Hiroyuki Muramatsu

Impact of a novel biopsy instrument with a 25‐mm side‐notch needle on the detection of prostate cancer in transrectal biopsy

To evaluate the impact of a novel biopsy instrument that extends the length of the side‐notch on the detection of prostate cancer in transrectal needle biopsy.

PD26-08 A LONG TERM COMPARISON OF ADHERENCE OF DRUG THERAPY IN 1,917 PATIENTS WITH OVERACTIVE BLADDER

INTRODUCTION AND OBJECTIVES: Antimuscarinic are the current pharmacological mainstay for overactive bladder (OAB). However, adverse events resulting from antimuscarinics are inevitable in some patients. Discontinuation rates of 70% to 90% within the first year of therapy have been reported for various OAB medications, because the therapy did not produce the treatment bene?t expected. Mirabegron, which acts as a subtype of relaxation of detrusor, appeared on the Japanese market in 2011, and it provides a new treatment option for OAB. Currently, there are few published studies on the long-term persistence with drug therapy among OAB patients. The purposes of this study were to evaluate OAB pharmacotherapy adherence. METHODS: Patients 18 years of age or older who received an OAB diagnosis and OAB medication prescription for one ß3-adrenoceptor and six antimuscarinics were identified from April 2013 to August 2016. The study cohort consisted of 1,917 OAB patients in Aichi Medical University Hospital. Medication status such as persistence, switching, adherence and the reasons for discontinuation were examined. Persistence was measured by the length of continuous medication with OAB drugs. Time to discontinuation was defined as the number of days between the first dispense date and the expected end date of the last refill. The cumulative incidence of medication persistence was estimated using Kaplan-Meier method. Patients who remained on treatment until the end of the follow-up were regarded as censored data, and the length of follow-up period was assigned as the time of persistence. The proportion of persistence was compared according to each drug using the log-rank test. RESULTS: The mean patient age and time of persistence were 72.0 years and 323.9 days, and the following drugs were prescribed to OAB patients for 245 of imidafenacin, 24 of oxybutynin, 747 of solifenacin, 17 of tolterodine, 67 of fesoterodine, 100 of propiverine hydrochloride, and 723 of mirabegron. The 1-year persistence rate of each drug were 31.6%, 17.4%, 35.9%, 12.5%, 21.9%, 36.5% and 41.7%, respectively. The median of time to discontinuation were 184 days, 112 days, 196 days, 182 days, 77 days, 189 days and 231 days, respectively. Patients taking mirabegron demonstrated statistically significantly greater adherence than those taking antimuscarinics in both sexes. CONCLUSIONS: Mirabegron was associated with higher levels of persistence and adherence than antimuscarinics in our large and long term cohort.

MP43-14 UTILITY OF A NOVEL BIOPSY INSTRUMENT WITH LONG SIDE-NOTCH NEEDLE IN THE SELECTION OF PATIENTS FOR ACTIVE SURVEILLANCE

Fig 1). After adjustment for confounders, the difference in bRFS between groups was no longer significant (HR 1⁄4 0.77; 95% CI, 0.41 to 1.46). CONCLUSIONS: AS patients that are reclassified to grade group 2 and above have a higher bRFS after surgery as compared to those undergoing IRP with similar grade disease. These differences are likely due to selection criteria for AS. Our findings help inform patient decisions regarding the risk of entering an AS program.

Axitinib-induced reversible posterior leukoencephalopathy syndrome in a patient with metastatic renal cell carcinoma

A 61-year-old woman with metastatic renal carcinoma was treated with axitinib as a second-line tyrosine kinase inhibitor. Thirteen days after the treatment, the patient developed reversible posterior leukoencephalopathy syndrome (RPLS). Her symptoms and imaging findings resolved after withdrawal of axitinib, blood pressure control, and administration of glycerin and levetiracetam. RPLS should be kept in mind as a possible rare adverse event after axitinib administration.

Abstract 4400: Targeting lactate dehydrogenase-A promotes docetaxel induced cytotoxicity predominantly in castration-resistant prostate cancer cells

