Radiographic Progression at Castration-Resistant Prostate Cancer Diagnosis: A Prognostic Indicator of Metastatic Hormone-Sensitive Prostate Cancer.

BACKGROUND: The critical role of radiographic assessment at the time of castration-resistant prostate cancer (CRPC) diagnosis is underscored by this study. We performed a retrospective analysis of radiographic changes in metastasis from the time of diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) to CRPC diagnosis. We also explored its impact on prognosis post-CRPC. MATERIALS AND METHODS: We retrospectively analyzed 98 men who underwent radiographic examinations (bone scans and computed tomography [CT]) at the time of CRPC diagnosis. When radiographic studies demonstrated progression at CRPC diagnosis, patients were assigned to the radiographic progressive disease (rPD) group. The remaining patients were placed in the "non-rPD" group. The overall survival (OS) post-CRPC was compared between the 2 groups. RESULTS: The median OS post-CRPC was significantly shorter in the rPD group (n = 50) compared to the non-rPD group (n = 48) (32 months vs. not reached, P = .0124). Multivariate analysis showed that radiographic progression and shorter time to CRPC were associated with a shorter OS post-CRPC (hazard ratio [HR] = 3.14; 95% confidence interval [CI], 1.21-8.12, P = .019). CONCLUSION: Radiographic progression at the point of CRPC diagnosis independently predicts a shorter OS post-CRPC in patients with mHSPC. Therefore, assessing radiographic changes at the time of CRPC diagnosis could be instrumental in managing CRPC in patients with mHSPC.

Site-Specific Differences of Eligibility for Adjuvant Immunotherapy Among Urothelial Carcinoma Patients Treated With Radical Surgery: Results From a Multicenter Cohort Study.

BACKGROUND: The CheckMate274 trial has reported enhanced disease-free survival rates in patients with stage pT3-4/ypT2-4 or pN+ urothelial carcinoma (UC) undergoing adjuvant nivolumab therapy. This study compares prognostic differences between urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively analyzed data from 719 patients with UC who underwent radical surgery, stratifying to patients at stage pT3-4 and/or pN+ without neoadjuvant chemotherapy (NAC) or at ypT2-4 and/or ypN+ with NAC (potential candidates for adjuvant immunotherapy), and to those who were not candidates for adjuvant immunotherapy. We used Kaplan-Meier curves to assess oncological outcomes, particularly nonurothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Risk factors were identified by Cox regression analysis. RESULTS: Kaplan-Meier curves showed significantly lower NUTRFS, CSS, and OS for potential adjuvant immunotherapy candidates than for noncandidates in each UCB and UTUC group. NUTRFS, CSS, and OS did not differ significantly between adjuvant immunotherapy candidates with UBC or UTUC. Trends were similar among patients ineligible for adjuvant immunotherapy. Pathological T stage (pT3-4 or ypT2-4), pathological N stage, and lymphovascular invasion (LVI) were independent predictors of oncological outcomes on multivariate analysis. CONCLUSION: The criteria for adjuvant immunotherapy candidates from the CheckMate 274 trial can also effectively stratify UC patients after radical surgery. Substantial clinical significance is attached to LVI status as well as to pathological T and N status, suggesting that LVI status should be considered when selecting suitable candidates for adjuvant immunotherapy.

Survival outcome of chemotherapy-naïve castration-resistant prostate cancer treated with new-generation androgen receptor axis-targeted agents in real-world analysis.

PURPOSE: The androgen receptor axis-targeted (ARAT) agents abiraterone and enzalutamide have been introduced against castration-resistant prostate cancer (CRPC). However, determining which of these agents should be used first is a clinical challenge. Therefore, in this study, we compared the efficacy of first-line abiraterone and enzalutamide treatments in chemotherapy-naïve patients with CRPC. METHODS: A total of 242 chemotherapy-naïve CRPC cases treated with first-line ARAT were analyzed. Outcome measures were PSA response, PSA progression-free survival (PSA-PFS), time to treatment failure (TTF), cancer specific survival (CSS), and overall survival (OS). RESULTS: Abiraterone (A) and enzalutamide (E) were administered to 61 and 181 patients, respectively. The median PSA response rate (- 65.4% [A] and - 78.8% [E], p = 0.0341), PSA decline ≥ 30% (55.7% [A] and 72.9% [E], p = 0.0183), PSA-PFS (median 4 months [A] and 8 months [E], p = 0.0126), TTF (median 6 months [A] and 14 months [E], p < 0.0001), CSS (median 45 months [A] and not reached [E], p < 0.0001), and OS (median 28 months [A] and 80 months [E], p < 0.001) were significantly better in the enzalutamide group. In the multivariate analyses for CSS and OS, ALP (p = 0.00376) and ARAT (p < 0.001) (CSS), evidence of metastasis (p = 0.0467), Hb (p = 0.00205), and ARAT (p = 0.00514) (OS) were significant factors, respectively. CONCLUSION: This study showed that PSA response, PSA-PFS, TTF, CSS, and OS were better with first-line enzalutamide administration. Direct inhibition of androgen receptor signaling by enzalutamide is associated with better clinical outcomes.

