The correlation of PSA nadir and biochemical freedom from cancer after external beam treatment: effects of stage, grade and pretreatment PSA groupings

Purpose: This study demonstrates the correlation of various post-irradiation PSA nadirs with long term biochemical freedom from disease (bNED) survival in patients treated mainly with conformal external beam radiation therapy. It also shows the effects of various groupings of pretreatment (prerx) PSA level, stage, and Gleason score on the rate of achieving a favorable PSA nadir. Materials and Methods: Three hundred forty patients with known pretreatment PSA, >2 years followup treated with radiation alone (278 conformal, 62 conventional) are reported. The median followup is 41 months (range 24 to 96 mos.). Patient grouping by pretreatment PSA levels are <10 ng/ml (143 patients), 10-19.9 ng/ml (108 patients), ≥20 ng/ml (89 patients); by palpation stage are T1C,2AB (240 patients) and T2C,3,4 (100 patients); and by differentiation are Gleason 2-4 (108 patients), Gleason 5-7 (221 patients), Gleason 8-10 (11 patients). The PSA nadir response is given for all patients, and for each of the above prerx groupings. The 5 year actuarial bNED survival is determined for all patients by PSA nadir. Biochemical failure is a PSA ≥1.5 ng/ml and rising on two consecutive measures. Multivariate analysis (MVA) is performed to determine factors predictive of favorable PSA nadir response and predictive of bNED survival. Results: The PSA nadir responses and 5 year bNED survival rates are shown in the table for all patients according to PSA nadir. 66% of patients achieved a favorable nadir (<1.0 ng/ml) which was associated with a 75%-87% 5 year bNED rate, while 34% achieved an unfavorable nadir associated with an 18-32% bNED survival rate at 5 years. The figure illustrates the dramatic separation in outcome associated with the nadir response. The table also illustrates the fraction of patients that achieve various nadir levels subdivided by prerx PSA level, palpation stage and Gleason score. A favorable PSA nadir is obtained in 90%, 63%, and 31% of patients with a prerx PSA <10, 10-19.9, and ≥ 20, respectively (p=0.001). A favorable PSA nadir is obtained in 72% and 51% of patients with palpation stage T1,2AB and T2C,3,4 respectively (p=0.001). A favorable PSA nadir is obtained in 71% and 63% of patients with Gleason score 2-4 and 5-7, respectively (p=NS). MVA demonstrates prerx PSA (p=0.0001) and dose (p=0.02) to be independent predictors of PSA nadir response <1.0 ng/ml. MVA also demonstrates PSA nadir (p<0.0001), dose (p=0.02), and stage (p=0.02) to be independent predictors of 5 year bNED survival. Conclusions: (1) Following external beam radiotherapy, the level of PSA nadir is the most significant predictor of bNED survival. (2) Patients achieving a PSA nadir <1.0 ng/ml have a favorable overall bNED survival rate. This is true for all patients, independent of prerx. PSA, palpation stage and Gleason score. (3) Prerx PSA and dose are predictive of PSA nadir. (4) Patients not achieving a PSA nadir <1.0 ng/ml may be candidates for early adjuvant therapy trials