“I’m not having another biopsy after the last one!”

It will come as no particular surprise that men who have had complications after a prior biopsy tend to be less enthusiastic when it is suggested that they need another one. However, …

A recent study designed to validate this hypothesis does provide us with some useful data about just how often such complications of biopsy can occur, and how such complications affect compliance with the need for later, repeat biopsies.

Logan et al. used data from the REDUCE trial (properly known as the “Reduction by Dutasteride of prostate cancer Events” trial) to conduct a retrospective analysis of whether previous prostate biopsy-related complications — and certain types of complication in particular — were associated with repeat prostate biopsy compliance and lack of compliance in a clinical trial with study-mandated, systematic biopsies.

In particular, they looked at data on four specific type of biopsy complication — hematuria (blood in the urine), urinary tract infection (UTI), acute urinary retention (AUR), and hematospermia (blood in the ejaculate) — among the 4,939 participants in the REDUCE study. This study design specified that men should have biopsies at 2 and 4 years after starting treatment with dutasteride to see if it would lower risk for diagnosis of prostate cancer.

Here is what the authors found:

  • 260/4,939 men (5.3 percent) had a prostate biopsy-related complication at their 2-year biopsy.
    • 180/4,939 men (3.6 percent) had hematuria.
    • 36/4,939 men (0.7 percent) had a UTI.
    • 26/4,939 men (0.5 percent) had AUR.
    • 102/4,939 men (2.1 percent) had hematospermia.
  • Thus 344 of the four specified types of complication occurred in 260 patients at their 2-year biopsy.
  • 474/4,939 (9.6%) men either actively refused or just never turned up to have their 4-year re-biopsy.
  • Among the men who had any type of complication after their 2-year biopsy, non-compliance at 4 years had an odds ratio (OR) of 1.56 on univariable analysis and 1.65 on multivariable analysis.
  • Among the men who had hematuria  after their 2-year biopsy, non-compliance at 4 years had an odds ratio (OR) of 1.19 on univariable analysis and 1.19 on multivariable analysis.
  • Among the men who had a UTI  after their 2-year biopsy, non-compliance at 4 years had an odds ratio (OR) of 2.72 on univariable analysis and 2.62 on multivariable analysis.
  • Among the men who had AUR after their 2-year biopsy, non-compliance at 4 years had an odds ratio (OR) of 4.24 on univariable analysis and 4.51 on multivariable analysis.
  • Among the men who had hematospermia after their 2-year biopsy, non-compliance at 4 years had an odds ratio (OR) of 1.78 on univariable analysis and 1.85 on multivariable analysis.
  • Having blood in the urine after a first biopsy did not affect men’s willingness to have a repeat biopsy at 4 years.
  • Having any one of the other three complications definitely did affect men’s willingness to have such a repeat biopsy.

It appears that having some blood in one’s urine is not as big a deal as having some blood in one’s ejaculate when  it comes to having a repeat biopsy — and this may have something to do with the (normal) involvement of a second party when there is blood in one’s ejaculate.

It is clearly understandable why, when a biopsy is associated with a UTI or AUR, the patient might be unenthusiastic about a repeat biopsy.

We can also reasonably assume that other reasons for non-compliance with a repeat biopsy could include significant pain associated with a first biopsy (although the researchers apparently did not assess this risk — possibly because “significant” pain is a subjective issue that can be very difficult to measure and report with accuracy).

It is worth noting that just over 90 percent of the men in this trial were actually willing to have a repeat biopsy at 4 years after starting on treatment with dutasteride. However, it should also be noted that these men may have had reasons for being motivated to do this (i.e., they may have had some reason to have enrolled in this trial because of a perceived risk for a diagnosis with prostate cancer).

How to deal with a patient who is less than enthusiastic about having a repeat biopsy when a repeat biopsy is really advisable is a difficult issue to address, however. For men who suffered pain the first time around, conduct of the biopsy under some type of local or systemic anesthesia is a clear possibility, and there are things that can certainly be done to minimize risk for a repeat UTI. However, prevention of hematuria, hematospermia, and AUR are going to be rather more challenging.

8 Responses

  1. Thanks for covering this important topic.

    Patients may consider the use of mpMRI + guided biopsies to mitigate biopsy risks. Also, they can explore MicrogenDx to identify customized, optimal antibiotic protocols.

  2. Impressively Low Odds of a Complication After Second Biopsy for Prostate Cancer

    It is remarkable that these odds of having a complication after a second biopsy are so low, basically around 2% or lower except for the least burdening and concerning, hematuria.

    I’m thinking that complications were likely carefully tracked in this clinical trial, which would suggest that these percentages, which come from a large trial population, are reliable.

    Thank you for pointing out this study.

  3. @jimwaldenfels says “It is remarkable that these odds of having a complication after a second biopsy are so low”. I agree, and am left with the same question I have on a lot of these biopsy-related studies. Namely: “what kind of biopsies are these?” The standard of care is changing rapidly. And higher complications of hematuria, hematospermia, AUR but lower of UTI are to be expected with transperineal saturation biopsies than 12-needle trans-rectal.

