Multiple Docetaxel Retreatments Without Prednisone for Metastatic Castration-Resistant Prostate Cancer in the Docetaxel-Only Era: Effects on PSA Kinetics and Survival

INTRODUCTION: This study aimed to assess the effects of multiple docetaxel (DOC) treatments on prostate-specific antigen (PSA) kinetics and survival among patients with metastatic castration-resistant prostate cancer (mCRPC) who were sensitive to first-line DOC and received no other life-prolonging agents. To eliminate the effect of cortisone on serum PSA, only patients who were treated without prednisone were included. METHODS: This IRB-approved retrospective study evaluated 52 patients with mCRPC who were retreated using DOC after first-line DOC (without prednisone in both cases), based on a PSA response of > 50% and no radiographic progression. Twenty-three PSA-based factors, including static and kinetic PSA measures, were evaluate for their ability to predict overall survival (OS) RESULTS: The patients received 688 cycles of DOC in 143 series, including 91 courses of retreatments (1 cycle: 28 patients, 2 cycles: 14 patients, 3 cycles: 8 patients, 4 cycles: 1 patient, and 7 cycles: 1 patient). The median overall number of cycles per patient was 12 (range: 7–31). The median durations of the first, second, and third holidays were 18 weeks (6–60 weeks), 16 weeks (3–44 weeks), and 17 weeks (8–51 weeks), respectively. The median OSs were 22 months (10.5–70 months) after the first DOC treatment and 14 months (3–65 months) after the second DOC treatment. The > 50% PSA decline rate was 48% after retreatment. Short treatment holidays (< 3 months) were associated with shortened OS (p = 0.01). In the multivariate analysis, a 25% PSA increase over the nadir was the strongest predictor of survival (HR: 3.20, 95% CI: 1.47–6.99, p = 0.003). CONCLUSIONS: DOC retreatment without prednisone had anti-tumor activity in a considerable proportion of mCRPC cases that were initially sensitive to first-line DOC. A 25% PSA increase over the nadir might predict acquired DOC resistance

Proteome profiling of enzalutamide-resistant cell lines and serum analysis identified ALCAM as marker of resistance in castration-resistant prostate cancer

Enzalutamide (ENZA) is a frequently used therapy in metastatic castration‐resistant prostate cancer (mCRPC). Baseline or acquired resistance to ENZA have been observed, but the molecular mechanisms of resistance are poorly understood. We aimed to identify proteins involved in ENZA resistance and to find therapy‐predictive serum markers. We performed comparative proteome analyses on ENZA‐sensitive parental (LAPC4, DuCaP) and ‐resistant prostate cancer cell lines (LAPC4‐ENZA, DuCaP‐ENZA) using liquid chromatography tandem mass spectrometry (LC‐MS/MS). The top four most promising candidate markers were selected using bioinformatic approaches. Serum concentrations of selected markers (ALCAM, AGR2, NDRG1, IDH1) were measured in pretreatment samples of 72 ENZA‐treated mCRPC patients using ELISA. In addition, ALCAM serum levels were measured in 101 Abiraterone (ABI) and 100 Docetaxel (DOC)‐treated mCRPC patients' baseline samples. Results were correlated with clinical and follow‐up data. The functional role of ALCAM in ENZA resistance was assessed in vitro using siRNA. Our proteome analyses revealed 731 significantly differentially abundant proteins between ENZA‐sensitive and ‐resistant cells and our filtering methods identified four biomarker candidates. Serum analyses of these proteins revealed only ALCAM to be associated with poor patient survival. Furthermore, higher baseline ALCAM levels were associated with poor survival in ABI‐ but not in DOC‐treated patients. In LAPC4‐ENZA resistant cells, ALCAM silencing by siRNA knockdown resulted in significantly enhanced ENZA sensitivity. Our analyses revealed that ALCAM serum levels may help to identify ENZA‐ and ABI‐resistant patients and may thereby help to optimize future clinical decision‐making. Our functional analyses suggest the possible involvement of ALCAM in ENZA resistance

Claros System: A Rapid Microfluidics-Based Point-of-Care System for Quantitative Prostate Specific Antigen Analysis from Finger-Stick Blood

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