Far from the truth: Real-world treatment patterns among newly diagnosed metastatic prostate cancer in the era of treatment intensification.

OBJECTIVES: Real-world uptake of treatment intensification (TI) with novel hormonal agents (NHA) or chemotherapy as treatment of metastatic prostate cancer remains low outside of trial settings. We aim to report the prescription patterns and treatment outcomes of de novo metastatic hormone-sensitive prostate cancer (mHSPC) in a tertiary institution. METHODS: This is a retrospective cohort study using real-world data from a prospectively maintained prostate cancer registry. We selected patients newly diagnosed with mHSPC from January 2016 to December 2020. Clinicopathological parameters were recorded to determine their impact on prescription patterns. RESULTS: In total, 585 patients with metastatic prostate cancer were identified. Prescription of NHA increased from 10.5% (2016) to 50.4% (2020), but that of chemotherapy declined. Factors associated with TI were (1) baseline health status: Charlson Comorbidity Index 0-2, ECOG 0-1, age ≤ 65, (2) disease burden: PSA (>400, CHAARTED high volume disease, p = 0.004), development of systemic complications and (3) physician factor: primary physician being uro-oncologist and medical oncologist versus general urologist. Patients with TI had a longer mean time to castration-resistant prostate cancer (45.0 vs. 32.5 months, HR 0.567, 95% CI: 0.441-0.730, p < 0.001) and overall survival (55.3 vs. 46.8 months, HR 0.612, 95% CI, 0.447-0.837, p = 0.001). CONCLUSION: This study demonstrated the trend of treatment prescription of mHSPC and factors contributing to the use of TI. TI improved mean time to CRPC and OS.

Incorporating artificial intelligence in urology: Supervised machine learning algorithms demonstrate comparative advantage over nomograms in predicting biochemical recurrence after prostatectomy.

OBJECTIVE: After radical prostatectomy (RP), one-third of patients will experience biochemical recurrence (BCR), which is associated with subsequent metastasis and cancer-specific mortality. We employed machine learning (ML) algorithms to predict BCR after RP, and compare them with traditional regression models and nomograms. METHODS: Utilizing a prospective Uro-oncology registry, 18 clinicopathological parameters of 1130 consecutive patients who underwent RP (2009-2018) were recorded, yielding over 20,000 data points for analysis. The data set was split into a 70:30 ratio for training and validation. Three ML models: Naïve Bayes (NB), random forest (RF), and support vector machine (SVM) were studied, and compared with traditional regression models and nomograms (Kattan, CAPSURE, John Hopkins [JHH]) to predict BCR at 1, 3, and 5 years. RESULTS: Over a median follow-up of 70.0 months, 176 (15.6%) developed BCR, at a median time of 16.0 months (interquartile range [IQR]: 11.0-26.0). Multivariate analyses demonstrated strongest association of BCR with prostate-specific antigen (PSA) (p: 0.015), positive surgical margins (p < 0.001), extraprostatic extension (p: 0.002), seminal vesicle invasion (p: 0.004), and grade group (p < 0.001). The 3 ML models demonstrated good prediction of BCR at 1, 3, and 5 years, with the area under curves (AUC) of NB at 0.894, 0.876, and 0.894, RF at 0.846, 0.875, and 0.888, and SVM at 0.835, 0.850, and 0.855, respectively. All models demonstrated (1) robust accuracy (>0.82), (2) good calibration with minimal overfitting, (3) longitudinal consistency across the three time points, and (4) inter-model validity. The ML models were comparable to traditional regression analyses (AUC: 0.797, 0.848, and 0.862) and outperformed the three nomograms: Kattan (AUC: 0.815, 0.798, and 0.799), JHH (AUC: 0.820, 0.757, and 0.750) and CAPSURE nomograms (AUC: 0.706, 0.720, and 0.749) (p < 0.001). CONCLUSION: Supervised ML algorithms can deliver accurate performances and outperform nomograms in predicting BCR after RP. This may facilitate tailored care provisions by identifying high-risk patients who will benefit from multimodal therapy.

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.