Clinical Significance of Intraductal Carcinoma of the Prostate After High-Dose Brachytherapy With External Beam Radiation Therapy: A Single Institution Series and an Updated Meta-Analysis.

BACKGROUND: We compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT). METHODS: We performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan-Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P. RESULTS: Kaplan-Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003). CONCLUSION: Amongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P.

Patients with PSA below 0.2 ng/mL at 8 years post high-dose-rate brachytherapy have an extremely low risk of subsequent recurrence.

OBJECTIVES: We have analyzed the long-term follow-up data of patients with prostate cancer (PCa) who underwent high-dose-rate brachytherapy (HDR-BT) and external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT). The objective was to determine the optimal time for cessation of PSA monitoring after HDR-BT. METHODS: We included 309 patients with clinical stage T1c-T4 N0-1 M0 PCa who received HDR-BT and EBRT combined with long-term ADT between 2005 and 2018. We stratified the patients based on their prostate-specific antigen (PSA) levels and identified the factors associated with biochemical recurrence (BCR) and clinical progression (CP). RESULTS: The median follow-up duration was 98 months (range: 31-207 months). Among the 306 patients, 76 developed BCR and 47 developed CP subsequently. We found that the PSA levels at 3, 5, and 8 years significantly correlated with the oncological outcomes of brachytherapy. No patient with a PSA level ≤ 0.2 ng/mL at 8 years later developed BCR or CP. CONCLUSION: Our long-term data suggest that in the presence of a PSA level ≤ 0.2 ng/mL at 8 years later, PSA monitoring may be safely discontinued due to the extremely low risk of subsequent oncological events. The data presented in this study will assist clinicians in determining the optimal management strategy for patients with PCa following HDR-BT and EBRT combined with long-term ADT.

Association between concomitant proton pump inhibitor use and survival of patients with metastatic prostate cancer receiving abiraterone acetate: a post-hoc analysis of pooled data from three randomized controlled trials.

BACKGROUND: Evidence suggests proton pump inhibitor (PPI) use may attenuate the effect of abiraterone acetate plus prednisone (AAP) in metastatic prostate cancer via the modification of gut microbiota. This study aimed to examine whether concomitant PPI use is associated with survival in patients with metastatic prostate cancer treated with androgen deprivation therapy (ADT) and AAP. METHODS: Post-hoc analysis was conducted in patients with metastatic castration-sensitive prostate cancer (mCSPC) and metastatic castration-resistant prostate cancer (mCRPC) treated in the LATITUDE, COU-AA-301, and COU-AA-302 trials (ADT vs. ADT plus AAP). PPI users and non-users were compared for restricted mean overall survival time (RMOST) and restricted mean progression-free survival time (RMPFST) based on inverse probability of treatment weight (IPTW)-adjusted Kaplan-Meier curves. IPTW-adjusted Cox regression models were used to assess heterogeneity of treatment effect. RESULTS: In patients treated with AAP, PPI use was associated with inferior RMOST [difference (95% confidence interval): -4.2 (-7.0 to -1.4)] and RMPFST [-3.5 (-6.6 to -0.4)] compared with non-users. However, RMOST and RMPFST were similar between PPI users and non-users in patients treated with ADT alone [RMOST, -2.6 (-5.8 to 0.6); RMPFST, -1.7 (-4.8 to 1.4)]. Interaction term analyses did not show evidence of heterogeneity in treatment effect between AAP and ADT, despite the prominent treatment effect shown in mCSPC vs. mCRPC. CONCLUSIONS: PPI use may be associated with inferior survival in patients with metastatic prostate cancer who receive ADT plus AAP. Discontinuing unnecessary PPI use might improve those outcomes.

The prognostic significance of the clinical T stage and Grade Group in patients with locally advanced prostate cancer treated via high-dose-rate brachytherapy and external beam radiation.

BACKGROUND: Although the optimal management of locally advanced prostate cancer (PCa) remains unclear, local definitive therapy, thus combined radiotherapy and androgen deprivation, is one option. We evaluated the long-term outcomes of patients with locally advanced PCa who underwent high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT). METHODS: We retrospectively analyzed 173 patients with locally advanced PCa (cT3a-4N0-1M0) who underwent HDR-BT and EBRT. We employed Cox's proportional hazards models to identify pre-treatment predictors of oncological outcomes. Treatment outcomes (biochemical recurrence-free survival [BCRFS], clinical progression-free survival [CPFS], and castration-resistant prostate cancer-free survival [CRPCFS] were compared according to the combination of the pre-treatment predictors. RESULTS: The 5-year BCRFS, CPFS, and CRPCFS rates were 78.5, 91.7, and 94.4% respectively; there were two PCa deaths. Multivariate analysis revealed that the clinical T stage (cT3b and cT4) and Grade Group (GG) 5 status were independent risk factors for poor BCRFS, CPFS, and CRPCFS. In the GG ≤ 4 group, the Kaplan-Meier curves for BCRFS, CPFS, and CRPCFS revealed excellent outcomes. However, in the GG5 group, patients with cT3b and cT4 PCa evidenced significantly poorer oncological outcomes than those with cT3a PCa. CONCLUSION: The clinical T stage and GG status were significantly prognostic of oncological outcomes in patients with locally advanced PCa. In patients of GG ≤ 4 PCa, HDR-BT was effective even in patients with cT3b or cT4 PCa. However, in patients with GG5 PCa, careful monitoring is essential, particularly of patients with cT3b or cT4 PCa.

Pagetoid spread of urothelial carcinoma controlled without resection.

Introduction: Extramammary Paget's disease is an eczematous skin condition that affects the vulva and perineum. Extramammary Paget's disease secondary to urothelial carcinoma is a rare condition that is typically treated with invasive surgical resection of the lesion. Case presentation: An 80-year-old woman with a 7-year history of urothelial carcinoma presented with erythema of the labia majora. Immunostaining of skin biopsy specimens suggested extramammary Paget's disease secondary to urothelial carcinoma. The patient did not consent to resection of the lesion. Nine cycles of first-line platinum-based chemotherapy for metastatic urothelial carcinoma were administered. As tumor cells remained after systemic chemotherapy, pembrolizumab will be administered to the patient for treating residual extramammary Paget's disease. Conclusion: Platinum-based chemotherapy can control extramammary Paget's disease secondary to urothelial carcinoma.

Chemical Components in Hedera rhombea Leaves and Their Cytotoxicity.

Two novel triterpene glycosides (1 and 2), 17 known triterpene glycosides (3-19), two known flavonoid glycosides (20 and 21), and two known norsesquiterpene glucosides (22 and 23) were isolated from Hedera rhombea (Araliaceae) leaves. The structures of 1 and 2 were determined by spectroscopic analysis, including two-dimensional NMR spectroscopy, and chromatographic analysis of the hydrolyzed products. The cytotoxicity of the isolated triterpene glycosides (1-19) against HL-60 human promyelocytic leukemia cells was evaluated. Compounds 9, 10, and 11 were cytotoxic to HL-60 cells with IC50 values of 7.2, 21.9, and 32.8 µM, respectively. Other compounds isolated from the leaves were not cytotoxic at sample concentrations of 50 µM.

Abiraterone acetate versus nonsteroidal antiandrogen with androgen deprivation therapy for high-risk metastatic hormone-sensitive prostate cancer.

