The prognostic implications of perineural invasion at the time of surgery

A recently published Italian study has reported on whether perineural invasion (PNI) has prognostic value in patients undergoing radical prostatectomy for organ-confined prostate cancer, and on its possible correlation with other recognized prognostic factors.

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.

36 Responses

  1. My Gleason score was 7 (3 + 4) in a common histologic adenocarcinoma. Volume: 3.7 cm3; peripheral zone (bilateral); perineural invasion (PNI): present; no vascular or capsular invasion; no seminal vesicle invasion; negative surgical margins.

    I had my radical prostatectomy in 2003. My PSA is now 2.14. I am taking finasteride.

    A year after the surgery my doctor gave me hormone therapy for 100 days — odancour. After this the PSA went down to 0.04 but from then it increased slowly till 2.14 now.

    I am 65 years old.

    Do you think have I metastasis or if the PNI is important to qualify my heath situation.

    Thanks for your information.

    Thanks too for your report. Very good indeed.

    My regards

  2. Dear Antonio:

    You may have a very small focus of (relatively indolent) cancer outside the prostate. However, it seems unlikely that you have truly metastatic disease at the present time if your PSA is only 2.14 ng/ml 7 years after your initial treatment, and you are only being treated with finasteride. However, you need to continue to monitor your PSA carefully so that if it continues to increase you and your doctor can take action if needed.

    If your PSA doubling time is more than about 15-18 months (which seems likely) then the chances are good that you will never have evident metastatic disease.

  3. I had a radical prostatectomy on 11 November 2010 and according to my pathology report my Gleason score was 7 (3 + 4) and I had a common histologic adenocarcinoma. only in the left lobule; perineural invasion (PNI) was also present. I had no vascular or capsular invasion; no seminal vesicle invasion; and negative surgical margins.

    Do I need radiotherapy?


  4. Dear Adalberto:

    I see no indication in the information you have provided that would specifically imply the need for immediate, adjuvant radiation therapy. However, you really need to discuss this with your doctor. And you can also get a second opinion if you want to.

    What I do not know is your PSA before you had surgery. If your PSA was high — say 15 ng/ml or higher — before surgery, then you might be a high-risk patient as opposed to an intermediate-risk patient. In that case, the use of adjuvant radiation therapy might become a good idea.

  5. Thanks for your answer, my PSA before surgery was 11.94 and my age is 54.

    If the radiotherapy is done with a linear acelerator, what kind of secondary efects can I expect and how many sessions should there be?


  6. Dear Adalberto:

    Exactly how many sessions and the possible side effects depends on exactly what dose level you are given overall (and therefore at each session) and the type of equipment used. You would have to discuss that with the radiation oncology team. I can’t answer then question for you.


  7. thanks again

  8. I was diagnosed with prostate cancer last December. My PSA before surgery was 3.06. I had a radical prostectomy.

    My Gleason score was 3 + 3 = 6; I am 57 years of age; tumor involves bilateral posterior of the prostate. Surgical margins were all clear; I had no extracapsular extension and no significant pathological change in my seminal vesicles. However, PNI was present. My TNM stage was pT2c. There was significant evidence of intraepithelial neoplasia.

    What is my prognosis?

    Can I go back to surgery and have one or both neuro bundles removed, to eliminate PNI.

  9. Dear Peter:

    First and most importantly — perineural invasion refers to the presence of cancer close to nerves running within the prostate, not the nerves outside the prostate that control your ability to have erections (and which your surgeon seems to have been able to spare). Thus, with the removal of your prostate, you have eliminated the perineural invasion. You don’t need further surgery or any other treatment if your PSA has dropped to < 0.1 ng/ml.

    Second, if your PSA has dropped to < 0.1 ng/ml since your surgery, you can use the Kattan post-treatment nomogram to estimate your long-term outcome. On the basis of the information that you have provided, the nomogram suggests that you have a 98% probability of progression-free survival at 10 years — which is about as good as it gets!

