Clinical Significance of Perineural Invasion by Prostate Cancer

In This Article

Abstract and Introduction

Abstract

Objectives: The clinical impact of the laterality of perineural invasion (PNI) by prostate cancer remains poorly understood. We herein compared radical prostatectomy (RP) findings and long-term oncologic outcomes in patients with prostate cancer with PNI in two prostate biopsy (PBx) sites.

Methods: We retrospectively assessed 170 consecutive patients undergoing systematic sextant PBx where PNI had been detected in two of six PBx sites, followed by RP.

Results: PNI occurred unilaterally in 140 (82.4%) cases and bilaterally in 30 (17.6%) cases. Compared with unilateral PNI, bilateral PNI was significantly associated with a higher number of cancer-positive sites and longer total tumor length on PBx. However, there were no significant differences in RP findings, including tumor grade/stage and tumor volume, between unilateral and bilateral PNI cohorts. Kaplan-Meier analysis revealed that patients with bilateral PNI had a significantly higher risk of disease progression after RP than those with unilateral PNI (P = .038). In multivariate analysis, bilateral PNI (vs unilateral PNI) showed significance for progression (hazard ratio, 2.281; P = .023).

Conclusions: In PBx specimens exhibiting PNI in two sextant sites, bilateral PNI was found to be associated with poorer prognosis as an independent predictor but not worse histopathologic features in RP specimens compared with unilateral PNI.

Introduction

Histopathologic features of prostate cancer on needle core biopsy, even those other than Gleason score/Grade Group (GG), often provide critical information for optimal patient care. Of these, perineural invasion (PNI) by prostate cancer has been associated with adverse pathology, particularly extraprostatic extension.^[1,2] The presence of PNI on biopsy has also been implicated as a key prognosticator in patients with prostate cancer undergoing radical prostatectomy or radiotherapy.^[2–5] By contrast, little is known about the role of PNI quantitation on prostate biopsy. In our recent study involving systematic biopsy specimens exhibiting PNI in one to six sextant sites, multisite PNI, compared with a single PNI site, was found to be associated with significantly poorer prognosis after radical prostatectomy.^[6] Nonetheless, the clinical impact of PNI laterality (ie, right or left only vs both sides) remains to be determined. The present study aimed to assess radical prostatectomy findings and long-term oncologic outcomes in men with prostate cancer whose sextant biopsy specimens had exhibited PNI in two of the sites.

Table 1. Clinicopathologic Findings in Cases Showing Unilateral vs Bilateral PNIs
Characteristic	Unilateral	Bilateral	P Value
No. of patients	140	30
Age, median/mean ± SD, y	63/62.3 ± 6.8	62/61.4 ± 7.4	.578
PSA, median/mean ± SD, ng/mL	6.04/8.23 ± 7.14	6.10/7.68 ± 4.69	.601
Bx cancer-positive sites, No. (%)			<.001
2	17 (12.1)	3 (10.0)
3	55 (39.3)	2 (6.7)
4	33 (23.6)	7 (23.3)
5	15 (10.7)	11 (36.7)
6	20 (14.3)	7 (23.3)
Bx tumor length, median/mean ± SD, mm	37.2/42.9 ± 26.8	53.2/56.6 ± 29.1	.023
Bx Grade Group (highest), No. (%)			.894
1	17 (12.1)	2 (6.7)
2	52 (37.1)	11 (36.7)
3	32 (22.9)	7 (23.3)
4	23 (16.4)	5 (16.7)
5	16 (11.4)	5 (16.7)
RP Grade Group, No. (%)			.693
1	3 (2.1)	0 (0)
2	68 (48.6)	18 (60.0)
3	42 (30.0)	7 (23.3)
4	7 (5.0)	0 (0)
5	20 (14.3)	5 (16.7)
pT, No. (%)			.451
2/2+	35 (25.0)	10 (33.3)
3a	78 (55.7)	13 (43.3)
3b	27 (19.3)	7 (23.3)
pN, No. (%)			1.000^a
0	106 (75.7)	23 (76.7)
1	28 (20.0)	6 (20.0)
X	6 (4.3)	1 (3.3)
Surgical margin, No. (%)			1.000
Negative	105 (75.0)	23 (76.7)
Positive	35 (25.0)	7 (23.3)
Tumor volume, median/mean ± SD, mL	8.3/10.9 ± 9.3	11.9/14.3 ± 14.7	.252
Adjuvant therapy before recurrence, No. (%)			.495
Not performed	101 (72.1)	24 (80.0)
Performed	39 (27.9)	6 (20.0)

Bx, biopsy; PNI, perineural invasion; PSA, prostate-specific antigen; RP, radical prostatectomy.
^apN0 vs pN1.

Table 2. Univariate and Multivariate Analyses of the Prognostic Factors Available After Biopsy
Variable	Univariate Analysis		Multivariate Analysis
Variable	HR (95% CI)	P Value	HR (95% CI)	P Value
Age (≤63 vs >63 y)	0.866 (0.505–1.486)	.601	0.620 (0.337–1.143)	.126
PSA (≤6.04 vs >6.04 ng/mL)	1.903 (1.107–3.273)	.020	1.288 (0.708–2.345)	.408
Cancer-positive sites
2	1		1
3	1.384 (0.521–3.679)	.515	1.163 (0.377–3.584)	.793
4	1.906 (0.714–5.091)	.198	1.235 (0.378–4.034)	.727
5	1.068 (0.299–3.818)	.920	0.784 (0.206–2.988)	.722
6	2.342 (0.870–6.302)	.092	1.394 (0.372–5.219)	.622
Cancer length (≤39.9 vs >39.9 mm)	1.715 (0.998–2.949)	.051	1.146 (0.575–2.286)	.699
Grade Group
1	1		1
2	3.361 (1.000–11.29)	.0499	5.448 (0.687–43.24)	.109
3	5.164 (1.906–13.99)	.001	10.44 (1.308–83.39)	.027
4	5.072 (1.763–14.59)	.003	12.44 (1.536–100.7)	.018
5	10.51 (3.316–33.32)	<.001	24.22 (2.882–203.5)	.003
PNI (unilateral vs bilateral)	2.342 (1.050–5.225)	.038	2.281 (1.112–4.637)	.023