BACKGROUND: Although prostate cancer is a very common form of malignancy in men, the clinical significance of androgen deprivation therapy (ADT) with abiraterone acetate versus the nonsteroidal antiandrogen bicalutamide has not yet been verified in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). The present study was designed to initiate this verification in real-world Japanese clinical practice. METHODS: We retrospectively analyzed the records of 312 patients with high-risk mHSPC based on LATITUDE criteria and had received ADT with bicalutamide (n = 212) or abiraterone acetate (n = 100) between September 2015 and December 2020. Bicalutamide was given at 80 mg daily and abiraterone was given at 1000 mg daily as four 250-mg tablets plus prednisolone (5-10 mg daily). Overall survival (OS), cancer-specific survival (CSS), and time to castration-resistant prostate cancer (CRPC) were compared. The prognostic factor for time to CRPC was analyzed by Cox proportional hazard model. RESULTS: Patients in the bicalutamide group were older, and more of them had poor performance status (≧2), than in the abiraterone group. Impaired liver function was noted in 2% of the bicalutamide group and 16% of the abiraterone group (p < 0.001). Median follow-up was 22.5 months for bicalutamide and 17 months for abiraterone (p < 0.001). Two-year OS and CSS for bicalutamide versus abiraterone was 77.8% versus 79.5% (p = 0.793) and 81.1% versus 82.5% (p = 0.698), respectively. Median time to CRPC was significantly longer in the abiraterone group than in the bicalutamide group (NA vs. 13 months, p < 0.001). In multivariate analysis, Gleason score ≧9, high alkaline phosphatase, high lactate dehydrogenase, liver metastasis, and bicalutamide were independent prognostic risk factors for time to CRPC. Abiraterone prolonged the time to CRPC in patients with each of these prognostic factors. CONCLUSIONS: Despite limitations regarding the time-dependent bias, ADT with abiraterone acetate significantly prolonged the time to CRPC compared to bicalutamide in patients with high-risk mHSPC. However, further study with longer follow-up is needed.

Initial dose reduction of enzalutamide does not decrease the incidence of adverse events in castration-resistant prostate cancer.

BACKGROUND: There was no clear evidence whether the initial dose of enzalutamide affects the incidence of adverse events (AEs), and oncological outcome in patients with castration-resistant prostate cancer (CRPC). METHODS: The clinical charts of 233 patients with CRPC treated with enzalutamide were reviewed retrospectively. After 1:3 propensity score matching (PSM), 124 patients were divided into a reduced dose group and a standard dose group, and the prostate specific antigen (PSA) response and the incidence of AEs were compared. RESULTS: 190 patients with CRPC initiated with standard dose enzalutamide were younger and better performance status compared with 43 patients beginning with reduced dose. After PSM, the baseline characteristics were not different between the standard and the reduced dose group. In the PSM cohort, the PSA response rate was significantly lower in the reduced dose group than in the standard dose group (-66.3% and -87.4%, p = 0.02). The incidence rates of AEs were not statistically different between the groups (22.6% and 34.4%, respectively, p = 0.24). CONCLUSION: Initiating treatment with a reduced dose of enzalutamide did not significantly decrease the incidence rate of AEs, and it showed poorer PSA response rate. There is no clear rationale for treating with a reduced initial dose of enzalutamide to reduce the incidence of AEs.

Trimodal therapy with high-dose-rate brachytherapy and hypofractionated external beam radiation combined with long-term androgen deprivation for unfavorable-risk prostate cancer.

PURPOSE: To assess the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiation therapy (EBRT) combined with long-term androgen deprivation therapy (ADT) in very-high-risk (VHR) versus high-risk (HR) prostate cancer (PCa), as defined in the National Comprehensive Cancer Network (NCCN) criteria. METHODS: Data from 338 consecutive HR or VHR PCa patients who had undergone this tri-modal therapy between 2005 and 2018 were retrospectively analyzed. Biochemical recurrence (BCR)-free, progression-free, overall, and cancer-specific survival (BCRFS/PFS/OS/CSS) rates were analyzed using the Kaplan-Meier method and Wilcoxon test. Cox regression models were used to evaluate candidate prognostic factors for survival. C­indexes were used to assess model discrimination. RESULTS: Within a median follow-up of 84 months, 68 patients experienced BCR, 58 had disease progression including only 3 with local progression, 27 died of any cause, and 2 died from PCa. The 5­year BCRFS, PFS, OS, and CSS rates were 82.2% (HR 86.5%; VHR 70.0%), 90.0% (HR 94.3%; VHR 77.6%), 95.7% (HR, 97.1%; VHR, 91.8%), and 99.6% (HR, 100%; VHR, 98.0%), respectively. In multivariable analyses that adjusted for standard clinicopathologic features, the risk subclassification was associated both PFS and OS (p = 0.0003 and 0.001, respectively). Adding the risk subclassification improved the accuracy of models in predicting BCRFS, PFS, and OS. CONCLUSION: While the outcome of this trimodal approach appears favorable, VHR PCa patients had significantly worse oncological outcomes than those with HR PCa. The NCCN risk subclassification should be integrated into prognostic tools to guide risk stratification, treatment, and follow-up for unfavorable PCa patients receiving this trimodal therapy.

