Low-risk prostate cancer, active surveillance, and perineural invasion

A previously unanswered question is whether a finding of perineural invasion in the biopsy cores of men who otherwise meet all relevant criteria for management by active surveillance does or does not actually increase risk for progressive forms of prostate cancer.

Al-Hussain et al. have conducted a retrospective analysis of data from > 300 patients in the Johns Hopkins database in an attempt to provide an initial answer to this question. These patients all met the Johns Hopkins biopsy-based criteria for eligibility of active surveillance (a Gleason score of ≤ 6, only 1 or 2  positive biopsy cores, and ≤ 50 percent involvement of cancer in any positive core). However, they all decided to forgo active surveillance and elected to have a radical prostatectomy (carried out at Johns Hopkins between 1992 and 2008).

For the purposes of this study, perineural invasion was defined as, “the presence of cancer tracking along or around a nerve” within the prostate. (Perineural invasion of the extraprostatic nerves that control erectile function implies that cancer has already escaped outside the prostate.)

The results of the analysis showed the following:

  • All 313 patients had a minimum of 12 biopsy cores removed.
  • 51/313 patients (16.3 percent) had perineural invasion on biopsy.
  • 262/313 patients (83.7 percent) showed no sign of perineural invasion on biopsy.
  • There was no significant difference in patient age or in average (mean) serum PSA value at diagnosis in men with or without perineural invasion.
    • The average (mean) age of all 313 patients was 58.2 years.
    • The average (mean) serum PSA level of all patinets was 5.7 ng/ml.
  • There was a small but significant difference in the maximum percentage of cancer in the biopsy cores between the two groups.
    • Men with perineural invasion had a maximum percentage of cancer of 18.6 percent in their biopsy cores.
    • Men without perineural invasion had a maximum percentage of cancer of 15.0 percent.
  • Men with perineural invasion were more likely to have two biopsy cores positive for cancer as opposed to just one.
    • 56.9 percent of men with perineural invasion had cancer in two biopsy cores.
    • 39.7 percent of men without perineural invasion had cancer in two biopsy cores.
  • The pathologic outcomes of the men with and without perineural invasion showed no significant difference.
    • The incidence of positive surgical margins in men with and without perineural invasion were similar (6.0 vs. 7.3 percent).
    • The incidence of organ-confined disease in men with and without perineural invasion were also similar (84.3 vs. 91.6 percent).
    • 12/51 men (23.5 percent) with perineural invasion on biopsy were found to have a post-surgical, pathologic Gleason score of 7.
    • 54/262 men (20.6 percent) without perneural invasion were found to have a post-surgical, pathologic Gleason score of ≥ 7 (including one man with Gleason 8 disease and four with Gleason 9).

Al-Hussain and his colleagues conclude that men who meet appropriate eligibility criteria for active surveillance should not be excluded from such a management strategy on the basis of a finding of perineural invasion. They are also careful to point out, however, that “we cannot exclude the possibility that continued monitoring of a man with [perimeural invasion] might eventually lead to a greater risk of harm from that cancer.”

The risk for progressive disease in a man found to have perineural invasion on biopsy comes up as a common question from men with newly diagnosed prostate cancer. However, it is becoming increasingly clear that, among patients with clearly lopw-risk, organ-confined prostate cancer, perineural invasion is not necessarily a prognostic sign of increased risk for progressive disease before or after first-line treatment. The current study now extends this likelihood back downstream into those men initially diagnosed with low-risk prostate cancer and for whom active surveillance is a reasonable clinical management strategy.

Al-Hussain et al. state in their discussion that — based on their database — between 26 and 33 percent of men treated with radical prostatectomy for low-risk prostate cancer have clinical stage T1c disease and pathologic findings that show a dominant tumor nodule of < 0.5 cm3 in volume, clearly organ-confined cancer, and no evidence of Gleason pattern 4 or 5.

The degree to which a finding of perineural invasion is a significant, independent prognostic risk factor for men with intermediate-risk, clinically localized prostate cancer and those patients found to have more advanced forms of prostate cancer based on pathologic examination of the prostate post-surgery is still not entirely clear.

4 Responses

  1. I get control PSA, find 9.5. Doctor urologist ask me for biopsy.

    After 10 sample taken … Right part Gleason 7 (3 + 4); 8 mm; 2/5, 40% with PNI. Left part benign.

    Age 67. On 17 June visit surgery doctor for da Vinci surgery on 13 July.

    I need some comments if I am going to do the right things.


  2. Mihai:

    If you join our social network we can walk you through all your possible options. … We will need some more information too, but you appear to have a “favorable” type of intermediate-risk prostate cancer. Immediate surgery is certainly an option, but it is not the only one.

  3. Dear Sir,

    My husband has PSA 5.7 and his Gleason score was 6 with perineural invasion. He is 67 years old. What would be the option? Many thanks.


  4. Dear Naina:

    A 67-year-old male with Gleason 3 + 3 = 6 prostate cancer and a PSA of < 10 ng/ml like your husband may be able to be managed for years on an active monitoring regimen (active surveillance) or he may be appropriate for treatment in a whole variety of different ways.

    If you were to join our social network, we can discuss the details with you in more depth. We would need some additional information to help us understand your husband’s situation in greater detail.

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