title: Evidence of increased failure in the treatment of prostate carcinoma patients who have perineural invasion treated with three-dimensional conformal radiation therapy.
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. > or = 20 ng/mL). Pathology records were reviewed for the presence or absence of PNI. bNED failure was defined as a PSA level > or = 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.
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Bonin
authors.forename: A L
authors.initials: AL
authors.lastname: Hanlon
authors.forename: W R
authors.initials: WR
authors.lastname: Lee
authors.forename: B
authors.initials: B
authors.lastname: Movsas
authors.forename: T I
authors.initials: TI
authors.lastname: al-Saleem
authors.forename: G E
authors.initials: GE
authors.lastname: Hanks
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010524:Peripheral Nervous System Neoplasms / Q000556:secondary*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology* / Q000532:radiotherapy* / Q000601:surgery; D017211:Treatment Failure
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen