Prognostic significance of lactate dehydrogenase in cabazitaxel chemotherapy for castration-resistant prostate cancer: a multi-institutional study.

This multi-institutional study aimed to identify prognostic factors for cabazitaxel treatment of castration-resistant prostate cancer (CRPC). This study included 74 Japanese patients with CRPC who were treated with cabazitaxel between 2014 and 2017. Associations between clinicopathological factors including serum markers and progression-free survival (PFS) and overall survival (OS) were investigated. On multivariate analysis, high Gleason score [≥9 vs. ≤7; hazard ratio (HR), 95% confidence interval (CI): 2.00 (1.01-4.34); P = 0.047], presence of pain [HR, 95% CI: 2.02 (1.14-3.58); P = 0.016], and lactate dehydrogenase (LDH) level [HR, 95% CI: 47.31 (3.79-577.49); P = 0.0019] were significantly associated with PFS. Similarly, number of docetaxel cycles [HR, 95% CI: 0.050 (0.0037-0.45); P = 0.0057], performance status [≥2 vs. 0; HR, 95% CI: 5.07 (1.57-16.24); P < 0.0001], and LDH level [HR, 95% CI: 2946 (50-420994); P = 0.0001] were significantly associated with OS. This study showed that LDH level is robustly prognostic for both PFS and OS in cabazitaxel chemotherapy for CRPC.

Predictive factors of biochemical recurrence after radical prostatectomy for high-risk prostate cancer.

OBJECTIVE: To identify risk factors of biochemical recurrence after radical prostatectomy in high-risk patients. METHODS: A total of 191 high-risk prostate cancer patients according to the D'Amico classification treated with radical prostatectomy at a single institution between April 2000 and December 2013 were enrolled. The pathological evaluation including intraductal carcinoma of prostate was reassessed, and the clinical and pathological risk factors of biochemical recurrence were analyzed. RESULTS: The median follow up after radical prostatectomy was 49 months. The 5-year biochemical recurrence-free survival rate after radical prostatectomy in high-risk prostate cancer patients was 41.6%. Initial prostate-specific antigen, pathological Gleason score, seminal vesicle invasion, extraprostatic extension and intraductal carcinoma of the prostate were significantly associated with biochemical recurrence-free survival. The 5-year biochemical recurrence-free survival rates in patients with zero, one, two and three of these risk factors were 92.9%, 70.7%, 38.3% and 28.8%, respectively. In patients with four or more factors, the biochemical recurrence-free survival rate was 6.1% after 18 months. CONCLUSIONS: In D'Amico high-risk patients treated with radical prostatectomy, risk factors for biochemical recurrence can be identified. Patients with fewer risk factors have longer biochemical recurrence-free survival, even among these high-risk cases.

[SIGNIFICANCE OF INTRADUCTAL CARCINOMA OF THE PROSTATE IN POST-OPERATIVE BIOCHEMICAL RECURRENCE].

(Objective) We investigated the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy specimens. (Materials and methods) We evaluated 441 patients treated with radical prostatectomy and analyzed data on IDC-P, lymph node metastases, Gleason score, seminal vesicle invasion, extraprostatic extension, surgical margin, total cancer volume, and zonal origin of dominant cancer focus in radical prostatectomy specimens. The median follow-up was 50 months (range 6-164 months). (Results) We identified IDC-P in 112 cases (25.4%). The five-year biochemical progression-free survival rate in patients with IDC-P was significantly lower than for those without IDC-P (35.8% vs 69.6%; p<0.0001). In a univariate analysis, IDC-P (p<0.0001), lymph node metastases (p=0.0022), Gleason score (p<0.0001), seminal vesicle invasion (p<0.0001), extraprostatic extension (p<0.0001), surgical margin (p<0.0001) and total cancer volume (p<0.0001) were significantly associated with the biochemical progression-free survival. In a multivariate analysis, Gleason score (p<0.0001), IDC-P (p=0.0002), seminal vesicle invasion (p=0.0011), extraprostatic extension (p=0.0012), surgical margin (p=0.0019) and lymph node metastases (p=0.0402) were significantly associated with biochemical progression-free survival. (Conclusions) The presence of IDC-P is an independent factor of biochemical recurrence in prostate cancer patients treated with radical prostatectomy. We therefore recommend that the presence of IDC-P in radical prostatectomy specimens be reported.

