Perineural invasion and Gleason 7-10 tumors predict increased failure in prostate cancer patients with pretreatment PSA <10 ng/ml treated with conformal external beam radiation therapy.

PURPOSE

It has been well established that prostate cancer patients with pretreatment PSA <10 ng/ml enjoy excellent bNED control when treated with definitive external beam radiation therapy. This report identifies predictors of failure for patients with pretreatment PSA <10 ng/ml. These predictors are then used to define favorable and unfavorable prognostic subgroups of patients for which bNED control is compared.

METHODS AND MATERIALS

Between 3/87 and 11/94, 266 patients with T1-T3NXM0 prostate cancer and pretreatment PSA values <10 ng/ml were treated with definitive external beam radiation therapy. Median central axis dose and median follow-up for the entire group was 72 Gy (63-79 Gy) and 48 months (2-120 months). Predictors of bNED control were evaluated univariately using Kaplan-Meier methodology and the log-rank test and multivariately using Cox proportional hazards modeling. Covariates considered were pretreatment PSA, palpation stage, Gleason score, presence of perineual invasion (PNI) and central axis dose. Independent predictors based on multivariate results were then used to stratify the patients into two prognostic groups for which bNED control was compared. bNED failure is defined as PSA > or = 1.5 ng/ml and rising on two consecutive determinations.

RESULTS

Univariate analysis according to pretreatment and treatment factors for bNED control demonstrates a statistically significant improvement in 5-year bNED control for patients with Gleason score 2-6 vs. 7-10, patients without evidence of perineural invasion (PNI) vs. those with PNI, and patients with palpation stage T1/T2AB vs. T2C/T3. Multivariate analysis demonstrates that Gleason score (p = 0.0496), PNI (p = 0.0008) and palpation stage (p = 0.0153) are significant independent predictors of bNED control. Based on these factors, patients are stratified into a more favorable prognosis group (Gleason 2-6, no PNI, and stage T1/T2AB, n = 172) and a less favorable prognosis group (Gleason 7-10 or PNI or T2C/T3, n = 94). A comparison of the two groups reveals that bNED control is significantly lower in the less favorable prognosis group (74% vs. 91% at 5 years, p = 0.0024).

CONCLUSIONS

(1) This report identifies Gleason 7-10 and the presence of PNI as well as palpation stage T2C/T3 as factors that predict worse bNED outcome for patients with pretreatment PSA <10 ng/ml who are treated with radiation therapy alone. (2) Patients with these pretreatment prognostic factors may benefit from adjuvant therapies or altered treatment programs. (3) In order to make fair comparisons between radiation therapy and prostatectomy series, the distribution of perineual invasion and Gleason 7-10 must be taken into account.