A prospective study of the relationship between CRPC patient's quality of life after enzalutamide and serum testosterone levels measured via LC-MS/MS.

BACKGROUND: Enzalutamide (ENZ) is used in the treatment of patients with castration-resistant prostate cancer (CRPC). The quality of life (QoL) of CRPC patients during ENZ treatment is very important, but predictive markers of QoL have not been identified. We investigated the relationship between the serum testosterone (T) level before ENZ treatment and QoL changes in CRPC patients. PATIENTS AND METHODS: This prospective study was conducted between 2014 and 2018 at Gunma University Hospital and related facilities. We analyzed 95 patients in whom QoL could be evaluated using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire at baseline, and after 4 and 12 weeks of ENZ treatment. Serum T levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The study population of 95 patients had a median age of 72 years and median prostate-specific antigen level of 21.6 ng/mL. The median overall survival from the commencement of ENZ treatment was 26.8 months. The median serum T level before ENZ treatment was 50.0 pg/mL. The mean total FACT-P scores at baseline, and after 4 and 12 weeks of ENZ treatment, were 95.8, 91.7, and 90.1, respectively. Differences in FACT-P scores between the high T level (High-T) group and low T level (Low-T) group (distinguished based on median split of the T level) were examined. The mean FACT-P scores were significantly higher in the High-T than Low-T group after both 4 and 12 weeks of ENZ treatment (98.5 vs. 84.6 and 96.4 vs. 82.2, respectively, both p < 0.05). The mean FACT-P score was significantly lower in the Low-T group after 12 weeks than before ENZ treatment (p < 0.05). CONCLUSION: The serum T level before treatment may be useful for predicting QoL changes after ENZ treatment in CRPC patients.

[Malignant Central Nervous System Lymphoma after Radical Total Cystectomy : A Diagnostic Challenge].

We report a case of primary central nervous system lymphoma (PCNSL) in an 81-year-old man who had undergone radical cystectomy with an ileal conduit urostomy due to a diagnosis of muscle-invasive bladder cancer. The postoperative diagnosis was invasive urothelial carcinoma (pT2bN1M0, stage IV). Gemcitabine-cisplatin therapy was provided as adjuvant chemotherapy, and there was no recurrence during follow-up. Four years after surgery, he visited the emergency department because of weakness of the lower extremities and stuttering. He was found to have a parietal lobe mass on magnetic resonance imaging (MRI) and hospitalized with suspicion of brain metastasis. Despite examination by a neurosurgeon, it was not possible to make a clinical diagnosis, and the patient gradually deteriorated and died 21 days later. The pathology results were diagnostic of PCNSL.

[A Case of Primary Renal Malignant Lymphoma Initially Managed as Severe Pyelonephritis in a Patient Undergoing Hemodialysis].

A 75-year-old male undergoing hemodialysis because of diabetic nephropathy was referred to our hospital complaining of high fever and swelling of the left kidney. Our initial clinical diagnosis was severe pyelonephritis. He was initially treated with intravenous antibiotics and his clinical symptoms subsequently improved but only temporarily. The high fever soon recurred, accompanied by progressive thrombocytopenia. His general condition deteriorated despite conservative treatment. He then underwent nephrectomy of the left kidney. However, the thrombocytopenia persisted and his general condition did not improve. The pathological diagnosis was malignant lymphoma (non-Hodgkin's lymphoma, diffuse large B-cell type). He received chemotherapy, but his status rapidly deteriorated and he died 1.5 months after the operation. Primary renal malignant lymphoma is very rare, because the kidney lacks lymphatic tissue.

A Prospective Study of the Relationship Between Clinical Outcomes After Enzalutamide and Serum Androgen Levels Measured via Liquid Chromatography-tandem Mass Spectrometry in Patients with Castration-resistant Prostate Cancer.

BACKGROUND: Enzalutamide (ENZ) is used to treat patients with castration-resistant prostate cancer (CRPC). However, the kinetics of serum androgens before and after ENZ treatment are unknown. OBJECTIVE: To elucidate the kinetics of serum androgens and explore the possibility of identifying a useful marker for predicting the effects of ENZ. DESIGN SETTING AND PARTICIPANTS: We conducted a prospective study from 2014 to 2018 at Gunma University Hospital and related facilities. Data were analyzed for 104 patients with CRPC treated with ENZ. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured serum androgen levels using liquid chromatography-tandem mass spectrometry. Relationships with outcomes were assessed using multivariable Cox regression and log-rank analyses. RESULTS AND LIMITATIONS: The median age of the patients was 73 yr. Median serum testosterone, dihydrotestosterone (DHT), androstenedione, and dehydroepiandrosterone sulfate levels were 49.0, 5.8, 222.2, and 326.3 pg/ml, respectively. We performed multivariate analysis using Cox regression to predict prostate-specific antigen progression-free survival (PSA-PFS) and overall survival (OS). Hemoglobin level (≥12.5 vs <12.5 g/dl), docetaxel treatment history (no vs yes), and DHT level (≥5.9 vs <5.9 pg/ml) were significant predictors of PSA-PFS (p < 0.05). Eastern Cooperative Oncology Group performance status (0 vs. 1-2), hemoglobin level (≥12.5 vs <12.5 g/dl), presence of visceral metastasis (no vs yes), amount of bone metastasis (extent of disease 0-2 vs 3-4), and docetaxel treatment history (no vs yes) were significant predictors of OS (p < 0.05). Binomial logistic analysis of the predictors of any grade of anorexia, malaise, and fatigue showed that the presence of visceral metastasis and a low DHT level (<5.9 pg/ml) were significant. CONCLUSIONS: Our results suggest that serum androgen levels before ENZ treatment may be useful for predicting efficacy, prognosis, and the incidence of adverse events. PATIENT SUMMARY: We measured blood levels of testosterone and other male hormones before treatment with enzalutamide among men with prostate cancer resistant to castration. We found that the levels of these hormones may be useful for predicting the efficacy of enzalutamide treatment, prognosis, and the occurrence of adverse side effects.

Two pedigrees of hereditary prostate cancer.

We encountered two pedigrees of hereditary prostate cancer. In one family, the father and his two sons had prostate cancer, and in the other family, three brothers developed prostate cancer. The mean age of these six individuals at the first examination was 65.3 years. Two individuals had stage B disease; three individuals, stage D disease; and one individual, disease of unknown stage. Histopathologically, two, one, and three individuals had well-, moderately, and poorly differentiated adenocarcinoma, respectively. As of September 28,2000, five of the six individuals were still alive. In a search of the literature, these were found to be the seventh and eighth pedigrees in Japan that met the criteria of hereditary prostate cancer proposed by Carter and colleagues in 1993.