  10. I am 65 and have a diagnosis of prostate cancer with adenocarcinoma. My Gleason score is 9 on both sides.

    Lymphovascular and perineural are also present.

    My PSA score was 67.6. I am under a doctors care.

    What do you recommend?

  11. Dear Mr. Bishop:

    I recommend that you join our social network, where you will be able to gain from the experiences of others. If your doctor has not already started you on such therapy, you are (almost) certainly going to need to have hormone therapy. Have you been given a bone scan?

  12. Hello,

    My name is Roger. I had a da Vinci radical prostatectomy on August 3rd, 2011. My gleason score on the pathology results is a 7 with seminal vesical invasion and perineural invasion.The doctor recommended radiation after my healing, which would be 3 to 4 moths. I am weighing the radiation to observation, but am very confused. The side effects from the radiation are very scarey for me. Any advise would be helpful! Thank you.

  13. Roger:

    I strongly suggest that you join our social network, where you can benefit from the experience and knowledge of many other men who have been exactly where you are today. We will need some more information to be able to give you the best possible support and guidance (your age, your pre-surgical PSA level, whether your post-surgical Gleason score is 3 + 4 = 7 or 4 + 3 = 7, whether the cancer had spead to one or both seminal vesicles, and perhaps some other stuff too). Do you have a copy of your port-surgical pathology report?

  14. Thank you for responding. Here is more information. To begin with, I am 59 years old. My pre-surgical PSA level was 8. My post-surgical Gleason score is 7 (4 + 3), stage pT3b. In the “Accessory Findings” it are noted: seminal vesicle invasion (present) and perineural invasion (present). I do have my post-surgical pathology report. I will join the social network also. Any info. would be appreciated.


  15. Hello,

    My father is 65 years old, with PSA 4.3 as of January 2012 (in Sept 2010 it was 3.99). He is Stage I.

    His biopsy results showed adenocarcinoma in the left lateral apex, left lateral base, right apex, right mid, right base, right lateral apex, right lateral mid, and right lateral base. 1 of 1 core was involved in each.

    Perineural invasion (PNI) was also present in the right apex, right base, and right lateral base.

    His Gleason score is 7 (3 + 4) for all of these areas except the right apex, where it is a 6 (3 + 3).

    He is going in to have a radical prostatectomy with a very well-respected surgeon at Yale, but cannot get in to see the surgeon (even for an initial consult) for another month. Moreover, the urologist seemed to feel that it might be beneficial to wait until he has time to recover from the biopsy last week (although that seems a little weird if he is having the whole organ removed anyway).

    Waiting makes me nervous because of the PNI.

    Would you be so kind as to speak a little about prognosis? And — also — is waiting a month dangerous? Should we go to a slightly less-beloved surgeon who can see him more quickly?

    Thanks SO much for your time and opinon, it is incredibly appreciated.

  16. Kim:

    Please join our social network and post the above information there, where we can address your questions in detail.

  17. Dear Doug:

    Please understand that there is a difference between “letting men know about” this test (which we have been doing for 3 years by writing about it as it has been going through development) and actually recommending it when it has never been show to be able to predict clinically significant cancer in a prospective clinical trial (and neither had the PSA test either).

    You have a complete right as an individual (as does anyone else) to ask your doctor whether he or she thinks this test is appropriate for you. However, our current view on this test is that it has a way to go before we will really know its prognostic value. You are also at complete liberty to disagree with that if you wish to.

    We would also bring to your attention that this is not a political blog, and we respectfully ask commentators to leave their politics at the door when they choose to comment on this site.

  18. Hello,

    My father is 75 years old and he has been diagnosed with prostate enlargement. His Gleason score is 2 + 3 = 5. No evidence of PNI.

    The report says “Sections show prostate tissue with 80% of tissue processed showing a malignant neoplasm composed of closely packed uniform acini, most of them lined by columnar epithelium with macronuclei and nucleoli. Few of the glands appear with irregular with ragged edges. No evidence of Perineural Invasion seen.”

    The doctor is saying my father has to under go a surgery to remove his testicles. Is this the best option at this stage?