Values of alkaline phosphatase at the diagnosis of castration resistance and response to primary androgen deprivation therapy as predictors of subsequent metastasis in non-metastatic castration-resistant prostate cancer.

PURPOSE: Among various therapeutic options available for metastatic castration-resistant prostate cancer (mCRPC), only apalutamide and enzalutamide have shown evidences of improved metastasis-free survival (MFS) for non-metastatic castration-resistant prostate cancer (nmCRPC). However, there is a paucity of evidence to indicate who may be targeted for aggressive therapy among patients with nmCRPC. The objectives of this retrospective study were to explore predictors of metastasis in patients with nmCRPC and to identify a subpopulation of patients with nmCRPC who may benefit from aggressive therapy. METHODS: A total of 115 patients with CRPC who had no metastasis detected at the time of diagnosis of CRPC were included in this retrospective study. All patients were treated at Jikei University and its affiliated hospitals. The primary outcome measure was MFS from the time of diagnosis of CRPC. Predictors of MFS were also explored with a multivariate Cox hazard model. RESULTS: The median observation period after diagnosis of CRPC was 30 months (range 2-143 months). Kaplan-Meier analysis revealed a median MFS of 76. Multivariate analysis demonstrated that low alkaline phosphatase (ALP) values at diagnosis of CRPC and favorable response to primary androgen deprivation therapy (ADT) were significant predictors of longer MFS (P = 0.011, and 0.031, respectively). CONCLUSIONS: Results of this study suggest that high ALP values at diagnosis of CRPC and poor response to primary ADT may predict the propensity of metastasis in patients with nmCRPC. Further prospective studies will be required enrolling more patients to confirm our findings.

Red Cell Distribution Width Predicts Prostate-Specific Antigen Response and Survival of Patients With Castration-Resistant Prostate Cancer Treated With Androgen Receptor Axis-Targeted Agents.

PURPOSE: To identify the impact of red cell distribution width (RDW) on treatment outcomes in patients with castration-resistant prostate cancer (CRPC) treated with androgen receptor axis-targeted agents (ARATs). PATIENTS AND METHODS: Baseline data were obtained from 153 patients with CRPC treated with ARATs. Patients were stratified according to the upper limit of the normal RDW range, measured within 1 month before starting treatment. Relationships between RDW levels and the best prostate-specific antigen (PSA) response, PSA progression-free survival, and overall survival were examined. RESULTS: Forty-nine patients were treated with abiraterone acetate in combination with corticosteroid and 104 with enzalutamide. The median RDW was 13.7% (interquartile range, 13.0-14.9). High RDW was significantly associated with prior use of docetaxel (P < .001), presence of lymph node metastasis (P = .031), presence of visceral metastasis (P = .001), and low hemoglobin (P < .001), low albumin (P = .016), and high C-reactive protein levels (P = .02). In a multiple linear regression model, there was a statistically significant negative association between RDW levels and the best PSA response (P = .046). In addition, multivariate Cox regression analyses showed that high RDW was an independent predictor of both shorter PSA progression-free survival (hazard ratio = 1.84; 95% confidence interval, 1.04-3.27; P = .037) and overall survival (hazard ratio = 2.62; 95% confidence interval, 1.15-5.98; P = .022), showing statistical significance. CONCLUSION: High RDW is an independent predictor of worse treatment outcomes in patients with CRPC treated with ARATs. RDW could be a readily available and inexpensive biomarker for predicting primary resistance to ARATs.

Earlier use of androgen receptor-axis-targeted drugs may improve overall survival in patients with non-metastatic castration-resistant prostate cancer.

