Outcomes Comparison Using Psa Cut-Off Values Of 0.1 Or 0.2 Ng/Ml At 6 Months In Localized High-Risk Prostate Cancer Treated With Androgen Deprivation Therapy And Radiotherapy: Prospective Data From A Phase Iii Trial

We evaluated if PSA response measured at 6 months after commencement of treatment predicts better clinical outcomes in patients with localized high-risk prostate cancer (HRPC) enrolled in a randomized trial (PCS4) and treated with androgen deprivation therapy (ADT) and radiotherapy (RT). A total of 547 patients with HRPC received ADT and RT. All patients received the same RT dose and were randomized to receive ADT for a total duration of either 18 or 36 months. ADT began 4 months before RT. Serum PSA was measured initially before ADT and then regularly during the follow-up period. Patients achieving a PSA level below the cut-off values of 0.1 or 0.2 ng/mL at 6 months were compared to those who did not reach these values. Clinical outcomes analyzed were biochemical failure (BF), prostate cancer progression (PCP), metastasis free survival (MFS) and overall survival (OS). BF and PCP were analyzed considering death as a competing event. Proportional sub distribution hazard models were used to estimate hazard ratios (HRs). HRs for MFS and OS were estimated with Cox models. Using the PSA cut-off of 0.1 ng/mL, 34.4% of patients achieved a PSA response of <0.1 at 6 months. At a median follow-up of 13.23 years, 17.0% of patients with PSA <0.1 developed BF compared to 35.9% for those with a PSA >0.1 [HR = 2.46 (1.68 to 3.61), p = <0.001]. Similarly, 8.5% of patients with PSA <0.1 developed PCP compared to 17.3% from the PSA >0.1 cohort [HR = 2.15 (1.24 to 3.71), p = 0.006]. Using the PSA cut-off of 0.2 ng/mL, fewer BF [HR = 3.12 (2.26 to 4.31), p = <0.001] and lower PCP [2.55 (1.61 to 4.02), p = <0,001] were also seen in the 58% of patients achieving a PSA <0.2 compared to those with a PSA >0.2. In multivariable Cox models, including treatment arm, baseline PSA and baseline Gleason score, association of PSA at 6 months for either cut-off remains significant for BF and PCP. None of the two PSA cut-off at 6 months was statistically associated with MFS or OS.MFS: HR for cut-off 0.1 was 0.92 (0.73 to 1.56), p = 0.457 while HR for cut-off 0.2 was 1.08 (0.86 to 1.36), p = 0.494 OS: HR for cut-off 0.1 was 0.85 (0.68-1.08), p = 0.181, while HR for cut-off 0.2 was 1.02 (0.81-1.28), p = 0.894. In a cohort of patients exclusively with HRPC treated with RT and ADT, a PSA response of <0.1 ng/ml or <0.2 ng/ml at 6 months post-ADT predicts fewer BF and lower PCP. These data suggest that patients remaining with a higher PSA after 6 months of ADT may harbor a more aggressive genetic phenotype and should be considered for trials testing new therapeutic strategies earlier on.