A case of metastatic renal cell carcinoma and bile duct carcinoma treated with a combination of sunitinib and gemcitabine.

BACKGROUND: Metastatic renal cell carcinoma (mRCC) had been a chemo-refractory disease, but recent advances in multiple kinase inhibitors such as sunitinib have dramatically changed the clinical course of mRCC. Sunitinib is used for mRCC chemotherapy based on the favorable results of a recent clinical trial, but specific biomarkers predicting efficacy and safety are not yet available. Locally advanced bile duct carcinoma (BDC) has generally been treated with single agent gemcitabine or as doublet therapy with cisplatin. Concomitant occurrence of mRCC and BDC is extremely rare, and a standard therapeutic strategy has not been established. CASE PRESENTATION: A 65-year-old woman was diagnosed as having multiple mRCC and intercurrent, locally advanced BDC. A single course of combination therapy with sunitinib (25 mg/day, day2-15) and gemcitabine (750 mg/m(2), days 1, 8) was administered, and this showed obvious effects, with partial response for mRCC and stable disease for BDC. However, the patient also experienced severe adverse events, including hematological and various non-hematological toxicities; the combination therapy was then terminated on day 13 after its initiation. She recovered on day 28 and is alive 3.5 years after the diagnosis. The plasma trough levels of sunitinib and its active metabolite SU12662 on day 13 were 91.5 ng/mL and 19.2 ng/mL, respectively, which were relatively higher than in previous reports. Analysis of her single nucleotide polymorphisms (SNPs) detected TC in ABCB1 3435C/T, TC in 1236C/T and TT in 2677G/T, suggesting a possible TTT haplotype. CONCLUSION: A rare case of double cancer of mRCC and BDC was treated by combination chemotherapy. Although unknown synergistic mechanisms of these agents may be involved, severe toxicities might be possibly associated with high sunitinib exposure. Further exploration of combination therapy with sunitinib and gemcitabine is required.

[Significance of the antimicrobial drug used to prevent febrile infection following prostate needle biopsy].

The rate of incidence of febrile infection and the antimicrobial drug used at the time of prostate needle biopsy was examined retrospectively. SPFX (sparfloxacin) 400 mg (January 2007 to March 2010) and LVFX (levofloxacin) 500 mg (April 2010, onward) were administered prophylactically in 1,034 patients undergoing transrectal or transperineal prostate biopsy. One febrile infection occurred and resolved in each group. A single dose of LVFX 500 mg before the procedure effectively prevented febrile infection in both transrectal and transperineal prostate needle biopsy.

[Distribution of intraductal carcinoma of the prostate and associated lesions in the cancer foci on radical prostatectomy specimens].

OBJECTIVE: The distribution of intraductal carcinoma of the prostate (IDC-P) and other intraductal lesions associated with IDC-P was evaluated in the cancer foci on radical prostatectomy specimens. MATERIALS AND METHODS: We reviewed slide in 412 cases treated by radical prostatectomy without neoadjuvant therapy. Mapping study was performed with regard to IDC-P, other intraductal lesions associated with IDC-P and invasive carcinoma. RESULTS: We identified 98 cases (23.8%) and 102 cancer foci associated with IDC-P. In these all cancer foci, IDC-P was associated with invasive carcinoma and other intraductal neoplastic lesions with tufting, micropapillary and loose cribriform patterns were contiguous and admixed with IDC-P in 83 cancer foci (81.4%). There were lesions with invasive carcinoma around the IDC-P in 95 cancer foci (93.1%) and lesions without invasive carcinoma around IDC-P in 66 foci (64.7%). The latter lesions existed in the marginal areas of the cancer foci in 63 (61.8%) and in the central areas of the cancer foci in 14 (13.7%). In 5 cancer foci (4.9%), volume of IDC-P was larger than that of invasive carcinoma. CONCLUSIONS: The distribution of IDC-P with dense cribriform and solid patterns varied in cancer foci, and intraductal lesions with tufting, micropapillary and loose cribriform patterns were frequently seen in area contiguous and admixed with IDC-P. The latter lesion may be low grade morphology of IDC-P, although the lesions could not be distinguished from high grade prostatic intraepithelial neoplasia.

Early Phase Persistent Changes in the White Blood Cell Fraction in Patients With Advanced Urothelial Carcinoma Treated With Pembrolizumab: A Multicenter Retrospective Study.

