Negative Biopsy but High PSA: What Happens Next?

A biopsy can’t rule out prostate cancer.  Some men have 2, 3 or even more biopsies before they finally detect cancer.  Sometimes, they just miss it, because the major flaw inherent in using a biopsy to search for cancer is that it only samples a very small percentage of the prostate tissue.  It’s also possible that there was no cancer originally and it developed after the first biopsy.  In fact, some studies indicate that prostatitis, BPH or atypia may increase your risk of future cancer, so being diagnosed with these means you need to keep a close check.  There are also apparently some areas of the prostate that are difficult to sample during a typical transrectal ultrasound (TRUS) biopsy. 

Fortunately, there are newer techniques for prostate biopsies other than the random 6 or 12 sample method done in in a typical urologist’s office.  Like the targeted MRI/TRUS fusion biopsy I had, there are also saturation and “mapping” biopsies that use more samples or some type of specialized imaging to improve the coverage and reduce the chance of a false negative.  Some of these are transperineal, meaning they are done through the skin, rather than through the rectum.  A biopsy like these might be considered by higher risk patients who have had a negative biopsy in the past. 

Because I had two other negative tests, I hope that I am in a lower risk situation than most men with a negative biopsy and relatively high PSA level.  My PCA3 test score was negative and also quite low overall.  I had an advanced “3 Tesla” MRI with 4 different types of scans and that showed nothing of significant clinical interest, either.  All together, it’s unlikely that I have an undetected cancer.  On the other hand, something is clearly abnormal, because my PSA is high for my age.  Most men in their early 40s have a PSA below 1.0, whereas mine has been between 2.4 and 2.7 for at least a year and a half, over 4 different PSA tests.  Also, my prostate is slightly enlarged, about 30cc.  Finally, my MRI indicated a pattern consistent with prostatitis and my biopsy did show a couple areas of atypia; both of these might be a precursor to cancer.

So, I do intend to keep a pretty close check on it.  I’ll probably have my PSA checked every 6 months with or so along with a DRE and perhaps get a PCA3 test each year.  I also plan to keep my appointment with Dr. Catalona.  I had scheduled this a while back, just in case my biopsy pathology showed cancer.  He’s pretty much THE expert on prostate issues in the Chicago area.  I want to get his input on what I should do in terms of checkups, health, diet and possibly even future studies that might be relevant to me.  My appointment isn’t for a couple weeks, but I’ll report on it at the end of this month.

24 thoughts on “Negative Biopsy but High PSA: What Happens Next?”

  1. Last march after I took my covid vaccination I tested PSA is 5.8 then I tested in april it was 6.8 then I went to urologist, it was 7.2. I went thru MRI, they found a spot on my prostate and prostate is almost normal size, I am 49 years old. I have also went thru Biopsy, but the report came negative , no evidence of cancer. What should I do? I am very much worried.

  2. My psa level was 9 last June had a biopsy no cancer had another psa test December same year it went down to 4.99 3 mounts later had another in march this year it was 5.75 I’m to take another biopsy in 2week I’m 66 black male is it to soon for another just asking

  3. Well in 2013 I had a PSA of 31 and had 5 weeks of radiation and was about the 5th person at Penrose Cancer Center to have Cyber Knife radiation on 12 and 15 July 2013. a year later my PSA was .06. in 2018 the doctor opened up my urethra because of dead tissue from the cyber knife radiation. I had my PSA check a week ago and it was 17 and then again on Monday and it is 19 and now I am not sure of what to do?

  4. Hello,
    I had a TURP in November 2016 for prostate stone which it also revealed Gleason 7 cancer. I just had a 3T MRI and fusion biopsy on February16 , the MRI showed 2 suspicious spots with 2 PI-RAD 4 lesions however the targeted biopsy was all clear. My Dr. said that sometimes the MRI can give false positive , my PSA is 0.7 . I am very concerned that the cancer got missed , I had cancer last November so it just vanished now? How is this possible?

