Comparison of partial and total cystectomy for colorectal cancer with histologically confirmed bladder invasion.

BACKGROUND: Although organs are preserved and quality of life is improved, insufficient evidence is available for the oncologic safety of partial cystectomy in patients with colorectal cancer with suspected bladder invasion. Therefore, we aimed to compare partial and total cystectomy outcomes in patients with pathologically confirmed or clinically suspected bladder invasion. METHODS: Patients with colorectal cancer with suspected bladder invasion who underwent R0 resection from 2000 to 2020 were evaluated. Long-term outcomes were determined in patients with histologically confirmed bladder invasion. RESULTS: Of the 151 consecutive patients, 96 (64.6%) had histologically confirmed bladder involvement, and 105 (69.5%) underwent partial cystectomy. Operative time, estimated blood loss, and reoperation rate in ≤30 days were significantly worse in the total cystectomy group than in the partial cystectomy group. The overall recurrence rate was significantly higher in the total cystectomy group than in the partial cystectomy group (39.1% vs 21.9%; P = .046). Five-year overall survival (75.8% vs 53.2%; P = .006) rates were higher in the partial cystectomy group than in the total cystectomy group; however, disease-free survival (60.8% vs 41.6%; P = .088) rates were similar in patients with suspected bladder invasion. In patients with histologically confirmed bladder invasion, 5-year overall survival rates (78.1% vs 52.1%; P = .017) were higher in the partial cystectomy group than in the total cystectomy group; however, disease-free survival rates (53.4% vs 41.2%; P = .220) did not differ significantly. CONCLUSION: R0 resection is associated with favorable long-term outcomes in patients with locally advanced colorectal cancer. If R0 resection is possible, partial cystectomy is considered safe.

Evaluation of histological variants of upper tract urothelial carcinoma as prognostic factor after radical nephroureterectomy.

PURPOSE: To evaluate the impact of variant histology on patients with upper tract urothelial carcinoma (UTUC) survival outcomes. MATERIALS AND METHODS: A total of 519 patients underwent radical nephroureterectomy without neoadjuvant therapy for UTUC at a single institution between May 2003 and December 2019. Multivariate Cox regression analysis evaluated the impact of variant histology on progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Among 84 patients (16.2%) with variant histology, the most frequent variant type was squamous cell differentiation (64.3%), followed by glandular differentiation (25.0%) and sarcomatoid variant (2.4%). They showed pathologically advanced T stage (for ≥ T3, 59.5% vs 33.3%, p < 0.001), higher tumor grade (96.4% vs 85.7%, p = 0.025), and higher rates of lymph node metastasis (17.9% vs 7.8%, p = 0.015), angiolymphatic invasion (41.7% vs 25.7%, p = 0.003), tumor necrosis (57.1% vs 29.0%, p < 0.001) and positive surgical margin (13.1% vs 5.7%, p = 0.015). On multivariate Cox regression analyses, variant histology was significantly associated with worse PFS (hazard ratio [HR] 2.23; 95% confidence interval [CI] 1.55-3.21; p < 0.001), CSS (HR 2.67; 95% CI 1.35-5.30; p = 0.005) and OS (HR 2.22; 95% CI 1.27-3.88; p = 0.005). In subgroup analysis, no significant survival gains of adjuvant chemotherapy occurred in patients with variant histology. CONCLUSIONS: Variant histology was associated with adverse pathologic features and poor survival outcomes. Our results suggest that patients with variant histology may require a close follow-up schedule and novel adjuvant therapy other than chemotherapy postoperatively.

Clinical value of prostate health index as an indicator for recommending magnetic resonance imaging in patients with gray-zone prostate-specific antigen level.