BACKGROUND/AIM: The association of clinical outcomes with posttreatment persistent changes in eosinophils and other white blood cell (WBC) subtypes in patients with advanced urothelial cancer (UC) treated with pembrolizumab after the failure of platinum-based chemotherapy is unclear. PATIENTS AND METHODS: We retrospectively analyzed 87 patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy. The changes in WBC subtypes from pretreatment were evaluated three and six weeks after pembrolizumab administration. The association between the changes in the WBC subtypes and clinical outcomes was then evaluated using the Kaplan-Meier method and a Cox regression model. RESULTS: Among WBC subtypes, significant changes in the absolute (AEC) and relative eosinophil count (REC) and the neutrophil-to-eosinophil ratio (NER) were observed at three and six weeks compared with pretreatment (p<0.001). Multivariable Cox regression analyses revealed that a persistent decrease in AEC and REC and a persistent increase in NER were associated with poor overall survival. CONCLUSION: Persistent increase in AEC and REC and decrease in NER in the early phase after pembrolizumab may be significant early predictive markers of improved clinical outcomes in patients with advanced UC receiving pembrolizumab.

External Validation of a Prognostic Model Predicting Metastatic Castration-Resistant Prostate Cancer Survival in Patients Receiving Post-Docetaxel Second-Line Chemotherapy.

Introduction: The Halabi model predicts the overall survival (OS) of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with second-line therapy after docetaxel. We aimed to validate this model externally with an independent cohort, outside the setting of a clinical trial. Methods: In a multi-institutional study, we included 66 patients treated with cabazitaxel after docetaxel for mCRPC. Patients were stratified according to the two- and three-risk groups of the Halabi nomogram. Kaplan-Meier and Cox proportional hazard analyses were performed to estimate survival and hazard ratios (HRs). The model performance was assessed using receiver operating characteristic curves, and the associated c-index (area under the curve [AUC]). Results: The median OS in the two-risk groups was 5.06 months in the high-risk group (n=22) and 12.9 months in the low-risk group (n=44, p<0.001). High-risk patients had an HR of 9.50 (95% confidence interval (CI) 4.12-21.6, p<0.001) compared to low-risk patients. For the three-risk groups, the median OS was 6.44 months in the high-risk group (n=15), 5.75 months in the intermediate-risk group (n=11), and 13.7 months in the low-risk group (n=40, p=0.84). Compared to low-risk patients, intermediate-risk patients had an HR of 7.49 (95% CI 3.08-20.4, p<0.001), and high-risk patients had an HR of 8.48 (95% CI, 3.39-21.7, p<0.001). The AUC was 0.72 (95% CI 0.64-0.76) for the two-risk stratification. When comparing different risks, the AUCs were 0.48 (high vs intermediate), 0.66 (high vs low), and 0.65 (intermediate vs low). Conclusions: The two-risk stratification version but not the three-risk group analysis confirmed the ability of the model to predict survival. These results support the value of the Halabi nomogram in men receiving post-docetaxel second-line chemotherapy for mCRPC.

Efficacy of Pembrolizumab in Patients With Variant Urothelial Carcinoma: A Multicenter Retrospective Study.

INTRODUCTION: Although variant urothelial carcinoma (VUC, defined here as urothelial carcinoma with any histological variant) is a clinically aggressive disease, the efficacy of pembrolizumab against VUC is not well characterized. This study assessed the therapeutic response and survival outcomes in patients with advanced VUC treated with pembrolizumab for unresectable recurrent or metastatic disease. PATIENTS AND METHODS: We retrospectively evaluated 103 patients with advanced bladder and upper urinary tract cancer who received pembrolizumab after failure of platinum-based chemotherapy at 6 institutions between January 2018 and June 2021. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with VUC. RESULTS: We identified 81 and 22 patients with PUC and VUC, respectively. Squamous differentiation (n = 14) was the most common variant element, followed by glandular differentiation (n = 3) and micropapillary variant (n = 3). Baseline characteristics were comparable between the groups. Patients with VUC showed significantly better ORR (59.1% vs. 29.6%, P = .014) and comparable DCR (68.2% vs. 49.4%, P = .150) compared to those with PUC. There were no significant differences between the PUC and VUC groups with respect to PFS (median 5.0 months vs. 10.4 months, P = .222) or OS (median 13.5 months vs. 23.8 months, P = .497). CONCLUSION: Response of VUC to pembrolizumab was not inferior to that of PUC in patients with advanced-stage bladder and upper urinary tract cancer.

