Assessment of Total, PTEN-, and AR-V7+ Circulating Tumor Cell Count by Flow Cytometry in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Enzalutamide.

INTRODUCTION: Metastatic castration-resistant prostate cancer (mCRPC) is a deadly disease. Enzalutamide is an oral second-generation anti-androgen that is active in mCRPC. Circulating tumor cells (CTC) count correlates with overall survival (OS) in mCRPC, whereas detection of the androgen-receptor splice variant 7 (AR-V7) in CTC predicts poor response to oral second-generation anti-androgens. Also, loss of PTEN (phosphatase and tensin homolog) in CTC is a biomarker of poor prognosis in mCRPC. PATIENTS AND METHODS: In this translational study, we employed flow cytometry to assess total, PTEN-, and AR-V7+ CTC count per 7.5 mL of whole blood in a prospective cohort of patients with mCRPC receiving enzalutamide. RESULTS: CTCs were assessed in a total of 45 men with mCRPC at baseline and at 12 weeks. Overall, CTC, PTEN- CTC, and AR-V7+ CTC detection rate was high, at baseline, with 84.4%, 71.1%, and 51.1% of samples showing at least 1 cell/7.5-mL blood, respectively, and after 3 months, with 93.3%, 64.4%, and 77.7% of samples showing at least 1 cell/7.5-mL blood, respectively. Median radiographic progression-free survival (rPFS) and OS were 6 (95% confidence interval [CI], 5.6-9) and 14.3 (95% CI, 12.8-20.3) months, respectively. Median (interquartile range) total CTC count at baseline was 5 (3; 8), whereas median (interquartile range) PTEN- CTC count was 2 (0; 4) and median (interquartile range) AR-V7+ CTC count was 1 (0; 3). At baseline, ≥ 5 versus < 5 total CTC count was associated with worse rPFS (hazard ratio [HR], 2.35; 95% CI, 1.14-4.84; P= .021) and OS (HR, 3.08; 95% CI, 1.45-6.54; P = .003), whereas ≥ 2 versus < 2 PTEN- CTC count was associated with worse rPFS (HR, 3.96; 95% CI, 1.8-8.72; P= .001) and OS (HR, 2.36; 95% CI, 1.12-5; P= .025). Finally, ≥ 1 versus < 1 AR-V7+ CTC count was also associated with worse rPFS (HR, 5.05; 95% CI, 2.4-10.64; P< .001) and OS (HR, 2.25; 95% CI, 1.1-4.58; P= .026). CONCLUSIONS: Despite multiple limitations, including the small sample size, our preliminary study suggests that assessment of CTC via flow cytometry may provide potentially useful prognostic and predictive information in advanced prostate cancer. Further studies are warranted. Micro-Abstract: In this study, men with metastatic castration-resistant prostate cancer, scheduled to start enzalutamide, were assessed for circulating tumor cell count and molecular characterization (total, PTEN-, and AR-V7+ circulating tumor cell count) by the use of flow cytometry. We found that flow cytometry could be used to enumerate circulating tumor cells, but also to assess molecular biomarkers on their surface.

Is Preoperative Assessment and Treatment of Asymptomatic Bacteriuria Necessary for Reducing the Risk of Postoperative Symptomatic Urinary Tract Infections After Urologic Surgical Procedures?

OBJECTIVE: To evaluate whether it is always necessary to test for the presence of asymptomatic bacteriuria (AB) in patients undergoing urologic surgical procedures, and if present, whether to treat AB with antimicrobial prophylaxis. MATERIALS AND METHODS: All patients who underwent urologic surgical procedures from December 2008 to October 2013 in a tertiary referral urologic center were considered for this study. All patients received antimicrobial prophylaxis in line with European Association of Urology guidelines on urologic infections. AB was diagnosed if ≥105 colony-forming units/mL were cultured. The population was subdivided into 2 groups: group A, patients with preoperative AB, and group B, patients without AB. Data on postoperative symptomatic urinary tract infections (UTIs) were compared for the 2 groups. RESULTS: A total of 2201 patients were considered eligible for this study and were analyzed; 668 (30.4%) patients were found to harbor AB (group A), and 1533 (69.6%) patients did not have AB (group B). Microbiologically verified symptomatic postoperative UTIs occurred in 198 patients (8.9%). No difference in terms of overall rate of postoperative symptomatic UTI was found between the 2 groups (group A: 70 [10.4%] and group B: 128 [8.3%]; OR: 1.28 95%CI 0.94-1.74; P = .12), as well as in terms of urosepsis (group A: 2 [0.30%] and group B: 4 [0.26%]; P = 1.0). CONCLUSION: In patients undergoing urologic surgical procedures who are receiving antimicrobial prophylaxis in accordance with European Association of Urology guidelines, the preoperative presence of AB in this study was not associated with a higher incidence of postoperative symptomatic UTI.