PSA (prostate specific antigen) and PSMA (prostate specific membrane antigen) serum levels were determined in over 235 prostate cancer patients from 8 different United States clinical urological cancer centers. The clinical data were not known until after the serum assay results were shared with all participants to attempt to eliminate possible clinical bias. PSA values are useful in the clinical diagnosis and staging of prostate cancer patients, and generally fall to low values in response to effective treatment, e.g., surgery, hormones, radiation, chemotherapy. PSMA values are not related to clinical stage but if elevated can fall in response to effective treatments. In contrast, PSMA values can be elevated post-treatment in the presence of very low PSA levels (0.01 to 0.00). The elevated PSMA levels predicted a state of clinical progression or clinical resistance in most cases (> 70%). PSMA levels in this study were of better prognostic value than PSA.