    What are his treatment options? Please advise.

    Thank you for your response.


  19. Dear Andrew:

    Your father may well have an enlarged prostate but he also has prostate cancer. We need to get more information, but at this point in time I know of no good reason why your father needs to have his testicles surgically removed. Who told him this?

    Here is what you need to do. … You need to collect all of the information listed below and then go join our social network. When you join the social network, enter all this information under the heading “About Me” where we ask about “your” prostate cancer … but tell us it is about your Dad’s cancer.

    Here is what we need to know:

    — Your Dad’s age (which you say is 75 years)
    — Your Dad’s PSA level
    — The clinical stage of his prostate cancer (probably T1c, but you may need to ask the doctor)
    — His Gleason score (which you say is 2 + 3 = 5)
    — The total number of biopsy cores that the urologist took at biopsy
    — The number of those biopsy cores that were positive for cancer
    — Any other significant health issues your Dad may have

    Please understand that based on what I know at this time, it is utterly possible that your Dad doesn’t need to to anything about this condition except monitor it either for quite a while or forever. He appears to have no more than low-risk disease.

  20. Thank you for your quick response. His PSA level was 210. The doctor told it is very high and that’s when they decided to go for Cystoscopy biopsy.

    The report says “Received multiple prostatic chips in aggregate measuring 9cm. [ PE-A1-A3 – 3 Blocks]

    Cystoscopy report says ” Under SA Cystoscopy revealed Grade II BHP . Trabeculated bladder. TURP done.

    He has High Blood Pressue (around 170 / 110), taking BP medicines regularly. Also he is diabetic sometimes.

    I dont have the information about homany biopsy cores were taken and how many were positive for cancer.

    I’m planning to take him to another Urologist for second opinion.

    He went through Bladder stone removal surgery 10 years ago. The stone was about the size of a golf ball.

    Thank you again for the details. I will create an account and join the social network.

  21. Andrew:

    I can already tell you that your Dad needs a bone scan and a CT scan. Does he have any symptoms like back pain or anything like bone pain or blood in his urine?

  22. Age 65, PSA 5, biopsy cancer in 3 of 6 cores on only one side with nodule, Gleason 3 + 4 = 7. Scheduled for surgery. Should I have a CT scan to see if it has spread?

  23. Dear Leslie:

    Please join our social network where we can appropriately address this type of personal issue in more detail.

  24. I am 69 years and have been having PSA readings around 4.5 to 5. My last reading in Sept 2012 went to 8.5 ng/ml. The urologist did not think the prostate was any more enlarged on rectal examination as might be expected for my age.

    He has recommended a biospsy taken with invasion through the rectum. I am told that can cause infection and that a better alternative is through the perennium. Could you advise?

    Also, when I took my last blood test I had had sex a few hours earlier and I am told that could raise the PSA too.



  25. Dear Devendra:

    If you would please join our social network, we can discuss your case there in detail.

  26. Have now joined the network.

  27. To whom it may concern,

    Had a radical prostatectomy August 2012.

    — Pre-surgery: Gleason 6; clincial stage T2, PSA 4.5 ng/ml.
    — Pathology post-surgical report: PNI present; Gleason 6 (3 + 3); stage pT2; all lymph nodes negative; bladder neck negative; seminal vesicles negative; and negative margins.
    — Post-surgerical PSA: < 0.1 at ~2 months

    Just wondering if you could help explain risk of recurrence with presence of PNI and negative margins.


  28. Paul:

    You can use the Kattan post-surgical nomogram to estimate your prognosis.

    You don’t give your age, but if I assume it is 60 and plug all the rest of your data into the nomogram I get the following:

    — Probability of progression-free survival at 5 years, 99%
    — Probability of progression-free survival at 10 years, 98%

    You can use the nomogram yourself with the correct age, but I don’t think it will change the outcome much.

  29. Dear Sitemaster,

    Thank you for the quick response.

    Just wondering what the difference between “progression-free survival” and “progression-free probability after surgery”? The nonogram uses the latter.



