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High PSA and Negative Biopsy What Next???


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Old 08-04-2016, 07:05 AM   #1
Max1822
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High PSA and Negative Biopsy What Next???

Hi just wanedt to share my story. I have a larger prostate about 70cc and have the classic symptoms of BHP. Numerous dre's all negative. After seeing a urologist with a hi PSA value of 15.0 (even after cipro) he sent me for a biopsy. All cores taken were negative. Repeated the psa test 5 months later and my PSA had small drop to 14.4? I realize that is still in the danger zone so my question is where do I go from here?? Never tried flomax or other medicinal products. Some of my symptoms include some difficulty peeing first thing in the morning. The rest of the day I'm fine. Any comments are welcome and thanks for your time. Max

 
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Old 08-05-2016, 08:11 AM   #2
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Re: High PSA and Negative Biopsy What Next???

Hi Max,

Here are some facts to keep in mind and tactics you could try to figure out what is happening.

As you seem to already know, an enlarged prostate of completely cancer-free cells produces more PSA than a smaller prostate, and there are some rules-of-thumb to estimate the amount of PSA produced by healthy cells. One is that each cc of healthy tissue will produce 0.067 of PSA (looks real precise, but the figure is actually an average, so it's more of an approximation); multiplying 0.067 by your prostate of 70 cc yields an estimate of 4.6 units of PSA from healthy cells. Another rule-of-thumb is that each cc produces about .1 units of PSA, so 70 times .1 yields an estimate of 7 units of PSA from healthy cells. Based on these rules-of-thumb, your last PSA of 14.4 - 4.6 for the first estimate from healthy cells equals an unexplained PSA of 9.8, and 14.4 - 7 equals an unexplained PSA of 7.4. It is worth noting that both fall into the 10 or lower range, which is good all by itself because a PSA exceeding 10 suggests (but does not prove) a higher risk in patients after a diagnosis of prostate cancer.

It's important to observe that your PSA did not increase, in fact it fell a bit from 15.0 to 14.4, over a five month period. That does not rule out prostate cancer, but it is inconsistent with the nature of the disease as each prostate cancer cell splits in a pretty steady length of time, with the result that the cancer, and its reflection in PSA, increases "exponentially", doubling in a length of time that generally does not change for each patient except when affected by outside influences, such as effective medications, other treatment, or sometimes lifestyle influences (we think). With cancer, we would expect to see some kind of increase over five months, and that's not what happened for you. For a very small portion of patients, their cancer is quite aggressive but makes little or even no PSA. That is possible for you but highly unlikely, especially with those multiple negative DREs and 100% negative biopsy cores; of course, while the odds after all that get quite low, it is possible that a small amount of cancer was missed by the DREs and also by the biopsy sampling.

So what else could be happening beyond BPH and cancer, with the latter looking unlikely? As you seem to know, infection would be a more likely cause of an increase in PSA than cancer, and that difficulty peeing could be a result of infection as well as the BPH, which you know you have. Cipro is typically used to try to knock back what might be an infection; if the PSA goes down, it's good evidence that an infection sensitive to Cipro was causing the elevated PSA. However, many other bacteria that Cipro cannot kill can cause infection. Therefore, the absence of a PSA response to Cipro does not at all rule out infection as the culprit. My hunch is that your urologist will try some other drugs to see if they do the trick.

Another tactic could work with both BPH and help smoke out whether there is any cancer. The tactic is to use one of the drugs in the drug class known as 5-alpha reductase inhibitors, and there are two of them, now both generic. The older, originally sold as Proscar, is now available as finasteride. The newer, Avodart, now available as dutasteride, is significantly more potent, but a few men cannot get a benefit because of their genes, so finasteride would be the alternative for them. These drugs reduce BPH, in fact that is the purpose for which the FDA approved them. However, many of us, including me, have been prescribed these drugs under the easy "off-label" prescribing rules for prostate cancer. (I've been on one or the other since the fall of 2000; I'm now on Avodart more or less as a safety net, as I think I'm cured.)

These drugs have several benefits, including reducing the blood supply to the prostate and to any tumor cells in it. They also reduce the PSA, mainly by shrinking BPH, but also by, as indicated by good evidence, killing lower grade cancer, such as up to Gleason grade (not Gleason score) 3 cancer. By making the prostate smaller, these drugs make PSA analysis from that new baseline, DREs, and biopsies more efficient in detecting the cancers, if any, that are more aggressive. There once was a concern that the drugs might promote more aggressive cancer, but that has been resolved in the minds of many experts (and me), who, among other points, see that by reducing the size of prostates, the drugs make it more likely that biopsy probes will hit that aggressive cancer.

Good luck sorting out the cause(s) of that elevated PSA.