Feasibility and utility of facemask sampling in the detection of SARS-CoV-2 during an ongoing pandemic.

Easy access to screening for timely identification and isolation of infectious COVID-19 patients remains crucial in sustaining the international efforts to control COVID-19 spread. A major barrier limiting broad-based screening is the lack of a simple, rapid, and cost-effective COVID-19 testing method. We evaluated the feasibility and utility of facemask sampling in a cohort of 42 COVID-19-positive and 36 COVID-19-negative patients. We used a prototype of Steri-Strips™ (3 M) applied to the inner surface of looped surgical facemasks (Assure), which was worn by patients for a minimum wear time of 3 h, then removed and sent for SARS-CoV-2 PCR testing. Baseline demographics and symptomatology were also collected. Facemask sampling positivity was highest within the first 5 days of symptomatic presentation. Patients with nasopharyngeal and/or oropharyngeal swab SARS-CoV-2 PCR Ct values < 25.09 had SARS-CoV-2 detected on facemask sampling, while patients with Ct values ≥ 25.2 had no SARS-CoV-2 detected on facemask sampling. Facemask sampling can identify patients with COVID-19 during the early symptomatic phase or those with high viral loads, hence allowing timely identification and isolation of those with the highest transmission risk. Given the widespread use of facemasks, this method can potentially be easily applied to achieve broad-based, or even continuous, population screening.

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.

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.

Benefits of robotic cystectomy compared with open cystectomy in an Enhanced Recovery After Surgery program: A propensity-matched analysis.

OBJECTIVES: To compare the perioperative and oncological outcomes between robot-assisted radical cystectomy with intracorporeal urinary diversion versus open cystectomy for bladder cancer in a contemporary Enhanced Recovery After Surgery cohort. METHODS: All consecutive patients who underwent radical cystectomy and managed under an Enhanced Recovery After Surgery protocol, from December 2013 to October 2018, were reviewed. Propensity score adjustment was carried out to reduce biases attributable to covariate imbalances. RESULTS: There were 19 robot-assisted radical cystectomy with intracorporeal urinary diversion and 21 open cystectomy patients. The robot-assisted radical cystectomy with intracorporeal urinary diversion cohort was associated with lower estimated blood loss (397 vs 787 mL, P = 0.05), with a trend toward shorter duration of ileus and postoperative opioid administration. These benefits were apparent, despite a longer operative time (581 vs 446 mins, P = 0.03), a higher proportion of orthotopic bladder reconstruction (26.3 vs 9.5%, P = 0.08), a more prevalent use of neoadjuvant chemotherapy and a higher number of salvage cystectomies for the robot-assisted radical cystectomy with intracorporeal urinary diversion group. Comparable perioperative complications and length of hospital stay were observed. The pathological and intermediate oncological outcomes were similar in both groups (locally advanced disease: 52.6 vs 47.6%, P = 0.85; lymph node yield: 29 vs 34, P = 0.23). The mean recurrence-free survival and overall survival in the robot-assisted radical cystectomy with intracorporeal urinary diversion group was 37.5 and 43.0 months, respectively, compared with 21.4 (P = 0.09) and 35.5 (P = 0.14) months, respectively, in open cystectomy. CONCLUSION: Robot-assisted radical cystectomy with intracorporeal urinary diversion has perioperative benefits of lower estimated blood loss, with a trend toward faster bowel recovery and a shorter duration of opioid analgesia when compared with open cystectomy. Robot-assisted radical cystectomy with intracorporeal urinary diversion also achieves similar intermediate-term oncological and survival outcomes.

Are small renal masses all the same?

