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montee
Regular Member


Date Joined Mar 2007
Total Posts : 315
   Posted 6/13/2011 9:33 AM (GMT -6)   
I almost always have seen that PNI in biopsy pre-op and post-op was not a significant finding. And since I had multi-focal PNI, that was a relief. I read the prostate Dr. bog that Tony Posted an link to each week and it is very informative reading. Todays blog was concerning PNI in which he states that men with PNI have a 2-3x greater chance of needing further treatment. Here is the last 2 paragraphs of his blog today.

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.
diagnosed sept 2006 @ 54 years old, live in Georgia, gleason 3+4=7, (r) lobe only

psa 4.7 (psa rose 1 point per year for 3 years, urologist said still under 4 and no concern. If I can find out about PSA velocity, why didn't he know!)

Told not to have surgery at Dana Farber as cancer had already penetrated prostate, in seminal vesicles, would have positive margins. Would only treat with radiation and HT

RP Emory Atlanta December 2006. Path-negative margin, negative lymph nodes, negative SV, both Lobes involved, 40% gland involved
multifocal perineural invasion, Gleason 3+4=7

1st psa April 2007-<0.04, 6 mos-<0.04, 9 mos <0.04, 1yr <0.04, 21 mos <0.04, 2 yr 0.04 (rising?) 26 mos-0.05, 27 mos-0.04, 29 mos 0.06 Sept 09 ,<0.04 3 year <0.04 39 mo. 0.07 (rising again) 0.07 2 different times 3 mos apart.,now seeing Rad. Onc. next 2 tests with him 3 mos apart <0.05.

clocknut
Veteran Member


Date Joined Sep 2010
Total Posts : 2667
   Posted 6/13/2011 9:48 AM (GMT -6)   
Thanks, Montee.  That's a very interesting post.  I've gotten the impression, though, that nearly all of us have PNI.
 
Would anyone NOT having PNI noted on their biopsy or surgery pathology report please raise your hand?
 
 

I use to be a fish
Regular Member


Date Joined Mar 2011
Total Posts : 57
   Posted 6/13/2011 9:55 AM (GMT -6)   
I'd like to know more about this PNI. I see that on my husband's biopsy report it notes that on one of his positive cores there is perineural invasion. I asked the Dr about it and he said that it has invaded the nerves within the prostate and has the potential to spread along the nerves. His gleason score is a 6. If it truly is the case that he would need more agressive treatment following surgery, what would the point be of doing surgery at all? Why not begin with radiation?
Husband diagnosed with Pca on 3/14/2011. Age 48. 4 out of 12 cores positive. Gleason 6 (3+3). First PSA test ever at age 47: 5.14 (1/4/10);
4.1 after 10 days of antiobiotics (2/1/10); 4.44 at doctors office (2/15/10); 2.26 (5/2010); 5.0 (11/10); 4.8 (1/11). Free PSA range 10-13%.

Reading and deciding on what course of treatment.

John T
Veteran Member


Date Joined Nov 2008
Total Posts : 4225
   Posted 6/13/2011 10:16 AM (GMT -6)   
There was a study posted on the New Prostate Cancer Infolink a few weeks ago that showed that 99% of all post op pathologies had PNI. The only effect of PNI was if the PNI extended past the capsul then the chance of reoccurrance was higher. If PNI is actually near 100% as indicated, how can it have any predictive value?
I'll try to post the study when I can get the pages to load.
JT
66 years old, rising psa for 10 years from 4 to 40; 12 biopsies and MRIS all negative. Oct 2009 DXed with G6 <5%. Color Doppler biopsy found 2.5 cm G4+3. Combidex clear. Seeds and IMRT, 4 weeks of urinary frequency and urgency; no side affects since then. 2 years of psa's all at 0.1.

montee
Regular Member


Date Joined Mar 2007
Total Posts : 315
   Posted 6/13/2011 10:33 AM (GMT -6)   
Here is the complete blog.

Perineural Invasion On Prostate Biopsy: How It May Change The Game Plan

Posted: 12 Jun 2011 08:26 PM PDT



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.

Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25380
   Posted 6/13/2011 11:08 AM (GMT -6)   
Montee,

Very good post on the subject of PNI. I personally subsribe to the view presented. My uro, my RO, plus 2 other RO's that I met with, and my new Medical Oncologist, all share the view presented in your report.

While PNI doesn't guarantee that cancer cells have escaped, it's a conduit of sorts that can allow that to happen, and once escaped, the new doctor said that stray cancer cells have a free passage to settled anywhere or even in multiple locations in a person's body.

This business on PNI has been given to me by doctors, as a possible explanation of why my cancer has been on the move rapidly, even before my official dx, manifesting itself in rapid PSA velocity, and why my 2 curative attempts failed so fast.

It's an interesting subject.

David
Age: 58, 56 dx, PSA: 7/07 5.8, 10/08 16.3
3rd Biopsy: 9/08 7 of 7 Positive, 40-90%, Gleason 4+3
open RP: 11/08, on catheters for 101 days
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos margin
Incont & ED: None
Post Surgery PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12, 4/8 .04, 8/6 .06, 2/11 1.24, 4/11 3.81
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, 21 Catheters, Ileal Conduit Surgery 9/10

Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25380
   Posted 6/13/2011 11:09 AM (GMT -6)   
P.S. To answer your other question, there are a handful of guys here, that in their pathology, it was spelled out that PNI wasn't present, can't remember their names, perhaps they will pipe in.
Age: 58, 56 dx, PSA: 7/07 5.8, 10/08 16.3
3rd Biopsy: 9/08 7 of 7 Positive, 40-90%, Gleason 4+3
open RP: 11/08, on catheters for 101 days
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos margin
Incont & ED: None
Post Surgery PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12, 4/8 .04, 8/6 .06, 2/11 1.24, 4/11 3.81
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, 21 Catheters, Ileal Conduit Surgery 9/10

Newporter
Regular Member


Date Joined Sep 2010
Total Posts : 225
   Posted 6/13/2011 4:46 PM (GMT -6)   
This is a report from the Prostate Cancer Infolink regarding PNI:

No significant long term survival differences between PNI present or absent:

Between January 2000 and December 2007, Masieri et al. carried out a careful prospectively designed study and collected data from 251
consecutive patients who had pathologically localized (organ-confined) prostate cancer after radical prostatectomy. Data from 239 of these
patients was usable for analysis. The authors defined PNI as adenocarcinoma observed within the perineural space adjacent to a nerve.
The results of their study showed that:
Intraprostatic PNI occurred in a total of 157/239 patients (65.7 percent).
PNI was more commonly observed in men with pathologic stage T2b/c (149/204 patients or 73 percent)) than in men with pathologic
stage T2a (8/35 patients or 26 percent).
PNI was also more common in men with a Gleason score of 7 to 10 (73/93 patients or 78.5 percent) than in men with a Gleason score
of 2 to 6 (84/146 patients or 57 percent).
Average (mean) follow-up was 65.4 months (range, 24 to 118 months).
11/239 patients (4.6 percent) had biochemical recurrence after surgery and 7 of these 11 patients (63.6 percent) showed PNI.
228/239 patients (95.4 percent) were free from biochemical progression after surgery and 150 of these 228 patients (65.7 percent) had
PNI.
The actuarial biochemical progression-free survival rate for all patients was 96.9 percent at 60 months and 93.5 percent at 84 months,
respectively.
Stratification based on the presence or absence of PNI did not allow for identification of different prognostic groups.
The authors conclude that, at least in their series of patients, men with pathological stage T2 disease and PNI were found to present with a
higher pT2 stage and Gleason score than men without PNI, but that the biochemical progression-free outcomes among these patients were
similar to the outcomes of patients without PNI at a follow up of between 2 and 12 years.
This study appears to suggest that the prognostic impact of PNI on risk for progressive prostate cancer is actually much lower than has been
assumed in the past. It may well be that as men have increasingly been diagnosed earlier in the progression of their disease, that perineural
invasion is a less significant prognostic factor for men with truly localized disease than it has been thought to be for men known to have
extraprostatic extension of their disease. In other words, PNI in men with pathological T3/4 disease may have greater prognostic significance
than it does in men with pathological T2 disease.
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