  5. I had a psa of 4 in 2004 a biopsy showed cancer cells and in 2004 had seed inplants 48 plus radiation treatment and psa dropped to .2 with cancer eliminated. In 2009 psa started to rise and biopsy was neg for cancer. In 2011 psa was up to 6 and I went to Freodert had two pet scans for flesh and bone and two more biopsy and all shows cancer free with a psa of 19. This is the end of 2012 and the oncologist does not know what he should do as I have no negative physical problems. If not for psa of 19 I would tell you I’m fine. This Doc is a good person and said to recheck in 3 months unless I have a problem. What else should I do???????

    1. Hi Joe, Your situation sounds complicated enough that really only another urologist or oncologist could probably advise you on what to do next, unless someone here happens to have been in a very similar circumstance. I wish you the best of luck in finding some answers!

  6. I had a biopsy a year ago. PSA has been up and down since I was 40. No known history of prostate cancer. Had a 7 in the fall and now it is up to 10. Dr. wants to do another biopsy in 2 weeks. Having concerns after reading the blog and other information that this may be a waste of time. Prostate is large, but I am 61. Have taken flomax for some time. It seems to work. If this biopsy is negative again, any suggestions on questions to ask the doc on the followup in late Feb?

  7. I’m 67, my PSA starts from 4.0 in 2001,rising to 21.0 last December.My father died of prostate cancer.I underwent to 8 biopsy, the last two weeks ago,24 samples that shows chronic prostatites and areas of athrophyes,no neoplasia evidence.Doctor suggested partial prostatectomy.I’ve not made my mind yet.

  8. Hi Darren,

    Thanks for the reply, I have now seen the urologist my prostate is enlarged although prostatitis was ruled out as it did not show on the biopsy, the urologist said that pin was present, which I understand is a change in the cell formation on more than one of the biopsy results, The intention is for me to have regular blood tests and depending upon the results of the PSA levels decisions will be made re. further biopsies, I am booked for an MRI in 6 weeks so will have to see how i get on with regular monitoring, Thanks for your response, I will come back if anything further to report Regards

  9. HI Just wondered if anyone can help?

    Age 47 – I have had a PSA level of 4.1 and a free level of 0.10 10% I think this means, Examination was ok, had 19 biopsy all were negative? – What now? could I just have a high psa and a low free psa with no real issues?

    1. Hi Kevin- you are kind of in a similar situation as I am. You might have a slightly enlarged prostate, prostatitis, BPH or some other condition that results in your PSA being a little high for your age. Since you’ve already had an exam and biopsy, there’s not much you can do but have annual checkups or perhaps get a second opinion from another urologist. A few will try an extended course of specific antibiotics to rule out an infection, but other than that, if you don’t have any other symptoms, there may not be anything else to do.

  10. If I understand the literature, 28% of biopsies prove “positive” with PSA’s in the 2.7 to 10 range and it is estimated that the same relative number of men are diagnosed with PCA with PSA’s <2.7. Also interesting is how many initial biopsies are negative, but eventually turn up positive.

    Are the pathologists missing the cancers in the first place? Is the cancer or abnormal cells growing so slowly as to be initially missed? Is the biopsy procedure truly just looking for a needle in the haystack? Or is it possible that the constant poking is somehow causing a cancerous scenario to develop? Far fetched as that idea may be, it has been holding me back from getting the damn biopsy despite the dire predictions of my two urologists.

    60 YO white male. PSA 5 then 2.6 on repeat in 2007. PSA of 5.4 in Jan 2010, 8 in June 2011, 4.9 in July 2011. Asymptomatic.

    1. A biopsy only samples a small percentage of the prostate tissue. It’s probably better than a needle in a haystack, but maybe not much. For most cancers, a biopsy is done to investigate if a known tumor is benign or malignant. For the prostate, it is used for detection and for that purpose it is not very effective. Then you have PSA levels that have high rates of false positives and negatives. The combination is not a very good diagnostic system. Hopefully, something better and less invasive will come along soon.