Association Between Immune-Related Adverse Events and Efficacy and Changes in the Relative Eosinophil Count Among Patients with Advanced Urothelial Carcinoma Treated by Pembrolizumab.

Background: To evaluate the association between immune-related adverse events (irAEs) and the clinical outcomes and also between irAEs and the post-treatment changes in the relative eosinophil count (REC) in advanced urothelial carcinoma (UC) patients treated with pembrolizumab. Materials and Methods: This retrospective study analyzed 105 advanced UC patients treated with pembrolizumab after disease progression on platinum-based chemotherapy between January 2018 and June 2021. The association between the occurrence of irAEs and the efficacy of pembrolizumab was investigated. The change in the REC from before the initiation of pembrolizumab therapy, to three weeks after treatment and the incidence of irAEs were determined. Results: Overall irAEs were associated with a significantly higher objective response rate (ORR) (58.8% vs 25.4%, P<0.001), a longer progression-free survival (PFS) (25.1 months vs 3.1 months, P< 0.001) and overall survival (OS) (31.2 months vs 11.5 months, P< 0.001) compared to patients without irAEs; however, grade ≥3 irAEs were not associated with the ORR (36.4% vs 36.2%, P=0.989), PFS (9.5 vs 5.5 months, P=0.249), or OS (not reached vs 13.7 months, P=0.335). Compared to a decreased REC at 3 weeks after pembrolizumab, an increased relative REC at 3 weeks was not associated with the incidence of any-grade irAEs (32.3% vs 32.5%, P=0.984) or of grade ≥3 irAEs (10.8% vs 10.0%, P=0.900). Multivariate analyses revealed a female sex (P=0.005), Eastern Cooperative Oncology Group Performance Status ≥1 (P=0.024), albumin <3.7 g/dl (P<0.001), decreased REC (3 weeks later) (P<0.001), and the absence of irAEs of any grade (P=0.002) to be independently associated with a worse OS. Conclusion: Patients with irAEs showed a significantly better survival compared to patients without irAEs in advanced UC treated with pembrolizumab. An increased posttreatment REC may be a marker predicting improved clinical outcomes and it had no significant relationship with the incidence of irAEs.

The Eosinophil Changes, Efficacy and Safety of Pembrolizumab in Advanced Urothelial Carcinoma Patients with an Older Age and a Poor Performance Status.

Background: To evaluate the eosinophil changes, efficacy and safety of pembrolizumab treatment in advanced urothelial carcinoma patients of older age and those with a poor performance status (PS). Materials and Methods: Consecutive patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy between January 2018 and June 2021 were retrospectively examined. Results: 105 patients (median age, 72 years), 71.4% of whom were men, were enrolled. Patients of ≥75 years of age were considered to be older patients (n=40), and patients with PS ≥2 were considered to have a poor PS (n=10). The objective response and disease control rates were 42.5% and 52.5%, respectively, in older patients and 0% and 10.0%, respectively, in patients with a poor PS. Overall survival (OS) in the older and younger groups did not differ to a statistically significant extent. However, a poor PS was significantly associated with poor survival. Safety analyses demonstrated no significant difference in the occurrence of any immune-related adverse events (irAEs), including grade ≥3, between the older and younger groups. However, a poor PS was significantly associated with the low occurrence of any irAEs. The change of the eosinophil count, the increase of the relative eosinophil count (REC) and the decrease of the neutrophil-to-eosinophil ratio (NER) did not differ to a statistically significant extent between the older and younger groups, but showed significant differences between the poor and good PS (PS 0-1) groups. Conclusion: Pembrolizumab for advanced UC demonstrated similar changes in the eosinophil count, efficacy and toxicity in both older and younger patients. In patients with a poor PS, although toxicity was significantly lower, survival was significantly worse, and neither an increase in REC nor a decrease in NER were observed, but these values showed significant changes in patients with a good PS.

Serum IgG4 Concentration Is a Potential Predictive Biomarker in Glucocorticoid Treatment for Idiopathic Retroperitoneal Fibrosis.

