Can a biopsy spread prostate cancer?

[Wendy_Winnall]

Prostate cancer is diagnosed by biopsy. Samples of the tumour are removed by needles during the biopsy procedure and analysed in a pathology laboratory. There are anecdotal reports that some men avoid prostate biopsies due to fear that the procedure will spread the cancer. This week's blog asks what is the risk that a biopsy could spread prostate cancer.

There are numerous tests for prostate cancer that include MRIs, ultrasounds, the PSA blood test and the dreaded digital rectal exam. But the internationally accepted standard for diagnosis is biopsy. During a prostate biopsy, needles to multiple sites in the gland remove small samples of cells. These are analysed by a pathology laboratory to look for cancerous cells.

The two most common prostate biopsy procedures are the transperineal biopsy and the transrectal ultrasound-guided (TRUS) biopsy. Transperineal biopsies were common until the 1990s. In the past 15-20 years, TRUS biopsies have been the most commonly used in Australia. Recently, use of transperineal biopsies is increasing again, and these are now often used with image-guiding systems.

Pros and cons of the prostate biopsy

The advantages of the prostate biopsy include the use of the Gleason scoring system that gives us information about how fast the cancer is growing. By testing multiple sites in the prostate, the biopsy can also indicate how much of the prostate is affected.

There are some disadvantages of prostate biopsies. The procedure can lead to bleeding, which is usually temporary. Infection by bacteria is a common complication, estimated to occur in 0.1%-7% of biopsies. Sepsis, a more serious response to infection, is rarer. Another disadvantage is that the biopsy might miss a region of cancer if the needles don't access that area by chance. Spreading of prostate cancer by the biopsy procedure is proposed by some doctors and scientists to be a disadvantage of biopsies. But estimating the risk of this happening is difficult.

Spreading of prostate cancer

Prostate cancer usually spreads in one of two ways. It can undergo a localised spread, called "locally advanced". This means that a tumour has pushed out of the prostate region and into the neighbouring tissues/organs. The second way prostate cancer can spread is by metastasis. This means that individual cancer cells break off from the tumour and move into the blood stream or lymphatic system (a circulatory system of immune cells somewhat similar to the blood). These cells then travel around and move out of the blood into other regions, where they "seed" new tumour growth. These new tumours usually grow at specific sites, such as inside bones, lymph nodes, liver, lungs and the brain.  Other regions of the body can also support prostate cancer growth, but these are less common.

Fears over the use of biopsy in spreading prostate cancer could refer to either type of spread. Men might fear that cancer cells could move through the holes made by the needles (needle-tracts) and grow in this region. They might also fear that the cancer could escape the prostate through these tracts and seed new metastatic tumours at distant sites.

Risk of needle-tract seeding

In 2014 a review article about the risk of needle-tract seeding by prostate biopsy was published in the journal BJU-International (aka British Journal of Urology). The authors of this review were from Addenbrooke University Hospital in Cambridge, UK. They systematically search the medical literature for all studies and case reports of biopsy needles spreading prostate cancer.

The Cambridge authors searched all the available medical literature and found 26 reliable publications reporting tumours growing along the needle-tract from prostate biopsies. 17 of these publications referred to case studies where only one patient was described. One reported two cases and another reported three cases. The remaining 7 publications studied many men having a biopsy to look for evidence of new tumours growing in the biopsy needle tract. These studies are summarised:

• 1962 Fortunoff (transperineal biopsies) - 346 biopsies were studied and 1 case was found.
• 1966 Burkholder and Kaufman (transperineal biopsies) - 1351 biopsies were studied and 1 case was found. This man had a 4cm tumour in the perineal region. He had external beam radiation therapy (EBRT) but died within 18 months.
• 1971 Blackard et al (transperineal biopsies) - 2086 biopsies were studied and 1 case was found. A 2cm tumour was found in the perineal region.
• 1975 Puigvert et al (transperineal biopsies) - 1500 biopsies were studied and 1 case was found - a 1cm perineal tumour.
• 1986 Emtage and Perez-Marrero (transperineal biopsies) - 575 biopsies were studied with 1 case found. The tumour was removed and patient treated with hormone therapy and chemotherapy.
• 1989 Moul et al (transperineal biopsies) - 2107 biopsies were studied and 6 cases found. Patients with these perineal tumours were more likely to have larger tumours and poorer outcomes. These varied in grade - some were low, some intermediate and some high-grade tumours.
• 1991 Bastacky et al (transperineal and TRUS biopsies) - 350 biopsies studied and 7 cases found. These tumours were intermediate or high grade.

