Predictive value of neutrophil-to-lymphocyte ratio in diagnosis of early prostate cancer among men who underwent robotic transperineal prostate biopsy.

ABSTRACT: To evaluate the predicted value of neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of early prostate cancer by using standardized Full blood count (FBC) performed within 4 weeks before biopsy and histology results from transperineal prostate biopsy (RTPB).Patients who underwent RTPB under general anesthesia (GA), at Urology Department, Singapore General Hospital between September 2006 and Febuary 2016 were retrospectively reviewed.NLR was calculated using full blood count (FBC) that was done as a pre-admission test before GA within 4 weeks before the biopsy. Statistical analyses were done to establish the correlation of NLR and different clinical parameters such as biopsy histology, pre-biopsy PSA, and prostate volume.A total of 652 patients who underwent RTPB for diagnostic purposes with a valid PSA level were included in this study. There was total of 409 (62.7%) benign histology and 243 (37.3%) prostate cancer. There was no significant difference in median NLR between the benign and prostate cancer group (2.00 vs 1.99; P = .29).In the subgroups analysis, there was also no significant difference of median NLR value in clinical significant cancer (defined as Gleason 3 + 4 and above) and benign histology group (NLR 2.00 vs 2.01, P = .41), as well as prostate cancer and benign group according to different pre-biopsy PSA levels: PSA (ug/l) < 4, 4 to 10, 10 to 20, and >20, respectively. (Median NLR 1.34 vs 1.76; 1.97 vs 1.97; 1.97 vs 2.18; 2.18 vs 1.98, P > .05). NLR is neither associated with prostate cancer using logestic regression model nor a strong predictor of the Gleason grade group and D'Amico risk stratification group using ordinal regression model. (P > .05)There was no statistically significant difference of NLR between the benign and prostate cancer group as a whole or in the subgroup analyses for patients who underwent robotic transperineal prostate biopsy. NLR may have a limited role in predicting early-stage prostate cancer.

Limitations of overlapping cores in systematic and MRI-US fusion biopsy.

OBJECTIVES: To evaluate the clinically-significant prostate cancer (csCaP) detection rate of systematic (SBx) vs. targeted biopsy (TBx), after accounting for the overlapping systematic cores within the MRI regions of interest. MATERIALS AND METHODS: We identified 398 consecutive men who underwent both transperineal systematic and targeted biopsy between January 2015 to January 2019. We reclassified overlapping systematic cores in the MRI regions of interest as target cores. The detection rates of SBx and TBx were compared using McNemar's test. RESULTS: Detection rate of csCaP (grade group ≥2) was 42% (168/398). Median number of systematic and targeted cores were 23 (IQR 19-29) and 9 (IQR 6-12) respectively. A median of 3 (IQR 2-4) overlapping systematic cores were reclassified as targeted cores. After accounting for overlap, csPC detection rate on SBx decreased from 37% and 21% while the csCaP detection rate of TBx increased from 34% to 39% (both P < 0.001), with TBx having a better detection rate (39% vs. 21%, P < 0.001). A previous negative biopsy was associated with a lower risk of having csCaP on non-targeted SBx (OR 0.27, 95% CI: 0.12 - 0.58, P = 0.001). Only 5% (13/243) of those who had no cancer detected on TBx had csCaP on non-targeted SBx compared to 45% (70/155) of those who had csCaP on TBx (P< 0.001). CONCLUSIONS: The utility of SBx in detecting csCaP decreases after accounting for overlap into the MRI region of interest, especially in men with a prior negative biopsy. Overlapping systematic cores improve the csCaP detection rate on TBx.

External validation and comparison of magnetic resonance imaging-based predictive models for clinically significant prostate cancer.

PURPOSE: Several multiparametric magnetic resonance imaging (mpMRI)-based models have been developed with significant improvements in diagnostic accuracy for clinically significant prostate cancer (csCaP), but lack proper external validation. We therefore sought to externally validate and compare all published mpMRI-based csCaP risk prediction models in an independent Asian population. PATIENTS AND METHODS: A total of 449 men undergoing combined transperineal fusion-targeted/systematic prostate biopsy at our specialist center between 2015 to 2019 were retrospectively analyzed. csCaP was defined as lesions with ISUP (International Society of Urological Pathology) grade group ≥2. The performance of 6 mpMRI-based risk models (MRI-ERSPC-3/4, Distler, Radtke, Mehralivand, van Leeuwen and He) were evaluated in terms of discrimination, calibration and clinical utility, using area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analyses. RESULTS: A total of 202 (45%) subjects were diagnosed with csCaP. All models demonstrated excellent accuracy with AUCs ranging from 0.75 to 0.86, and most significantly outperformed mpMRI PIRADSv2.0 (Prostate Imaging Reporting and Data System version 2.0) alone. The models by Mehralivand and He showed good calibration to our validation population, with respective intercepts of -0.08 and -0.84. All models were nevertheless recalibrated to the csCaP prevalence in our population for analysis. Decision curve analysis showed that above a threshold probability of 10%, all mpMRI-based models demonstrated superior net benefit compared to mpMRI PIRADSv2.0 or a biopsy-all-men strategy. The van Leeuwen model had the greatest net benefit, avoiding 39% of unnecessary biopsies while missing only 4% of csCaP, at a threshold probability of 15%. CONCLUSIONS: The mpMRI-based risk models demonstrate excellent discrimination and clinical utility and are easy to apply in practice, suggesting that individualized risk-based approaches can be considered over mpMRI alone to avoid unnecessary biopsies.