  4. A 12- or 18-core blind biopsy, holey prostate! One million dangerous prostate blind biopsies are performed in the USA each year and they should be banned. Men with a high PSA tests result are often sent to an urologist for a blind biopsy. Men should be told about other options; percent free PSA test, 4KScore test, PCA3 test or a MRI, 3D color-Doppler test before receiving any biopsy. These tests can often eliminate the need for a risky and invasive blind biopsy. Insertion of 12 or 18 large hollow needles through the rectum into a gland the size of a walnut, a blind biopsy, can result in pain, infections, a high risk of temporary or permanent erectile dysfunction (22.3% mild ED, 15.5% mild-to-moderate ED, 10% moderate ED, and 13.6% severe ED [22,23]). Biopsies can cause urinary problems, 6.9% hospitalization within 30 days from a complication[11], sometimes even death from sepsis (about 1.3 to 3.5 deaths per 1,000 [5]). There is also debate that a biopsy may spread cancer because of needle tracking. A blind biopsy can also increase PSA reading for several weeks or months, further frightening men into unnecessary treatment. Blind biopsies are almost never performed on other organs.

    One prestigious hospital biopsy information states: “Notice that your semen has a red or rust-colored tint caused by a small amount of blood in your semen”. Another well-known hospital states: “Blood, either red or reddish brown, may also be in your ejaculate.” These statements are frequently an extreme exaggeration (mostly lies). Often after a biopsy a man’s semen will turn into jet black goo. This could be an unpleasant surprise for a man and especially for his unsuspecting partner. However if a biopsy is performed before Halloween or April Fools’ day this may be of benefit to a few men. If some prestigious hospitals are not factual about the color of semen, what other facts are being misrepresented?

    5. Medscape Urology WebMD: Mortality Risk With Prostate Biopsy Raises Concern – Medscape – Jun 17, 2013.
    11. Loeb, S. J Urol. 2013 Mar; 189(3): 867–870. Is Repeat Prostate Biopsy Associated with a Greater Risk of Hospitalization? Data from SEER-Medicare.
    22. Murray KS and Thrasher JB. “Have We Underestimated Erectile Dysfunction after Prostate Biopsy?” AUANews. 2015; 20(12): 11.
    23. BJUI. A prospective study of erectile function after transrectal ultrasonography-guided prostate biopsy. Katie S. Murray, Volume 116, Issue 2 August 2015 Pages 190–195.

  5. Dear SUM:

    As far as I am aware, in the REDUCE study, all biopsies were standard, TRUS-guided, 12-core systematic biopsies. This study was done done a number of years ago now. However, this type of biopsy remains — by far — the most common type of biopsy carried out in a man whose only indicator of risk is an elevated PSA level.

  6. Dear Jim:

    Perhaps you should focus your efforts on ensuring that insurance companies and other payers covered the costs of all the other tests that could be given to men as potential forms of clinical assessment prior to use of any form of biopsy. Most such organizations are very unwilling to cover these costs. We absolutely agree with you that unnecessary biopsies should be avoided.

  7. Sitemaster, In my opinion: Thanks for the insurance company payout information. I try to inform men of the dark side of prostate cancer testing and treatment. Sometimes details are overlooked. Jim

  8. Incorrect and Misleading Figures in Jim’s Post Above – June 20, 10:57 pm

    Jim, the figures you quoted for ED after a biopsy — 22.3% mild ED, 15.5% mild-to-moderate ED, 10% moderate ED, and 13.6% severe ED — looked wildly high to me based on other research I have read, so I checked. These figures are from the Murray et al, paper that you cite (thanks for providing references), but they are the figures for ED before the biopsy — the figures needed to compare with the post-biopsy figures. In other words, these are ED figures for men who tend to be older. Unfortunately, I did not see the post-biopsy figures conveniently displayed in the complete paper, which is available free online, though I did not do a thorough search.

    However, Figure 2 displays the “IPSS” total score that summarizes the results at each data point. While there is some decline in the score — meaning more ED, at 1, 2, and 12 weeks post-biopsy, the decline is relatively small. For example, at 12 weeks, for the men then returning the survey, the baseline IPSS score was 9.6 and the post-biopsy number at 12 weeks is 9.3, just a fraction of a point lower.

    Regarding the hospitalization percentage after a first biopsy, 6.9%, that number is three times (strictly speaking, 2.98 times) the hospitalization for the control group who were not having biopsies. Therefore, 6.9% divided by 3 = 2.3%, and 6.9% minus 2.3% = 4.6%. That is still worthy of concern, but relatively small compared to the 95.4% not hospitalized after having a biopsy, having deducted the “normal” hospitalization number. Moreover, the study included data from 1991 to 2007, and biopsy technology has improved considerably since those earlier years.

    The death rate, per the Loeb paper, was actually lower for the men biopsied compared to their Medicare controls, which the paper suggested was due to healthier men being biopsied than their age peers. I’m thinking this means more health conscious men than their age peers got biopsied.

    The death rate in reference 5 is from Dr. Gerald Chodak, who perhaps may see this and can comment further. It is based on the PLCO trial, and compares death rates for men in the trial, a screening trial of men not known to have prostate, lung, or colorectal cancer at the outset. It compares the death rate for biopsied men who did not have cancer of any type (1.3 per 1,000) to the rate for men who were found to have cancer of any type (3.5 per 1,000). I found no mention of sepsis in this short article or any other clear description of causes of death. What is critically missing here is death rates for age-matched peers. For example, what if age matched peers had a death rate of 1.3%, or even higher (as hinted at in Loeb, just above)? It seems natural to me that men diagnosed with prostate cancer, and perhaps lung and colorectal cancer patients also, would tend to be older than other participants in PLCO, and therefore I suspect that the higher death rate in the cancer group is due to cancer diagnosis being characteristic of older age, and therefore being associated with a higher death rate just due to age.

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