BACKGROUND: To evaluate the role of androgen receptor-axis-targeted drugs (ARAT) in non-metastatic castration-resistant prostate cancer (nmCRPC) versus mCRPC. METHODS: Chemotherapy-naive patients (n = 114) with CRPC who had no metastasis at the time of diagnosis were included in this retrospective study. All patients were treated with ARAT at Jikei University and its affiliated hospitals from July 2014 to March 2017. The patients were stratified into nmCRPC (n = 81) and mCRPC (n = 33) groups according to their metastatic status at ARAT induction. The primary outcome measure was difference in overall survival (OS) between groups from the time of CRPC diagnosis. The patients were compared for progression-free survival (PFS) and prostate-specific antigen (PSA) response. The predictors of OS were explored by a multivariate Cox model. RESULTS: The baseline demographics did not differ significantly between the groups. The median observation period from the diagnosis of CRPC was 24.5 months (range: 3-135) and 20 months (range: 1-66) in nmCRPC and mCRPC groups, respectively. The nmCRPC group demonstrated better OS from the time of diagnosis of CRPC in Kaplan-Meier analysis than mCRPC group (86 months vs 40 months; P = 0.004), with similar results obtained for PFS (P = 0.048) and PSA response (P = 0.0014). Multivariate analysis demonstrated non-metastatic status, low PSA, and long PSA doubling time (PSADT) at ARAT induction as the significant predictors of longer OS (P = 0.044, 0.0001, and 0.026, respectively). CONCLUSIONS: Early use of ARAT may improve OS, PFS, and PSA response in CRPC. Larger, prospective studies will be required to confirm our findings.

Does docetaxel prolong survival of patients with non-metastatic castration-resistant prostate cancer?

BACKGROUND: Guidelines define docetaxel as a first-line therapeutic option for metastatic castration-resistant prostate cancer (mCRPC). However, the role of docetaxel in non-metastatic castration-resistant prostate cancer (nmCRPC) has not been fully investigated. The aim of this retrospective study was to evaluate the potential role of docetaxel in nmCRPC. Clinical outcomes including overall survival were compared between CRPC patients who had docetaxel introduced while in nonmetastatic versus metastatic diseases. METHODS: A total of 98 CRPC patients had docetaxel therapy. Of these 46 patients received docetaxel for nmCRPC, and 52 had distant metastases. Clinical outcomes from the time of diagnosis of CRPC were compared retrospectively between groups. RESULTS: The median observation period after the diagnosis of CRPC in these patients was 42 months (range, 3-166). Overall survival (OS) was significantly longer in the nmCRPC group than in the mCRPC group (not reached vs 52.2 months, respectively, P = 0.006). Multivariate analysis showed that longer time to CRPC, docetaxel use in nmCRPC, and use of abiraterone acetate and/or enzalutamide were significant predictors for improved OS (P = 0.04, 0.019 and 0.002, respectively). The incidence and profile of adverse events did not differ significantly between groups. CONCLUSIONS: Earlier induction of docetaxel in nmCRPC patients may prolong OS. Further prospective studies in more patients will be required to confirm our findings.

Prospective comparison of the efficacy of caudal versus periprostatic nerve block, both with intrarectal local anesthesia, during transrectal ultrasonography-guided prostatic needle biopsy.

OBJECTIVE: The aim of this study was to compare the effectiveness of caudal block (CB) versus periprostatic nerve block (PPNB), both with intrarectal local anesthesia (IRLA), in reducing pain during transrectal ultrasonography (TRUS)-guided prostatic biopsy. MATERIALS AND METHODS: This study included 532 patients: 266 patients received CB with IRLA and 266 patients PPNB with IRLA. A visual analogue scale (VAS) was applied to prospectively evaluate pain (1) at induction of anesthesia, (2) at insertion of the TRUS probe, (3) at needle penetration to the prostate, and (4) throughout the biopsy procedure. Pain scores were compared to evaluate differences between groups. The secondary endpoint of serious complication rate was also evaluated. As a subanalysis, the pain scores were compared in patients with high body mass index (BMI ≥25 kg/m²). RESULTS: Overall, the pain score in the PPNB group was significantly lower than in the CB group at induction of anesthesia (mean ± SD: 2.0 ± 1.9 vs 2.9 ± 2.1, p = .0001) but higher at insertion of the TRUS probe (2.7 ± 2.5 vs 1.9 ± 1.7, p = .009). The pain score did not differ significantly between groups at needle penetration or throughout the biopsy. Univariate analyses indicated no significant association between VAS scores and patient demographics. Overall rates of serious complications did not differ between the two groups (5.6% vs 5.3%, p = .85). In patients with high BMI, the pain score was significantly lower in the PPNB group than in the CB group throughout the procedure (2.5 ± 2.0 vs 3.5 ± 2.5, p = .03). CONCLUSIONS: Both procedures were equally effective in reducing pain, and the incidence of serious complications was similar. PPNB with IRLA may be more applicable than CB with IRLA in obese patients.