PURPOSE: To evaluate the usefulness of prostate health index (PHI) as an indicator for recommending magnetic resonance imaging (MRI) in patients with prostate-specific antigen (PSA) gray zone level < 10 ng/mL. METHODS: 443 patients who underwent prostate biopsy (PB) after serum PHI test and MRI between April 2019 and December 2022 were enrolled. For patients with visible lesion on MRI with Prostate Imaging Reporting and Data System Score (PI-RADS) ≥ 3, MRI-targeted PB was performed in addition to systematic 12-core PB. RESULTS: The optimal cutoff value of PHI for predicting PI-RADS ≥ 3 lesions was 39.6, which was significantly associated with overall prostate cancer (OR 3.07, p = 0.018) and clinically significant prostate cancer (csPCa) (OR 4.15, p = 0.006) at MRI-targeted PB cores. When MRI was restricted to patients with PHI ≥ 39.6 alone, 28.7% of unnecessary MRI could be saved at the cost of missing 13.6% of csPCa. When omitting MRI for patients with PHI < 39.6 and PSAD < 0.12 ng/mL2, unnecessary MRI could be reduced by 20.1% with the risk of missing 6.2% of csPCa. With addition of systematic PB, 21.0% of patients with negative MRI-targeted PB were diagnosed as csPCa. CONCLUSIONS: For patients in PSA gray zone, PHI of 39.6 might be an indicator for MRI and further MRI-targeted PB in additional to PSAD of 0.12 ng/mL2, reducing 20.1% of unnecessary MRI with the minimal risk of missing 6.2% of csPCa. To maximize csPCa detection, combining both MRI-targeted and systematic PB should be also considered.

Partial gland ablation using high-intensity focused ultrasound versus robot-assisted radical prostatectomy: a propensity score-matched study.

Background: We compared the clinical outcomes of robot-assisted radical prostatectomy (RARP) and partial gland ablation (PGA) using high-intensity focused ultrasound (HIFU) in localized prostate cancer. Methods: We analyzed 3,859 patients who had undergone RARP and PGA using HIFU. According to the propensity score for each treatment, 137 patients after PGA were matched to 3,722 patients after RARP at a 1:4 ratio using the nearest neighbor method. Results: The matched cohort comprised 685 subjects (RARP, 548; PGA, 137), with a median follow-up period of 22 months. Treatment failures were identified in 13.9% and 9.1% of patients in the PGA and RARP groups, respectively, after a median follow-up of 36 months postoperatively. Kaplan-Meier analyses revealed significantly longer failure-free (P < 0.001) and salvage-free survival (P = 0.003) in the RARP group than in the PGA group. There was no significant difference in the postoperative urinary symptom score (P = 0.748), but the postoperative erectile function score was significantly higher in the PGA group (P < 0.001). The rate of urinary incontinence (any pad) was significantly lower in the PGA group than that in the RARP group (P < 0.001). Postoperative complications were more frequent in the PGA group (P = 0.003); however, there was no significant difference in high-grade complications (≥3) (P = 0.467). Conclusion: PGA using HIFU showed statistically inferior oncological outcomes compared with RARP for failure-free survival and salvage-free survival. However, functional outcomes regarding postoperative incontinence and erectile dysfunction were more favorable in the PGA group.

Computer tomography-based shape of tumor contour and texture of tumor heterogeneity are independent prognostic indicators for clinical T1b-T2 renal cell carcinoma.

PURPOSE: To evaluate association between computer tomography (CT)-based features of renal cell carcinoma (RCC) and survival outcomes. METHODS: Data of 958 patients with clinical T1b-T2 RCC who underwent partial/radical nephrectomy from June 2003 to March 2022 were retrospectively evaluated. CT images of patients were reviewed by two radiologists for texture analysis of tumor heterogeneity and shape analysis of tumor contour. Patients were divided into three groups according to patterns of CT-based features: (1) favorable feature group (n = 117); (2) intermediate feature group (n = 606); and (3) unfavorable feature group (n = 235). Kaplan-Meier survival analysis and multivariate Cox regression analysis were performed to evaluate overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS). RESULTS: RCCs with unfavorable CT-based feature showed larger size on CT, higher nuclear grade, higher rate of histologic necrosis, and higher rate of capsular invasion than those in the other two groups (all p < 0.001). Unfavorable feature was associated with poorer OS (p = 0.001), CSS (p < 0.001), and RFS (p < 0.001) on Kaplan-Meier analysis. In multivariate analysis, intermediate and unfavorable features were independent predictors for recurrence (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.09-5.79, p = 0.031 and HR 3.71, 95% CI 1.58-8.73, p = 0.003, respectively), but not for overall death or RCC-specific death. CONCLUSIONS: A combination of irregular tumor contour feature with heterogeneous tumor texture feature on CT is associated with poor RFS in clinical T1b-T2 RCC preoperatively.