OBJECTIVES: To evaluate variables that can predict synchronous metastasis in patients presenting with small renal masses. METHODS: We reviewed our institution's prospectively maintained database of 565 patients diagnosed with small renal masses (≤4 cm) over a 16-year period. Variables associated with synchronous metastasis and subsequent relapse were analyzed using χ2 and logistic regression models. RESULTS: A total of 16 patients (2.7%) presented with synchronous metastasis. Just three patients with tumor size <3 cm had metastatic disease at presentation. On multivariate analyses, tumor size >3 cm, symptomatic cancer, age >65 years and ipsilateral synchronous tumors were independent predictors of M1 renal cell carcinoma. A weighted predictive model (concordance index 0.786) showed that a score ≥2 significantly increases the risk of synchronous metastasis (7.9% vs <1% for score <2, P < 0.01, hazard ratio 12.56, 95% confidence interval 5.52-22.85). A total of 498 (90.7%) patients underwent nephrectomies, 27 (4.9%) had ablative therapies and 24 (4.4%) continued on active surveillance/watchful waiting. Over a median follow-up period of 62.8 months, 30 patients (6.1%) had disease recurrence. On multivariate analyses, higher Fuhrman grade and lymphovascular invasion were independent predictors of recurrence. A separate predictive model (concordance index 0.723) showed that either pathological outcome increases recurrence risk up to 15% (P < 0.01, hazard ratio 11.83, 95% confidence interval 5.82-18.76). CONCLUSIONS: Several clinical variables can better identify the metastatic potential of small renal masses. The two proposed predictive models can be valuable tools in future clinical practice.

Tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the PI3K/Akt/GSK-3ß signaling pathway.

OBJECTIVE: We investigated the protective effect of tetramethylpyrazine (TMP) on injury related to acute myocardial ischemia (AMI) induced by isoproterenol (ISO). MATERIALS AND METHODS: Rats were randomly assigned to five groups: control, ISO, ISO + propranolol (10 mg/kg), ISO + TMP (10 mg/kg) and ISO + TMP (20 mg/kg). The rats in the three ISO + groups were pretreated with propranolol or TMP, while the rats in the control and ISO groups were pretreated with an equal volume of saline. Afterwards, the rats in the four administration groups were subcutaneously injected with ISO for two consecutive days. The levels of creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß in the serum were measured using ELISA. The expressions of B-cell lymphoma-associated X-2 (Bax-2), B-cell lymphoma-2 (Bcl-2), phosphoinositide-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3ß (GSK-3ß), MDA5 and SOD1 were determined using western blotting assay. The phosphorylation of PI3K, Akt and GSK-3ß were also determined using western blotting assay. The left ventricles of the rats were extracted and stained using hematoxylin and eosin (H&E). The ST segment was recorded using electrocardiograms (ECGs). RESULTS: Administration of TMP (10, 20 mg/kg) reduced the levels of MDA and CK and the activities of SOD and LDH in the serum. Pretreatment with TMP significantly reduced the levels of pro-inflammatory cytokines, including IL-1ß, IL-6 and TNF-α. Treatment with TMP also improved the histopathological alteration and decreased the ST elevation. Furthermore, TMP ameliorated the expressions of Cu, SOD1, MDA5, Bax-2, Bcl-2, p-PI3K, p-Akt and p-GSK-3ß in ISO-induced rats. CONCLUSIONS: Tetramethylpyrazine protected against injury due to AMI by regulating the PI3K/Akt /GSK-3ß signaling pathway.

Low-risk non-muscle-invasive bladder cancer: Further prognostic stratification into the "very-low-risk" group based on tumor size.

OBJECTIVE: To validate the significance of the entity of "very-low-risk" bladder cancer by analyzing the clinical outcomes of low-risk bladder cancer when further stratified by tumor size. METHODS: We accessed our prospectively maintained, single-institution, electronic bladder cancer registry to extract the clinicopathological data of patients who were diagnosed with primary, solitary, Ta, low-grade tumors that were <3 cm. Patients were divided into two prognostic groups based on tumor size (≤1.0 cm vs >1.0 cm). The survival data of the two groups were compared for recurrence, progression and mortality. RESULTS: A total of 165 patients were followed up for a median period of 79 months (interquartile range 47-118 months). A total of 45% (75/165) of the study cohort had tumors that were ≤1.0 cm. Recurrences were found in 40% (66/165) of the study cohort. On Kaplan-Meier analysis, patients with tumor size ≤1.0 cm had significantly longer time to recurrence (P < 0.001, log-rank test). Using multivariate Cox modeling, only tumor size >1.0 cm was significantly associated with shorter time to recurrence (HR 2.54, 95% CI 1.35-4.77, P = 0.004). Tumor size was not significantly associated with any differences in time to overall progression, muscle-invasive progression or overall mortality (P = 0.108, P = 0.362 and P = 0.225, respectively, log-rank test). CONCLUSIONS: Low-risk bladder cancer can be further stratified based on tumor size. Larger tumors (>1.0 cm) are significantly associated with shorter time to recurrence compared with smaller tumors (≤1.0 cm). However, there were no significant differences in the probability of developing disease progression or overall mortality between larger and smaller tumors.