Last edited by mod85; 10-13-2016 at 09:14 PM. Reason: Typos.

 
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Old 08-05-2016, 11:49 AM   #3
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Re: High PSA and Negative Biopsy What Next???

Wow IADT, thanks so much for sharing your informative and detailed experience with me. You have given me some good info on how to move forward and question my urologist when I see him soon again. Forgot to say I'm a 59 year old male still quite fit with a relatively high psa since my late 40's. One friend suggested I take the 4K prostate test which helps determine if there may be an aggressive cancer hiding in there somewhere. I realize that my negative biopsy doesn't get me out of the woods yet and I need to be vigilant going forward. That's why I decided to join this Board. Do you think a 4K test is a good idea? I just hope he doesn't rush me into another biopsy as I had one less than 5 months ago. I know having a larger prostate and BPH problems may be part of all this. I will definitely speak to him about the drug inhibitors you mentioned. I will be travelling to Europe soon so I would love to have some relief from the difficulty of peeing each morning. Funny thing after the morning struggle, I'm relatively fine during the day. Go figure ??? Do you think if he sends me for another biopsy I should suggest an MRI to target suspicious areas of the prostate instead of another blind 14 cores? A saturation biopsy? Thanks so much for replying to my post. I see from your other posts you have helped many people in here. I'm sure it is much appreciated as we go through this fight together. I'm so glad you are over the hump with this crazy disease and I wish you nothing but the best. Max

 
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Old 08-06-2016, 01:16 PM   #4
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Re: High PSA and Negative Biopsy What Next???

Hi again Max.

You're welcome, and I'm glad to help. It's a pay-it-forward deal for most of us, and we are happy to do it.

Regarding the 4K test: I'm hoping you get some replies from some men who have used this test (not me), but I can offer only information based on research. It really looks good in research, probably enough for a lot of us to consider the $395 cost worthwhile, even if not covered by insurance.

Here's the link to the study on a US government web site (PubMed): http://www.ncbi.nlm.nih.gov/pubmed/25454615 The lead author was Punnen. This very large and rather high quality US study has been interpreted to show that the 4K test is considered extremely good (“near perfection” per one source) at picking out likely cases for higher risk cancer (Gleason score of 7 – “intermediate risk”, though other factors can elevate intermediate risk to high risk - or “high risk” – Gleason 8 to 10), which is what we want – not caring much about Gleason 6 and lower cancer that is so often a nuisance and cause for anxiety rather than a threat. That helps avoid biopsy in 30-58% of patients depending on the threshold used as a trigger for biopsy, with a risk of delayed diagnosis (not good of course for higher risk cancer) in only 1.3-4.7% of higher risk cases. Therefore, it is not a slam dunk or grand slam, but pretty close, especially when the doctor is also considering other facts that can lower the risk even further of stealthy high risk disease (factors such as the, PSA doubling time, possibly genetic analysis, possibly multi-parametric MRI (mpMRI), family history, etc., as well as monitoring).

Here’s a link to another encouraging study about the 4K, and the complete paper is available for free with the link at the site: http://www.ncbi.nlm.nih.gov/pubmed/26839521 . The following final study is interesting, especially Figure 4, a simple and dramatic table, which compares biopsies avoided as a result of 4K with the very small proportion of added risk due to aggressive cancer missed by not biopsying: http://www.ncbi.nlm.nih.gov/pubmed/26028995 .


Regarding mpMRI, you asked:
Quote:
Originally Posted by Max1822 View Post
Do you think if he sends me for another biopsy I should suggest an MRI to target suspicious areas of the prostate instead of another blind 14 cores? A saturation biopsy? ... Max
An mpMRI would certainly give you some good information, helpful both in deciding whether a biopsy was even necessary or in targeting some of the cores of the biopsy. mpMRIs have become a lot more popular in the past five years, and there is a lot of research published about them. I wanted one before finalizing my decision to go ahead with radiation for my high-risk case, but I had already had two very sensitive tests for bone and soft-tissue (lymph glands, etc.) metastases, and the oncologist did not think the added information from a mpMRI would change anything in the context of the thorough radiation that was planned, including radiation beyond the prostate to the pelvis. While my curiosity over where exactly the cancer was located was unsatisfied, his judgement made sense, and so far the decision looks good as I am doing exceptionally well.

Again, I hope you get some responses from patients who have actually used the 4K and mpMRIs. It is always reassuring to get first hand information.

Take care,

Jim

Last edited by IADT3since2000; 08-06-2016 at 01:21 PM. Reason: Minor.

 
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Old 08-06-2016, 01:59 PM   #5
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Re: High PSA and Negative Biopsy What Next???