OBJECTIVES: To evaluate the management and outcome of idiopathic retroperitoneal fibrosis (iRPF) in Japan, and to identify its clinical biomarker. METHODS: We retrospectively analyzed 129 patients with iRPF treated between January 2008 and May 2018 at 12 university and related hospitals. Patients treated with glucocorticoid were analyzed to identify a predictive biomarker. These patients were classified into three groups according to overall effectiveness (no change: NC, complete response: CR, and partial response groups: PR), and each parameter was compared statistically. RESULTS: Male-female ratio was 5:1, and median age at diagnosis was 69 (33-86) years. Smoking history was reported in 59.6% of the patients. As treatment, 95 patients received glucocorticoid therapy with an overall response rate of 84%. As a result, serum concentration of IgG4 was significantly decreased in NC group compared with the other two groups (56.6 mg/dL vs. 255 mg/dL, 206 mg/dL, p = 0.0059 and 0.0078). ROC analysis was performed between the nonresponder (NC) and responder groups (CR + PR) to identify the cut-off value of serum IgG4 as a predictive marker. As a result, AUC of 0.793 was confirmed. CONCLUSIONS: Pre-treatment serum IgG4 concentration may have potential as a predictive biomarker of steroid treatment.

[Clinical outcome in prostate cancer patients undergoing high-dose-rate brachytherapy with external beam radiotherapy in our institute].

OBJECTIVES: We investigate the biochemical control rates and adverse events for local and locally advanced prostate cancer patients undergoing high-dose-rate brachytherapy with external beam radiotherapy (EBRT + HDR-BT) in our institute. PATIENTS AND METHODS: From May 2004 through March 2010, 154 patients with local and locally advanced prostate cancer underwent EBRT + HDR-BT. One hundred thirteen patients with more than 6 months follow-up were evaluated. A median follow-up was 33 months. The patients consisted of 12 low-, 65 intermediate- and 36 high-risk patients. No patients received adjuvant androgen deprivation therapy with EBRT + HDR-BT. Biochemical freedom from failure (bFFF) was determined using the Phoenix definition. RESULTS: The 5-year bFFF rate was 100%, 94.7%, and 59.2% for low-, intermediate- and high-risk patients. The 58-month bFFF rate of high-risk patients with one ominous factor was significantly lower than that of high-risk patients with more than ominous two factors (87.4% vs 26.9%, p = 0.022). With respect to acute adverse events, transurethral electric coagulation was performed for vesical bleeding and tamponade after removal of applicator needles in only one patient. Regarding late adverse events 14.2% of patients had grade 3 genitourinary toxicity, mostly consisted of urethral stricture and 0.9% of patients had grade 3 gastrointestinal toxicity. CONCLUSIONS: EBRT + HDR-BT without adjuvant androgen deprivation therapy yields excellent bFFF in low- and intermediate-risk prostate cancer patients. However, to challenge higher bFFF rate in a part of high-risk patients and lower rate of adverse events, modified designing protocols and therapeutic plannning of EBRT + HDR-BT may be necessary.

Clinical Outcomes of Mixed Response to Pembrolizumab in Advanced Urothelial Carcinoma After Platinum-based Chemotherapy.

BACKGROUND/AIM: Despite the presence of a mixed response (MR) in patients with urothelial carcinoma (UC) who receive immune checkpoint inhibitors, the clinical outcome of these patient has not been reported. We evaluated the clinical outcome of MR to pembrolizumab for advanced UC. PATIENTS AND METHODS: Advanced UC patients who received pembrolizumab after platinum-based chemotherapy failure with measurable disease in multiple organs were retrospectively analyzed. RESULTS: Among 31 patients, MR [including progressive disease (PD)+complete response (CR) or partial response (PR)] was confirmed in 4 (12.9%). The median overall survival (OS) of the CR+PR (including CR+SD±PR), stable disease (SD), PD (including PD±SD) and MR groups was 16.0, 5.1, 5.4 and 4.3 months, respectively. There was no significant difference in the OS between the MR and CR+PR response groups (log-rank test, p=0.069). CONCLUSION: A mixed response to pembrolizumab in advanced UC was not uncommon. Despite the non-significant difference in the OS between the mixed and CR+PR response groups, the OS of the MR group tended to be similar to that of the SD and PD response groups.

Efficacy and safety of cabazitaxel therapy in elderly (≥75 years) patients with castration-resistant prostate cancer: A multiinstitutional study.

