Utility of Risk Models in Decision Making After Radical Prostatectomy: Lessons from a Natural History Cohort of Intermediate- and High-Risk Men

Abstract

Background: Current guidelines suggest adjuvant radiation therapy for men with adverse pathologic features (APFs) at radical prostatectomy (RP). We examine at-risk men treated only with RP until the time of metastasis.

Objective: To evaluate whether clinicopathologic risk models can help guide postoperative therapeutic decision making.

Design, setting, and participants: Men with National Comprehensive Cancer Network intermediate- or high-risk localized prostate cancer undergoing RP in the prostate-specific antigen (PSA) era were identified (n=3089). Only men with initial undetectable PSA after surgery and who received no therapy prior to metastasis were included. APFs were defined as pT3 disease or positive surgical margins.

Outcome measurements and statistical analysis: Area under the receiver operating characteristic curve (AUC) for time to event data was used to measure the discrimination performance of the risk factors. Cumulative incidence curves were constructed using Fine and Gray competing risks analysis to estimate the risk of biochemical recurrence (BCR) or metastasis, taking censoring and death due to other causes into consideration.

Results and limitations: Overall, 43% of the cohort (n=1327) had APFs at RP. Median follow-up for censored patients was 5 yr. Cumulative incidence of metastasis was 6% at 10 yr after RP for all patients. Cumulative incidence of metastasis among men with APFs was 7.5% at 10 yr after RP. Among men with BCR, the incidence of metastasis was 38% 5 yr after BCR. At 10 yr after RP, time-dependent AUC for predicting metastasis by Cancer of the Prostate Risk Assessment Postsurgical or Eggener risk models was 0.81 (95% confidence interval [CI], 0.72-0.97) and 0.78 (95% CI, 0.67-0.97) in the APF population, respectively. At 5 yr after BCR, these values were lower (0.58 [95% CI, 0.50-0.66] and 0.70 [95% CI, 0.63-0.76]) among those who developed BCR. Use of risk model cut points could substantially reduce overtreatment while minimally increasing undertreatment (ie, use of an Eggener cut point of 2.5% for treatment of men with APFs would spare 46% from treatment while only allowing for metastatic events in 1% at 10 yr after RP).

Conclusions: Use of risk models reduces overtreatment and should be a routine part of patient counseling when considering adjuvant therapy. Risk model performance is significantly reduced among men with BCR.

Patient summary: Use of current risk models can help guide decision making regarding therapy after surgery and reduce overtreatment.

Keywords: Adjuvant therapy; Adverse pathologic features; Biochemical recurrence; Metastasis; Nomograms; Prostate cancer; Salvage therapy.