The simple answer is NO, however it should change your treatment game plan.

A member of one of my support groups who has been doing active surveillance for about 5 years recently reported that their current biopsy indicated that they now have perineural invasion (PNI). They did not understand what was the significance of this finding and they wanted to know if they now had advanced prostate cancer.

In reality, PNI is found in almost 30% of positive biopsies.

However, before I discuss the significance of this finding it is important to understand what this means. When a pathologist finds that there is PNI they are saying that they have found prostate cancer cells surrounding or tracking along a nerve fiber within the prostate. This does not mean that the cancer has left the gland.

Not withstanding this the importance of this finding , it takes on a new light when you realize that nerves within the prostate travel outside of the gland through microscopic holes in the prostate capsule. The capsule is the outer covering of the prostate gland, which for some period of time can manage to contain cancer cells within the gland. In essence it is a barrier protecting the rest of your body from prostate cancer cells.

However, the nerves do pierce the capsule and can offer an easy exit point for cancer cells from the gland to the rest of your body.

The real concern about the presence of PNI in a biopsy is it indicates that there is a higher likelihood that the prostate cancer has or will escape from the prostate gland, or become advanced prostate cancer.

There have been studies that have compared the final pathologic findings (after radical prostatectomy) to men with and men without PNI on a biopsy. These studies have shown that men with PNI have a 2-3 times higher rate of extra-capsular 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.

Simply put, the presence of PNI doubles the chance of a man having T3 disease (tumors that have broken through the capsule).

The other important findings are that finding PNI on biopsy is associated with a higher Gleason grade (Gleason 8-10) or a higher grade disease even when only low grade disease (Gleason <7) is found on biopsy (possible sampling error) and that men with PNI are at a higher risk of seminal vesicle invasion and lymph node metastases.

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.

Having PNI after a Prostatectomy has negative impact on prognosis. At Johns Hopkins there was a study that followed 1256 men with prostate cancer for an average of 3 years after radical prostatectomy. One hundred eighty eight men (188) of this population (15%) had PNI on prostate biopsy. Despite the short three year 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. This finding has been duplicated in other studies.

What about the prognosis after radiation therapy? The story is similar; the presence of PNI on prostate biopsy has a negative implication. 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.

The presence of PNI on a biopsy could instantly transform an otherwise low risk prostate cancer into a high risk disease.

Since having PNI on final pathology clearly and negatively affects prognosis its presences should influence the treatment decisions.

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.

It stands to reason that men going forward with surgery should consider not having nerve sparing surgery. In addition, given the high likelihood of positive margins and T3 disease, men with PNI on biopsy should also discuss with their doctors undergo radiation therapy following the radical prostatectomy.

Similarly, men opting for treatment with radiation with PNI should consider themselves high risk no matter what their Gleason or PSA score and opt for a combination of radiation and hormonal therapy rather than radiation therapy alone.

Perineural invasion (PNI) on biopsy is a very significant and needs to be treated as such, despite Gleason grading and PSA scores. It can indicate high risk prostate cancer, even in men with who otherwise we would consider to be low risk.

PNI is not necessarily advanced prostate cancer, but it is often associated with a poorer prognosis, leading to a higher risk of recurrent and metastatic disease.

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Joel T. Nowak, M.A., M.S.W.