Prognostic factors for non­metastatic castration­resistant prostate cancer treated with androgen receptor signaling inhibitors.

The treatment paradigm for non-metastatic castration-resistant prostate cancer (nmCRPC) has changed in recent years. An observational multicenter study was conducted to evaluate the effectiveness of androgen receptor signaling inhibitors (ARSIs) as a first-line treatment for patients with nmCRPC. The present study included native Japanese patients from four hospitals who received ARSIs as a first-line treatment for nmCRPC. The primary endpoint of the study was to evaluate the efficacy and safety of ARSI in patients with nmCRPC. The secondary endpoint was to develop a novel system to stratify the prognoses of these patients. In total, 160 patients were included in the present study. Within a median follow-up period of 23 months, the median overall survival (OS) was not reached, whereas the median progression-free survival was 26 months. Multivariate Cox regression analyses showed that the time to CRPC, prostate-specific antigen (PSA) level at the initiation of nmCRPC treatment and Geriatric Nutritional Risk Index (GNRI) were independent predictors of OS. The patients for whom information about all three independent OS predictors was available were subsequently divided into three groups as follows: Group 1, 57 patients with negative or one positive independent OS predictor; group 2, 38 patients with two positive independent OS predictors; and group 3, 10 patients with three independent OS predictors. The OS differed significantly among the three groups (P<0.0001). In conclusion, ARSIs as a first-line treatment may be associated with favorable outcomes in Japanese patients with nmCRPC. Time to CRPC, PSA level at the initiation of nmCRPC treatment and GNRI are potential predictors of OS in Japanese patients with nmCRPC who received ARSIs as a first-line treatment.

Effectiveness and safety of enzalutamide and apalutamide in the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC): a multicenter retrospective study.

OBJECTIVE: Phase III clinical trials demonstrated the efficacy of enzalutamide and apalutamide in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and PSA doubling time ≤10 months. Although these drugs have been shown to vary in their adverse event (AE) profiles, the differences in their efficacy profiles remain to be evaluated. Therefore, this retrospective study was conducted to evaluate the efficacy of these drugs in patients with nmCRPC. METHODS: This study evaluated 191 patients with nmCRPC treated with enzalutamide (n = 137) or apalutamide (n = 54) in the first-line setting at Jikei University Hospital or its affiliated hospitals between May 2014 and November 2022. Endpoints were defined as oncological outcomes (i.e., PSA response, PFS, PSA-PFS, MFS, CSS, and OS) and AEs. RESULTS: No significant differences were noted in patient backgrounds between the two groups. Patients exhibiting a maximum PSA response of >50% and >90% accounted for 74.5% and 48.9% of patients in the enzalutamide group, and 75.9% and 42.6% of patients in the apalutamide group, respectively, with no significant difference between the groups. The median PSA-PFS was 10 months in the enzalutamide group but not in the apalutamide group, with no significant difference between the groups (P = 0.48). No significant differences were observed in MFS, CSS, or OS between the groups. Patients reporting AEs of all grades and grade 3 or higher accounted for 56.2% and 4.3% of those in the enzalutamide group and 57.4% and 7.4% of those in the apalutamide group, respectively. The most common AE was fatigue (26.3%) in the enzalutamide group and skin rash (27.8%) in the apalutamide group. CONCLUSION: In this retrospective study of their efficacy and safety, enzalutamide and apalutamide were shown to exhibit comparable oncological outcomes but quite different AE profiles, suggesting that their differential use may be warranted based on these findings.

Improving the identification of high-risk non-metastatic castration-resistant prostate cancer patients in clinical practice.

Non-metastatic castration-resistant prostate cancer (nmCRPC) represents a challenging disease state in prostate cancer care. nmCRPC patients with a high risk of progression to metastatic disease who are identified by a prostate-specific antigen doubling time (PSADT) ≤10 months are eligible for treatment with the novel androgen receptor inhibitors (ARIs), shown to delay disease progression and extend survival. However, nmCRPC is often unexploited in clinical practice due to a lack of standardization in the methodology and in the tools used for its identification. In this article, a group of Urology and Oncology specialists with acknowledged expertise in prostate cancer reviews the state of the art in the management of high-risk nmCRPC patients, identifies gaps and unmet needs, and proposes strategies to optimize the identification of this patient subgroup in the clinical practice and improve their health outcomes.

