Bone scan index (BSI) scoring by using bone scintigraphy and circulating tumor cells (CTCs): predictive factors for enzalutamide effectiveness in patients with castration-resistant prostate cancer and bone metastases.

Reports of Bone Scan Index (BSI) calculations as imaging biomarkers to predict survival in patients with metastatic castration-resistant prostate cancer (mCRPC) have been mainly from retrospective studies. To evaluate the effectiveness of enzalutamide (ENZ) in Japanese patients with mCRPC and bone metastases using BSI (bone scintigraphy) and circulating tumor cell (CTC) analysis. Prospective, single-arm study at Juntendo University affiliated hospitals, Japan. Patients were administered 160 mg ENZ daily, with 3 monthly assessments: BSI, prostate specific antigen (PSA), CTC and androgen receptor splicing variant-7 (AR-V7) status. Primary endpoint: BSI-decreasing rate after ENZ treatment. Secondary endpoints: PSA-decreasing rate and progression free survival (PFS). Statistical analyses included the Wilcoxon t-test, Cox proportional hazard regression analysis, and log-rank test. Median observation period: 17.9 months, and median PFS: 13.8 (2.0-43.9) months (n = 90 patients). A decrease in BSI compared to baseline as best BSI change on ENZ treatment was evident in 69% patients at the end of the observation period (29% patients showed a complete response, BSI 0.00). At 3 months 67% patients showed a ≥ 50% PSA reduction, and 70% after ENZ treatment. PSA decline (3 months) significantly associated with a prolonged median PFS: 18.0 (estimated) versus 6.4 months (HR 2.977 [95% CI 1.53-5.78], p = 0.001). Best BSI decline response significantly associated with a prolonged PFS: 18.1(estimated) versus 7.8 months (HR 2.045 [95% CI: 1.07-3.90], p = 0.029). CTC negative status (n = 20) significantly associated with a prolonged PFS: 13.4 [estimated] vs 8.6 months (HR 2.366, 95% CI 0.97-5.71, p = 0.041). CTC positive/AR-V7 positive status significantly associated with a shorter PFS: 5.9 months (HR 8.56, 95% CI 2.40-30.43, p = 0.0087). -reduction (3 months) and BSI-reduction (on ENZ treatment) were significant response biomarkers, and a negative CTC status was a predictive factor for ENZ efficacy in patients with mCRPC.

Prediction of recovery time of urinary incontinence following robot-assisted laparoscopic prostatectomy.

OBJECTIVES: Postoperative urinary incontinence recovery following robot-assisted laparoscopic prostatectomy is an important outcome. We investigated whether factors that affect urinary incontinence can predict the duration of postoperative incontinence recovery. METHODS: A total of 310 patients underwent robot-assisted laparoscopic prostatectomy. Continence recovery was defined as either pad-free or a safety pad only status. Univariate and multivariate analyses were performed on clinical variables to identify those that were associated with continence recovery. A scoring system to predict recovered continence was constructed using statistically significant variables. The validity of this tool was tested in a new cohort of 273 patients. RESULTS: Factors associated with recovery of urinary incontinence were membranous urethral length, preservation of bilateral neurovascular bundles, and a preoperative Prostate Imaging Reporting and Data System score of ≥3 in the apex. Age was related only to incontinence recovery at 1 month. To prepare the score, weighting was performed using the estimated values. Using the developed scoring system, participants in the verification set were divided into three groups. The early recovery group had a median incontinence recovery of 4 (4-12) weeks, the medium recovery group, 12 (4-24) weeks, and the late recovery group, 24 (24-48) weeks, which was a significant difference (p < 0.001). CONCLUSIONS: The applied scoring system based on preoperative factors related to incontinence and derived from patient groups was significantly associated with continence recovery time. In patients undergoing robot-assisted laparoscopic prostatectomy, our unit-weighted regression model of clinical variables can predict the duration of continence recovery.

Prostate-specific membrane antigen in circulating tumor cells is a new poor prognostic marker for castration-resistant prostate cancer.

