PNI as detected in the nerves within the prostrate gland
I append an interesting post about PNI findings in biopsies for prostrate cancer. This is generally not discussed by the Urulogist/Oncologist when deciding the best course of treatments. Read below a detail explaination to PNI and its impact to treatment decisions. Discuss PNI with your Oncologist.
Perineural Invasion On Prostate Biopsy: How It May Change The Game Plan
A reader recently
asked me to share my thoughts on perineural invasion found on a prostate
biopsy. In formulating my response to this question, I was surprised that I did
not cover this topic sooner. After all, perineural invasion (PNI) is found in
approximately 30% of biopsies. The presence of PNI on a prostate biopsy can
sometimes be a sign that the prostate cancer found on the biopsy may be just the
tip of the iceberg in terms of the cancer within the prostate. As such, PNI can
change both the prognosis and treatment course for men with newly diagnosed
prostate cancer. In this post, I will describe PNI and explain its impact on
treatment plans and prognosis.
Defining Perineural
Invasion
Before I explain the
importance of perineural invasion, we must first be on the same page as to what
this finding on a prostate biopsy actually means. The presence of PNI means
that the pathologist has seen prostate cancer cells surrounding or tracking along
a nerve fiber within the prostate. The importance of this finding becomes
apparent when you realize that nerves within the prostate travel outside of the
gland through microscopic holes within the prostate capsule. The capsule, as
you may remember from my previous post about positive margins, is the outer
covering of the prostate. This covering serves as a barrier preventing the
spread of cancer outside of the prostate, at least for a while. Because nerves
travel through holes in the capsule, prostate cancer growing around these
nerves can follow them all the way out of the prostate without needing to
overcome the resistance of the capsule. As a result, the presence of PNI on a
biopsy portends a higher likelihood of prostate cancer that has or will escape
the prostate gland. Studies have, indeed, validated this theory while also
demonstrating other negative impacts of PNI.
The Impact of
Perineural Invasion on Final Pathology
Numerous clinical
studies have compared the final pathologic findings (after radical
prostatectomy) of those patients with and without PNI on initial biopsy. The
results are very striking. Large studies have demonstrated that men with PNI
have a 2-3 times higher rate of extracapsular extension (prostate cancer
outside of the gland) and nearly twice the likelihood of positive margins after
prostatectomy when compared to men without PNI on their prostate biopsy. That
means that the presence of PNI at least doubles the chance of T3 disease in a
man undergoing treatment for what is clinically localized, T2 disease. In
addition, numerous studies have demonstrated that PNI on biopsy is associated
with higher grade disease (Gleason 8-10) on final pathology even when only low
grade disease (Gleason <7) is found on biopsy. In fact, one study demonstrated
that over 40% of men with PNI and low grade disease on biopsy are subsequently
found to have high grade disease on final pathology after prostatectomy. The
reason for this disparity appears to be sampling error, with high grade disease
not caught in the original biopsy specimens. Hence when a prostate biopsy
demonstrates Gleason 6 disease and PNI, there is a high likelihood that higher
grade, more aggressive cancer is present in the prostate but was not detected.
Other studies have also demonstrated a higher risk of seminal vesicle invasion
and lymph node metastases in men found to have PNI.
Perineural Invasion
and Prognosis After Prostatectomy
Given the significant
adverse impact of PNI on final pathology, it is not surprising that PNI has also
been demonstrated to negatively affect prognosis after surgery. One study out
of Johns Hopkins followed 1256 men with prostate cancer for an average of 3
years after radical prostatectomy. Out of this patient population, 188 men
(15%) were found to have PNI on prostate biopsy. Even over this relatively
short follow up period, men with PNI on biopsy were found to have three times
the likelihood of PSA recurrence as compared to those men without PNI. Similar
findings were reported in 6 out of 10 studies of the impact of PNI on men
undergoing radical prostatectomy for prostate cancer. Not surprisingly, men
with low risk prostate cancer (Gleason 6, T1-T2a, and PSA<1O) and PNI are
three times more likely to require salvage radiation than their low risk counterparts
without PNI.
Perineural Invasion
and Prognosis After Radiation Therapy
The prognosis after
radiation therapy, as well, appears to be negatively impacted by the presence
of PNI on prostate biopsy. One study followed 381 men undergoing radiation therapy
for localized prostate cancer, 86(23%) of whom were found to have PNI on
prostate biopsy. After 5 years of follow up, 69% of men without PNI were free
of cancer as compared to only 47% of men with PNI. When dividing men into risk
categories, the study demonstrated that only 50% of men with low risk prostate
cancer (Gleason 6, T1a-T2a, PSA <10) and PNI were free of cancer at 5 years
of follow up. This rate of cancer free survival was lower than the 53% rate
achieved by men with high risk prostate cancer (Gleason 8-10 or T2c-T4 or PSA
>20) but without PNI. Hence, the presence of PNI could instantly transform
an otherwise low risk prostate cancer into a high risk disease. Such findings
were validated in 5 out of 10 large studies of men treated with radiation
therapy. Interestingly, one large study of men undergoing brachytherapy for
prostate cancer did not demonstrate a difference in treatment outcomes of men
with and without PNI. Of note, however, is that men selected for brachytherapy
generally have lower risk disease than those who undergo external beam
radiation.
How Perineural
Invasion Can Change the Treatment Plan
Given the significant
impact of PNI on final pathology and prognosis, it seems obvious that the
presence of PNI can influence the treatment course chosen by patients and their
doctors. A study of surgical approaches in men with PNI demonstrated that
removing the nerves on the side of the prostate with PNI on biopsy led to a
positive margin rate of 11%. In contrast, the positive margin rate was 100%
when the nerves were spared on the side of PNI. Of note, a recent study from
Johns Hopkins reported that nerve sparing did not impact positive margin rates
or prognosis in men with PNI. This data needs to be taken with an enormous
grain of salt however in that all men in the study were operated on by Dr
Patrick Walsh, the urologist credited for the development of the modern day
open radical prostatectomy. It would see unlikely (at best) that such outcomes
could be replicated by the typical urologist performing the surgery. As a
result, most urologists will sacrifice nerve sparing in order to assure
negative margins in men with PNI. In addition, given the high likelihood of
positive margins and T3 disease, urologists often counsel patients with PNI on
biopsy that they may likely need to undergo radiation therapy following radical
prostatectomy. Similarly, radiation oncologists treating men with PNI often
approach them as high risk patients regardless of clinical stage, PSA, or
Gleason score. As a result, they often treat men with PNI with a combination of
radiation and hormonal therapy rather than radiation therapy alone. In
addition, they may also use dose escalation as part of their radiation
protocol.
Take Home Message
Perineural invasion is
a very significant finding on a prostate biopsy. It often indicates high risk
prostate cancer, even in men with seemingly low risk disease. PNI is also
usually associated with a poorer prognosis, leading to a higher risk of recurrent
disease. As a result, men with prostate cancer that are found to have PNI on
prostate biopsy are often provided with more aggressive therapy, whether it be
in the form of surgery or radiation. Understanding the significance of PNI on
prostate biopsy is crucial to formulating a successful battle plan against
prostate cancer.
Link to the post above:
http://www.healingwell.com/community/default.aspx?f=35&m=2135015
Take care
Allen Lai
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