A single early prostate-specific antigen (PSA) level has been correlated with a higher likelihood of prostate cancer diagnosis and death in younger men. PSA testing in older men has been considered of limited utility. We evaluated prostate cancer death in relation to age and PSA level immediately prior to prostate cancer diagnosis. Using the Veterans Affairs database, we identified 230,081 men aged 50-89 years diagnosed with prostate cancer and at least one prior PSA test between 1999 and 2009. Prostate cancer-specific death over time was calculated for patients stratified by age group (e.g., 50-59 years, through 80-89 years) and PSA range at diagnosis (10 ranges) using Kaplan-Meier methods. Risk of 10-year prostate cancer mortality across age and PSA was compared using log-rank tests with a Bonferroni adjustment for multiple testing. 10.5% of men diagnosed with prostate cancer died of cancer during the 10-year study period (mean follow-up = 3.7 years). Higher PSA values prior to diagnosis predict a higher risk of death in all age groups (p < 0.0001). Within the same PSA range, older age groups are at increased risk for death from prostate cancer (p < 0.0001). For PSA of 7-10 ng/mL, cancer-specific death, 10 years after diagnosis, increased from 7% for age 50-59 years to 51% for age 80-89 years. Men older than 70 years are more likely to die of prostate cancer at any PSA level than younger men, suggesting prostate cancer remains a significant problem among older men (even those aged 80+) and deserves additional study.

Background

Although the Decipher genomic classifier has been validated as a prognostic tool for several prostate cancer endpoints, little is known about its role in assessing the risk of biopsy reclassification for patients on active surveillance, a key event that often triggers treatment.

Objective

To evaluate the association between Decipher genomic classifier scores and biopsy Gleason upgrading among patients on active surveillance.

Design setting and participants

This was a retrospective cohort study among patients with low- and favorable intermediate-risk prostate cancer on active surveillance who underwent biopsy-based Decipher testing as part of their clinical care.

Outcome measurements and statistical analysis

We evaluated the association between the Decipher score and any increase in biopsy Gleason grade group (GG) using univariable and multivariable logistic regression. We compared the area under the receiver operating characteristic curve (AUC) for models comprising baseline clinical variables with or without the Decipher score.

Results and limitations

We identified 133 patients for inclusion with a median age of 67.7 yr and median prostate-specific of 5.6 ng/ml. At enrollment, 75.9% had GG1 and 24.1% had GG2 disease. Forty-three patients experienced biopsy upgrading. On multivariable logistic regression, the Decipher score was significantly associated with biopsy upgrading (odds ratio 1.37 per 0.10 unit increase, 95% confidence interval [CI] 1.05-1.79; p = 0.02). The Decipher score was associated with upgrading among patients with biopsy GG 1 disease, but not GG2 disease. The discriminative ability of a clinical model (AUC 0.63, 95% CI 0.51-0.74) was improved by integration of the Decipher score (AUC 0.69, 95% CI 0.58-0.80).

Conclusions

The Decipher genomic classifier score was associated with short-term biopsy Gleason upgrading among patients on active surveillance.

Patient summary

The results from this study indicate that among patients with prostate cancer undergoing active surveillance, those with higher Decipher scores were more likely to have higher-grade disease found over time. These findings indicate that the Decipher test might be useful for guiding the intensity of monitoring during active surveillance, such as more frequent biopsy for patients with higher scores.