Yuto Matsushita

Comparison of Alternative Androgen Receptor-axis-targeted Agent (ARATA) and Docetaxel as Second-line Therapy for Patients With Metastatic Castration-resistant Prostate Cancer With Progression After Initial ARATA in Real-world Clinical Practice in Japan

&NA; The present study included 222 patients with metastatic castration‐resistant prostate cancer. Of the 222 patients, 108 and 114 received an alternative androgen receptor‐axis‐targeted agent (ARATA) or docetaxel, respectively, after the failure of initial ARATA. We found that the oncologic outcomes, including the response rate, progression‐free survival, and overall survival, were significantly superior in the 114 patients receiving docetaxel compared with those of the 108 patients receiving ARATA. Background: The objective of the present study was to assess the oncologic outcomes of patients receiving second‐line therapy against metastatic castration‐resistant prostate cancer (mCRPC). Patients and Methods: The present study included 222 consecutive mCRPC patients with progression during initial androgen receptor‐axis‐targeted agent (ARATA) therapy with either abiraterone acetate (AA) or enzalutamide (Enz). Of these 222 patients, 108 subsequently received an alternative ARATA (AA‐to‐Enz, n = 49; Enz‐to‐AA, n = 59) and 114 received docetaxel (DTX; AA‐to‐DTX, n = 54; Enz‐to‐DTX, n = 60). Results: The prostate‐specific antigen (PSA) level in the 114 patients receiving DTX was significantly greater than that in the 108 patients receiving ARATA. However, no significant differences were found in the remaining parameters between the 2 groups. The PSA response rate, PSA progression‐free survival (PFS), and overall survival (OS) during second‐line therapy in the DTX group (n = 114) were significantly superior to those for the ARATA group (n = 108; PSA response rate, 42.1% vs. 21.3%; median PSA PFS, 7.2 vs. 4.2 months; median OS, 17.5 vs. 14.5 months). Similar trends were confirmed by comparing these outcomes among 4 therapy groups, with significant differences (PSA response rate, Enz‐to‐AA vs. AA‐to‐DTX and Enz‐to‐AA vs. Enz‐to‐DTX; PSA PFS, AA‐to‐Enz vs. Enz‐to‐AA, AA‐to‐Enz vs. AA‐to‐DTX, Enz‐to‐AA vs. AA‐to‐DTX, and Enz‐to‐AA vs. Enz‐to‐DTX; and OS, Enz‐to‐AA vs. AA‐to‐DTX and Enz‐to‐AA vs. Enz‐to‐DTX). Furthermore, the introduction of DTX was independently associated with improved PSA PFS, but not OS, on multivariate analysis. Conclusion: Favorable oncologic outcomes can be expected with DTX treatment, rather than with alternative ARATA, for mCRPC patients after failure of an initial ARATA.

PD10-12 NO SIGNIFICANT IMPACT OF RESPONSE TO PRIOR ANDROGEN RECEPTOR-AXIS-TARGETED AGENTS ON THE EFFICACY OF SUBSEQUENT DOCETAXEL IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER

Background To investigate whether the response to an androgen receptor-axis-targeted (ARAT) agent is associated with the efficacy of subsequent docetaxel in metastatic castration-resistant prostate cancer (mCRPC) patients.

Clinical characteristics of self-reported nocturia in patients with interstitial cystitis, and effects of bladder hydrodistention (with fulguration of Hunner lesions) on nocturia

The aim of this study was to investigate the clinical characteristics of nocturia in patients with interstitial cystitis (IC), and the effects of bladder hydrodistention (with fulguration of Hunner lesions) on nocturia.

