Bleeding Complications

Bleeding is the most common complication associated with TRUS-bx and includes hematuria, rectal bleeding, and hematospermia.

Visible hematuria is reported in 10–84% of cases; however <1% is severe enough to require catheterization and hospitalization. More than 90% of men reported that hematuria was not a significant burden. Most hematuria resolves within 3 days; however, for 22% of patients it may persist for a longer period. This is associated with a larger prostate and transition zone volume. Additional factors that increase the risk of hematuria are pre-biopsy enemas and use of anticoagulation. Repeat biopsies and needle size are not associated with increased hematuria. There are conflicting data on whether the number of cores sampled impacts hematuria severity or duration.

Rectal bleeding is observed in 1.3–45% of cases. Usually patients consider this minor with <2.5% of cases considered moderate or severe. Factors influencing the risk of rectal bleeding include number of cores sampled and use of anticoagulation. As with hematuria, needle size does not appear to impact risk of rectal bleeding.

The frequency of hematospermia after biopsy varies widely in the literature, with reported rates of 1.1–93%. However, hematospermia is also transient and resolves with repeated ejaculation. The reported median duration is 12–20 days or approximately eight ejaculations, although this also varies. Patients should be counseled on the specific risk of hematospermia as social factors and cultural barriers could prevent patients from seeking medical attention if this occurs. Factors increasing the risk of he­matospermia are larger prostate volume, previous transurethral resection prostate (TURP), and the number of cores sampled.

It is important to note that while the majority of bleeding complications are self-limiting, in rare cases significant hematuria or rectal bleeding can be life threatening. Patients should be appropriately counseled on these risks as part of the informed consent process for prostate biopsy.

The impact of anticoagulation on bleeding is a concern for many urologists. Comparison of patients on aspirin and off aspirin has not been associated with any difference in significant bleeding events. However, patients on aspirin do seem to notice that minor bleeding may have a longer duration than for patients not on anticoagulation. Current practice recommendations have concluded that it is therefore safe to continue antiplatelets during prostate biopsy.

There are fewer data on the effects of anticoagulants such as warfarin and clopidogrel. Additionally the impact of newer anticoagulation drugs such as factor X inhibitors rivaroxaban and apixaban have not been well-studied in this context, and the risk of serious complications is unknown.

Infectious Complications

Some well-documented risks of prostate biopsies include infectious complications such as urinary tract infection, bacteremia, sepsis, and, in rare cases, death. The risk of hospitalization due to infection ranges from 0% to 6.3%. Data from SEER-Medicare showed that men undergoing prostate biopsy had a 2.26 greater risk of 30-day hospitalization for infection compared to randomly selected controls. Furthermore, there has been a plethora of data showing a significant increase in hospitalization rates over time in the United States and globally.

This is thought to be due to increased prevalence of fluoroquinolone-resistant Escherichia coli worldwide, with up to 37% of E. coli isolates being flouroquinolone resistant in parts of Asia. This has also been reported in the African continent as well as parts of Europe. It has been shown that foreign travel is an independent risk factor for post-biopsy infection and sepsis, with approximately a six times increased risk of fluoroquinolone-resistant E. coli for patients who recently traveled abroad. Additionally, recent antibiotic use increases the risk of post-biopsy infection, as antibiotics can cause a change in normal bowel flora.

It has been shown that a particular E. coli strain, ST131, has demonstrated an increased resistance to fluoroquinolones worldwide. A small number of studies have isolated this strain as a significant contributor to the increased rate of sepsis associated with prostate biopsies in recent years. Up to 35% of patients who suffered from post-biopsy sepsis grew this E. coli strain.

Other patient-specific factors shown to increase the risk of prostate biopsy infections include comorbid medical conditions such as diabetes and conditions with immunosuppression. These patients at baseline are more prone to infections and sepsis and should undergo further counseling on the increased risks prior to proceeding with prostate biopsy. Diabetic patients should additionally be counseled on the importance of glucose control and compliance with medical therapy.

Factors such as age, prostate specific antigen (PSA), and prostate volume do not appear to be associated with an increased risk of infection. However, there has been a reported five-fold increased risk of developing sepsis if preprocedure WBC was greater than 11.2 /µL. Certainly any patients with a symptomatic urinary tract infection should undergo testing and treatment for that prior to prostate biopsy.

Procedural factors may also increase the risk of infectious complications. There are documented instances of infections related to contaminated ultrasound gel and improper processing of the equipment.

Finally, the impact of repeat biopsies on the risk of infection has received significant attention, since approximately 38% of US men with a negative biopsy undergo another biopsy within 5 years. This is also germane in light of recent increases in the use of active surveillance, with an estimated 40–50% of low-risk men in the United States choosing conservative management as of 2013. More recent data from Sweden reported higher rates of active surveillance, with 2014 rates of 91% of very-low-risk, 74% of low-risk, and 19% of intermediate-risk patients diagnosed nationwide. In the major prospective active surveillance programs, the frequency of repeat prostate biopsy ranges from annual to every 5 years. As this strategy increases globally, this can be expected to increase the number of patients continuing to have repeated prostate biopsies over the course of many years after their diagnosis.

