Comparative Assessment of Efficacies Between 2 Alternative Therapeutic Sequences With Novel Androgen Receptor-Axis-Targeted Agents in Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: The objective of this study was to compare the efficacies of sequential therapies with novel androgen receptor-axis-targeted (ARAT) agents in patients with docetaxel-naïve metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: This study included 108 consecutive patients with mCRPC who sequentially received abiraterone acetate (AA) and enzalutamide (Enz), in either order, without prior treatment with docetaxel. The combined prostate-specific antigen (PSA) progression-free survival (PFS) was defined as the sum of PFS1 and PFS2, representing PSA PFSs on the first and second ARAT agents, respectively. RESULTS: Of these patients, 49 and 59 received ARAT therapy with the AA-to-Enz sequence (AA-to-Enz group) and with the reverse sequence (Enz-to-AA group), respectively. No significant differences in the baseline characteristics were noted between the 2 groups. In the overall patient population, the PSA response rate to the second-line ARAT agent (21.3%) was significantly lower than that of the first-line ARAT agent (58.3%). The combined PSA PFS in the AA-to-Enz group (median, 18.4 months) was significantly superior to that of the Enz-to-AA group (median, 12.8 months). Furthermore, multivariate analysis identified the treatment sequence (ie, AA-to-Enz vs. Enz-to-AA group) in addition to performance status as an independent predictor of combined PSA PFS in these patients. However, there was no significant difference in overall survival (OS) between the 2 groups. CONCLUSIONS: Although cross-resistance between ARAT agents is a common phenomenon in docetaxel-naïve patients with mCRPC, different efficacies were observed favoring the AA-to-Enz rather than Enz-to-AA sequence in this series with respect to combined PSA PFS but not OS.

Resistive index: a newly identified predictor of outcome of transurethral prostatectomy in patients with benign prostatic hyperplasia.

OBJECTIVE: To examine the usefulness of several preoperative parameters obtained through transrectal ultrasonography in predicting the outcome of transurethral resection of the prostate (TURP). METHODS: A total of 572 men aged 51-85 years scheduled to undergo TURP for benign prostatic hyperplasia were prospectively enrolled, and 560 were ultimately evaluated. We preoperatively assessed International Prostate Symptom Score (IPSS), quality of life (QOL) score, maximum urinary flow rate (Q(max)), and postvoid residual urine volume (PVR), and measured total prostate volume (TPV), transition zone (TZ) index, and resistive index (RI) using transrectal ultrasonography. To compare the usefulness of the latter 3 indices, we calculated the area under the receiver operating characteristic (ROC) curve for each index and for IPSS. RESULTS: IPSS (total, postmicturition symptoms, storage symptoms, voiding symptoms), QOL score, Q(max), and PVR were significantly improved after TURP. Significant differences between the effective and noneffective groups were observed with regard to age, IPSS (total, postmicturition symptoms, storage symptoms, voiding symptoms), QOL score, TPV, TZ index, RI, Q(max), and PVR. The area under the ROC curve was 0.663 for IPSS, 0.691 for TPV, 0.719 for the TZ index, and 0.845 for the RI. CONCLUSIONS: The RI is a useful predictor of an effective outcome after TURP in patients with benign prostatic hyperplasia and may be useful for determining suitability for surgical intervention.

Significance of 5-fluorouracil-related enzyme activities in predicting sensitivity to 5-fluorouracil in bladder carcinoma.

BACKGROUND: The association between 5-fluorouracil (5-FU)-related enzyme activity and the sensitivity of bladder urothelial carcinoma (BUC) to 5-FU were investigated, and methods to improve 5-FU sensitivity were analyzed. MATERIALS AND METHODS: Tumor specimens were obtained from 127 patients. Orotate phosphoribosyl transferase (OPRT) activity was analyzed by the paper disc method and thymidine phosphorylase and dihydropyrimidine dehydrogenase (DPD) activities were measured by ELISA. 5-FU sensitivity was assessed in 99 cases by an in vitro chemosensitivity test. RESULTS: A significant positive correlation between OPRT activity level and the sensitivity of BUC to 5-FU was identified. Moreover, the combination of 5-FU and 5-chloro-2,4-dihydroxypyrimidine significantly enhanced 5-FU sensitivity in BUC, particularly in cases showing higher DPD activity. CONCLUSION: OPRT was the most important enzyme in predicting sensitivity to 5-FU in BUC. These results may have implications for tailor-made medication using 5-FU-related compounds as postoperative adjuvant chemotherapy in BUC patients.