Significance of De Ritis (Aspartate Transaminase/Alanine Transaminase) Ratio as a Significant Prognostic But Not Predictive Biomarker in Japanese Patients with Metastatic Castration-resistant Prostate Cancer Treated with Cabazitaxel

Background/Aim: To date, there have not been any established biomarkers predicting the efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). The objective of this study was to evaluate the significance of the aspartate aminotransaminase (AST)/alanine aminotransaminase (ALT) ratio (De Ritis ratio) as a biomarker for mCRPC patients receiving cabazitaxel. Patients and Methods: This study included 74 consecutive docetaxel-refractory mCRPC patients treated with cabazitaxel. It assessed the impact of the pretreatment De Ritis ratio, in addition to conventional clinicopathological parameters, on the oncological outcomes in these patients. Results: After treatment with cabazitaxel, 22 (29.7%) of the 74 patients achieved a prostate-specific antigen (PSA) response; however, there was no significant difference in the PSA response rate between patients with a low De Ritis ratio (<1.35) and those with a high ratio (≥1.35). In this series, the median periods of PSA progression-free survival (PFS) and overall survival (OS) after the introduction of cabazitaxel were 4.2 and 14.7 months, respectively. No significant difference was noted in PSA PFS between the low and high De Ritis ratio groups, whereas OS in the high De Ritis ratio group was significantly poorer compared with that in the low De Ritis ratio group. Univariate analysis showed the significant impact of the De Ritis ratio on OS, but not PFS, in these 74 patients. Furthermore, the De Ritis ratio, in addition to the performance status and lactate dehydrogenase level, was shown to be independently associated with OS on multivariate analysis. Conclusion: Assessment of the De Ritis ratio may provide useful prognostic, but not predictive, information on cabazitaxel therapy in mCRPC patients.

Significance of Age in Japanese Patients Receiving Sunitinib as First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: Comparative Assessment of Efficacy and Safety between Patients Aged <75 and ≥75 Years

Background/Aim: To date, it has not been well characterized whether sunitinib is effective in elderly patients with metastatic renal cell carcinoma (mRCC). The objective of this study was to investigate the impact of age on clinical outcomes of mRCC patients receiving sunitinib. Patients and Methods: The efficacy and safety of first-line sunitinib in 154 consecutive mRCC patients were retrospectively compared between patients aged <75 (n=125) and ≥75 (n=29) years. Results: There were no significant differences in the major clinicopathological characteristics between younger and older patients; however, the reduction of the initial dose of sunitinib was significantly more frequent in older than younger patients. No significant difference in response rate, clinical benefit rate or proportion of patients going on to receive second-line therapy was noted between these two groups. Furthermore, there was no significant difference in progression-free survival (PFS) or overall survival (OS) between the two groups, and no significant impact of age on PFS or OS was documented by the Cox proportional hazards regression analyses. Of several adverse events, only anemia and fatigue were significantly more frequently observed in older than younger patients. Although there was no significant difference in the incidence of dose reduction or discontinuation of sunitinib between the two groups, the interruption of sunitinib was more frequently required in older than younger patients. Conclusion: These findings suggest that advanced age alone should not be regarded as a contraindication to the introduction of sunitinib as first-line systemic therapy for mRCC patients.

PD24-01 COMPARATIVE ASSESSMENT OF EFFICACIES BETWEEN TWO ALTERNATIVE THERAPEUTIC SEQUENCES WITH NOVEL ANDROGEN RECEPTOR-AXIS-TARGETED AGENTS IN PATIENTS WITH CHEMOTHERAPY-NAIVE METASTATIC CASTRATION-RESISTANT PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Accumulating findings suggest that sequential treatment with androgen receptor-axis-targeted (ARAT) agents, abiraterone acetate (AA) and enzalutamide (Enz), in either order has limited efficacy for metastatic castration-resistant prostate cancer (mCRPC). Furthermore, there has been a strong trend toward the movement of novel ARAT therapies into the front-line for mCRPC treatment prior to the introduction of docetaxel within the last few years, due to the favorable tolerability of ARAT agents compared with taxanes. Considering these findings, it is still important to determine the optimal sequencing order of novel ARAT agents for mCRPC patients. The objective of this study was to compare the efficacies of sequential therapies with novel ARAT agents in patients with docetaxelnaive mCRPC. METHODS: This study included 108 consecutive mCRPC patients who sequentially received AA and 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 the 108 patients, 49 and 59 received ARAT therapy with the AA-to-Enz sequence (AA-to-Enz group) and that with the reverse sequence (Enz-to-AA group), respectively. No significant differences in the baseline characteristics were noted between the two groups. In the overall patient population, the PSA response rate to the second-line ARAT agent (56.5%) was significantly lower than that to the first-line ARAT agent (21.3%). The combined PSA PFS in the AA-toEnz group (median, 18.4 months) was significantly superior to that in the Enz-to-AA group (median, 12.8 months). Furthermore, multivariate analysis identified the treatment sequence (i.e., AA-to-Enz versus Enzto-AA group) in addition to performance status as an independent predictor of combined PSA PFS in these patients. CONCLUSIONS: Although cross-resistance between ARAT agents is a common phenomenon in docetaxel-naive mCRPC patients, different efficacies were observed favoring the AA-to-Enz rather than Enz-to-AA sequence in this series. Thus, when ARAT agents are to be introduced sequentially, it may be advisable to provide ARAT therapy according to the AA-to-Enz sequence.

