PSA Kinetics as Prognostic Markers of Overall Survival in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone Acetate.

BACKGROUND: Abiraterone acetate (AA) is widely used in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). However, a significant percentage of patients will still progress, highlighting the need to identify patients more likely to benefit from AA. Parameters linked to prostate-specific antigen (PSA) kinetics are promising prognostic markers. We have examined clinical and PSA-related factors potentially associated with overall survival (OS) in patients treated with AA. METHODS: Between 2011 and 2014, 104 patients with mCRPC treated with AA after progression to docetaxel at centers of the Catalan Institute of Oncology were included in this retrospective study. Patients were assessed monthly. Baseline characteristics and variables related to PSA kinetics were included in univariate and multivariate analyses of OS. RESULTS: Median OS was 16.4 months (range 12.4-20.6) for all patients. The univariate analysis identified the following baseline characteristics as significantly associated with OS: ECOG PS, location of metastases, time between starting androgen deprivation therapy and starting AA, time between stopping docetaxel treatment and starting AA, neutrophil-lymphocyte ratio (NLR), alkaline phosphatase levels, and PSA levels. Factors related to PSA kinetics associated with longer OS were PSA response >50%, early PSA response (>30% decline at four weeks), PSA decline >50% at week 12, PSA nadir <2.4ng/mL, time to PSA nadir >140 days, the combination of PSA nadir and time to PSA nadir, and low end-of-treatment PSA levels. The multivariate analysis identified ECOG PS (HR 37.46; p<0.001), NLR (HR 3.7; p<0.001), early PSA response (HR 1.22; p=0.002), and time to PSA nadir (HR 0.39; p=0.002) as independent prognostic markers. CONCLUSION: Our results indicate an association between PSA kinetics, especially early PSA response, and outcome to AA after progression to docetaxel. Taken together with other factors, lack of an early PSA response could identify patients who are unlikely to benefit from AA and who could be closely monitored with a view to offering alternative therapies.

[Targeted biopsies using magnetic resonance imaging/ultrasonograpgy fusion compared with sistematic biopsies prostate cancer detection. Initial experience.] / Comparación entre la biopsia prostática con fusión de imagen ecografía/resonáncia magnética y la biopsia sistemática para la detección de cáncer de próstata. Experiencia inicial.

OBJECTIVE: To describe the initial experiencein our center on targeted prostate biopsies (TB) using Magnetic Resonance imaging/ultrasonography (MRI/US) fusion and to compare PCa detection with systematic biopsies (SB). PATIENTS AND ME THODS: A retrospective, descriptive and comparative study was conducted on the first 94 men who underwent TB using MRU/US fusion in our center since February 2017 to March 2018. All patients underwent a protocol of 6-12 cores of systematic biopsies (SB) (except 9) and 2-6 targeted coreson the MRI index lesion. The Hitachi/HiVision Preirus equipment was used with RVS software (Real-time virtual sonography) and a biplane transducer for the fusion imaging procedure. Clinically significant PCa (csPCa) was defined as: at least one core with a Gleason score of 3+4. RESULTS: The proportion of patients diagnosed with PCa was higher in TB compared with SB (p=0.035) and the mean of core performed for diagnosis was lower in TB compared with SB (p<0.001). A trend towards an improved detection of csPCa in TB compared to SB was observed (p=0.063). CONCLUSIONS: The MRI/US fusion targeted biopsies (TB) showed a higher detection rate of PCa, with less cores taken for diagnosis and a tendency to better identification of csCaP compared to SB.

OBJETIVO: El objetivo de este estudio es describir la experiencia inicial en nuestro centro de las primeras 94 Biopsias de Próstata dirigidas (BD) con fusión de imagen ecografía/Resonancia magnética (US/RMmp) y comparar la tasa de detección de CaP con las biopsias sistemáticas.MATERIAL Y MÉTODOS: Se realizó un estudio retrospectivo, descriptivo y comparativo de los primeros 94 pacientes sometidos a BD por fusión de imagen US/RMmp en nuestro centro desde febrero de 2017 hasta marzo de 2018. Todos los pacientes fueron sometidos a un protocolo de 6-12 cilindros de biopsias sistemáticas (BS) (menos 9) y de 2-6 cilindros dirigidos a las lesiones diana visualizadas en la RMmp. Se utilizó el equipo Hitachi/HiVision Preirus con software RVS (Real-time virtual sonography) y un transductor biplanar para la fusión de imagen. Se definió como CaP clínicamente significativo un GS ≥ 3+4 en, al menos, 1 de los cilindros realizados. RESULTADOS: La proporción de detección de CaP fue mayor en las BD que en las BS (p=0,035) y el número de cilindros realizados para su diagnóstico fue menor en las BD comparado con las BS (p<0,001). Se observó  una clara tendencia a una mayor identificación de CaP clínicamente significativo (CaPcs) en las BD comparado con las BS (p=0,063). CONCLUSIONES: Comparado con las BS, las BD por fusión de imagen US/RMmp presentaron una mayor tasa de detección de CaP y una tendencia a una mayor identificación de CaPcS con una necesidad menor de cilindros realizados.

