Are high-risk prostate cancer patients being treated equally? The impact of PSA

Patients with high-risk (HR) prostate cancer (PCa) represent a heterogeneous group, however, current treatment guidelines do not consider their specific features. The objective of this study was to evaluate treatment trends and outcomes in HR patients defined by PSA alone and otherwise low-risk features.

Using the National Cancer Database, we identified patients diagnosed with HR PCa between 2010 and 2016. A study group of patients defined by PSA >20 ng/ml alone and otherwise low-risk features, was compared to a group of HR patients defined by Gleason score or stage. We compared treatment rates over time, the use of concomitant androgen deprivation therapy (ADT), and overall survival (OS). Examination of treatment trends was done using a Z-test analysis. A Kaplan-Meier survival analysis was used to determine 5-year OS with the Log-rank test for comparison. Statistical analyses were completed using R Version 3.5.2.

We identified 5,652 patients in the study group and 71,922 in the comparison group. Only 6.8% of the study group had disease ≥cT2, compared to 43.7% in the comparison group. In the study group, 12.5% (709), underwent active surveillance (AS), 36.4% (2,055) radiation therapy (EBRT) and 51.1% (2,888) radical prostatectomy (RP), while the rate of AS, EBRT, and RP in the comparison group were 0.3% (191), 43.0% (30,928), and 56.7% (40,803), respectively. Over the study period, adoption of AS increased from 6.2% in 2010 to 25.0% in 2016 in the study group (P< 0.001), but not in the comparison group. In patients undergoing EBRT, ADT treatment increased from 2010 to 2016 in both groups, though by 2016 only 45.3% of patients in the study group and 86.3% in the comparison group received ADT. The 5-year OS was 93.7% (95% CI 92.8-94.6) in the study group and 89.7% (95% CI 89.2-90.1) in the comparison group (P< 0.001).

Men with HR PCa defined by PSA with otherwise low risk features present at an earlier stage and receive less aggressive therapy than other HR patients. Despite increased rates of AS and decreased use of ADT, these patients appear to have improved survival when compared to other HR patients. These findings suggest that not all HR patients will benefit from aggressive definitive treatment.