Factores clínicos determinantes para la realización de pruebas de imagen en cáncer de próstata resistente a la castración no metastásico en la práctica clínica: resultados del estudio IDENTIFICA / Clinical drivers for imaging testing in non-metastatic castration-resistant prostate cancer in clinical practice: Results of the IDENTIFICA study

Introducción: El objetivo del estudio consistió en describir los factores clínicos que llevan a los médicos a realizar pruebas de imagen para identificar metástasis en pacientes con cáncer de próstata (CP) resistente a la castración no metastásico (CPRCnm).MétodosEstudio observacional transversal realizado en los servicios de Urología de 38 hospitales españoles; 188 pacientes diagnosticados con CPRCnm sometidos una prueba de imagen para evaluar la presencia de metástasis fueron incluidos. Se solicitó a los médicos, en una única visita del estudio, que especificaran los factores clínicos que los llevaron a realizar estas pruebas. Se presentaron los resultados de las pruebas de imagen y las características clínicas de los pacientes desde el diagnóstico de CP. Se utilizaron análisis de regresión para determinar factores predictivos de los resultados de las pruebas de imagen.ResultadosEl valor del «prostate-specific antigen» (por sus siglas en inglés, PSA), fue el factor más importante que determinó la solicitud de pruebas de imagen (57,1%), seguido de un seguimiento habitual (16,5%) y del tiempo de duplicación del PSA (TDPSA) (12,0%). Aunque estos factores no guardaron relación con la detección de metástasis, los pacientes con una concentración de PSA ≥ 20 ng/ml tuvieron un mayor riesgo de metástasis que aquellos con una concentración <4 ng/ml (p=0,004), mientras que los pacientes con CPRC diagnosticados de metástasis (CPRCm) tuvieron una mayor mediana de concentración de PSA (20,9; intervalo intercuartílico [IIC]: 6,7-38,6) que aquellos con CPRCnm (9,1; IIC: 5,0-18,0) (p=0,005). Un 66% no se sometió a ninguna prueba de imagen entre el diagnóstico de CPRC y la visita del estudio (10,6, IIC: 4,0-19,5 meses). El tratamiento con intención curativa en el momento del diagnóstico de CP y la puntuación de Gleason predijeron un mayor tiempo transcurrido entre los diagnósticos de CP y CPRC. (AU)

Introduction: The aim of the study was to describe the clinical drivers that lead physicians to perform imaging tests in search of metastasis in non-metastasic castration prostate resistant cancer (nmCRPC) patients.MethodsObservational, cross-sectional study conducted at the Departments of Urology of 38 Spanish hospitals. The study included 188 patients diagnosed with nmCRPC who underwent an imaging test for the assessment of metástasis. In one study visit, physicians were requested to specify the clinical factors that led them to perform these tests. The results of the imaging tests and the clinical characteristics of the patients since the time of prostate cancer (PC) diagnosis, were reported. Regression analyses were used to determine predictors of imaging test results.ResultsProstate-specific antigen (PSA) level was the most important driver to order imaging tests (57.1%), followed by regular follow-up (16.5%) and PSA doubling time (PSADT) (12.0%). Although these drivers were not associated to detection of metastasis, patients with PSA levels ≥20 ng/mL had a greater risk of metastasis than patients with PSA levels <4ng/mL (P=.004) and CRPC patients diagnosed with metastasis (mCRPC) had higher median PSA levels (20.9; interquartile range [IQR]: 6.7-38.6) than nmCRPC (9.1; IQR: 5.0-18.0) (P=.005). Sixty-six percent of the patients did not undergo any imaging test after CRPC diagnosis until the study visit (10.6, IQR: 4.0-19.5 months). Curative-intent treatment at PC diagnosis and Gleason score predicted longer time from PC to CRPC diagnosis.ConclusionsPhysicians based their decisions to order imaging tests for metastasis detection in nmCRPC patients mainly on PSA and PSA kinetics, including the regular follow-up stated by guideline recommendations. (AU)