Standard versus continuous administration of capecitabine in metastatic breast cancer (GEICAM/2009-05): a randomized, noninferiority phase II trial with a pharmacogenetic analysis.

BACKGROUND: The approved capecitabine regimen as monotherapy in metastatic breast cancer (MBC) is 1,250 mg/m(2) twice daily for 2 weeks on and 1 week off (Cint). Dose modifications are often required because of severe hand-foot syndrome (HFS). We tested a continuous regimen with a lower daily dose but a similar cumulative dose in an attempt to reduce the severity of adverse events (AEs) while maintaining efficacy. METHODS: We randomized 195 patients with HER-2/neu-negative MBC to capecitabine 800 mg/m(2) twice daily throughout the 21-day cycle (Ccont) or to Cint to assess noninferiority in the percentage of patients free of progression at 1 year. Secondary endpoints included efficacy and safety. Associations between polymorphisms in capecitabine metabolism-related genes and drug response were assessed. RESULTS: The percentage of patients free of progression at 1 year was 27.3% with Cint versus 25.3% with Ccont (difference of -2.0%; 95% confidence interval: -15.5% to 11.5%, exceeding the 15% deemed noninferior). Differences regarding other efficacy variables were also not found. Grade 3-4 HFS was the most frequent AE (41.1% in Cint vs. 42.3% in Ccont). Grade 3-4 neutropenia, thrombocytopenia, diarrhea, and stomatitis were more frequent with Cint. A 5' untranslated region polymorphism in the carboxylesterase 2 gene was associated with HFS. One polymorphism in cytidine deaminase and two in thymidine phosphorylase were associated with survival. CONCLUSION: Our study was unable to show noninferiority with the continuous capecitabine regimen (Ccont) compared with the approved intermittent regimen (Cint). Further investigation is required to improve HFS. Polymorphisms in several genes might contribute to interindividual differences in response to capecitabine.

Bone turnover markers as predictive indicators of outcome in patients with breast cancer and bone metastases treated with bisphosphonates: results from a 2-year multicentre observational study (ZOMAR study).

BACKGROUND: We evaluated the evolution and predictive value of bone turnover markers (BTMs) and circulating tumor cells (CTCs) with respect to mortality, disease progression (DP) and skeletal-related events (SREs), in patients with bone metastatic breast cancer (BmBCa). The correlation between BTMs and CTCs was also studied. METHODS: In a 2-year observational, multicenter study, the levels of three BTMs (N- and C-terminal telopeptides of collagen I [NTX and αα-CTX], and bone-specific alkaline phosphatase [BSAP]) and CTCs were analyzed every three months. Patients received zoledronic acid (4mg every 28days) from the baseline visit. RESULTS: 234 patients were analyzed. The levels of the BTMs were increased at baseline and significantly decreased after 3months (P<0.05). In the Cox regression univariate analyses significant hazard ratios (HRs) for death were found for pathological BSAP values at baseline (5.03 [95% CI: 1.214-20.839; P=0.0259]) and at 3months (3.41 [95% CI: 1.367-8.498; P=0.0085]). HRs >2 were found for increased baseline and 3-month levels of NTX and CTC (P<0.05). Only increased baseline BSAP levels were associated with DP (HR=2.25 [95% CI: 1.391-3.626; P=0.0009]). No biomarker was associated with SREs. In the multivariate analysis, pathologic levels at 3months of NTX and BSAP were significantly associated with mortality (HRs=3.59 [95% CI: 1.375-9.382; P=0.0091] and 3.25 [95% CI: 1.293-8.189; P=0.0120], respectively). CTC and BSAP were correlated during all study timepoints (P<0.05). CONCLUSIONS: Baseline levels of NTX, BSAP and CTCs, and changes after treatment initiation with bisphosphonates, may be useful for the prognostic assessment of patients with BmBCa. BSAP showed the strongest prognostic value.