BACKGROUND: There is little data on the outcome of cabazitaxel (CBZ) treatment of elderly patients with castration-resistant prostate cancer (CRPC). This study assessed the efficacy and safety of CBZ chemotherapy in patients with CRPC aged 75 years or older in a multiinstitutional study. METHODS: We retrospectively reviewed the 74 patients with CRPC treated with CBZ enrolled in 10 institutions. Clinicopathological backgrounds, prognosis including prostate-specific antigen decline, time to treatment failure, progression-free survival, overall survival, and safety profiles were compared between younger (<75 years) and elder (≥75 years) patients. RESULTS: In total, 74 patients were enrolled; 50 patients were younger than 75 years and 24 were ≥75 years. Clinicopathological characteristics were comparable between younger and elder patients, with the exception of serum albumin values at the time of CBZ treatment. The median prostate-specific antigen decline in younger and elder men was -8.8% and -32.3% from baseline, respectively. The median time to treatment failure, progression-free survival, and overall survival for younger and elder men were 0.24 and 0.33 years, 0.23 and 0.43 years, and 0.69 and 1.17 years, respectively. In addition, safety profiles were comparable between younger and elder patients. CONCLUSIONS: This multiinstitutional study suggests that patients with CRPC aged 75 years or older eligible for CBZ treatment can be treated safely and with noninferior efficacy compared with those younger than 75 years.

Organ-Specific Tumor Response to Pembrolizumab in Advanced Urothelial Carcinoma After Platinum-Based Chemotherapy.

BACKGROUND: To evaluate the organ-specific therapeutic effect of pembrolizumab after the failure of platinum-based chemotherapy for advanced urothelial carcinoma (UC). MATERIALS AND METHODS: Patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy and who had measurable disease were retrospectively analyzed. The objective response rate (ORR) and organ-specific response rate (OSRR) were evaluated according to Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: We analyzed 69 patients (male, n=51; median age, 71 years) with 226 metastases. The ORR was 23.2%. In total, 32, 31, 16, 14, 13 and 7 patients had measurable lung (OSSR 31.3%), lymph node (OSSR 29.0%), local recurrence (OSSR 12.5%), primary tumor organ (OSSR 7.1%), liver (OSSR 23.1%) and bone (OSSR 28.6%) disease, respectively. The median overall survival (OS) for pembrolizumab was 10.9 months (95% confidence interval, 5.9­13.7 months). Regarding organ-specific OS, a Log rank test significant differences in OS were confirmed between patients with and without primary tumor organ disease (p=0.046) and liver metastasis (p<0.001). CONCLUSION: Metastases and primary tumor organ disease showed different tumor responses to pembrolizumab. The most prominent tumor response was found in lung metastasis and the least response was found in primary organ sites. The mechanisms of these different responses were unclear and there does not appear to be a constant trend between tumor shrinkage and OS in tumor sites. Further studies are needed.

The Association of Clinical Outcomes with Posttreatment Changes in the Relative Eosinophil Counts and Neutrophil-to-Eosinophil Ratio in Patients with Advanced Urothelial Carcinoma Treated with Pembrolizumab.

BACKGROUND: To evaluate the association of clinical outcomes with posttreatment changes in the relative eosinophil count (REC) and neutrophil-to-eosinophil ratio (NER) in patients with advanced urothelial cancer (UC) treated with pembrolizumab. MATERIALS AND METHODS: We retrospectively analyzed 105 patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy. The REC and NER before and three weeks after pembrolizumab were recorded. A receiver operating characteristic curve was used to determine the optimal cut-off values for analyzing the risk. RESULTS: There were no significant differences in the overall survival (OS) between the REC ≥4.8% and <4.8% groups and the NER ≥13.7 and <13.7 groups before pembrolizumab (p=0.997 and 0.669, respectively). However, a significant difference in the OS was confirmed between the increased and decreased REC groups and between the decreased and increased NER groups at 3 weeks after pembrolizumab (p<0.001 and 0.002, respectively). Multivariate analyses revealed that an Eastern Cooperative Oncology Group Performance Status ≥2 (P=0.003), albumin <3.7 g/dl (p=0.002), LDH >246 U/L (p=0.011), disease site ≥3 organs (p=0.019), decreased posttreatment REC (3 weeks later) (p=0.002) and increased posttreatment NER (3 weeks later) (p=0.022) were independent prognostic factors for a worse OS. CONCLUSION: An increased REC and decreased NER after pembrolizumab may be significant early predictive markers of improved clinical outcomes in patients with advanced UC receiving pembrolizumab.