Introduction and objectives: It is well known as Warburg effect that anaerobic glycolytic pathway is activated in various type of advanced cancers including prostate cancer (PC). Lactate dehydrogenase-A (LDH-A) controls the conversion of pyruvate to lactate and plays an important role in glucose metabolism. Since LDH-A pathways have been implicated in chemoresistance in various cancers, we investigated whether inhibition of LDH-A pathway could mediate the sensitivity to docetaxel (DOC) in human PC cells. Materials and Method: Four PC cell lines (PC3, DU145, LNCaP, LN-CSS ) were used. LN-CSS is one of the LNCaP-derived castration-resistant PC (CRPC) cell lines established in our laboratories. Sodium oxamate (SO) was used as a specific LDH-A inhibitor. The protein expression was detected by western blot analysis using specific antibodies. Cell growth and survival were evaluated by WST-1 assays. Cell cycle progression and apoptotic inducibility were evaluated by flow cytometry using propidium iodide and Annexin V. The cytotoxicity of SO/DOC combination on PC cells was evaluated using the Chou-Talalay combination index (CI) method which offers quantitative definition for additive effect (CI = 1), synergism (CI 1) in drug combinations. Result: Western blot analysis showed that LDH-A protein was highly expressed in LN-CSS cells compared with other PC cell lines including the parental LNCaP. WST-1 assays showed that treatment with SO (50 mM) for 72 hours in PC cells resulted in growth inhibition (PC3; ~30%, DU145; ~55%, LNCaP; ~20%,LN-CSS; ~55% ), while SO has little growth inhibitory effects on normal lymphocytes in the concentrations between 1-100 mM. IC50 to DOC in PC cells were showed to be 4 nM, 1 nM, 1nM, and 4.5 nM in PC3, DU145, LNCaP and LN-CSS, respectively, suggesting that both PC3 and LN-CSS were relatively resistant to DOC compared with DU145 and LNCaP. Synergistic cytotoxicity was observed after the combination therapy with DOC and SO in LN-CSS (CI: 0.5) but not in PC3 (CI: 1.9), DU145 (CI: 2.0), or LNCaP (CI: 6.5). Cell cycle analyses revealed that the combination with DOC and SO for 72 hours resulted in the accumulation of cells in G2-M phase followed by sub-G1 accumulation in LN-CSS cells. Annexin V assays showed that 43% apoptosis was induced by the combination therapy in LN-CSS cells, while only 12% by DOC only in LN-CSS cells. Conclusion: Our results strongly suggest that LDH-A plays an important role in DOC resistance in advanced PC cells and inhibition of LDH-A promotes DOC-sensitivity especially in CRPC cells. Our study may provide valuable information for the future development of targeted therapies in patients with CRPC. Citation Format: Hiroyuki Muramatsu, Makoto Sumitomo, Shingo Morinaga, Hiroshi Saiki, Ikuo Kobayashi, Keishi Kajikawa, Genya Nishikawa, Yoshiharu Kato, Masahito Watanabe, Kent Kanao, Kogenta Nakamura, kazuhiro Yoshikawa. Targeting lactate dehydrogenase-A promotes docetaxel induced cytotoxicity predominantly in castration-resistant prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4400. doi:10.1158/1538-7445.AM2017-4400

PD47-04 PATHOLOGICAL FEATURES OF THE INDEX AND NON-INDEX LESIONS IN RADICAL PROSTATECTOMY SPECIMENS: IMPLICATIONS FOR FOCAL THERAPY.

INTRODUCTION AND OBJECTIVES: Data regarding the expression of estrogen receptors (ER) and prostate cancer (PCa) outcomes are limited. We evaluated the relationship of expression profiles of ERb; isoforms and the membrane bound estrogen receptor GPR30 with patient factors and outcomes following radical prostatectomy (RP). METHODS: Tissue microarrays constructed from 566 men who underwent RP for localized PCa were analyzed with immunohistochemistry targeting ERb1, ERb2, ERb5 and GPR30. An experienced, blinded pathologist scored receptor distributions and staining intensities. Demographic and clinical data were evaluated with descriptive statistics. Correlations between PCa ERb; isoform and GPR30 expression and clinicopathologic data were analyzed with c2 tests. Cox proportional hazards models were used to examine associations between each ER’s staining pattern and time to recurrence and prostate cancer-specific mortality (PCSM). Receptor sub-type staining patterns found to have a significant association with recurrence or PCSM were further analyzed using the Kaplan-Meier method. Significance was set at a <0.05, two-tailed test. RESULTS: PCa cells had unique staining patterns with ERb1 demonstrating predominantly nuclear localization, while ERb2, ERb5 and GPR30 were predominantly cytoplasmic. Median follow-up among was 10.5 years. After controlling for patient factors, increasing cytoplasmic ERb1 (cERb1) (HR 1.53, 95% CI 1.01-2.32, p1⁄40.047) and nuclear ERb2 (nERb2) (HR 1.55, 95% CI 1.01-2.38, p1⁄40.043) staining were associated with significantly worse 5-year recurrence-free survival (RFS). Increasing cERb1 (HR 4.67, 95% CI 1.80 e 12.11, p1⁄40.002) and nERb2 (HR 2.49, 95% CI 1.08 e 5.80, p1⁄40.033) expression were also associated with significantly increased risk of PCSM. Patients with cERb1 and nERb2 co-staining had significantly worse 15-year PCSM vs. patients expressing only cERb1, only nERb2, or neither (16.4% vs. 4.3% vs. 0.0% vs 2.0 %, respectively p1⁄40.001) (Figure). CONCLUSIONS: Increased cERb1 and nERb2 expression are associated with worse PCa-specific outcomes following RP. These findings suggest that evaluating tumor ERb1 and ERb2 staining patterns following RP may provide prognostic information Source of Funding: R01-CA056678, R01-CA092579, R03CA137799, and P50-CA097186