The aim of this study is to elucidate the clinical significance of prostate-specific membrane antigen (PSMA) expression in circulating tumor cells (CTCs) from castration-resistant prostate cancer (CRPC) patients. We analyzed a total of 203 CTC samples from 79 CRPC patients to investigate the proportion of positive mRNA expressions at different treatment phases. Among them, we elected to focus on specimens from 56 CRPC patients who progressed on therapy and were subsequently provided a new treatment (treatment-switch cohort). In this cohort, we investigated the association between PSMA expression in CTCs and treatment response. CTCs were detected in 55/79 patients and median serum PSA in CTC-positive patients was 67.0 ng/ml. In the treatment-switch cohort of 56 patients, 20 patients were positive for PSMA in CTCs. PSMA expression was inversely associated with percentage of change in prostate-specific antigen (PSA). The median PSA progression-free survival and overall survival were significantly shorter in the PSMA-positive cohort. Furthermore, PSMA expression was predictive of poorer treatment response, shorter PSA progression-free survival and overall survival. PSMA expression in circulating tumor cells may be a novel poor prognostic marker for CRPC.

Consequences of Different Corticosteroids on Serum Potassium and Prostate-Specific Antigen in Patients Receiving Abiraterone for Castration-Resistant Prostate Cancer: A Retrospective Observational Study.

BACKGROUND: Abiraterone acetate is an androgen synthesis inhibitor approved for the treatment of castration-resistant prostate cancer (CRPC). Although co-administration of either prednisone or prednisolone at 10 mg/d has been recommended to reduce the risk of abiraterone-induced hyperaldosteronism (notably hypokalemia) and to give adjunctive pain relief effects, whether these glucocorticoids can be substituted by dexamethasone remains unknown. METHODS: We performed a retrospective review of medical records of patients who were given abiraterone for the treatment of CRPC with either prednisolone (ABI/PSL) 10 mg/d or dexamethasone (ABI/DEX) 0.5 or 1 mg/d between 2014 and 2017 in Juntendo University Nerima Hospital. Demographic and biochemical data including prostate-specific antigen (PSA) level were retrieved from the electronic medical records. RESULTS: Fifty-three eligible patients (27 in ABI/PSL group and 26 in ABI/DEX group) were extracted from the records. Both groups showed no significant changes in serum potassium level before and after starting treatment. In the ABI/PSL group, 12 patients (46%) showed elevations of PSA and 7 patients (27%) discontinued treatment within 3 months. In contrast, in the ABI/DEX group, only 6 patients (25%) showed elevations of PSA and 3 patients (13%, all were given dexamethasone 1 mg/d) discontinued treatment. CONCLUSIONS: Dexamethasone and prednisolone may be equally effective in preventing abiraterone-induced hypokalemia.

Effectiveness of platinum-based adjuvant chemotherapy for muscle-invasive bladder cancer: A weighted propensity score analysis.

OBJECTIVES: To evaluate the clinical benefit of adjuvant platinum-based chemotherapy after radical cystectomy for muscle-invasive bladder cancer in routine clinical practice. METHODS: The present observational study was carried out to compare the effectiveness of adjuvant chemotherapy versus observation post-radical cystectomy in patients with clinically muscle-invasive bladder cancer. Cancer-specific survival and overall survival between the adjuvant chemotherapy group and radical cystectomy alone group were compared using Kaplan-Meier method and log-rank test. After adjusting for background factors using propensity score weighting, differences in cancer-specific survival and overall survival between these two groups were compared. Subgroup analyses by the pathological characteristics were carried out. RESULTS: In total, 322 patients were included in the present study. Of these, 23% received adjuvant chemotherapy post-radical cystectomy. Clinicopathological characteristics showed that patients in the adjuvant chemotherapy group were pathologically more advanced and were at higher risk than the radical cystectomy alone group. In the unadjusted population, although it is not significant, the adjuvant chemotherapy group had lower overall survival (3-year overall survival; 61.5% vs 73.6%, HR 1.33, P = 0.243, log-rank test, adjuvant chemotherapy vs radical cystectomy alone). In the weighted propensity score analysis, although it is not significant, the adjuvant chemotherapy group were superior to radical cystectomy alone groups (overall survival: HR 0.65, 95% CI 0.39-1.09, P = 0.099, log-rank test, adjuvant chemotherapy vs radical cystectomy alone). Subgroup analyses showed that adjuvant chemotherapy significantly reduced the hazard ratio of overall survival and cancer-specific survival in the ≥pT3, pN+, ly+ and v+ subgroups. CONCLUSIONS: Platinum-based adjuvant chemotherapy might be associated with increased cancer-specific survival and overall survival in patients with high-risk invasive bladder cancer.

Development and Validation of a Novel Recurrence Risk Stratification for Initial Non-muscle Invasive Bladder Cancer in Asia.