Defining prostate cancer size and treatment margin for focal therapy: does intralesional heterogeneity impact the performance of multiparametric MRI?

OBJECTIVES: To evaluate the impact of intralesional heterogeneity on the performance of multiparametric magnetic resonance imaging (mpMRI) in determining cancer extent and treatment margins for focal therapy (FT) of prostate cancer. PATIENTS AND METHODS: We identified men who underwent primary radical prostatectomy for organ- confined prostate cancer over a 3-year period. Cancer foci on whole-mount histology were marked out, coding low-grade (LG; Gleason 3) and high-grade (HG; Gleason 4-5) components separately. Measurements of entire tumours were grouped according to intralesional proportion of HG cancer: 0%, <50% and ≥50%; the readings were corrected for specimen shrinkage and correlated with matching lesions on mpMRI. Separate measurements were also taken of HG cancer components only, and correlated against entire lesions on mpMRI. Size discrepancies were used to derive the optimal tumour size and treatment margins for FT. RESULTS: There were 122 MRI-detected cancer lesions in 70 men. The mean linear specimen shrinkage was 8.4%. The overall correlation between histology and MRI dimensions was r = 0.79 (P < 0.001). Size correlation was superior for tumours with high burden (≥50%) compared to low burden (<50%) of HG cancer (r = 0.84 vs r = 0.63; P = 0.007). Size underestimation by mpMRI was more likely for larger tumours (51% for >12 mm vs 26% for ≤12 mm) and those containing HG cancer (44%, vs 20% for LG only). Size discrepancy analysis suggests an optimal tumour size of ≤12 mm and treatment margins of 5-6 mm for FT. For tumours ≤12 mm in diameter, applying 5- and 6-mm treatment margins would achieve 98.6% and 100% complete tumour ablation, respectively. For tumours of all sizes, using the same margins would ablate >95% of the HG cancer components. CONCLUSIONS: Multiparametric MRI performance in estimating prostate cancer size, and consequently the treatment margin for FT, is impacted by tumour size and the intralesional heterogeneity of cancer grades.

Prostatic ductal adenocarcinoma variant predicts worse pathological and oncological outcomes: Insight from over 1000 consecutive patients from a large prospective uro-oncology registry.

OBJECTIVE: To evaluate if prostatic ductal adenocarcinoma (PDA) independently predicts poorer pathological and oncological outcomes after radical prostatectomy (RP). METHODS AND MATERIALS: Utilizing a large prospective uro-oncology registry, clinicopathological parameters of 1027 consecutive patients who underwent RP (2008-2017) were recorded. Oncological outcomes were determined by failure to achieve unrecordable PSA postoperatively and biochemical failure (BCF). RESULTS: PDA was present in 79 (7.7%) patients, whereas 948 (92.3%) patients had conventional prostatic acinar adenocarcinoma (PAA). Patients with PDA were older (mean 64.4 vs. 62.8-years old; p = .045), had higher PSA at diagnosis (mean 12.53 vs. 10.80 ng/ml; p = .034), and a higher percentage of positive biopsy cores (mean 39.34 vs. 30.53%; p = .006). Compared to PAA, PDA exhibited a more aggressive tumor biology: (1) Grade groups 4 or 5 (26.6 vs. 9.4%, p < .001), (2) tumor multifocality (89.9 vs. 83.6%; p = .049), and (3) tumor size (mean 2.97 vs. 2.00 cm; p < .001). On multivariate analysis, PDA was independently associated with locally advanced disease (p = .002, hazard ratio [HR]: 2.786, 95% confidence interval [CI]: 1.473-5.263), with a trend towards positive surgical margins (p = .055) and nodal involvement (p = .061). Translating the poorer pathological features to oncological outcomes, presence of PDA independently predicted less likelihood of achieving unrecordable PSA (p = .019, HR: 2.368, 95% CI: 1.152-4.868, and higher BCF (p = .028, HR: 1.918, 95% CI: 1.074-3.423). Subgroup analysis demonstrated that a higher ductal component greater than 15% proportionally predicted worse oncological outcomes, with a shorter time to BCF of 14.3 months compared to 19.8 months in patients with ductal component lesser than 15% (p = .040, HR: 2.660, 95% CI: 1.046-6.757). CONCLUSION: PDA is independently associated with adverse pathological and oncological outcomes after RP. A higher proportion of PDA supports a higher BCF rate with a shorter time interval. An aggressive extirpative approach with close monitoring of postoperative serum PSA levels is warranted for these patients.