Once again, thank you Jim for your insights. Much appreciated. I will check out those links you sent me on the 4k prostate test and keep you updated on my situation as I go see the urologist in a week. It's so encouraging to hear from people like yourself and those who have been in the trenches in this fight. I realize I'm not a full fledged member yet since there has been no diagnosis but the worry for the reasons to why my psa is so freaking high is a dark cloud that lingers and will not go away. Forums such as this really help.

I read most of the postings about those undergoing a first time prostate biopsy and it really helped me prepare for what to expect. Truthfully, I shared much of the same experiences relative to anxiety, worry, pain and after effects. It's inspiring to hear some success stories like yours and the valuable information you impart. Please stay in touch. Max

 
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Old 08-08-2016, 02:12 PM   #6
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Re: High PSA and Negative Biopsy What Next???

Went to the Urologist today to meet about my latest PSA score. He recommended that the next step after slightly lowered but still high PSA was to do an MRI before ordering another biopsy. I understand that this would be a targeted biopsy in the event the MRI shows suspicious areas. I did discuss the 4k test which he agreed was a very good test but very pricey here in Canada. I told him money was not my concern here. He did prescribe medicine that helps relax the prostate (alpha blocker) so I can have easier urine flow called Rapaflo or Silodosin 8 mg/day. Have you heard of this medicine? I understand that it does not shrink the prostate but only relaxes the muscles in the bladder and the prostate. Could this possibly help lower my psa?? The possible side effects include dizziness, lightheadedness and ejaculation problems. Yikes, the last one scared me a bit lol. Now, I await my MRI appointment date and go from there. Will keep you posted in my travels.

 
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Old 08-09-2016, 09:44 AM   #7
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Re: High PSA and Negative Biopsy What Next???

I haven't hear of Rapaflo or Silodosin 8, but they are likely fine drugs as I am just not very knowledgeable about blockage issues other than knowing that finasteride and dutasteride can help.

Where are you in Canada? Canada has some of the best prostate cancer doctors in the world, and they have contributed greatly to research. Centers in Vancouver and Toronto have been particularly active over many years, but there are other locations of expertise also. A doctor I find particularly awesome is Laurence Klotz, MD, from U. of Toronto, Sunnybrook. It would take a long time just to review the titles of all the research papers with which he has been involved, often playing the key role.

Do you know if that MRI would be an endo-rectal MRI (known for being helpful but uncomfortable) or a 3T multiparametric MRI, which is rapidly becoming very popular in biopsy and treatment decision making? My impression is that Canada, while among the leaders in prostate cancer management in many ways, is not in the forefront of imaging. That's an impression from several years ago, based on statements from American and Canadian experts, and it may now be outdated.

I hope you get other responses.

 
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Old 08-09-2016, 11:33 AM   #8
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Re: High PSA and Negative Biopsy What Next???

Hi Jim,

I am just outside of Toronto. My urologist has been called one of the best in this area and he's recommended an MRI that I take with a dye. Not sure what it entails as it is my first imaging procedure. I know its not endo-rectal as he described my procedure as non invasive. I wont be having the MRI for a while yet as I'm heading out on a vacation over seas (in Sept for 3 weeks) and will do it when I get back. This is why I requested help with my BPH. The Rapaflo is an alpha blocker that relaxes the prostate and bladder to have an easier stream but it also reduces ejaculate almost to none. This is what worries me. Does Flowmax and the Avodart do the same things? I guess if they dont see anything on the MRI (fingers crossed), a 4k test may be my next steps. Your insights are always appreciated and thanks for mentioning that Canada is at the fore in prostate cancer research and treatment. Since this is my first rodeo with this PSA adventure, I will have better commentary about our system as this plays through. Thanks for keeping in touch. I get a sense of relief knowing we have keen people like yourself on our side! Cheers Jim

 
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Old 08-09-2016, 01:55 PM   #9
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Re: High PSA and Negative Biopsy What Next???

Hi again Max,

I suspect the planned MRI is an mpMRI as using a contrast agent enables one of the characteristics usually measured in an mpMRI. You could call to be sure to satisfy your curiosity, but a respected doctor in the Toronto urology community is probably well up to speed on what should be done in your present circumstances whether a regular MRI or an mpMRI.

I have heard about Flomax so many times, but am still not that familiar with it as it addresses one of the problems I have not had to face. I hope you get some other replies on that. Avodart works differently. It shrinks the prostate, and by doing so makes it easier to urinate - less pressure on the urethra. My recollection is that it has no effect on the bladder. For a small percentage of men, my recollection is about 10%, it lowers libido and may cause a decrease in erectile function, but for the vast majority of us it has no such effects at all. Dr. Klotz has researched it some, especially in his large group of active surveillance patients, so it is likely that Toronto area doctors are well aware of its role.

Hope you have a great vacation!