  11. I had a high PSA and a byopsy in May this year. The 12 point byopsy, ultra sound and rectal exams were all negative but I just had a recent PSA test and I am worried that it may come back higher. What should I do if it does come back higher than before?

    1. A moderate PSA level that is slowly increasing usually indicates the size of your prostate is increasing. This is most likely because of inflammation (BPH) or infection (prostatitis), but in some cases could be due to cancer. It’s not an exact science. A prostate biopsy, unlike many modern diagnostics, has a relatively high rate of false negatives. The combination of the two relatively poor diagnostics results in a lot of guessing. It’s too bad modern medicine hasn’t come up with something better yet.

  12. My dad is 63 years old. He has had an elevated PSA for about 7 years, I know at one time it was 14. He has had two negative biopsies, the last one in 2006. A few months ago he began to complain of pain in his tail bone. His doctor kept ordering pain meds for him. Finally another PSA was checked – it was 80. He is now in the hospital with Stage 4 Prostate cancer. He is being treated with Ketakonazole and Radiation but they have yet to do another biopsy. What’s the hold up??

    1. Hi Jennifer- My understanding is that a biopsy is usually used to find cancer. If your father has already been diagnosed with cancer and is undergoing treatment, there isn’t much need for another biopsy until after the treatment is done. I wish I could offer you some better advice, but the best advice is probably to seek a second medical opinion from a urologist or oncologist if you think his treatment plan is not right.

  13. PSA 10.0 Age 58 biopsy normal tissue. Free PSA zero. Recommended that I repeat PSA every 6 months and do nothing until PSA is greater than 18.0 Why not do a radical prostatetomy on PSA value alone instead of taking a chance of a positive bone scan or CAT scan later when we finially do get a positive biopsy?

    1. Eugene: Your situation in 2011 sounds similar to mine and I hope you have fared well since your posting. Age:57; PSA 8.0 was 9.1; Negative biopsy; Free PSA 1 (I think, I don’t have the paperworkin front of me); MRI PIRADS 1-2. I hate catheters and giving up sex would not be my preference but I’d gladly sacrifice my prostate sooner rather than too late. I’m just starting this journey but looking for some sage advice.

  14. Hi John,

    I tried Saw Palmetto and Selenium for about 6 months with no effect. I do know that many people who are diagnosed with prostate cancer had no other symptoms, so that alone isn’t a good reason to avoid a biopsy. My understanding is that the physical symptoms occur when the prostate has become signifcantly enlarged, due to BPH, prostatitis, PC, or some combination. My only suggestion is that if you are not sure about your doctor’s advice is to see another doctor for a second opinion. You could also ask the doc about less invasive diagnostics before a biopsy, like measuring free PSA or a PCA3 test.

  15. Trying to avoid the Biopsy that is the usual “matter of course” for the urologist….I am 62 and the previous 2 years had a “normal” 3.75 that went down the 2nd year (Dr. appt.) 1 year later to 3.25….Last DR. appt.(July ’09) it elevated to 5.75 that caused DR. mild alarm….Tried some supplements (Beta sisterol/saw palmento the last six months and have yearly DR. checkup (general practice)in several months…Any thoughts on my prognosis? It seems I have elevated PSA BUT NONE OF THE USUAL SYMPTOMS ASSOCIATED WITH PROSTATE PROBLEMS–ENLARGED PROSTATE/URINARY PROBLEMS/UP ALL NITE ETC. Would apppreciate a reply…Thank you…John

    1. I’l be 73 in March of 2016 and two years ago my PSA was3.9. My PSA went to 5.3 had a negative biopsy I am not going to bathroom excessively. This year PSA went to 8.7 and just two weeks ago I had another biopsy that turned out negative. I feel great. I have another PSA check up in 6 months. It would surprise me to see it go down.

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