Survival outcomes of Asian younger men (< 55 years) undergoing radical prostatectomy: a review of prostate cancer database in a tertiary hospital in Singapore.

PURPOSE: Prostate cancer largely affects older men. This study aims to investigate prostate cancer in younger men (< 55 years) to shed light on the survival outcomes of this unique subset of patients in Asian context. METHODS: Data were obtained from the Singapore General Hospital Prostate Cancer Registry. Data on all men with clinically organ confined prostate cancer who underwent radical prostatectomy between 1998 and 2016 were obtained from the registry. Tumor characteristics, follow-up data, and cause of death were acquired. RESULTS: A total of 1120 men underwent radical prostatectomy between 1998 and 2016. Of these, 12 were aged ≤ 44 years, 106 were aged 45-54 years, 596 were aged 55-64, 397 were aged 65-74 and 9 were aged ≥ 75. There was no difference across age groups when comparing Gleason ≤ 7 vs Gleason ≥ 8 disease, T1/2 vs T3/4 disease and the median PSA values were similar. No difference was observed in overall survival or prostate cancer specific survival among 4 age groups (≤ 44, 45-54, 55-64, 65-74) (p = 0.156 and p = 0.227 respectively). Although there was a trend of increasing rate of biochemical recurrence for older patients, it's not statistically significant (p = 0.157). Time to biochemical recurrence was similar as well (p = 0.257). CONCLUSION: This large cohort of Asian patients who underwent radical prostatectomy did not show significant age-related differences in important parameters and outcomes.

Multiparametric MRI-ultrasonography software fusion prostate biopsy: initial results using a stereotactic robotic-assisted transperineal prostate biopsy platform comparing systematic vs targeted biopsy.

OBJECTIVE: To compare the detection rates of prostate cancer between systematic biopsy and targeted biopsy using a stereotactic robot-assisted transperineal prostate platform. MATERIALS AND METHODS: We identified consecutive patients with suspicious lesion(s) on multiparametric magnetic resonance imaging (mpMRI), who underwent both systematic and MRI-transrectal ultrasonography (US) fusion targeted biopsy using our proprietary transperineal robot-assisted prostate biopsy platform between January 2015 and January 2019 at our institution, for retrospective analysis. Comparative analysis was performed between systematic and targeted biopsy using McNemar's test, and the cohort was further stratified by prior biopsy status and Prostate Imaging Reporting and Data System (PI-RADS) v2.0 score. International Society of Urological Pathology (ISUP) grade group (GG) ≥2 cancers (previously known as Gleason grade ≥7) were considered to be clinically significant. RESULTS: A total of 500 patients were included in our final analysis, of whom 67 (13%) were patients with low-risk cancer on active surveillance. Of the 433 patients without prior diagnosis of cancer, 288 (67%) were biopsy-naïve. A total of 248 (57%) were diagnosed with prostate cancer, with 199 (46%) having clinically significant prostate cancer (ISUP GG ≥2). There were no statistically significant differences in the overall prostate cancer and clinically significant prostate cancer detection rate between systematic and targeted biopsy (51% vs 49% and 40% vs 38% respectively; P = 0.306 and P = 0.609). Of the 248 prostate cancers detected, 75% (187/248) were detected on both systematic and targeted biopsy, 14% (35/248) were detected on systematic biopsy alone and 11% (26/248) were detected on targeted biopsy alone. Of the 199 clinically significant cancers detected, 69% (138/199) were detected on both systematic and targeted biopsy, 17% (33/199) on systematic biopsy alone and 14% (28/199) on targeted biopsy alone. There were no statistically significant differences in the detection rate between systematic and targeted biopsy for both overall and clinically significant prostate cancer, even when the cohort was stratified by prior biopsy status and PI-RADS score. Targeted biopsy has greater sampling efficiency compared to systematic biopsy for both overall and clinically significant prostate cancer (23.2% vs 9.8%, P < 0.001 and 14.8% vs 5.6%, P < 0.001). CONCLUSIONS: Using our robot-assisted transperineal prostate platform, combined MRI-US targeted biopsy with concurrent systematic prostate systematic biopsy probably represents the optimal method for the detection of clinically significant prostate cancer.

