Vincenza Conteduca1, Orazio Caffo2, Luca Galli3, Antonio Maugeri4, Emanuela Scarpi5, Francesca Maines2, Vincenzo Emanuele Chiuri6, Cristian Lolli7, Stefania Kinspergher2, Giuseppe Schepisi7, Matteo Santoni8, Daniele Santini9, Lucia Fratino10, Salvatore Luca Burgio7, Samanta Salvi11, Cecilia Menna7, Ugo De Giorgi7. 1. Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. Electronic address: vincenza.conteduca@irst.emr.it. 2. Medical Oncology Department, Santa Chiara Hospital, Trento, Italy. 3. Department of Oncology, Azienda Ospedaliero, Universitaria Pisana, Istituto Toscano Tumori, Santa Chiara Hospital, Trento, Italy. 4. Oncology Pharmacy Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 5. Department of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 6. Medical Oncology Department, Vito Fazzi Hospital, Lecce, Italy. 7. Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 8. Department of Medical Oncology, University Hospital of Ancona, Ancona, Italy. 9. Medical Oncology Department, Campus Bio-Medico, University of Rome, Rome, Italy. 10. Medical Oncology Department, National Cancer Institute, Aviano, Italy. 11. Biosciences Laboratory Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Abstract
BACKGROUND: Metabolic syndrome (MS) and inflammation (INF) alterations are among the factors involved in cancer progression. The study aimed to assess the relationship between MS and INF and its effect on progression-free/overall survival (PFS/OS) in metastatic castration-resistant prostate cancer (mCRPC) treaed with abiraterone or enzalutamide. METHODS: We, retrospectively, evaluated patients with mCRPC in 7 Italian Institutes between March 2011 and October 2016. MS was defined by modified adult treatment panel-III criteria. INF was characterized by at least one of these criteria: neutrophil to lymphocyte ratio ≥ 3, elevated erythrocyte sedimentation rate or C-reactive protein. RESULTS: Eighty-three of 551 (15.1%) patients met MS criteria at baseline and 34 (6.2%) during treatment. MS patients (MS+) presented a greater INF profile compared to MS- (P<0.0001). Median PFS was 3.7 for MS+ vs. 8.7 months for MS- (hazard ratio [HR] = 2.77; 95% CI: 2.12-3.61; P<0.0001). Median OS was 6.9 and 19 months in MS+ and MS-, respectively (HR = 3.43; 95% CI: 2.56-4.58; P<0.0001). We also demonstrated INF led to shorter PFS and OS (4.5 vs. 8.5 months, HR = 1.48, 95% CI: 1.15-1.90, P = 0.002, and 11.2 vs. 18.8 months, HR =1.66, 95% CI: 1.26-2.18, P = 0.0003, respectively). The combination of MS with INF provided the identification of high-risk prognostic group (MS+/INF+ vs. MS-/INF-) with worse PFS (3.7 vs. 9 months, HR = 2.7, 95% CI: 1.88-3.89, P<0.0001) and OS (6.3 vs. 20.4 months, HR = 4.04, 95% CI: 2.75-5.93, P<0.0001). Multivariable analysis confirmed that MS was independently associated with PFS (HR = 2.07; 95% CI: 1.03-4.18; P = 0.041) and OS (HR = 4.87; 95% CI: 2.36-10.03; P<0.0001). The absence of INF as an independent predictor of survival underlined the correlation between MS/INF. CONCLUSIONS: Pretreatment identification of MS and INF alterations might represent an available and easy tool for better prognostication of patients with mCRPC. A prospective evaluation is warranted.
BACKGROUND:Metabolic syndrome (MS) and inflammation (INF) alterations are among the factors involved in cancer progression. The study aimed to assess the relationship between MS and INF and its effect on progression-free/overall survival (PFS/OS) in metastatic castration-resistant prostate cancer (mCRPC) treaed with abiraterone or enzalutamide. METHODS: We, retrospectively, evaluated patients with mCRPC in 7 Italian Institutes between March 2011 and October 2016. MS was defined by modified adult treatment panel-III criteria. INF was characterized by at least one of these criteria: neutrophil to lymphocyte ratio ≥ 3, elevated erythrocyte sedimentation rate or C-reactive protein. RESULTS: Eighty-three of 551 (15.1%) patients met MS criteria at baseline and 34 (6.2%) during treatment. MS patients (MS+) presented a greater INF profile compared to MS- (P<0.0001). Median PFS was 3.7 for MS+ vs. 8.7 months for MS- (hazard ratio [HR] = 2.77; 95% CI: 2.12-3.61; P<0.0001). Median OS was 6.9 and 19 months in MS+ and MS-, respectively (HR = 3.43; 95% CI: 2.56-4.58; P<0.0001). We also demonstrated INF led to shorter PFS and OS (4.5 vs. 8.5 months, HR = 1.48, 95% CI: 1.15-1.90, P = 0.002, and 11.2 vs. 18.8 months, HR =1.66, 95% CI: 1.26-2.18, P = 0.0003, respectively). The combination of MS with INF provided the identification of high-risk prognostic group (MS+/INF+ vs. MS-/INF-) with worse PFS (3.7 vs. 9 months, HR = 2.7, 95% CI: 1.88-3.89, P<0.0001) and OS (6.3 vs. 20.4 months, HR = 4.04, 95% CI: 2.75-5.93, P<0.0001). Multivariable analysis confirmed that MS was independently associated with PFS (HR = 2.07; 95% CI: 1.03-4.18; P = 0.041) and OS (HR = 4.87; 95% CI: 2.36-10.03; P<0.0001). The absence of INF as an independent predictor of survival underlined the correlation between MS/INF. CONCLUSIONS: Pretreatment identification of MS and INF alterations might represent an available and easy tool for better prognostication of patients with mCRPC. A prospective evaluation is warranted.
Authors: Juan José Serrano Domingo; Teresa Alonso Gordoa; Javier Lorca Álvaro; Javier Molina-Cerrillo; Arantzazu Barquín García; Olga Martínez Sáez; Javier Burgos Revilla; Alfredo Carrato; Sara Álvarez Rodríguez Journal: Ther Adv Urol Date: 2021-09-17