to turn off Maspin, which may depend on invasion of the tumor with RANK ligand-producing cells that activate IKKα,” said Karin.

Malignancies progress through stages. In early, non-metastatic tumors, a high level of Maspin is present, but it is turned off in late stages. Early tumors contain low amounts of active nuclear IKKα, whereas late-stage tumors contain the highest levels of active nuclear IKKα. The researchers also found a striking elevation in expression of RANK ligand in late tumors, but it was not expressed by the cancer cells. Instead, it is expressed by invading inflammatory cells. Interference with RANK ligand production or activation, as well as interference with IKKα activation, may offer new therapeutic strategies for prevention of metastatic disease.

The study was funded by the National Institutes of Health, the U.S. Army Medical Research and Material Command, the Prostate Cancer Foundation, the Aventis-UICC Translational Cancer Research Fellowship, the Lopiccola Fellowship of the UCSD Moores Cancer Center, and the Life Science Research Fellowship.

Additional contributors include first author Jun-Li Luo,Wei Tan and Olexandr Korchynskyi, UCSD Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Moores Cancer Center; David A. Cheresh and Jill M. Ricono, UCSD Department of Pathology and the Moores Cancer Center; and Ming Zhang, Baylor College of Medicine, Department of

Kongo's picture
Kongo
Posts: 1167
Joined: Mar 2010

Hey, Ira. No red flags. Obviously I don't have the "facts" on this issue other than the ones I referred to earlier. I just get very suspicious of one-liner dismissals about the potential impact of things relating to cancer. I don't think we know enough about too many things and in this case there is so much vested interest in continuing biopsies that I doubt we will ever see a costly study to examine it...who would sponsor it? Way too political.

I have recently read that dogs can be trained to sniff urine to determine if there is prostate cancer. Of course, dogs spend most of their lives sniffing urine so maybe they have a good nose for it. I would draw the line on a DRE though...wouldn't want a pit bull going there!

It seems to me that the hardest part about diagnosing cancer without a biopsy is determining the right Gleason equivilent without actually looking at the cell structure and the only way I can imagine doing that with technology today is via biopsy. But I do think some savvy researcher will find a way to do it in our lifetime.

Although given that we do know that cancer spreads via the bloodstream and lymph system and we do know that even a thin biopsy needle pierces these systems while drawing core samples, it makes sense to me that there is a very likely chance that there are some cancer cells that are going to get loose during the process. Studies or no, I will remain suspicious of the procedure and avoid it where I can.

A similar corollary is the amount of vitamins and supplements many men with cancer take without hard studies showing value. There is much we do (or don't do) that can't be absolutely supported by studies.

mister mike
Posts: 1
Joined: Nov 2010

I am a young 70 recently diagnosed with PC, Gleason 3+3, three out of twelve hits on biopsy and a PSA of 7. I was going with AS until an MRI showed that the tumor was nestled up against the seminal vesicle. Bone scan normal and PSA actually went down to 6.7. The proximity to SV quickly put me in the same treatment maze that so many of you have been in. I am coming out of the maze looking strongly at radiation therapy and and am deciding between CyberKnife and TomoTherapy. I noticed from prior communications that Kongo chose CyberKnife after considering many options. I apologize for being off topic but this is my first post and I didn't know how to get in the conversation without just entering through this door. Does anyone have advice or information or anything else on TomoTherapy versus CyberKnife?

All of these posts I have read in the past have been very helpful to me generally and I appreciate the involvement and opinions of you fellow travelers.

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Kongo
Posts: 1167
Joined: Mar 2010

Hi, Mike and welcome to the forum. When I was researching CyberKnife I also looked at TomoTherapy and asked a lot of questions about it from two different radiologists. I would encourage you to do the same so that you really understand the nuances between the two.

In many wasy there are very similar...both deliver very accurate dosages of radiation. TomoRadiation uses a process that modulates the intensity of the radiation beams to concentrate dosage in the exact area the radiologist wishes to target. As I recall, In TomoRadiation the equipment fuses at CT and MRI image in near real time and delivers radiation within about 1 mm accuracy. CyberKnife delivers < 1 mm accuracy and uses gold fiducials to track the prostate movement in real time via low level x-rays and adjusts equipment placement accordingly.

With IGRT (Which is what Tomo is...Image Guided RT) you lay in a tube and the radiating part of the machine spins about you. In CK you lay on a bed and the robot arm moves about you.

With CK you typically have 5 sessions, each about 40 minutes. With Tomo you have abut 40 session, each consisting of about 5 minutes of actual radiation. The biological equivilent dosage is about the same between both methods.