Stereotactic robot-assisted transperineal prostate biopsy under local anaesthesia and sedation: moving robotic biopsy from operating theatre to clinic.

This IRB-approved prospective pilot study evaluates the safety and feasibility of performing stereotactic robot-assisted transperineal MRI-US fusion targeted prostate biopsy under local anaesthesia (LA) with sedation. 30 patients who underwent robotic transperineal prostate biopsy between September 2017 and June 2018 were recruited. All biopsies were performed with the iSR'obot Mona Lisa® and BK3000 ultrasound system. Intravenous paracetamol 1 g, with midazolam and fentanyl were given at positioning. After administration of 5 mL of 1%-lidocaine into the perineal skin 2 cm above and lateral to the anus, periapical prostatic block with 10 mL mixture of 1%-Lidocaine and 0.5%-Marcaine was given. The median age of patients was 66 years (range 53-80 years). Median PSA and mean prostate volume were 8.1 ng/ml (range 4.2-20.6 ng/ml) and 40.1 cc (range 18.6-70 cc). 24 (80.0%) patients had targeted prostate biopsy, with median number of targeted cores of 8 (range 5-16). All patients had saturation biopsy and median number of saturation cores was 21 (range 9-48). Mean dose of intravenous midazolam given was 1.5 mg (range 0-5 mg) and intravenous fentanyl was 75 mcg (10-150 mcg). No patient required conversion to GA. Two patients required motion compensation of 3 mm and 7.5 mm, respectively, due minor movement. Immediate post-operative pain score was 0 for all patients. 29 of 30 patients (96.7%) were discharged within 24 h of procedure. There were no immediate severe complications. Adenocarcinoma was detected in 19/30 (63.3%) cases. This pilot feasibility study showed that stereotactic robotic transperineal MRI-US fusion targeted prostate biopsy can be safely and accurately performed under LA with sedation.

Local and systemic morbidities of de novo metastatic prostate cancer in Singapore: insight from 685 consecutive patients from a large prospective Uro-oncology registry.

OBJECTIVE: To evaluate the incidence and management of local and systemic complications afflicting patients with de novo metastatic prostate cancer (mPCa) in Singapore. DESIGN: Retrospective analysis of a large prospective Uro-oncology registry of mPCa. SETTING: This study is carried out in a tertiary hospital in Singapore. PARTICIPANTS: We reviewed our institution's prospectively maintained database of 685 patients with mPCa over a 20-year period (1995-2014). Patients with non-mPCa or those progressed to metastatic disease after previous curative local treatments were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was to evaluate the systemic and local morbidity rates associated with mPCa. Local complication was defined as the need for palliative procedures to relieve urinary obstruction, worsening renal function or refractory haematuria, while systemic complication was related to radiographic evidence of skeletal-related pathological fractures. Secondary outcomes analysed were the management and overall survival patterns over 20 years. RESULTS: 237 (34.6%) patients required local palliative treatments. 88 (12.8%) patients presented with acute urinary retention, 23 patients (9.7%) required repetitive local palliative treatments. On multivariate analyses, prostate-specific antigen >100 (p=0.02) and prostate volume >50 g (p=0.03) were independent prognostic factors for significant obstruction requiring palliative procedures. 118 (17.2%) patients developed skeletal fractures, with poor Eastern Cooperative Oncology Group Performance (ECOG) status (p=0.01) and high volume bone metastasis (p<0.01) independently predictive of skeletal fractures. Altogether, 653 (95.3%) patients received androgen deprivation therapy (ADT), with the median time to castrate resistance of 21.4 months (IQR 7-27). The median overall survival was 45 months (IQR 20-63), with prostate cancer mortality of 81.4%. Improved overall survival was observed from 41.6 months (1995-1999) to 47.8 months (2010-2014) (p<0.01). CONCLUSION: Morbidities and complications arising from mPCa are more common and debilitating than we thought, often requiring immediate palliative treatments, while many necessitate repeated interventions with progression.

Evaluation of neutrophil-to-lymphocyte ratio as a prognostic indicator in a Singapore cohort of patients with clinically localized prostate cancer treated with prostatectomy.