Whether men undergoing repeat biopsy have greater risks has been previously studied. Data from SEER-Medicare reported that, although performing repeat biopsies increases the chance of patients experiencing a complication in a cumulative way, the actual repeat biopsy procedure had a similar risk of serious infectious complications compared to the initial biopsy procedure. A recent series from the Prostate Cancer Research International Active Surveillance (PRIAS) study reported infection after 2.5% of biopsies. Biopsy number was not a significant independent predictor of infectious complications. However, it is noteworthy that patients experiencing a complication were less likely to undergo their next protocol-recommended biopsy. The risks of serial prostate biopsy are an important component of patient counseling regarding active surveillance.

Lower Urinary Tract Symptoms and Acute Urinary Retention

In the immediate postprocedure period, patients may experience symptoms such as dysuria in approximately 6–25% of cases. These symptoms are usually transient and resolve.

The risk of acute urinary retention is 0.2–1.7% following transrectal prostate biopsy, although higher rates have been reported following transperineal biopsy. The use of alpha-blockers such as tamsulosin has been shown to produce a statistically significant decrease in International Prostate Symptom Score (IPSS). Therefore these can be prescribed to patients who may be at higher risk for urinary retention, although premedication is not necessary for every patient.

Factors that have been shown to increase the risk of urinary problems after biopsy include larger prostate size, ratio of transition zone volume to total prostate volume, and higher IPSS scores. There does not appear to be a correlation between the number of biopsy cores taken or the number of repeat serial biopsies performed and LUTS.

Erectile Dysfunction

There are mixed data regarding the impact of prostate biopsy on erectile dysfunction. The most common measure of erectile dysfunction post-biopsy is the International Index of Erectile Function (IIEF).

The exact etiology of erectile dysfunction after biopsy is unknown, but it may be due to inflammation in the immediate post-procedure period as well as minor damage to the neurovascular bundle from needles. There has been some speculation that a component of erectile dysfunction may be related to the psychological impact of concerns about cancer or receiving a prostate cancer diagnosis. It has been shown that 19% of men who underwent a negative prostate biopsy were more worried about prostate cancer and had a moderate to severe impact on sexual function compared to 10% of age-matched control patients. Another study showed that men who underwent TRUS-bx and received a positive prostate cancer diagnosis had a lower post-biopsy IIEF score compared to those men who had a negative prostate biopsy.

However, studies that have established a baseline of erectile function prior to biopsy have shown that IIEF scores return to normal within 6 months. While there may be a transient short-term increase in erectile dysfunction after a single biopsy, most patients return to baseline after an initial prostate biopsy. Factors that have been associated with the risk of erectile dysfunction include periprostatic local anesthetic nerve block and the psychological impact of the anxiety associated with prostate cancer diagnosis. Factors that have not been show to impact erectile dysfunction after biopsy include PSA, prostate volume, and number of cores.

Another factor that has been associated with the risk of erectile dysfunction is biopsy number. In particular there is concern as to whether repeated biopsies performed during active surveillance could increase the risk of erectile dysfunction. In the Johns Hopkins active surveillance program, there was a reduction in sexual function scores on later transrectal prostate biopsies. Similarly, a recent study from the United Kingdom found that erectile function scores returned to baseline 6 months after the first transperineal sector biopsy, but had not fully returned to baseline at 6 months after the second transperineal sector biopsy. Other active surveillance studies did not find a significant relationship between repeated prostate biopsy with erectile dysfunction. It is important to recognize that during the course of active surveillance patients are also aging and may experience changes in other risk factors as well, making it difficult to isolate the effects of repeated prostate biopsies. Nevertheless, this possible issue should be discussed with men considering active surveillance, particularly since preservation of sexual function is one of the reasons patients may opt to defer radical treatment.

Pain

Use of analgesia has been shown to reduce pain during prostate biopsy. Factors worsening pain include anorectal compliance, number of biopsy cores, younger age, and anxiety. Pain can be a significant barrier for men requiring a repeat biopsy, with up to 18% of men reporting they would refuse repeat biopsy. There are multiple options for prostate biopsy anesthesia, ranging from local options such as lidocaine gel and periprostatic nerve block, to sedation and general anesthesia. Combined approaches to anesthesia are also possible, such as combining gel and periprostatic nerve block, or sedation plus periprostatic nerve block.

There has also been investigation into other simple techniques to reduce pain and anxiety with prostate biopsy. A recent study showed that waiting an additional 5 minutes after administering periprostatic nerve block did not significantly reduce pain. However, simple maneuvers like patient positioning also may affect the level of pain, and listening to music is another optional technique to reduce anxiety.

Mortality

The risk of death after prostate biopsy is extremely small, likely due to careful patient selection for prostate biopsy. Some studies have even shown a lower risk of overall mortality within a 30-day period among men undergoing biopsy compared to controls from the population. However, the risk of death after prostate biopsy is significantly higher in patients who develop sepsis, highlighting the importance of prevention and effective management for infection in this population.

During the preprocedure, informed consent and the need for prompt follow-up with a health-care provider if the patient experiences any symptoms should be discussed thoroughly. Understanding where and how these patients with complications present can also be crucial in timely management of TRUS biopsy complications.