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CONTEXT: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have rising prostate-specific antigen (PSA) and castrate testosterone levels, with no radiological findings of metastatic disease on computed tomography and bone scan. Given recent drug approvals for nmCRPC, with many other therapeutics and imaging modalities being developed, management of nmCRPC is a rapidly evolving field that merits detailed investigation.OBJECTIVE: To review current nmCRPC management practices and identify opportunities for improving care of nmCRPC patients.EVIDENCE ACQUISITION: A literature search up to July 2018 was conducted, including clinical trials and clinical practice guidelines (National Comprehensive Cancer Network, European Society for Medical Oncology, European Association of Urology, Prostate Cancer Clinical Trials Working Group, Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence). Keywords included prostate cancer, nonmetastatic, castration resistance, rising PSA, and biochemical relapse.EVIDENCE SYNTHESIS: Recommendations regarding indications for, and frequency of, imaging and PSA testing, as well as for initiating systemic therapy in nmCRPC are based on PSA rise kinetics and symptoms. Both enzalutamide and apalutamide have been shown to significantly increase metastasis-free survival in phase III placebo-controlled randomised trials in nmCRPC patients with PSA doubling time (DT) ≤10 mo. The expected impact of new imaging techniques in the assessment of nmCRPC is also reviewed.CONCLUSIONS: nmCRPC is a heterogeneous disease; while observation may be an option for some patients, enzalutamide and apalutamide may be appropriate to treat nmCRPC patients with PSA-DT ≤10 mo. The emergence of more accurate imaging modalities as well as circulating tumour biomarker assays will likely redefine the assessment of nmCRPC in the near future.PATIENT SUMMARY: Herein, we review key literature and clinical practice guidelines to summarise the optimal management of patients with prostate cancer and rising prostate-specific antigen despite castrate testosterone levels, but with no evidence of distant metastasis on traditional imaging. New drugs are being developed for this disease setting; novel imaging and tumour biomarker blood tests are likely to define this disease state more accurately.

Until 2010, docetaxel was the only agent with proven survival benefit for castration-resistant prostate cancer. The development of cabazitaxel, abiraterone acetate, enzalutamide, radium-223, and sipuleucel-T has increased the number of treatment options. Because these agents were developed concurrently within a short period of time, prospective data on their sequential use efficacy are scarce. The challenge now is to reach a consensus on the best way to sequence effective treatments, ideally by the use of an approach specific to patient subgroups. However, the absence of robust surrogates of survival and the lack of predictive biomarkers makes data for the sequential use of these agents difficult to obtain and interpret.

SummaryToward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals.

Aim To test the hypothesis that computed tomography (CT)-based signs might precede symptomatic malignant spinal cord compression (MSCC) in men with metastatic castration-resistant prostate cancer (mCRPC). Materials and methods A database was used to identify suitable mCRPC patients. Staging CT images were retrospectively reviewed for signs preceding MSCC. Signs of malignant paravertebral fat infiltration and epidural soft-tissue disease were defined and assessed on serial CT in 34 patients with MSCC and 58 control patients. The presence and evolution of the features were summarized using descriptive statistics. Results In MSCC patients, CT performed a median of 28 days prior to the diagnostic magnetic resonance imaging (MRI) demonstrated significant epidural soft tissue in 28 (80%) patients. The median time to MSCC from a combination of overt malignant paravertebral and epidural disease was 2.7 (0–14.6) months. Conversely, these signs were uncommon in the control cohort. Conclusions Significant malignant paravertebral and/or epidural disease at CT precede MSCC in up to 80% of mCRPC patients and should prompt closer patient follow-up and consideration of early MRI evaluation. These CT-based features require further prospective validation.

Resumen Introduccion El Inventario Neuropsiquiatrico (NPI) es una escala que valora la presencia de alteraciones psicopatologicas en pacientes con enfermedades neurologicas, principalmente demencias. A pesar de sus ventajas, existen pocos estudios publicado en pacientes con traumatismo craneoencefalico (TCE). Con la informacion derivada del NPI pretendemos describir las alteraciones psicopatologicas en un grupo de pacientes con TCE severo en fase cronica y determinar si se correlacionan con antecedentes psiquiatricos y medidas de resultado. Metodo Se administro el NPI a los informantes de 53 pacientes con traumatismo craneoencefalico grave que se encontraban en fase cronica. Asi mismo, se recogieron escalas de funcionalidad y de integracion a la comunidad. Resultados El 92,5% de la muestra estudiada presentaba alguna alteracion psicopatologica segun el NPI, siendo los sintomas mas frecuentes la irritabilidad/labilidad, la apatia y la depresion/disforia. El antecedente de consumo habitual de toxicos mostro una relacion significativa con la presencia de psicopatologia. Sintomas como la agitacion, la apatia y la desinhibicion se correlacionaron de forma significativa con el grado de discapacidad. Conclusiones Las alteraciones psiquiatricas son frecuentes en pacientes con TCE. El nNPI es una herramienta que recoge de manera sistematica las alteraciones conductuales y emocionales mas frecuentes en estos pacientes. Algunos de los sintomas influyen negativamente en el grado de discapacidad.

La hemoptisis masiva es una situacion de emergencia vital que raramente ocurre en el contexto de una insuficiencia cardiaca, menos aun si la causa subyacente es una miocardiopatia dilatada. Aportamos el caso de un enfermo de 69 anos de edad, cuya cardiopatia no era conocida previamente, que se inicio con un cuadro de hemoptisis grave, presentando imagenes radiologicas de insuficiencia cardiaca franca. La rareza del caso obligo a descartar otros procesos patologicos antes de iniciar el tratamiento de su enfermedad de base