One might be tempted to conclude from these studies that transperineal biopsies are more likely to be associated with spreading tumours than TRUS. But transperineal biopsies were by far the most commonly used and studied biopsy at the time, so this conclusion is illogical. Another trap would be to assume that allowing tumours to escape will cause higher-risk tumours to grow. It is equaliy likley that high-risk tumours are the only ones capable of growing in the needle tracts, so they have escaped because they were high-risk in the first place.

The total number of needle-tract seeded tumour cases detected was 40. This number includes the larger studies and case studies put together. There is little information about the fate of the men in whom these new tumours were discovered, aside from the one patient who died. The Cambridge authors estimated an approximate risk of 1%. This means that in 1% of biopsies, a new tumour in the needle tract might occur. But the authors admit that the quality of the data is poor and the true risk is currently difficult to quantify. One problem is that many of the studies are very old, and new technology, including better imaging, is able to do a better job at finding these new tumours. The Cambridge authors do state that:

Reassuringly, the increase in the number of biopsies and cores taken at each biopsy over the years has not resulted in an increase in the reported cases of seeding, despite closer patient follow-up and advances in imaging.

Needle-tract spreading of prostate tumours after biopsy does indeed appear to be a risk of prostate biopsy, but this risk is relatively low. The authors do not recommend avoiding biopsies in cases where prostate cancer is suspected (due to PSA test, imaging and digital rectal exam results). They believe that the benefits of appropriate cancer diagnosis and management would usually outweigh any potential risks from seeding.

 Risk of metastasis after prostate cancer biopsy

It is difficult to measure this risk and difficult to find studies that have specifically addressed this question. A good reason for this is that the internationally-recognised definition of prostate cancer diagnosis comes from having a biopsy. So we cannot compare men with prostate cancer who had a biopsy to those who did not.

But the necessity for biopsy is not the case for all cancer diagnoses. A study of pancreatic cancer showed that patients who received a biopsy had a better outcome and longer survival than patients who did not have a biopsy.

Scientists are not able to accurately determine whether biopsy has caused a prostate cancer to spread in an individual case. But looking at patterns over large numbers of people can help to predict whether this could be a problem. In the past 20 years, the number of biopsies performed has increased significantly. It's estimated that over 1 million procedures are performed each year in Europe and the US. Biopsy use is now common for men on active surveillance, who are not being actively treated. There has not been an obvious increase in metastatic prostate cancer that has correlated with this increase in biopsies. But this is far from a perfect way to estimate the link between biopsies and metastasis. Progression to metastasis is affected by many different factors, such as treatments, new imaging and PSA tests, which have all changed considerably over this time period.

One line of thought that might put our minds at ease is the lack of logic for biopsies causing spread by metastasis. There are two important misconceptions that need to be understood:

• It is a misconception that all prostate cancers will eventually progress to metastasis. The majority of these cancers stay localised. We know this from an autopsy study that showed 59% of men have tumours in their prostates by the age of 79. These men did not die of prostate cancer or have any evidence of metastatic disease or even any symptoms. We also know that low-risk, localised prostate cancers are usually safe to manage with active surveillance. They have a very low chance of turning metastatic despite repeat biopsies during active surveillance.
• It is also a misconception that being contained in the prostate stops the tumour cells from accessing the blood or lymphatic system. Solid tumours, like prostate cancer, rely on a steady blood supply. Blood vessels grow into the tumours, supplying nutrients and oxygen. If the cancer cells have the ability to spread through the blood by metastasis, then they have easy access to the blood and lymphatic vessels that are present inside the prostate and in the tumour.

From what we know of anatomy and how prostate cancer cells behave, it seems likely that a prostate tumour that gains the ability to spread to distant sites will be able to do this by entering the blood stream directly from the prostate, regardless of the presence of a needle-tract. Having the needle tract, caused by a biopsy, is unlikely to make metastasis possible where it wasn't possible already.

The caveat to this reasoning is that what is logical, given our knowledge of biology and cancer cell behaviour, is not what always happens when these risks are tested in proper clinical trials. Unfortunately testing whether biopsy promotes metastasis for prostate cancer is not really possible with our current diagnosis protocols, since every man diagnosed with this disease has already had a biopsy.

Overall the answer to the question of whether biopsies can spread prostate cancer is yes, but the risk, as best we can tell, is relatively low. The benefits from biopsies are considerable; being able to gauge the speed at which the cancer is growing and how far it has spread is the main basis for our treatment decisions. A man without a biopsy, under our current health system, is not officially diagnosed, therefore will not be able to receive Medicare-subsidised treatments for this cancer.