PURPOSE: Recent evidence suggests that the presence of a systemic inflammatory response plays an important role in the progression of several solid tumors. The neutrophil-to-lymphocyte ratio (NLR) has been proposed as easily assessable markers of systemic inflammation and has been shown to represent a prognostic marker in prostate cancer in previous studies. METHODS: Data from 668 patients with localized prostate cancer treated with prostatectomy (open and robot assisted) in Singapore General Hospital from 1998 to 2014 were analyzed. Correlation between NLR and histopathological status was analyzed. Association between NLR and distant metastases-free survival (MFS), cancer-specific survival (CSS), overall survival (OS), and biochemical disease-free survival (BDFS) was assessed. RESULTS: NLR was not significantly correlated with histopathological status, including Gleason score (≤ 6 versus 7 versus ≥ 8, p = 0.159), lymph node metastasis (negative versus positive, p = 0.159), or surgical margin status (negative versus positive, p = 0.494). NLR was categorized into two groups (< median and ≥ median, median = 2.09) and NLR ≥ 2.09 was not a prognostic factor for decreased MFS (p = 0.609), CSS (p = 0.302), OS (p = 0.722) and BDFS (p = 0.589). No difference was observed for NLR even in high-risk subgroup patients compared to the rest (p = 0.058). The area under the ROC curve (AUC) of NLR as a prognosticator for biochemical recurrence was only 0.53. CONCLUSION: Our findings indicate that pre-treatment NLR may not predict prognosis in patients with localized prostate cancer treated with prostatectomy in an Asian cohort.

Neutrophil-to-lymphocyte ratio independently predicts advanced pathological staging and poorer survival outcomes in testicular cancer.

Purpose: An elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with adverse outcomes in various malignancies. However, its role in prognosticating testicular cancer (TC) has not been validated. We aim to study the relationship between NLR and TC. Materials and Methods: We retrospectively reviewed 160 patients with histological proven TC from January 2005 to June 2016. Youden's index was used to analyse NLR and a cut-off point of 3.0 was obtained, with statistical receiver operating characteristics of 0.755. Chi-square test, Kaplan-Meier (log rank test) and logistics regression models were used to predict NLR association with survival outcomes. Results: Median age was 34 years old (range, 17-68 years old). There were 102 pure seminomas and 58 non-seminomatous germ cell tumours. Median follow-up period was 8 years (range, 2.5-17 years). NLR ≥3.0 was independently associated with lymph node involvement (p=0.031; odds ratio [OR], 2.91; 95% confidence interval [CI], 1.67-5.83; p=0.038; OR, 4.12; 95% CI, 1.26-6.51) and metastatic disease (p=0.041; OR, 2.48; 95% CI, 1.22-3.98; p=0.043; OR, 2.21; 95% CI, 1.17-3.65) in both seminomatous and non-seminomatous germ cell tumours, translating to a more advanced disease. Moreover, NLR ≥3.0 also predicts poorer cancer specific survival in these patients. Conclusions: NLR can be an inexpensive haematological marker in predicting advanced TC staging and poorer survival outcome. NLR complements the traditional cancer staging by identifying a group of high risk patients who may benefit from multimodal treatment and closer surveillance to achieve long term survival.

External validation of the updated Leibovich prognostic models for clear cell and papillary renal cell carcinoma in an Asian population.

PURPOSE: The Leibovich model was updated to prognosticate oncological outcomes in postnephrectomy nonmetastatic renal cell carcinoma (RCC) for each major histological subtype including clear cell (ccRCC), papillary (papRCC), and chromophobe RCC. We evaluated its performance in an independent population of predominantly Asian patients from Singapore. MATERIALS AND METHODS: Nine hundred and forty two binephric patients with nonmetastatic unilateral RCC treated with radical/partial nephrectomy from 1990 to 2015 from Singapore were retrospectively reviewed. Based on the Leibovich model, ccRCC patients were scored from 0 to 25 and papRCC patients divided into 3 risk groups. Primary outcomes of progression-free survival (PFS) and cancer-specific survival (CSS) were assessed with the Kaplan-Meier method. Receiver operating characteristic curves and calibration plots were obtained to determine discrimination and calibration respectively. RESULTS: Eight hundred and twenty nine patients (88%) had ccRCC where 16.2% experienced disease progression while 11.9% died of RCC over a median follow-up of 76 (42-117) months. There was good discrimination (c-index 0.81 for PFS, 0.83 for CSS) and calibration (PFS calibration-in-the-large 0.002 and calibration slope 0.99, CSS calibration-in-the-large 0.005 and calibration slope 0.96). One hundred and thirteen patients (12%) had papRCC, where 18.6% progressed while 14.2% died from RCC over a median follow-up of 69.5 (36.0-112.0) months. Discrimination was slightly weaker (c-index 0.72 for PFS, 0.74 for CSS), and the model was only calibrated for CSS (calibration-in-the-large 0.002, calibration slope 0.98), not for PFS (calibration-in-the-large 0.09, calibration slope 1.93). CONCLUSIONS: The updated Leibovich score is applicable for prognostication of progression and death in both ccRCC and papRCC, even when applied to an independent population of Asian patients. Further validation is required to ensure accuracy in prognosticating PFS for papRCC.

Primary androgen deprivation therapy as monotherapy in unfavourable intermediate- and high-risk localised prostate cancer: a Singaporean single-centre perspective.

