pathPNI

"Focused on the Prostate since 1996"

Evidence of increased failure in the treatment of prostate carcinoma patients with perineural invasion treated with three-dimensional conformal radiation therapy.

Perineural invasion of prostate carcinoma cells is associated with reduced apoptotic index.

Prediction of Extraprostatic Extension of Prostate Cancer Based on Needle Biopsy Findings: Perineural Invasion Lacks Significance on Multivariate Analysis

Evidence of increased failure in the treatment of prostate carcinoma patients with perineural invasion treated with
three-dimensional conformal radiation therapy.

Steven R. Bonin, M.D.1, Alexandra L. Hanlon, M.S.1, W. Robert Lee, M.D.1,
Benjamin Movsas, M.D.1, T. I. Al-Saleem, M.D.2, Gerald E. Hanks, M.D.

Cancer 1997, 79: 75-80.

1 Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. 2 Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

ABSTRACT

BACKGROUND. The detection of perineural invasion (PNI) in the diagnostic transrectal biopsy of the prostate is associated with a 93% frequency of extracapsular disease extension in patients treated by prostatectomy for adenocarcinoma of the prostate. Extracapsular extension is associated with an inferior outcome compared with that of patients who have organ-confined disease. This study examined the association of PNI and treatment failure in a consecutive series of patients treated with three-dimensional conformal radiation therapy (3DCRT) alone.

METHODS. The authors report actuarial biochemical no evidence of disease (bNED) survival rates for 484 consecutive patients with clinically localized prostate carcinoma diagnosed by transrectal needle biopsy who completed 3DCRT alone between May 1989 and December 1994. The median follow-up time was 28 months (range, 2-75 months), and the median dose to the center of the prostate was 7368 centigray (cGy) (range, 6316-8074 cGy). Patients were subdivided into 2 groups according to pretreatment prostate specific antigen (PSA) levels (<20 ng/mL vs. 20 ng/mL). Pathology records were reviewed for the presence or absence of PNI. bNED failure was defined as a PSA level 1.5 ng/mL and rising on 2 consecutive occasions. bNED survival rates were calculated using Kaplan-Meier methodology and comparisons of survival curves were accomplished using the log rank test.

RESULTS. The 3-year bNED survival for all 484 patients was 77%. The presence of PNI predicted decreased bNED survival in all patients. This detrimental effect, however, was confined to patients with pretreatment PSA values < 20 ng/mL. The bNED survival rates for patients with pretreatment PSA < 20 ng/mL demonstrated a highly significant decrease if PNI was present versus when it was absent (65% vs. 88% at 3 years, 39% vs. 65% at 5 years; P = 0.0009 for overall curve comparison). For patients with pretreatment PSA < 20 ng/mL, multivariate analysis of prognostic variables demonstrated a significant association between bNED survival and PNI (P = 0.002), palpation stage (P = 0.02), and pretreatment PSA (P = 0.006). Gleason score, age, and dose were not independent predictors of bNED survival in this group of patients.

CONCLUSIONS. To the authors' knowledge, this is the first report demonstrating that PNI detected on diagnostic transrectal biopsy is a significant predictor of decreased bNED survival in patients treated with radiotherapy. The subgroup of patients affected are those with pretreatment PSA < 20 ng/mL. This result suggests that such patients may benefit from more aggressive treatment, particularly the use of larger planning target volumes or adjuvant therapies.

Perineural invasion of prostate carcinoma cells is associated with reduced apoptotic index.

Yang G, Wheeler TM, Kattan MW, Scardino PT, Thompson TC.
Cancer 1996, 78: 1267-1271.

This interesting paper indicates that prostatic cancer cells next to nerve have a lower apoptotic index compared
with cells away from nerves. This suggests that there may be an interaction between the two giving such cells a
proliferative advantage. The relevance of this to pathological specimens containing prostatic cancer showing
perineural association or growth is yet to be explored.

Prediction of Extraprostatic Extension of Prostate Cancer Based on Needle Biopsy Findings: Perineural Invasion Lacks Significance on Multivariate Analysis

A.J. Matthew Egan, M.B.B.S., and David G. Bostwick, M.D.

Extraprostatic extension (EPE) and seminal vesicle invasion
(SVI) are adverse prognostic factors in prostate cancer, and
their prediction before prostatectomy would be useful. Perineural
invasion in needle biopsy has been advocated as a marker of
extraprostatic extension, but its independent value as a predictor
of stage has not been established. We studied 349 previously
untreated men with prostatic adenocarcinoma who underwent
bilateral pelvic lymphadenectomy and radical retropubic
prostatectomy. All patients were clinically free of
metastases and had cancer that was diagnosed on needle biopsy.
Five preoperative variables were collected: clinical stage
(TNM staging system), serum prostate-specific antigen (PSA),
Gleason score on needle biopsy, presence or absence of perineural
invasion, and proportion of the biopsy involved by cancer.
The subsequent prostatectomy specimens were completely
embedded, and whole mount sections were used to evaluate
four outcome staging variables: EPE (absent/present), EPE (absent/unilateral/bilateral). seminal vesicle invasion, and patho-
logic stage (TNM). On univariate analysis, each preoperative
variable was significantly associated with each outcome variable
except for a lack of association between clinical stage and SVI.
Perineural invasion in the biopsy predicted EPE with a sensitivity
of 5 1 %, specificity of 70%, positive predictive value of 49%,
and negative predictive value of 7 1%. On multivariate
analysis (stepwise logistic regression), only preoperative PSA,
proportion of the biopsy involved by cancer, and Gleason score
were significant (p < 0.05); perineural invasion and clinical
stage had no independent predictive value for any of the out-
come variables. We conclude that the finding of perineural
invasion in needle biopsy of prostatic carcinoma has no inde-
pendent predictive value for the presence of extraprostatic ex-
tension, seminal vesicle involvement, or pathologic stage in the
radical prostatect. Accordingly, we no longer routinely evaluate
this finding in biopsy specimens.
-S~aging-l'erineural invasion.