summarizes the distribution of men by pretreatment age, Gleason score, T-stage, and iPSA. The population was relatively favorable, with 75% having a Gleason score of 2-6, 95% having T1-T2 disease, and 60% having a pretreatment initial PSA <10 ng/mL (overall median, 8.5 ng/mL). shows various other patient characteristics. Median time to nPSA was 35 months and the median nPSA achieved was 0.4 ng/mL. The median nPSA12 achieved was 1.2 ng/mL. With a median follow-up of 58 months, 26% of patients had BF (n = 260), 5% had DM (n = 50), 2% died from prostate cancer (n = 17), and 13% died from any cause (n = 126).
Distribution of Patients by Age, Gleason Score, T Classification, and iPSA
Patient Characteristics (n = 1000)
is a scatterplot showing the correlation between nPSA and nPSA12 for the population (r = 0.975, P < .0001). There was also a significant correlation between nPSA12 and iPSA (, r = 0.392; P < .0001), although the relation was much weaker. For those in whom PSADT was available (n = 657), there was no correlation between nPSA12 and PSADT (r = −0.03859; P = .32).
Scatterplot of (A) nadir prostate-specific antigen (nPSA) versus nadir PSA at 1 year (nPSA12) and (B) iPSA versus nPSA12 for all patients.
Multivariate Cox proportional hazard analyses were performed using the entire cohort (). The covariates included iPSA (continuous), Gleason score (2-6 versus 7-10), RT dose (continuous), T-stage (T1-2 versus T3), age (continuous), and nPSA12 (continuous). The nPSA12 was an independent predictor of BF (P = .0056), DM (P < .0001), CSM (P < .0001), and OM (P < .0001).
Multivariate Analyses for the Entire Cohort (n = 1000): nPSA12 as a Continuous Covariate
shows the multivariate Cox proportional hazard model results in the population in which PSADT was available (n = 657). The covariates included iPSA (continuous), Gleason score (2-6 versus 7-10), RT dose (continuous), T-stage (T1-2 versus T3), age (continuous), PSADT (continuous), and nPSA12 (continuous). The nPSA12 was an independent predictor of BF (P = .0147), DM (P < .0001), CSM (P < .0001), and OM (P < .0001).
Multivariate Analyses for the PSADT Patient Subset (n = 657): nPSA12 as a Continuous Covariate
To assess the optimal dichotomization of nPSA12, we evaluated the sequential model likelihood ratio chi-square values and P-values associated with each dichotomized nPSA12 variable (). The clinical utility of using a high nPSA12 cutpoint is questionable because the proportion of patients with unfavorable nPSA12s becomes vanishingly small (ie, high specificity and low sensitivity). As a compromise, we decided to use an nPSA12 cutpoint of 2 ng/mL; 27% of the patients had an nPSA12 >2.0 ng/mL. The 5- and 10-year BF rates for those with an nPSA12 >2 ng/mL were 36% and 46%, versus 26% and 30% for an nPSA12 ≤2 ng/mL (P = .0015). An nPSA12 >2 ng/mL was associated with an 8% risk of DM at 5 years, whereas for an nPSA12 of ≤2 ng/mL the risk was 2%. At 10 years the risk of DM for an nPSA12 >2 ng/mL was 19%, whereas for an nPSA12 of ≤2 ng/mL the risk was 4% (P ≤.0001; see ). In terms of CSM, an nPSA12 of ≤2 ng/mL was associated with a <1% risk of CSM at 5 years, whereas for an nPSA12 >2 ng/mL of the risk was 3% (P = .0029; see ). These numbers are about double at 10 years (2% and 7%). We did not find a statistically significant difference for OM (26% for an nPSA12 ≤2 ng/mL versus 35% for an nPSA12 >2 ng/mL at 10 years; P = .1781).
Full MVA Based on Covariates From Optimal Model in With nPSA12 Cut at “X” ng/mL
(A) Distant metastasis and (B) cause-specific mortality based on the 2.0-ng/mL nadir prostate-specific antigen at 1 year (nPSA12) cutpoint.
When tested as a dichotomous variable (≤2 versus > 2 ng/mL) in MVA using the entire patient cohort (n = 1000), nPSA12 was related to DM (P
< .0001) and CSM (P
= .0078) (). With the inclusion of PSADT as a continuous variable (n = 657), nPSA12 as a dichotomous variable remained significant for BF (P
= .0392), DM (P
< .0001), and CSM (P
= .0094), but not OM. When PSADT was included as a dichotomous variable (≤3 versus >3 months), as described by D’Amico et al.29,30
nPSA12 >2 ng/mL remained independently predictive of DM (P
Multivariate Analyses for nPSA12 as a Dichotomous Covariate (n = 1000; Cutpoint for nPSA12 = 2.0)