[High-dose-rate brachytherapy with external beam radiotherapy for localized or locally advanced prostate cancer].

PURPOSE: To evaluate the therapeutic outcomes and late toxicities in patients treated by high-dose-rate brachytherapy (HDR-BT) with external beam radiotherapy (EBRT) for localized or locally advanced prostate cancer. MATERIALS AND METHODS: From May 2004 to September 2008, 86 men were treated by HDR-BT with EBRT for localized or locally advanced prostate cancer at the National Hospital Organization Kyushu Medical center. The median EBRT and HDR-BT doses were 40 Gy and 30 Gy, respectively. RESULT: With a median follow-up of 24 months, the 3-year overall, disease specific, and biochemical relapse-free survival rates in all patients were 97.3%, 100%, and 83.6% respectively. The 3-year biochemical relapse-free survival rate of the patients categorized to low or intermediate risk group (91.8%) was significantly better than that of the patients categorized to the high risk group (74.3%) (p = 0.042). There was no significant difference of biochemical relapse-free survival regarding to the other clinical factors (age, T-stage, Gleason score, initial prostate-specific antigen level, neoadjuvant hormone therapy, and total dose of EBRT and HDR-BT). Late Grade2 and Grade3 gastrointestinal toxicities were observed in 8 patients (9.3%) and 2 patients (2.3%), respectively. Late Grade2 genitourinary toxicities were observed in 12 patients (13.9%). There was no patient suffered from late Grade3 or greater genitourinary toxicities. CONCLUSION: HDR-BT with EBRT can be safe and effective for localized or locally advanced prostate cancer.

Prognostic Impact of Prior Androgen Receptor Axis-targeting Agents in Cabazitaxel Chemotherapy After Docetaxel.

BACKGROUND/AIM: The novel taxane cabazitaxel has been shown to exert excellent anticancer effects after androgen receptor axis-targeting (ARAT) agents in clinical data, but not in in vitro data. We investigated the clinical outcome of cabazitaxel chemotherapy after docetaxel according to use of ARAT agents. PATIENTS AND METHODS: Prostate specific antigen (PSA) response, progression-free survival, and overall survival were compared between cases with and without prior use of ARAT agents in 74 Japanese patients with metastatic castration-resistant prostate cancer treated with cabazitaxel chemotherapy. RESULTS: Background characteristics were comparable between patients with and without prior use of ARAT agents. PSA response, progression-free survival, and overall survival in cabazitaxel chemotherapy were comparable between patients with and without prior use of ARAT agents. CONCLUSION: No detrimental effects of prior ARAT agents on clinical outcome were observed for cabazitaxel chemotherapy in the post-docetaxel setting, suggesting that cabazitaxel can be expected to remain active even after ARAT agent therapy.

Efficacy and safety of cabazitaxel for castration-resistant prostate cancer in patients with > 10 cycles of docetaxel chemotherapy: a multi-institutional study.

This multi-institutional study aimed to investigate the efficacy and safety profiles of cabazitaxel after prior docetaxel chemotherapy in patients with castration-resistant prostate cancer (CRPC). This study included 63 Japanese patients with CRPC who were treated with cabazitaxel from 2014 to 2017. The oncological outcomes and adverse events (AEs) were documented, and prognostic factors for oncological outcomes and predictive factors for AEs were analysed. PSA decline was observed in 68.3% of patients, including 25.4% who achieved a ≥ 50% decline. The median progression-free survival, treatment failure-free survival, and overall survival were 4.3, 4.1, and 9.0 months, respectively. More cycles of prior docetaxel therapy was identified as common favourable prognostic factors for progression-free survival, treatment failure-free survival, and overall survival. Severe neutropenia, febrile neutropenia, and severe non-haematological AEs were observed in 73.0%, 33.3%, and 23.8% of patients, respectively. However, > 10 cycles of docetaxel was not associated with increased incidence of AEs. In conclusion, cabazitaxel chemotherapy was still active in Japanese CRPC patients treated with > 10 cycles of docetaxel chemotherapy, with an acceptable risk of AE burden. Treatment with cabazitaxel after > 10 cycles of docetaxel may be an appropriate option when it can be administered.