I chose CK over Tomo or straight IMRT because I felt that the real time tracking of prostate movement offered a slight clinical advantage and the treatment could be accomplished much quicker. I believe the side effects are pretty much the same for either method.

I would encourage you to meet with radiologists who specialize in both and get their opinions about which method might be best for your particular situation. In the end it may well come down to which doctor you prefer.

Good luck and keep us posted on what you learn and how things work out.

hopeful and opt...
Posts: 2218
Joined: Apr 2009

that there are side effects from everything....so as far as biopsies, I want to have less...less chance of infection, sexual problems, etc., and the same is true for vitamins...some of these vitamins , and also prescribed drugs have unknown negative effects.... ...there are people errors in what ever you do....

Frankly , at this time I also do not have the facts about biopsies spreading cancer, only input from various docs who I respect, who support biopsies and state that biopsies do not spread cancer.............however to be honest , many doctors used to support smoking, so who knows what we will come up with in the future, but for now, I believe that it is advisable to go along with current medical protocol, and not second guess....I for one am not qualified and do not know more that the vast majority of the personnel in the medical profesion, and I beleive that even you who I respect greatly are not qualifed.

I also believe that there will be improved diagnostic tests for PC... not needed for DRE's
.....airport security already does the best job.

worriedwife
Posts: 15
Joined: Oct 2010

After this past test being 3.7, I had the same question. The urologist explained that when the prostate is removed, there are small parts that remain. There are usually no problems if all the cancer is removed, but, if a very small amount of cancer remains, over the course of years, the PSA can rise and thus the recurrence. My husband had been at 0.02 for 10 years. I still am a bit befuddled. He also said other glands could cause the sudden rise and that is why they wait the 3 months to be sure it just wasn't from another gland out of whack. Either way, my husband and I would do it again. He has been cancer free for 10 years and that is alot of stress relieved. We will work it out again if that is what the results show this year. I was really scared a few weeks ago but just chatting on this site has actually eased a bit of my fears. Keep the faith.

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Kongo
Posts: 1167
Joined: Mar 2010

Worried Wife:

I'm about confused about what your doctor relayed to you when he explained potential rises in your husband's PSA reading. I certainly agree with his discussion about prostate tissue left behind after an RP. That is always the case after surgery. What I do not understand is his discussion about another gland being "out of whack." I don't know what that means unless he is suggesting that prostate cancer has spread to another place, such as a lymph node or seminal vesicle, liver, lung, or bone but technically those aren't "glands." PSA comes from prostate cells. When a man has a prostate, non cancerous PSA elevations can be caused by a urinary tract infection, BPH, a biopsy, or other inflammation. Short term PSA elevations can come from ejaculation, a DRE examination, a hard stool, or even bicycle riding. Since your husband had his prostate removed more than 10 years ago, there really isn't another potential cause of the PSA elevation except for a return of prostate cancer where these cells (regardless of where they now are in the body) are generating PSA. The only possibility I can imagine that could be an alternate explanation is an error in the PSA reading due to equipment calibration, human error, or some accidental contamination of the blood sample. I would be fascinated to know what other glands he is talking about when he suggested to you that "... other glands could cause the sudden rise..."

I am certainly not trying to scare you or give you gloomy news but I think you and your husband deserve accurate and precise information about what is happening and why and what options you have to deal with it. Doctors should take pains to explain to you what is going on in exact terminology and make sure you understand it. Terms like "out of whack" only make sense if you understand the chemistry and biology of what is going on at the microscopic level. I do hope that your next reading comes back at the very low levels you have experienced for so long but you should also be prepared for what you should do if it comes back and shows another increase.

I was also surprised to see than in antother post on this thread that you indicated that your urologist doesn't believe in hormone therapy and would probably do radiation instead. Radiation is a common treatment for recurring prostate cancer but so is hormone therapy or a combination of both hormone therapy and radiation. Most studies show that there is a much higher long term prognosis with a combination of hormone therapy and radiation than with either treatment used alone.

As with any diagnosis of this serious nature, I would seek a second opinion on your doctor's recommendations.

Best of luck to both of you.

hopeful and opt...
Posts: 2218
Joined: Apr 2009

........basically he believes that it is a good idea to hold off hormone therapy; after other salvage treatment(radiation) because of the potential ill effects....(I did not ask for source information)...just mentioning here for possible discussion.

worriedwife
Posts: 15
Joined: Oct 2010

I agree that if things are not explained properly, I will seek another opinion. I replied above to correct myself in that my husbands PSA was at 0.002 not0.02 in April and then jumped to 3.7 6 months later.