Systematic regional lymph node dissection for upper tract urothelial carcinoma improves patient survival

Objective Unlike for bladder cancer, the impact of regional lymph node dissection for upper tract urothelial carcinoma is unclear. We explored whether patient survival was influenced by systematic regional lymph node dissection, using resection templates according to the main tumor location, during radical nephroureterectomy for upper tract urothelial carcinoma. Methods The systematic regional lymph node dissection group was defined as cases in which the dissection of nodes and surrounding tissues followed the established template, and the non-systematic regional lymph node dissection group as cases undergoing limited or no lymph node dissection. We performed radical nephroureterectomy on 98 consecutive patients with various stages of upper tract urothelial carcinoma from May 1994 to September 2014 at our institution. Of these, 77 patients with cTanyN0M0 of upper tract urothelial carcinoma undergoing radical nephroureterectomy were grouped into systematic regional lymph node dissection or non-systematic regional lymph node dissection cohorts according to the extent of dissection, and their outcomes compared. Results Forty-four patients were categorized as systematic regional lymph node dissection and 33 as non-systematic regional lymph node dissection, including 17 with more limited nodal dissection and 16 with no nodal dissection. Five-year recurrence-free survival and cancer-specific survival were significantly higher in the systematic regional lymph node dissection (93% and 94%, respectively) than in the non-systematic regional lymph node dissection group (75% and 77% recurrence-free survival and cancer-specific survival, respectively). Further, 5-year recurrence-free survival and cancer-specific survival of muscle-invasive upper tract urothelial carcinoma (pT2-4) were significantly higher in the systematic regional lymph node dissection (87% and 91%, respectively) than in the non-systematic regional lymph node dissection group (59% and 62%, respectively) (P = 0.0237 and P = 0.0224). Neither recurrence-free survival nor cancer-specific survival was significantly prolonged by systematic dissection in patients with pTis-1 histology. Conclusions Systematic regional lymph node dissection during radical nephroureterectomy for cTanyN0M0 upper tract urothelial carcinoma patients has a significantly beneficial impact on survival compared with patients undergoing more limited dissection, especially in the cases involving muscle invasion.

Contralateral pneumothorax during retroperitoneal laparoscopic donor nephrectomy: A case report: Pneumothorax during donor nephrectomy

This report presents a case of a 46‐year‐old woman in whom contralateral pneumothorax occurred during retroperitoneal laparoscopic donor nephrectomy without any evidence of diaphragmatic injuries. After the start of carbon dioxide‐induced pneumoperitoneum, the patients end‐tidal carbon dioxide pressure and heart rate suddenly increased. The surgery was then paused, and a chest X‐ray revealed a right pneumothorax accompanied by pneumomediastinum. After a thoracostomy tube was inserted, these symptoms immediately improved. After conversion to an open procedure, the surgery was completed. The thoracostomy tube was removed the next day, and the patient was discharged without any complications. As the pneumothorax occurred on the opposite side to the operative field and there was no evidence of diaphragmatic injury, it is suspected to have been caused by a pneumomediastinum‐induced rupture of the barrier between the mediastinum and pleural space. This may have occurred due to the insufflated carbon dioxide gas passing directly into the mediastinum and then the pleural space.