A. Bossi

The postchemotherapy PSA surge syndrome

BACKGROUND Chemotherapy has emerged as a standard treatment in patients with castration-refractory prostate cancer (CRPC). Consensus criteria are available to define response in CRPC as at least a 50% decline in serum prostate-specific antigen (PSA) confirmed 4 weeks later. The objective of this work was to study early serum PSA changes in patients under chemotherapy and to correlate these changes with subsequent response assessment. PATIENTS AND METHODS Serum PSA levels were monitored every 3 weeks in 79 patients with CRPC treated with chemotherapy and a time course of serum PSA levels was obtained. Correlation with response was studied. RESULTS According to consensus criteria, 21 (40%) and 20 (38%) patients achieved a PSA response and stabilization, respectively, after first-line chemotherapy. Among patients who achieved either a response or a stabilization, 8 of 41 (20%) had a serum PSA rise during the first 8 weeks of chemotherapy, followed by a subsequent decline in serum PSA. The same observation was made in patients receiving second-line chemotherapy: 6 of 20 patients achieving a response or stabilization had an initial serum PSA rise. The postchemotherapy increase in serum PSA could reach more than twice the baseline value. The duration of the PSA surge ranged from 1 to 8 weeks. When considering responders only, 6 of 30 (20%) had a postchemotherapy serum PSA surge, followed by a drop. CONCLUSION Postchemotherapy PSA surges occur not infrequently in patients with CRPC who respond to chemotherapy. Physicians should be aware of this effect to avoid inadequate early discontinuation of chemotherapy.

Urinary N-telopeptide (uNTx) is an independent prognostic factor for overall survival in patients with bone metastases from castration-resistant prostate cancer

BACKGROUND In patients with bone metastases from castration-resistant prostate cancer (CRPC) not pretreated with a bisphosphonate elevated N-telopeptide of type I collagen (uNTx), a marker of bone resorption, predicts skeletal-related events (SRE). The aim of this study was to assess the prognostic value of uNTx for overall survival (OS) and the incidence of SRE in patients with bone metastases from CRPC receiving zoledronic acid. METHODS From 2004 to 2007, 94 patients with bone metastases from CRPC receiving zoledronic acid for at least 2 months were screened for uNTx. RESULTS Median age was 66 years (range 46-88). Median serum prostate-specific antigen (PSA) was 66 ng/ml (0-3984) and median uNTx was 19 nmol/mM creatinine (3-489). During follow-up, 38 patients (40%) experienced an SRE. Median OS was 20 months [95% (CI) confidence interval 15-24). In the multivariate analysis, elevated uNTx [hazard ratio (HR) 2.2 (95% CI 1.2-4.0)], serum PSA [HR 2.8 (95% CI 1.6-5.1)], and ECOG performance status were the only independent prognostic factors for OS. Median OS was 12 months (10-16) and 25 months (21-34) in patients with uNTx > or =20 nmol/mM creatinine and in those with uNTx <20 nmol/mM creatinine, respectively. CONCLUSION An elevated uNTx level is an independent prognostic factor for OS in patients with bone metastases from CRPC receiving a bisphosphonate.

Locoregional symptoms in patients with de novo metastatic prostate cancer: Morbidity, management, and disease outcome ☆

BACKGROUND The paradigm change observed over the last few years in several solid tumors emphasizes the value of locoregional treatment in the presence of metastatic disease, currently ignored in de novo prostate cancer (CaP). We investigated the effect of the primary tumor that is left untreated on prostate cancer-specific morbidity and mortality, time to castration resistance, and overall survival (OS). METHODS We performed a bicentric cohort study. The overall population included de novo metastatic CaP managed at the Genito-Urinary Oncology Unit of the Gustave Roussy Institute and the Urology Clinic of the University Hospital of Pointe-à-Pitre, France. Descriptive statistical and outcome analyses were performed in the overall cohort and also separately in the N+M0 and M+subgroups. RESULTS The overall cohort included 263 patients. Approximately two-thirds of patients (64%) presented with locoregional symptoms at diagnosis, and 78% throughout the disease. Of the symptomatic patients, 59% required a locoregional procedure. Median OS of patients with locoregional symptoms at diagnosis was shorter than in those who were asymptomatic (47 vs. 86 mo, P = 0.0007); this difference was maintained in the N+M0 and M+subgroups. Median OS and time to castration resistance showed a nonsignificant trend in favor of patients undergoing a locoregional treatment at diagnosis. CONCLUSION The presence of symptoms due to locoregional disease in de novo metastatic CaP entails significant morbidity and even mortality and requires active management. Randomized prospective trials are needed to evaluate the role of initial definite locoregional treatment in these patients.