PURPOSE: Primary ADT (pADT) monotherapy is used significantly for patients with clinically localised disease in Asia and is acceptable even by guidelines, especially in intermediate- and high-risk disease. This occurs despite controversy in the West and data suggesting association with adverse effects, notably cardiovascular events. We therefore sought to assess the impact of pADT on all-cause mortality and prostate cancer-specific mortality (PCSM) in Asian men with high-risk and unfavourable intermediate-risk PCa. METHODS: With cancer registry data, men from a single centre in Singapore with clinically localised high-risk/unfavourable intermediate-risk PCa diagnosed between 2004 and 2014 and either treated conservatively with no therapy or started on pADT within 1 year of diagnosis were followed up through January 2017. Patients with non-localised PCa (clinical stage T4, regional/distant lymph node involvement, metastases), or receipt of local therapy (radical prostatectomy/radiotherapy) were excluded. The primary outcomes of all-cause mortality and PCSM were analysed with Cox proportional hazards regression models. RESULTS: Three hundred and forty Asian men were analysed, and 177 (52.1%) were started on pADT, with mean age of 77 (49-98) years. There were 119 deaths in the cohort, and 68 (38.4%) occurred in patients treated with pADT (median follow-up, 4.4 years). After adjusting for comorbidities and clinical characteristics, pADT did not provide benefit to all-cause mortality, PCSM or cardiovascular mortality. CONCLUSION: For clinically localised unfavourable intermediate-risk and high-risk PCa, starting pADT within 12 months of diagnosis is not associated with improved 5-year all-cause mortality or PCSM compared to patients treated conservatively with no therapy and should be discouraged due to lack of mortality benefit.

High neutrophil-to-lymphocyte ratio predicts worse overall survival in patients with advanced/metastatic urothelial bladder cancer.

OBJECTIVES: To study the role of the neutrophil-to-lymphocyte ratio in predicting survival outcomes for patients with advanced bladder cancer. METHODS: We retrospectively reviewed 150 patients diagnosed with advanced or metastatic bladder cancer between January 2004 and June 2014. The neutrophil-to-lymphocyte ratio was computed on diagnosis and after the first cycle of chemotherapy. A neutrophil-to-lymphocyte ratio cut-off of 3.0 was determined, with a concordance index of 0.89. Kaplan-Meier curves, log-rank tests, Cox proportional hazards and logistic regression models were used to predict the association of the neutrophil-to-lymphocyte ratio with survival outcomes. RESULTS: Just five patients were alive at the end of the study; the rest died from metastatic bladder cancer. On multivariate analysis, higher Eastern Cooperative Oncology Group status, lymphadenopathy, visceral metastases and neutrophil-to-lymphocyte ratio ≥3.0 were associated with poorer overall survival (hazard ratio 1.67, P = 0.03; hazard ratio 1.97, P = <0.01; hazard ratio 2.02, P = <0.01; hazard ratio 5.06, P = <0.01), whereas chemotherapy conferred better overall survival (hazard ratio 0.546, P = 0.01). Furthermore, the role of chemotherapy prolonged survival longer in patients with a neutrophil-to-lymphocyte ratio <3.0 (median overall survival 13.0 vs 22.0 months, hazard ratio 0.273, P = 0.008) compared with a neutrophil-to-lymphocyte ratio ≥3.0 (median overall survival 4.0 vs 7.0 months, hazard ratio 0.452, P = 0.020). More importantly, when dichotomized to the four different pre- and post-chemotherapy groups, patients with a pre- and post-chemotherapy neutrophil-to-lymphocyte ratio <3.0 had the best additional median overall survival of 19.0 months compared with patients with a pre- and post-chemotherapy neutrophil-to-lymphocyte ratio ≥3.0 (3.0 months). CONCLUSIONS: Elevated neutrophil-to-lymphocyte ratio is independently associated with poorer chemotherapeutic response and overall survival in patients with advanced or metastatic bladder cancer. The neutrophil-to-lymphocyte ratio can be an inexpensive novel factor in prognosticating disease progression and providing better patient counseling.

Automating the Renal Cell Carcinoma Registry in Singapore: A Case Study on the Integration of the Research Electronic Data Capture System with the Enterprise Data Warehouse.