Evolving trends in the surgical management of renal masses over the past two decades: A contemporary picture from a large prospectively-maintained database.

OBJECTIVES: To investigate the trends in the presentation and surgical management of renal tumors at Singapore General Hospital, Singapore. METHODS: We accessed our uro-oncological registry to extract the clinicopathological data of patients with renal tumors who underwent nephrectomy from 2000 to 2015. Binary logistic regression was used to identify predictors of nephron-sparing surgery utilization, Clavien-Dindo grade ≥III complications and progression to stage ≥3 chronic kidney disease. Cox regression models were created to evaluate the proportional hazards of the risk factors for overall survival and cancer-specific survival. RESULTS: A total of 1208 cases of nephrectomy were carried out between 2000 and 2015. The proportion of cT1a tumors increased from 2000-2004 to 2010-2015, which was accompanied by the doubling of utilization rates of nephron-sparing surgery and minimally invasive surgery. Charlson Comorbidity Index score <2, asymptomatic presentation, clinical T1a tumors and having an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 were all independent predictors of nephron-sparing surgery utilization. Age, symptomatic presentation and nephron-sparing surgery utilization were all significantly associated with greater odds of having Clavien-Dindo grade ≥III complications, whereas minimally invasive surgery was associated with decreased risk. The utilization of partial nephrectomy and minimally invasive surgery was significantly associated with a decreased risk of developing postoperative stage ≥3 chronic kidney disease. Both overall survival and cancer-specific survival were not significantly affected by whether nephron-sparing surgery was utilized. CONCLUSIONS: There has been an increasing proportion of small renal masses diagnosed incidentally with a shift towards nephron-sparing surgery for clinically localized tumors. With the adoption of nephron-sparing surgery, progression to stage 3 chronic kidney disease has decreased, without any compromise in oncological and survival outcomes.

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.

Role of computed tomography-calculated intraparenchymal tumor volume in assessment of patients undergoing partial nephrectomy.

OBJECTIVES: To determine the complexity of renal masses by using an objective novel imaging parameter (intraparenchymal tumor volume) based on computed tomography scans, to correlate this parameter to perioperative outcomes and to the RENAL nephrometry score. METHODS: After institutional review board approval, 87 patients who underwent partial nephrectomy between 2012 and 2016 at Singapore General Hospital, Singapore, were retrospectively analyzed. Preoperative computed tomography intravenous pyelogram scans were reviewed by a single senior radiologist who calculated the intraparenchymal tumor volume. Once the intraparenchymal tumor volume scores were obtained, they were compared with perioperative renal and surgical outcomes, and nephrometry scores. Furthermore, intraparenchymal tumor volume was subdivided into two categories, low and high intraparenchymal tumor volume, both using the 89th percentile. RESULTS: The mean patient age was 60 years, and the mean tumor size was 2.9 cm. The mean nephrometry score was 7.8, and the mean intraparenchymal tumor volume score was 12.7 cm³. The cut-off for high intraparenchymal tumor volume was >27.26 cm³. As a continuous variable, intraparenchymal tumor volume showed a significant relationship with the percentage of creatinine change (P = 0.009) and nephrometry scores (P < 0.001). As a categorical variable, high intraparenchymal tumor volume showed significance when compared with absolute creatinine change (P = 0.018), percentage of creatinine change (P = 0.004) and nephrometry score (P < 0.001). CONCLUSIONS: Intraparenchymal tumor volume represents a novel objective tool based on computed tomography imaging to determine the complexity of a renal mass. This tool correlates with renal functional outcomes of partial nephrectomy, and it also shows good correlation with RENAL nephrometry score.

