Association Of Nadir Psa > 0.5ng/Ml After Dose Escalated External Beam Radiation With Prostate Cancer-Specific Endpoints

Prior studies have suggested that prostate specific antigen (PSA) nadir of 0.5ng/mL is an important surrogate endpoint for prostate cancer specific and all-cause mortality. This study analyzed our well-followed patient cohort to assess whether this endpoint was associated with differences in prostate-cancer specific survival (PCSS) as well as other prostate cancer specific endpoints. Patients with intermediate or high risk prostate cancer (≥T2b, or prostate specific antigen > 10ng/mL, or Gleason score ≥7) who were treated with external beam radiation +/- androgen deprivation between 2003-2011 were identified. Biochemical control, distant metastatic-free survival (DMFS), (PCSS), and overall survival (OS) was compared between those who achieved a nadir PSA ≤0.5 with those who did not via Kaplan Meier analysis using the log-rank test. Univariable and multivariable Cox Regression was performed on all endpoints to assess for their impact on OS. There were 367 patients identified. There were 236 patients (64%) still alive at last follow up, with a median follow up of 99.5 months. Two hundred five patients (55.9%) received androgen deprivation for a median of 24 months (range 1-81 months). Most patients (n=308, 83.9%) achieved a nadir PSA <0.5ng/mL. The 10 year biochemical control was 68.0% for nadir PSA <0.5 versus 24.0% for nadir PSA >0.5 (p<0.001). The 10 year distant-metastatic free survival was 89.6% for PSA <0.5ng/mL versus 80.8% for PSA >0.5ng/mL (p=0.019). The 10 year PCSS was 91.1% for nadir <0.5ng/mL versus 85.7% for PSA >0.5ng/mL (p=0.01), and the 10 year OS was 55.7% for nadir PSA <0.5ng/mL versus 45.8% for nadir PSA >0.5ng/mL (p=0.048). On multivariable analysis, nadir PSA >0.5ng/mL was associated with a higher risk of biochemical failure (HR 7.60, 95% CI 4.92-11.76, p<0.001), distant metastases (HR 7.17, 95% CI 3.17-16.21, p<0.001), prostate cancer specific mortality (HR 13.91, 95% CI 4.77-40.60, p<0.001), and all-cause mortality (HR 2.04, 95% CI 1.39-2.99, p<0.001). We found that a nadir PSA >0.5ng/mL after completion of ≥7560cGy +/- androgen deprivation was associated with a higher risk of biochemical failure, distant metastatic failure, prostate-cancer specific mortality, and all-cause mortality.