BACKGROUND: Some risk classifications to determine prognosis of patients with non-muscle invasive bladder cancer (NMIBC) have disadvantages in the clinical setting. We investigated whether the EORTC (European Organization for Research and Treatment of Cancer) risk stratification is useful to predict recurrence and progression in Japanese patients with NMIBC. In addition, we developed and validated a novel, and simple risk classification of recurrence. METHODS: The analysis was based on 1085 patients with NMIBC at six hospitals. Excluding recurrent cases, we included 856 patients with initial NMIBC for the analysis. The Kaplan-Meier method with the log-rank test were used to calculate recurrence-free survival (RFS) rate and progression-free survival (PFS) rate according to the EORTC risk classifications. We developed a novel risk classification system for recurrence in NMIBC patients using the independent recurrence prognostic factors based on Cox proportional hazards regression analysis. External validation was done on an external data set of 641 patients from Kyorin University Hospital. FINDINGS: There were no significant differences in RFS and PFS rates between the groups according to EORTC risk classification. We constructed a novel risk model predicting recurrence that classified patients into three groups using four independent prognostic factors to predict tumour recurrence based on Cox proportional hazards regression analysis. According to the novel recurrence risk classification, there was a significant difference in 5-year RFS rate between the low (68.4%), intermediate (45.8%) and high (33.7%) risk groups (P<0.001). INTERPRETATION: As the EORTC risk group stratification may not be applicable to Asian patients with NMIBC, our novel classification model can be a simple and useful prognostic tool to stratify recurrence risk in patients with NMIBC. FUNDING: None.

Analysis of prostate cancer localization toward improved diagnostic accuracy of transperineal prostate biopsy.

PURPOSE: Delineating the precise localization of prostate cancer is important in improving the diagnostic accuracy of prostate biopsy. METHODS: In Juntendo University Nerima Hospital, initial 12-core or repeat 16-core biopsies were performed using a transrectal ultrasound guided transperineal prostate biopsy method. We step-sectioned prostates from radical prostatectomy specimens at 5-mm intervals from the urethra to the urinary bladder and designated five regions: the (1) Apex, (2) Apex-Mid, (3) Mid, (4) Mid-Base, and (5) Base. We then mapped prostate cancer localization on eight zones around the urethra for each of those regions. RESULTS: Prostate cancer was detected in 93 cases of 121 cases (76.9%) in the Apex, in 115 cases (95.0%) in the Apex-Mid, in 101 cases (83.5%) in the Mid, in 71 cases (58.7%) in the Mid-Base, and in 23 cases (19.0%) in the Base. In 99.2% of all cases, prostate cancers were detected from the Apex to Mid regions. For this reason, transperineal prostate biopsies have routinely been prioritized in the Apex, Apex-Mid, and Mid regions, while the Base region of the prostate was considered to be of lesser importance. Our analyses of prostate cancer localization revealed a higher rate of cancer in the posterior portion of the Apex, antero-medial and postero-medial portion of the Apex-Mid and antero-medial and postero-lateral portion of the Mid. The transperineal prostate biopsies in our institute performed had a sensitivity of 70.9%, a specificity of 96.6%, a positive predictive value (PPV) of 92.2% and a negative predictive value (NPV) of 85.5%. CONCLUSIONS: The concordance of prostate cancer between prostatectomy specimens and biopsies is comparatively favorable. According to our study, the diagnostic accuracy of transperineal prostate biopsy can be improved in our institute by including the anterior portion of the Apex-Mid and Mid regions in the 12-core biopsy or 16-core biopsy, such that a 4-core biopsy of the anterior portion is included.

[Prostate cancer of unknown primary origin with multiple lymph nodes metastasis; a case report].

A 62-year-old man were referred our hospital complaining of high prostate specific antigen (PSA) value (32.4 ng/ml) in May 2010. Two sets of biopsies preformed previously at another hospital had not detected any cancers in the prostate. In our hospital, prostate biopsies were performed in July 2010 and February 2011, but cancer was not detected in either occasion. In March 2011, his PSA increased up to 126.7 ng/ml, CT scan showed the swelling of left supraclavicular and para-aortic lymph nodes. Biopsy of the supraclavicular lymph node was performed. Pathology revealed poorly differentiated adenocarcinoma with positive immunohistochemistry for PSA, which was suggestive of metastatic prostate cancer. After 1 year of treatment with androgen deprivation therapy, the patient developed castration resistant prostate cancer and have undergone chemotherapy with docetaxel.

[Diffusion-weighted imaging for prostate cancer localization: comparison of apparent diffusion coefficient values in cancerous and non-cancerous tissues, and the Gleason score of the radical prostatectomy specimens].

