What does it mean if you have a prostate cancer biopsy and are told that you have Perineural Invasion (PNI)?
PNI means that the pathologist saw that the cancer cells had infiltrated in and around the small nerves connected to the nerve bundles (ganglia) outside the prostate. This infiltration can become a route for a metastatic spread (see this link) of the prostate cancer.
It would be best if you considered that having PNI is a risk factor, nothing more, for the progression of the cancer.
PNI is detected in approximately 15% to 38% of biopsies of men who have a prostate cancer diagnosis.
The data on whether PNI is a prognostic indicator for T3 stage after surgery is unclear, even though PNI is often the mechanism for extracapsular extension of the cancer.
For post-surgical patients, PNI does not seem to add a lot of information after considering the Gleason score, PSA, stage, and tumor volume. Also, PNI does not seem to add much to the risk of recurrence after surgery. PNI is not associated with higher surgical margin rates, and it is not considered sufficient to preclude nerve-sparing surgery. An open question is whether PNI raises risk enough to warrant more aggressive radiation options, like brachy-boost therapy, whole-pelvic radiation, and long-term adjuvant ADT.
In a retrospective study, Peng et al. examined the records of 888 men treated with external beam radiation at Johns Hopkins from 1993 to 2007. Twenty-one percent (21%) of them had biopsy-detected PNI. When compared to men who did not have PNI, those with PNI had:
· lower 10-year biochemical failure-free survival (40% vs. 58%)
· lower 10-year metastasis-free survival (80% vs. 89%)
· lower 10-year prostate cancer-specific survival (91% vs. 96%)
· similar 10-year overall survival (68% vs. 78%)
·
It isn't surprising that PNI is associated with higher risk, but does having PNI add any new information that we don't already know by Gleason score, stage, and PSA, the NCCN criteria for risk stratification?
After correcting for those other risk factors, PNI was still found to be associated with lower rates of biochemical failure-free survival, but not of metastasis-free survival, prostate cancer-specific survival or overall survival.
PNI independently predicted lower biochemical failure-free survival in low-risk and high-risk patients, but not for intermediate-risk patients. Although it is a relatively rare finding among low-risk men when found, PNI also predicted lower prostate cancer-specific survival.
Biochemical failure in low-risk men with PNI differed according to whether they received adjuvant ADT or not:
An earlier analysis of 651 men treated at the University of Michigan similarly found an association between PNI and biochemical failure-free survival, freedom from metastases, prostate cancer-specific survival, but not overall survival at seven years after radiation treatment. They also found a more marked effect among high-risk patients. A meta-analysis of 5 studies among men who received EBRT found that PNI increased the risk of biochemical recurrence by 70%.
Although PNI may increase the risk associated with an unfavorable intermediate-risk or high-risk diagnosis markedly, brachy boost therapy is the best treatment for any such patient regardless of PNI, according to our best retrospective study and prospective studies like ASCENDE-RT. This study also suggests that adding ADT may be beneficial for these patients. Low and intermediate-risk patients with PNI who opt for conventional IMRT may also benefit from the addition of short-term ADT.
According to a ten-year follow-up of the TROG 03.04 RADAR randomized trial, Delahunt et al. found that PNI detected when the biopsy was performed independently associated with later appearance of bone metastases.
Reporting Methodologies for PNI is Problematic.
PNI is sometimes not reported, and there is no uniform method for quantifying it when it is reported. Just indicating that PNI was present does not tell us how much was present, or even if it is outside or inside the nerve sheath. PNI is only reported as being present. Without standardized reporting protocols, PNI cannot help us to stratify and really understand our risk.