  30. Dear Paul:

    Well if you die from something other than prostate cancer (e.g., you get hit by a bus), then prostate cancer has nothing to do with your demise. Otherwise there is no difference between the two statements: your prostate cancer hasn’t progressed and you are alive.

  31. My husband is 52 years old and has just been diagnosed with prostate cancer. His initial PSA was 58. His eight biopsies were malignant with three showing perineural invasion and high PIN present and all eight had Gleason scores of 7 (4 + 3). We are waiting results from our MRI and bone scan for further staging results. Could you tell me if you think this qualifies for high-risk grouping and without the other scan results what treatment plan you think would be good.

  32. Dear Luanne:

    These data definitively categorize your husband as having D’Amico “high-risk” prostate cancer because his PSA level is > 20 ng/ml.

    If you haven’t already done this, we recommend that you join our social network, where it would be possible to discuss your husband’s treatment options in more detail.

  33. I am a 47-year-old male who was recently diagnosed with prostate cancer. Out of my 12 biopsy cores, three came back benign; six came back with a Gleason score of 6; the other three had a Gleason score of 7 (3 + 4) with one of those showing perineural invasion. I am scheduled for a bone scan and CT scan. What are the chances that the cancer has spread? The core in question was core 1 near the base of prostate. I am going crazy with this whole situation.

  34. Dear Ron:

    If you join our social network, that is where we can help you to work through your risk factors and consider the potential treatment options. Do you also know your clinical stage (e.g., T1c, T2a, T2b, etc.)?

  35. My husband (age 61) has PSA 7, Adcnocarcinoma of the prost:rte Gleason score 3+3
    CLINICAL DIAGNOSIS: DRE – Normal prostate
    NATURE OF SPECIMEN: Prostate biopsy
    1l Left. slde: Specimen of 7 cores ranging in size from 1.5-1 cm. AII embed-A
    2) Right side: Specimen of Tcores ranging in size from 2.5-1 cm. A11 embed-B
    1 , ProstaLe, left side (core biopsy) : * Adenocarcinoma of prostate, acinar tlpe.
    – Gleason score is 3+3 = 5, out of 10.
    – Tumor invo1ves all cores, with an overal-1 average of 20%.
    – Perineural invasion is present.
    2 ,Prostate, right side (core biopsy) :
    – Adenocarcinoma of prostate, acinar trce.
    – Gleason score is 3+3 = 6, out of 10.
    – Gleason score is 3 out of 7 cores, wlLh an owerall average of <10%;.
    – Perineuraf invasion is present.
    MRI PELVIS :Urinary bladder is normal in size and signal intensity. No focal mass lesion,/
    calculi. Wall thickness is normal.
    Prostate is mildly enlarged in size. Lateral aspect of the peripheral gland
    on both the sides appear hyperintense on T1, turning hypointense on T2-
    suggestive of bleed. Post contrast study demonstrates minimal
    inhomogenous enhancement.
    / ,llowever, no extracapsular spreadr/seminal vesicle extension/neurovascular bundle involvement.
    Solitary lymph node is seen adjacent to the external iliac artery on either
    side. Largest on the right side, measuring 9.0×6.0rnm in size.
    Seminal vesicles appear normal.
    Pelvic bones and joints are normal.
    No free fluid seen in the pelvis.
    Spermatic cords show normal signal intensity.
    No evidence of focal lesion.
    Bilateral testis and epididymis are normal.
    No evidence of hydrocoele.
    IMPRESSION: KnownIMPRESSION: Known case of Ca prostate, post biopsy.
    Present study shows:Haemorrhage in the lateral aspect of peripheral gland on both sides .
    solitary lymh node adjacent to the external iliac artery on either side-? Metastatic .
    No scinitigraphic evidence of skeletul metastases.
    what treatment should my husband opt. Till now he has no symptoms . . when he went for regular medical check up before 45 days this result came out

  36. Dear Tirtha:

    If you click here and apply to join our social network, we can help you there, we cannot get into this sort of detail on this web site.

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