The renal cell carcinoma registry (RCCR) at the Singapore General Hospital was established in the 1980s. In 2012, the registry transited to a partially automated system using Research Electronic Data Capture (REDCap) and Oracle Business Intelligence Enterprise Edition (OBIEE), which is a platform for retrieval of electronic data from the Electronic Health Intelligence System (eHIntS). A committee was formed of experts from the department of urology and the health services research center, as well as an information technology (IT) team to evaluate the efficacy of the partially automated system. In the 5 years after the new system was implemented, 1,751 cases were recorded in the RCCR. The casefinding completeness increased by 1.9%, the data accuracy rate was 97%, and the efficiency increased by 12%. Strengths of the new system after partial automation were: (1) secure access to the registry via the hospital Web, (2) direct access to REDCap via the electronic medical records system, (3) automated and timely data extraction, and (4) visual presentation of data. On the other hand, we also encountered several challenges in the process of automating the registry, including limited IT support, limited expertise in matching data variables from RCCR and eHIntS, and limited availability and accessibility of eHIntS information for import into REDCap. In summary, despite these challenges, partial automation was achieved with the REDCap/OBIEE system, enhancing efficiency, data security, and data quality.

Post hoc analyses of East Asian patients from the randomized placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer.

BACKGROUND: Enzalutamide is an androgen receptor (AR) inhibitor that acts on different steps in the AR signaling pathway. In PREVAIL, an international, phase III, double-blind, placebo-controlled trial, enzalutamide significantly reduced the risk of radiographic progression by 81% (hazard ratio [HR], 0.19; P < .0001) and reduced the risk of death by 29% (HR, 0.71; P < .0001) compared with placebo in chemotherapy-naïve men with metastatic castration-resistant prostate cancer. METHODS: To evaluate treatment effects, safety, and pharmacokinetics of enzalutamide in East Asian patients from the PREVAIL trial, we performed a post hoc analysis of the Japanese, Korean, and Singaporean patients. PREVAIL enrolled patients with asymptomatic or mildly symptomatic chemotherapy-naïve metastatic castration-resistant prostate cancer who had progressed on androgen deprivation therapy. During the study, patients received enzalutamide (160 mg/d) or placebo (1:1) until death or discontinuation because of radiographic progression or skeletal-related event and initiation of subsequent therapy. Centrally assessed radiographic progression-free survival (rPFS) and overall survival (OS) were coprimary endpoints. The secondary endpoints of the PREVAIL trial were investigator-assessed rPFS, time to initiation of chemotherapy, time to prostate-specific antigen (PSA) progression, and PSA response (≥50% decline). RESULTS: Of 1717 patients, 148 patients were enrolled at sites in East Asia (enzalutamide 73, placebo 75). Treatment effect of enzalutamide versus placebo was consistent with that for the overall population as indicated by the HRs (95% confidence interval) of 0.38 (0.10-1.44) for centrally assessed rPFS, 0.59 (0.29-1.23) for OS, 0.33 (0.19-0.60) for time to chemotherapy, and 0.32 (0.20-0.50) for time to PSA progression. In East Asian patients, PSA responses were observed in 68.5% and 14.7% of enzalutamide- and placebo-treated patients, respectively. The enzalutamide plasma concentration ratio (East Asian:non-Asian patients) was 1.12 (90% confidence interval, 1.05-1.20) at 13 weeks. Treatment-related adverse events grade ≥ 3 occurred in 1.4% and 2.7% of enzalutamide- and placebo-treated East Asian patients, respectively. CONCLUSIONS: Treatment effects and safety of enzalutamide in East Asian patients were generally consistent with those observed in the overall study population from PREVAIL. CLINICALTRIALS. GOV NUMBER: NCT01212991.

Focal Therapy for Prostate Cancer with In-Bore MR-guided Focused Ultrasound: Two-Year Follow-up of a Phase I Trial-Complications and Functional Outcomes.

Purpose To report the safety profile and 2-year functional outcomes of in-bore magnetic resonance (MR)-guided focused ultrasound on single cancer foci in men with prostate cancer. Materials and Methods Ethics approval was obtained from the centralized institutional review board for this prospective single-arm study, and patients provided informed consent. Patients with untreated low-volume low-grade prostate cancer (clinical stage T2a or lower; Gleason score, 3+3; index tumor ≤10 mm3) underwent MR-guided focused ultrasound between July 2011 and February 2013. All patients underwent robotic transperineal mapping biopsy and multiparametric MR imaging. Only those with a maximum of two lesions smaller than 10 mm at mapping biopsy were included. Target areas were sonicated with real-time MR thermometry monitoring, excluding critical areas from the beam path. Serum prostate-specific antigen (PSA) and Expanded Prostate Index Composite (EPIC) scores were obtained at baseline and at 1, 3, 6, 12, 18, and 24 months and were plotted to observe their trend. Mean EPIC subdomain score changes at each serial time point were compared with the baseline score by using paired t tests (level of significance, P < .007). Repeat transperineal biopsy was performed at 6 and 24 months. Results Fourteen men (mean age, 62.8 years; median PSA level, 8.3 ng/mL) underwent treatment, with 12 men completing 2-year follow-up. A median reduction of PSA level by 2.9 ng/mL was observed at 6 months. Seven men had Clavien-Dindo grade 1-2 complications. There was a slight insignificant deterioration of EPIC urinary symptom score (mean increase of 7.8 points compared with baseline, P = .012) noted at 1 month, but it returned to baseline by 3 months. There was a trend to deterioration in sexual function score (mean decrease, 4.4 points; P = .04 [not significant]) that normalized at 3 months. There was no significant change in EPIC subdomain scores from baseline over the 24 months. At 6-month template biopsy, one man had cancer with a Gleason score greater than 6; at 24 months, three men had cancer with a Gleason score greater than 6. Conclusion MR-guided focused ultrasound is technically feasible for focal prostate ablation and appears to have a favorable early safety and functional profile. Further clinical trials are necessary to establish oncologic efficacy. © RSNA, 2017 Online supplemental material is available for this article.