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.

[Effects of Butylphthalide on the expressions of HMGB1 and RAGE in frontal lobe of rats after chronic sleep deprivation].

OBJECTIVE: To investigate the effects of Butylphthalide on the expressions of HMGB1 and RAGE in frontal lobe of rats after chronic sleep deprivation. METHODS: Chronic sleep deprivation and butylphthalide treatment was performed in Sprague Dawley(SD)rats and the rats were divided into three groups (n＝6): platform control group, chronic sleep deprivation group and chronic sleep deprivation + butylphthalide intervention group. Rats suffering chronic sleep deprivation were put in multiple platforms box for 18 h per day and sleep deprivation lasted for 28 days. Rats in butylphthalide intervention group were intraperitoneally injected with butylphthalide 100 mg/(kg·d) for 14 days after sleep deprivation. After collecting brains, high-mobility group box (HMGB1) and nuclear transcription factor kappB (NF-κB)p65 were detected by immunohistochemistry. The expression of HMGB1, silent information regulator of transcription 1 (SIRT1), receptor for advanced glycation end-products (RAGE) and NF-κB in frontal lobe were determinated by Western blot. RESULTS: Compared with platform control group, the expression levels of HMGB1, RAGE and nuclear NF-κB p65 were increased significantly, while the expression of SIRT1 was decreased siginificantly in frontal lobe of chronic sleep deprivation group (all P＜0.05). Compared with chronic sleep deprivation group, the expression levels of of HMGB1, RAGE and nuclear NF-κB p65 were decreased significantly, while the expression of SIRT1 was increased significantly in chronic sleep deprivation + butylphthalide intervention group (all P＜0.05). CONCLUSION: Butylphthalide can inhibit HMGB1/RAGE/NF-κB pathway in frontal lobe of rats after chronic sleep deprivation by changing the expression of HMGB1 and RAGE, and reducing the nuclear translocation of NF-κBp65.

Intravesical Bacillus Calmette-Guerin and its complications: 12 years of learning experience in a single local institution.

INTRODUCTION: Intravesical Bacillus Calmette-Guerin (BCG) therapy is the standard adjuvant treatment for non-muscle-invasive bladder carcinoma (NMIBC) with carcinoma in situ, in addition to tumour resection. We aimed to study BCG complications that preclude adequate treatment of NMIBC in an Asian population. METHODS: This retrospective study was conducted using a large, prospectively maintained bladder cancer database. 336 patients received intravesical BCG therapy for bladder cancer in our institution between 2004 and 2016, with an average follow-up duration of 63 months. RESULTS: The study included 258 (76.8%) male and 78 (23.2%) female patients. The median age of the patients at diagnosis of bladder cancer was 69 (range 17-94) years, and the median number of BCG instillations was 6 (range 1-27). 52 (15.5%) patients received maintenance therapy. The most common complications included urinary tract infection with/without sepsis (n = 18, 5.4%), haematuria (n = 9, 2.7%) and acute urinary retention (n = 4, 1.2%). 93.3% of the patients with complications presented early, within one month of completion of therapy. 22 out of 30 complications were Clavien-Dindo grade ≤ 2. 10 (33.3%) patients were admitted to hospital because of BCG-related adverse effects. The most common reasons for termination were urosepsis (2/30, 6.7%) and acute urinary retention (2/30, 6.7%). Patients aged ≥ 80 years at diagnosis were at higher risk of developing BCG-related complications (19.0% vs. 7.5%, p = 0.01). CONCLUSION: This retrospective cohort and subgroup study showed that intravesical BCG therapy is well tolerated and has a low incidence of complications even in the elderly and patients with multiple comorbidities.

Clinicopathological features of non-conventional renal cell carcinoma histological subtypes: Learning points from a large contemporary series spanning over three decades.