[EXPRESSION OF PLAKIN FAMILY IN UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT].

(Objective) To determine whether the plakin family proteins periplakin, desmoplakin, plectin, and envoplakin could be markers of urothelial carcinoma of the upper urinary tract. (Materials and methods) Fifty-seven surgical specimens were obtained from patients with urothelial carcinoma of the upper urinary tract, who were admitted to the Jikei University Hospital between April 2000 and December 2005. The expression of plakin family proteins in cancerous and normal tissues was investigated using immunohistochemistry, and its association with clinicopathological parameters was analyzed. (Results) The expression of periplakin, envoplakin, and desmoplakin was significantly lower in cancerous tissue than in normal urothelium (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). Strong desmoplakin expression in cancerous tissue was significantly associated with poor cancer-specific survival and overall survival (P = 0.023 and P = 0.034, respectively, compared with cancerous tissue with slight or less desmoplakin expression). Furthermore, strong plectin expression was significantly associated with poor metastasis-free survival (P = 0.034, compared with cancerous tissue with slight or less plectin expression). (Conclusion) Plakin family, particularly desmoplakin was suggested to be a prognostic marker of urothelial carcinoma of the upper urinary tract.

OUTCOMES AFTER SURGICAL TREATMENT OF UPPER TRACT UROTHELIAL CARCINOMA.

(Objectives) We retrospectively investigated the prognostic factors and the role of adjuvant chemotherapy against upper tract urothelial carcinoma (UTUC) after surgery. (Materials and methods) 343 patients of UTUC who underwent radical nephroureterectomy at Jikei University Hospital and affiliated institutions between January 2004 and February 2012 were retrospectively analyzed. A chi-squared test was used for categorical variables. Survival probabilities after surgery were estimated using the Kaplan-Meier method. Multivariate Cox regression models addressed overall survival and cancer-specific survival after surgery. (Results) The 5-year overall and cancer-specific survival rates were 64.6% and 74.6%, respectively. On multivariate analysis, higher age, male, higher pT-stage and lymphovascular invasion (LVI) were associated with worse overall survival and higher pT-stage and LVI were associated with worse cancer-specific survival. 44 patients (G3 and ≥pT3) who received cisplatin-based adjuvant chemotherapy had improved overall survival (P=0.044). (Conclusions) Higher pT-stage, LVI were important prognostic variables associated with oncologic outcomes. Cisplatin-based adjuvant chemotherapy offered a significant benefit to overall survival in high risk UTUC (G3 and ≥pT3), but more investigations are needed to confirm its utility.

[CLINICAL CHARACTERISTICS OF T1 HIGH GRADE BLADDER CANCER].

OBJECTIVES: We retrospectively evaluated characteristics of T1 high-grade bladder cancer in patients in our hospitals. PATIENTS AND METHODS: Data was reviewed from 134 patients who were diagnosed with T1 high-grade bladder cancer and who underwent transurethral resection (TUR) in our hospitals between January 2006 and December 2012. The clinical course for each patient, the recurrence and progression rates, and the risk factors for recurrence and progression were evaluated. RESULTS: The median follow-up was 31.5 months. A second TUR was performed in 55 patients (41.0%), and showed 32 cases of residual tumor (58.2%) and 4 cases of upstaging (7.3%). The recurrence rate was 41.5%. The risk factors for recurrence were (1) no muscle obtained in initial TUR, (2) no BCG, and (3) no second TUR. The progression rate was 10.5%; no significant risk factors were identified for progression. Within the T1 high-grade bladder cancer cohort, a total of 31 patients underwent radical cystectomy (RC). When we graphed cancer-specific survival (CSS) curves stratified by pathological T stage at the time of RC, and then compared findings from the upstage group (greater than pT2) and the non-upstage group (less than pT2), the CSS rate was significantly higher in the non-upstage group (p = 0.0027). CONCLUSION: No muscle in initial TUR, no BCG, and no second TUR are factors associated with recurrence of T1 high-grade bladder cancer. Further investigation is needed for preventing recurrence and progression and for improving survival following radical cystectomy in T1 high-grade bladder cancer.