Should reporting of peri-neural invasion and extra prostatic extension be mandatory in prostate cancer biopsies? correlation with outcome in biopsy cases treated conservatively

Abstract

The identification of perineural invasion (PNI) and extraprostatic extension (ECE) in prostate cancer (PC) biopsies is time consuming and can be difficult. Although this is required information in many datasets, there is little evidence on their effect on outcome in patients treated conservatively. Cases of PC were identified from three cancer registries in the UK from men with clinically localized prostate cancer diagnosed by needle biopsy from 1990–2003. The endpoint was prostate cancer death (DOD). Patients treated radically within 6 months, those with objective evidence of metastases or who had prior hormone therapy were excluded. Follow-up was through cancer registries up until 2012. Deaths were divided into those from PC and those from other causes, according to WHO criteria. 988 biopsy cases (6522 biopsy cores) were centrally reviewed by three uropathologists and assigned a Gleason score and Grade Group (GG). The presence of both PNI and ECE was recorded. Of 988 patients, PNI was present in 288 (DOD = 75) and ECE in 23 (DOD = 5). On univariable analysis PNI was highly significantly associated with DOD (hazard ratio [HR] 2.28, 95% CI: 1.68, 3.1, log-rank test p-value = 4.8 × 10–8), but ECE was not (log-rank test p-value = 0.334). On multivariable analysis with GG, serum PSA (per 10%), clinical stage and extent of disease (per 10%), PNI lost significance (HR 1.16, 95% CI: 0.83, 1.63, likelihood ratio test p-value = 0.371). The utility of routinely examining prostate biopsies for ECE and PNI is doubtful as it is not independently associated with higher grade, stage or prognosis.

Perineural invasion by prostate adenocarcinoma in needle biopsies predicts bone metastasis: Ten year data from the TROG 03.04 RADAR Trial

“…Four previous studies have investigated the prognostic significance of PNI in biopsies from patients who were not treated with curative intent. 10,11,19,20 In two of these studies patients underwent active surveillance and the presence of PNI was correlated with tumour progression. 19,20 In a separate study a cohort of patients diagnosed by transurethral resection of prostate were enrolled in a watchful waiting programme and PNI was correlated with cancerspecific death on univariable analysis, but not on multivariable analysis.…”

“…These studies have employed a variety of methodologies, being based upon the detection of PNI in either diagnostic prostate biopsies, samples from transurethral resection of prostate or radical prostatectomy specimens. 1,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] The outcome parameters for these studies are similarly variable and in most instances the presence of PNI was assessed against surrogate markers of tumour aggressiveness such as Gleason score/ ISUP grade, tumour stage, cell cycle activity, extraprostatic extension of tumour, seminal vesicle involvement, surgical margin positivity and the presence of lymph node metastases. The most frequently investigated outcome parameter was prostate specific antigen biochemical failure, while in some studies more meaningful outcome parameters (time to localized/systemic tumour progression, development of castration resistance, and cancer-specific and overall survival intervals) were available as clinical endpoints.…”

Defining clinically significant prostate cancer on the basis of pathological findings

“…Similarly to that of PNI, the significance of EPE in needle biopsies is controversial. A recently published study demonstrated an association between disease‐specific mortality and PNI (univariate analysis), but there was no association with EPE . It is very unusual to see EPE in the needle biopsy and still meet all other criteria for AS.…”

“…A recently published study demonstrated an association between diseasespecific mortality and PNI (univariate analysis), but there was no association with EPE. 80 It is very unusual to see EPE in the needle biopsy and still meet all other criteria for AS. As mentioned above, EPE is associated with increased risks of BCR and positive margins at RP.…”

Perineural invasion, Gleason score and prostate specific antigen; is there any association?

“…It seems that PNI in biopsy specimens is in association with extra-prostatic invasion. In addition, recent studies have presented that maximum diameter of PNI is associated with prostate cancer prognosis (8).…”