PURPOSE: We compared magnetic resonance imaging (MRI) with radical prostatectomy specimens to evaluate the diagnostic performance of diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) value for prostate cancer localization. MATERIALS AND METHODS: We performed a retrospective study of 44 patients who underwent radical prostatectomy. We compared MRI with pathological specimens (74 tumors) to evaluate their diagnostic performance of cancer localization. The ADC value was measured in cancerous and non-cancerous prostate tissues. RESULTS: Of 74 tumors, digital rectal examination, transrectal ultrasonography, T2-weighted imaging (T2WI), DWI, T2WI and DWI detected 9 (12.2%), 9 (12.2%), 26 (35.1%), 30 (40.5%), and 48 (64.9%) tumors, respectively. The mean ADC value was lower in cancerous tissues than in non-cancerous tissues (0.86 +/- 0.15 versus 1.24 +/- 0.16 x 10(-3) mm2/s). The mean ADC values of cancerous and non-cancerous tissues were: 0.85 +/- 0.15 versus 1.28 +/- 0.17 x 10(-3) mm2/s in the peripheral zone; and 0.87 +/- 0.15 versus 1.19 +/- 0.14 x 10(-3) mm2/s in the transition zone. The mean ADC value in patients with a Gleason score of 8 or 9 (0.76 +/- 0.12 x 10(-3) mm2/s) was lower than that in patients with a Gleason score of 6 or 7 (0.86 +/- 0.15 x 10(-3) mm2/s). CONCLUSION: DWI and ADC value were considered to be useful for the diagnosis of prostate cancer localization.

Urothelial carcinoma of the renal pelvis with rhabdoid features.

Reported herein is the case of a 70-year-old man with high grade urothelial carcinoma (UC) with rhabdoid features of the renal pelvis. For the most part, the tumor was composed of pleomorphic, non-cohesive round tumor cells with abundant cytoplasm. In situ high-grade UC composed of cohesive tumor cells was seen only in a small portion. Pleomorphic dyscohesive tumor cells often showed rhabdoid features, containing eosinophilic inclusions. These pleomorphic/rhabdoid tumor cells were immunohistochemically positive for vimentin but negative for cytokeratins, CD45, CD20, CD79a, CD3, CD45RO, CD38, and CD138. Loss of heterozygosity (LOH) analysis demonstrated identical allelic losses as well as additional allelic losses for the dyscohesive and cohesive UC lesion, indicating that these two lesions originated from a single clonal lesion.

Hypoxia-inducible protein 2 (HIG2), a novel diagnostic marker for renal cell carcinoma and potential target for molecular therapy.

To identify molecules to serve as diagnostic markers for renal cell carcinoma (RCC) and as targets for novel therapeutic drugs, we investigated genome-wide expression profiles of RCCs using a cDNA microarray. We subsequently confirmed that hypoxia-inducible protein-2 (HIG2) was expressed exclusively in RCCs and fetal kidney. Induction of HIG2 cDNA into COS7 cells led to secretion of the gene product into culture medium and resulted in enhancement of cell growth. Small interfering RNA effectively inhibited expression of HIG2 in human RCC cells that endogenously expressed high levels of the protein and significantly suppressed cell growth. Moreover, addition of polyclonal anti-HIG2 antibody into culture medium induced apoptosis in RCC-derived cell lines. By binding to an extracellular domain of frizzled homologue 10 (FZD10), HIG2 protein enhanced oncogenic Wnt signaling and its own transcription, suggesting that this product is likely to function as an autocrine growth factor. ELISA analysis of clinical samples identified secretion of HIG2 protein into the plasma of RCC patients even at an early stage of tumor development, whereas it was detected at significantly lower levels in healthy volunteers or patients with chronic glomerulonephritis. The combined evidence suggests that this molecule represents a promising candidate for development of molecular-targeting therapy and could serve as a prominent diagnostic tumor marker for patients with renal carcinomas.

[Primary signet ring cell carcinoma of the bladder: a case report].

A 71-year-old man complained of dyspnea and general fatigue. His blood tests showed severe renal dysfunction. Computed tomographic scan, bone scintigram, and cystoscopy revealed primary signet ring cell carcinoma of the urinary bladder with multiple bone metastases (cT2N0M1). As the general condition of the patient was poor, nephrostomy was performed. He died one month after the diagnosis due to cancer progression. The prognosis of signet ring cell carcinoma of the bladder is poor because many cases presented at an advanced stage. Fifty cases of signet ring cell carcinoma in the urinary bladder reported in Japan are reviewed.