I was not happy with his explanation and he seemed surprised that I met with him after he spoke with my husband and told him he would retest in 3 months. My husband had a brain injury last year and is almost back to his normal self with some residual minor issues. He had a great neuro surgeon. But, due to this issue, I have to get first hand information to understand what is going on. I also was not happy that he seemed so aloof about it all.

I am thinking of calling his original surgeon if it turns out it is cancer again. This urologist talked to us like it was no big deal. He said since it is 10 years out he doubts recurrence, rather it would be more likely a new cancer????? Yes, that made me feel good. Then as we were leaving he said if it is recurrence, they would just shoot radiation into that area and it would be all better. Then he said he was not a fan of hormone therapy.

Thank you for all your words of wisdom.

2ndBase's picture
2ndBase
Posts: 220
Joined: Mar 2004

When I was first diagnosed 7 years ago this week I was told by my urologist that another gland also puts out small amounts of a tertosterone type chemical that makes the cancer grow faster. It may have been the throid but its been a long time and my memory is not that good. Anyway, he put me on some pill to discourage this from happening. I too am not a fan of hormone therapy and speak from experience. Side effects are not worth the time in my opinion.

worriedwife
Posts: 15
Joined: Oct 2010

Thank you for letting me know and I think in my stressful visit, he might have mentioned
the thyroid gland.

What kind of side effects have you had with the radiation and/or hormone therapy?

I am so glad there are people here to talk to and vent. I truly appreciate any and all input.

Kongo's picture
Kongo
Posts: 1167
Joined: Mar 2010

I understand the frustration you have with your urologist and in my opinion he should have taken more time to explain his thoughts. I also understand your anxiety from dealing with these new issues as your husband recovers from his brain surgery.

In your original post you mentioned that your husband’s original PSA was 1.4 and that some prostate cancer was discovered during a TURP procedure. I am assuming that the TURP was performed to alleviate some urinary discomfort from an enlarged prostate. Prostate cancer frequently begins to show itself at the same time as BPH (benign prostate hyperplasia). As you may know, very often incidental prostate cancer is found in men beyond the age of 50 without any other indications. Frequently this incidental cancer is indolent, very slow growing, and never poses a threat to the patient. Without knowing the details of the post RP biopsy this is just speculation but it’s certainly possible that the PSA you are seeing now is a result of a small amount of cancer left behind from the original surgery that has taken ten years to reach a stage where it is making enough PSA to show up. Remember that most forms of prostate cancer are very, very slow growing and these cancer cells only divide about every year and a half.

Prostate cancer spreads through the blood stream and the lymphatic system so it is possible that in the years since the original RP that prostate cancer has taken hold in a nearby lymph node or seminal vesicle (you will want to check the records from the prior surgery to see if they were removed or not). Outside the prostate, cancer grows faster than it does inside the prostate and PSA will tend to increase more quickly. Some scientists believe that the prostate produces protective tissue that acts to isolate the cancer but that outside the prostate this does not happen.

Given that your husband’s prostate was removed, it is difficult to imagine that this is a new prostate cancer distinct from the earlier form. Although since there was undoubtedly some prostate tissue left behind after his RP, I suppose it is possible but I have never heard of that happening. Most likely, it is a continuation of the previous cancer and recurrences after ten years or more while uncommon are not unheard of.

It’s entirely possible that if you do discover that prostate cancer has returned that it is a very slow growing, indolent type of cancer that does not pose a health threat. I would be prepared to calculate the PSA velocity which is a valuable tool in determining the severity of any recurring cancer. I also urge you to seek out second opinions, particularly if you’re second guessing whether or not your existing medical team is meeting your needs.

worriedwife
Posts: 15
Joined: Oct 2010

Yes, the turp was a result of what was believed to be BPH. He was having trouble urinating.

The cancer was found when biopsies were done during the turp and his PSA was 1.4.

The surgeon did a nerve sparing prostatectomy. It was the new urologist, since we moved, that said that there is tissue left even during the RP.

I guess I will know in about 2 weeks what the numbers mean. It was the VA report I was going by and he was staying at .002 to .003 for the past couple of years, the latest in April of this year.

In October is when the urologist ran the test that came back at 3.7 and the VA is doing another next week with a follow up with the doc the following week. This way I can compare and ask a few more questions.

He did not cancel the January appt with the urologist for his follow up PSA test. I am guessing if all 3 come back this high, there will be decisions to make. He had this new urologist for 6 years, but, during this stressful visit he seemed to have no bedside manner and I guess that is where I got a bit upset.

I will keep posting on his next results and am grateful for everyone's input and support.

Thanks to everyone here. Together we can all conquor this!

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