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

Amar S Ahmad,Henrik Møller,Vishnu Parameshwaran,Jack Cuzick,David Greenberg,Daniel M Berney,Gabrielle Fisher,Bernard V North,Geraldine Soosay,Peter Scardino,Luis Beltran

doi:10.18632/oncotarget.24994

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.

Highlights

In spite of the fact that prostate cancer is the fourth most common cancer globally and the second most common cancer in men there remains uncertainty on the optimal management strategy for clinically localized tumors of low and intermediate grades
On univariable analysis Perineural invasion (PNI) was highly significantly associated with prostate cancer death (DOD), but extraprostatic extension (ECE) was not
On univariable analysis PNI was highly significantly associated with DOD (HR 2.28, 95% confidence interval (CI): 1.68, 3.1, log-rank test p-value = 4.77 × 10–8), but extra prostatic extension (EPE) was not

Summary

Introduction

In spite of the fact that prostate cancer is the fourth most common cancer globally and the second most common cancer in men there remains uncertainty on the optimal management strategy for clinically localized tumors of low and intermediate grades. Increasing detection has led to many men who are more likely to die with their prostate cancer than of it. Prostate cancer is diagnosed primarily by biopsy, and many factors have been used to predict the likelihood of progressive disease and need for radical therapy. Gleason score and recently the establishment of Grade Groups by the International Society of Urological Pathology [1] allows reasonable risk stratification, together with serum PSA, clinical stage and more recently imaging. Perineural invasion (PNI) by prostate cancer has long been considered a risk factor for disease progression

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