Identifying A Subgroup Of High-Risk Prostate Cancer Patients With Worse Clinical Outcomes: Should There Be A "Very High-Risk" Group?

Standard recommendation for treatment of high-risk prostate cancer patients currently includes external beam radiation therapy and long-term hormone ablation therapy with a GnRH agonist, which has a greater than 20% biochemical relapse rate. However, high-risk prostate cancer encompasses a large spectrum of disease with variable response to standard treatment. This analysis attempts to identify a group of high-risk patients with poorer outcomes with standard treatment who may benefit from more aggressive therapy. 741 patients with high-risk prostate cancer (stage ≥T3a, Gleason score ≥8, or prostate specific antigen (PSA) ≥20 ng/ml) treated between 1987 and 2004 at a single institution were included in this study. Among these patients, 108 patients who had both stage ≥T3a and Gleason score ≥9 were identified. Clinical outcome of this cohort was compared to the remaining high-risk patients using a log-rank test. Biochemical relapse was defined as PSA above nadir + 2 ng/mL. All patients were treated to the prostate and seminal vesicles to a median radiation dose of 70 Gy (range 60-79.2 Gy) given at 1.8 to 2.0 Gy per fraction. Pelvic lymph nodes were not treated. All patients received androgen deprivation therapy (ADT). ADT was started 2 to 3 months before radiation therapy and continued for a median of 2.9 years (range 2-18 years). Median follow-up was 8.3 years (range 0.13-20 years). Patients with both stage ≥T3a and Gleason score ≥9 prostate cancer had decreased 10-year salvage treatment free survival (56% vs 78%, P<0.0001), distant metastases-free survival (70% vs 90%, P = 0.009), and overall survival (52% vs 68%, P = 0.0424) than high-risk patients who did not have both of these risk factors. Patients with both risk factors also had decreased 10-year prostate cancer specific survival and nodal relapse free survival; however these differences were not statistically significant (74% vs 90%, P = 0.162 and 86% vs 92%, P = 0.158, respectively). There was no difference in the 10-year local relapse free survival (96% vs 96%, P = 0.992). Patients with both stage ≥T3a and Gleason score ≥9 prostate cancer had increased risk of recurrence needing salvage treatment and distant metastases and decreased overall survival in this analysis. This finding suggests that these patients may require the addition of more aggressive therapies (such as chemotherapy or one of the newer hormonal agents) to standard treatment to achieve better clinical outcomes. This hypothesis should be further tested with a larger patient population, ideally in a prospective setting.