Tumor size and Fuhrman grade further enhance the prognostic impact of perinephric fat invasion and renal vein extension in T3a staging of renal cell carcinoma.

OBJECTIVE: To evaluate the prognostic values of perinephric fat invasion and renal vein invasion in pT3a renal cell carcinoma, as stand-alone factors and in combination with tumor size and Fuhrman grade. METHODS: Survival data of pT1 and pT2 renal cell carcinomas were analyzed alongside pT3a tumors of similar size bands (pT1 vs pT3a <7 cm, pT2 vs pT3a >7 cm). Patients with adjuvant therapy, positive surgical margins, metastasis or pT3b-pT4 tumors were excluded. RESULTS: No significant baseline demographic differences existed between the groups. Patients with renal vein invasion had larger tumors (median, 7.2 ± 3.0 cm vs 5.5 ± 3.6 cm, P = 0.039), and were more symptomatic (90.0% vs 61.7%, P = 0.028) compared with patients with perinephric fat invasion alone. Patients with perinephric fat invasion alone appeared to have better disease-free survival compared with those with renal vein invasion (P = 0.009). Having both perinephric fat invasion and renal vein invasion did not result in a poorer disease-free survival. pT3a (perinephric fat invasion) tumors <4 cm and 4-7 cm have significantly worse disease-free survival compared with pT1a and pT1b tumors (P < 0.001). Similarly, pT3a (perinephric fat invasion) tumors measuring ≥7 show a trend of poorer disease-free survival compared with pT2a and pT2b tumors (P = 0.267). Disease-free survival correlated with Fuhrman grading for patients with perinephric fat invasion (P = 0.008). In multivariate analysis, the survival curve of pT3a perinephric fat invasion group closely approximates that of pT2 group, whereas survival of the renal vein invasion group was significantly worse than the pT2 and perinephric fat invasion groups (P = 0.001). CONCLUSION: pT3a tumors with perinephric fat invasion appear to have better prognosis than those with renal vein invasion. Further stratification of pT3a renal cell carcinomas with regard to tumor size and Fuhrman grade further enhances the prognostic value in this group.

Renal cell carcinoma in patients with end-stage renal disease is associated with more favourable histological features and prognosis.

OBJECTIVE: End-stage renal disease (ESRD) patients with acquired cystic kidney disease are at higher risk of developing renal cell carcinoma (RCC) than the general population. The aim of this study was to investigate the clinical and histopathological differences between ESRD patients and the general population with RCC. MATERIALS AND METHODS: Data were retrospectively collected from all nephrectomies performed for localized RCC from 2000 to 2010. Age at nephrectomy, gender, race, symptoms, baseline Eastern Cooperative Oncology Group (ECOG) performance status, Charlson Comorbidity Index score and histological data were extracted. Independent-samples t test and Mann-Whitney test were used for quantitative data, while chi-squared (two-sided) and Fisher's exact tests were used for qualitative data. RESULTS: This study included 627 patients: 73 with and 554 without ESRD. The majority of patients were Chinese. The male to female ratio of 2:1 was identical in both groups. Baseline ECOG performance status and Charlson Comorbidity score were higher in the ESRD group. RCC in ESRD patients was more frequently asymptomatic (56.2% vs 44.9%, p = 0.071), diagnosed earlier (53.6 ± 11.8 years vs 57.9 ± 12.2 years, p = 0.004) and of lower stage (p < 0.001). The ESRD cohort had a higher proportion of the papillary histological subtype (21.9% vs 9.7%, p < 0.001). Importantly, there was a trend towards more favourable outcomes in ESRD patients in terms of cancer-specific (p = 0.203) and relapse-free survival (p = 0.096). CONCLUSION: This study suggests that RCC in ESRD patients is associated with more favourable clinical and histological features and oncological outcome compared with that in patients with normal renal function.