 
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Old 08-10-2016, 09:28 AM   #10
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Re: High PSA and Negative Biopsy What Next???

Thanks for the best wishes on my trip. I think the Rapaflo will help me with the partying I will be doing with friends that are joining us. I will have to watch my alcohol intake as my prostate has already gone through enough. lol

Still waiting on my MRI date. Jim can you please tell me what they will be looking for to determine what is wrong with my prostate on this 3d imagining test. For example will they be able to determine if I have an acute infection, bladder infection, prostatits, serious case of BPH , or other. Just wondering what are other things they can positively identify during this MRI that may be causing the PSA elevation. I realize that a suspicious areas will need to be biopsied for the possibility of PCa.

 
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Old 08-10-2016, 11:56 AM   #11
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Re: High PSA and Negative Biopsy What Next???

Hi Max,

I know about the cancer side, and I believe the 3T mpMRI scan is useful for other purposes, perhaps some or all of the ones you mention, but I'm not sure. You could try researching that, or hopefully one of our other participants can help with an answer.

The scan usually covers three or four different sub-tests among the following, and it can get pretty technical: "T1-weighted" - if you can figure it out, please explain it to me; T2-weighted - likewise; diffusion weighted (DWI-MRI) deals with the speed of water diffusion through cells, with cancer cells behaving differently than normal cells; dynamic contrast enhancement (DCE-MRI) is similar to the water test in concept, as there is a difference in the way cancer and normal cells take up the contrast agent; and spectroscopy (MRI-S), where the "signal" for cancer is different from the signal for normal tissue, using choline and citrate, as I recall, as the specific signals of interest.

 
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Old 10-03-2016, 12:24 PM   #12
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Re: High PSA and Negative Biopsy What Next???

Just reporting in to say I had my mpMRI after getting back from an amzing trip in Europe. I'm awaiting results from my Uro to try to explain why PSA is so elevated. My last PSA saw it go down just a little after a 5 month wait . I have a large prostate (around 70CC) and BPH symptoms along with 1 negative biopsy under my belt so now we hope the MRI can figure all this out.
People in this newsgroup are so knowledgeable and helpful and I find solace in seeking information, help and support in this group.

 
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Old 10-11-2016, 01:33 PM   #13
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Re: High PSA and Negative Biopsy What Next???

Hello All,

Today I met the Urologist to say my mpMRI was negative. His recommendation is to now have shorter intervals for the PSA monitoring. Every 3 months and if the PSA remians elevated to repeat a biopsy. He told me I did have a large prostate and will have to live the symptoms of BPH. No imflamation or infection was evident. So after a negatibe biopsy , a negative MRI not sure what the future holds becuase I still have a high PSA. Note sure whether I should celebrate yet but I'll take one step at a time.

 
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Old 10-13-2016, 12:25 PM   #14
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Smile Re: High PSA and Negative Biopsy What Next???

Hi Max,

Great news!

That PSA monitoring program looks sound, but I'm puzzled about the urologist's statement that you would have to live with the side effects of BPH. Of course your urologist is a doctor who has just seen you, and I have no medical credentials, but I'm wondering why the doctor did not mention some of the ways to lessen the burden of BPH. The ones I know about best are the ones I mentioned in post #2, the 5-ARI drugs, specifically Proscar/finasteride and Avodart/dutasteride, and they have the added benefits of improving the effectiveness of PSA testing and DRE exams, as well as helping reduce or eliminate mild prostate cancer.

But enough about the cancer and BPH. Back to your GREAT NEWS!

 
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Old 10-14-2016, 08:01 AM   #15
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Re: High PSA and Negative Biopsy What Next???

Thanks for the congrats Jim. As much as I can rejoice about the negative MRI I'm still at a loss at why my psa is elevated. My last PSA went down half a point after 5 months. My urologist did say I have a very large prostate, there were no signs of infection or signs of cancer. He did (previously) give me a prescription for Rapaflo which is similar to those A5 medicines you stated. Right now my symptoms seem to be controlled by just using Saw palmetto 900mg 1 per day. The rapaflo caused way too many negative side effects (complete loss of ejaculation) which I hated but it does work to help you pee! Needless to say I stopped it after a few weeks and wen the natural route. He suggested repeated PSA and possible repeated biopsy should the readings swing higher in the future. So small steps forward. I really appreciate your expertise here and I've noticed you have helped so many with advice in this forum. Kudos for all your help and support Jim. I'll keep posting updates here but I really do think I can relax for a bit. On a side note my Urologist was tracking my PSA reading from about 13 years ago and said I have always had high PSA with a baseline of about 6.5 with an acceptable free PSA . He says I'm a unique case LOL. A freak of sorts possibly? Anyway thanks for the reply and I hope you never leave this place !!! Cheers Max

 
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