PURPOSE: To perform a retrospective review of the clinicopathological features of patients with conventional and non-conventional renal cell carcinoma (cRCC and ncRCC). MATERIALS AND METHODS: A large prospectively maintained uro-oncological registry was accessed to extract clinicopathological data of patients diagnosed with renal tumors who subsequently underwent nephrectomy from 1990-2019. Demographics and operative parameters were extracted. Analyses of overall survival (OS) and cancer-specific survival (CSS) were performed using the Kaplan-Meier method. Cox proportional-hazards analysis was used to identify risk factors which influenced survival. RESULTS: There were a total of 1,686 consecutive nephrectomies which was retrieved, with 1,286 cRCC and 400 ncRCC. The commonest ncRCC subtypes were papillary (n=198, 11.7%), clear cell papillary (n=50, 3.0%) and chromophobe (n=49, 2.9%) RCC. Kaplan-Meier estimates of OS were higher in cRCC (0.74; 95% confidence interval [CI], 0.71-0.78) than ncRCC (hazard ratio, 1.47; 95% CI, 1.16-1.87). Among individual subtypes, chromophobe RCC had the highest 5-year OS (0.90; 95% CI, 0.79-1.0). Among ncRCC subtypes, acquired cystic RCC demonstrated the highest association with end-stage renal failure and hypertension, with the highest CSS. MiT family translocation RCC had the youngest mean age at presentation (45.6±12.8 y) and excellent CSS. Factors associated with increased OS in the entire cohort included shorter operative time, partial nephrectomy and lower tumor stages. CONCLUSIONS: This study provides a comprehensive contemporary overview of ncRCCs which are yet poorly characterized, in comparison to cRCCs. Data from this study would contribute towards tailored patient counseling and healthcare resource planning.

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.

Serum testosterone levels and testosterone 'bounce' phenomenon predict response to novel anti-androgen therapies in castration-resistant prostate cancer.

BACKGROUND: The relevance of continuous testosterone (TT) monitoring in castration-resistant prostate cancer (CRPC) remains in question. OBJECTIVE: To determine if TT levels before and during novel anti-androgen therapies (NAAT), and the TT 'bounce' phenomenon may predict treatment response in CRPC. MATERIALS AND METHODS: From 2014 through 2018, we identified 92 CRPC patients treated with either Abiraterone or Enzalutamide from a prospectively maintained cancer registry. The TT levels measured before and during NAAT were correlated with the oncological outcomes, determined by PSA response (% change), PSA progression-free survival (PFS) and overall survival (OS). RESULTS AND LIMITATIONS: At CRPC, 58 (63.0%) and 34 (37.0%) patients opted for Abiraterone and Enzalutamide respectively. Median TT levels at CRPC status before and during NAAT were 10.37 ng/dl and 20.46 ng/dl respectively. PSA response was superior in patients with a higher TT before NAAT (P:0.048, median difference: 18.22%, 95% CI 0.70 - 40.37) and longer time to CRPC (P: 0.041, median difference: 15.31%, 95% CI 1.84 -34.84), with a trend towards lower TT during NAAT (P: 0.062). Over a follow up of 33.0 months, 65 patients (70.7%) developed PSA progression. PSA PFS was longer in patients with higher TT before NAAT (16.3 vs. 10.8 months; P: 0.023), lower TT during NAAT (17.0 vs. 9.1 months; P: 0.001), and longer time to CRPC (13.4 vs. 8.0 months; P: 0.032). Importantly, better OS was observed in lower TT during NAAT (45.0 vs. 33.0 months; P:0.029) and longer time to CRPC (43.0 vs. 31.0 months; P: 0.025). The TT 'bounce' phenomenon was observed in 28 patients (33.3%), and was associated with a poorer PSA response (P: 0.029, median difference: 18.90%, 95% CI 3.83 - 41.45), shorter PSA PFS (8.6 vs 15.2 months, P: 0.002) and shorter OS (29.0 vs. 45.0 months, P: 0.012). CONCLUSION: In CRPC patients, TT behaviors before and during NAAT, and the 'bounce' phenomenon continue to predict treatment response and could guide clinical decisions.

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.