[Biochemical monitoring of prostate cancer treated exclusively by radiotherapy: prognostic value of pretreatment PSA, PSA nadir and PSA half-life]. / Suivi biologique du cancer de la prostate traité par radiothérapie exclusive: valeur pronostique du PSA pré-thérapeutique, du PSA Nadir et de la demi-vie du PSA.

OBJECTIVES: Retrospective evaluation of the prognostic value of pretreatment PSA, PSA nadir and PSA half-life compared to grade and stage after treatment of prostate cancer by radiotherapy. PATIENTS AND METHODS: 122 patients (19 T1 (15.6%), 31 T2a (25.4%), 26 T2b (21.3%), 20 T3a (16.4%), 19 T3b (15.6%), 7 Tx (5.7%)) treated by exclusive radiotherapy were studied with a median follow-up of 75.4 months. Treatment consisted of high energy irradiation to the prostate for 31 patients (25.4%) and to the pelvis and prostate for 91 patients (74.6%). PSA was assayed retrospectively. The influence of various parameters on the absence of laboratory failure, defined according to the ASTRO criteria, and on overall survival was studied by univariate and multivariate analysis with a Cox model. RESULTS: 29.5% of patients did not develop any biochemical recurrence after a mean follow-up of 82 months, while biochemical recurrence occurred in 70.5% of patients after a mean interval of 5 months. Among these patients, 28 (33%) developed clinical recurrence after a mean interval of 26 months (4 to 80 months) leading to death in 17 cases. The modalities of irradiation and pretreatment PSA had no influence on the prognosis. The median PSA nadir of patients without recurrence was 0.24 ng/ml. The recurrence rate was lower for a PSA nadir less than 0.5 ng/ml for biochemical recurrence (45.5% vs 86.8%) (p < 0.0001) and clinical recurrence (9.1% vs 31.6%) (p < 0.05). On multivariate analysis, the PSA nadir (p = 0.009), PSA half-life (p < 0.001) and Gleason score (p = 0.004) were prognostic factors influencing survival, while PSA nadir was the only prognostic factor for biochemical recurrence (p = 0.001). Classification of patients into two groups with a significantly different prognosis according to the presence or absence of at least two favourable prognostic factors (PSA nadir less than 0.5 ng/ml, Gleason score less than 7, PSA half-life greater than 6 months) showed that the 9-year mortality rate was twofold higher in the poor prognosis group than in the good prognosis group (85.5% versus 38.6%). CONCLUSION: A nadir PSA level less than 0.5 ng/ml, a PSA half-life greater than 6 months and a Gleason score less than 7 were predictive of a low risk of biochemical recurrence and prolonged survival after treatment by exclusive radiotherapy, in our patients.

Selective recognition of enzymatically active prostate-specific antigen (PSA) by anti-PSA monoclonal antibodies.

Prostate-specific antigen (PSA) is widely used as a serum marker for the diagnosis of prostate cancer. To evaluate two anti-free PSA monoclonal antibodies (mAbs) as potential tools in new generations of more relevant PSA assays, we report here their properties towards the recognition of specific forms of free PSA in seminal fluids, LNCaP supernatants, 'non-binding' PSA and sera from cancer patients. PSA from these different origins was immunopurified by the two anti-free PSA mAbs (5D3D11 and 6C8D8) as well as by an anti-total PSA mAb. The composition of the different immunopurified PSA fractions was analysed and their respective enzymatic activities were determined. In seminal fluid, enzymatically active PSA was equally purified with the three mAbs. In LNCaP supernatants and human sera, 5D3D11 immunopurified active PSA mainly, whereas 6C8D8 immunopurified PSA with residual activity. In sera of prostate cancer patients, we identified the presence of a mature inactive PSA form which can be activated into active PSA by use of high saline concentration or capture by an anti-total PSA mAb capable of enhancing PSA activity. According to PSA models built by comparative modelling with the crystal structure of horse prostate kallikrein described previously, we assume that active and activable PSA could correspond to mature intact PSA with open and closed conformations of the kallikrein loop. The specificity of 5D3D11 was restricted to both active and activable PSA, whereas 6C8D8 recognized all free PSA including intact PSA, proforms and internally cleaved PSA.