Diagnostic performance of MRI for prediction of recurrent prostate cancer after high-intensity focused ultrasound: a systematic review and meta-analysis.

Purpose: This article aims to evaluate the pooled diagnostic performance control MRI for prediction of recurrent prostate cancer (PCa) after high-intensity focused ultrasound (HIFU). Materials and methods: MEDLINE, EMBASE, and Cochrane library databases up to December 31, 2021, were searched. We included studies providing 2×2 contingency table for diagnostic performance of MRI in predicting recurrent PCa after HIFU, using control biopsy as reference standard. The quality of the included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Sensitivity and specificity were pooled and displayed in a summary receiver operating characteristics (SROC) plot. Meta-regression analysis using clinically relevant covariates was performed for the causes of heterogeneity. Results: Nineteen studies (703 patients) were included. All included studies satisfied at least four of the seven QUADAS-2 domains. Pooled sensitivity was 0.81 (95% CI 0.72-0.90) with specificity of 0.91 (95% CI 0.86-0.96), with area under the SROC curve of 0.81. Larger studies including more than 50 patients showed relatively poor sensitivity (0.68 vs. 0.84) and specificity (0.75 vs. 0.93). The diagnostic performance of studies reporting higher nadir serum prostate-specific antigen levels (>1 ng/mL) after HIFU was inferior, and differed significantly in sensitivity (0.54 vs. 0.78) rather than specificity (0.85 vs. 0.91). Conclusions: Although MRI showed adequate diagnostic performance in predicting PCa recurrence after HIFU, these results may have been exaggerated.

Germline DNA-Repair Genes and HOXB13 Mutations in Korean Men with Metastatic Prostate Cancer: Data from a Large Korean Cohort.

PURPOSE: Germline mutations in DNA damage repair (DDR) genes such as BRCA2 have been associated with prostate cancer (PC) risk but has not been thoroughly evaluated for metastatic prostate cancer (mPC) in Asian men. This study attempts to evaluate frequency of DDR mutations in the largest cohort of Koreans. MATERIALS AND METHODS: We recruited 340 patients with mPC unselected for family history of cancer and compared to 495 controls. Whole genome sequencing was applied to assess germline pathogenic/likely pathogenic variants (PV/LPVs) in 26 DDR genes and HOXB13, including 7 genes (ATM, BRCA1/2, CHEK2, BRIP1, PALB2, and NBN) associated with hereditary PC. Comparisons to published Caucasian and Japanese cohorts were performed. RESULTS: Total of 28 PV/LPVs were identified in 30 (8.8%) patients; mutations were found in 13 genes, including BRCA2 (15 men [4.41%]), ATM (2 men [0.59%]), NBN (2 men [0.59%], and BRIP1 (2 men [0.59%]). Only one patient had HOXB13 mutation (0.29%). A lower rate of overall germline variant frequency was observed in Korean mPC compared to Caucasians (8.8% vs. 11.8%), but individual variants notably differed from Caucasian and geographically similar Japanese cohorts. PV/LPVs in DDR genes tended to increase gradually with higher Gleason scores (GS 7, 7.1%; GS 8, 7.5%; GS 9-10, 9.9%). CONCLUSIONS: BRCA2 was the most frequently mutated gene common to different cohorts supporting its importance, but differences in variant distribution in Korean mPC underscore the need for ethnic-specific genetic models. Future ethnic-specific analyses are warranted to verify our findings.

Aptamer Nanoconstructs Crossing Human Blood-Brain Barrier Discovered via Microphysiological System-Based SELEX Technology.

Blood-brain barrier (BBB) remains one of the critical challenges in developing neurological therapeutics. Short single-stranded DNA/RNA nucleotides forming a three-dimensional structure, called aptamers, have received increasing attention as BBB shuttles for efficient brain drug delivery owing to their practical advantages over Trojan horse antibodies or peptides. Aptamers are typically obtained by combinatorial chemical technology, termed Systemic Evolution of Ligands by EXponential Enrichment (SELEX), against purified targets, living cells, or animal models. However, identifying reliable BBB-penetrating aptamers that perform efficiently under human physiological conditions has been challenging because of the poor physiological relevance in the conventional SELEX process. Here, we report a human BBB shuttle aptamer (hBS) identified using a human microphysiological system (MPS)-based SELEX (MPS-SELEX) method. A two-channel MPS lined with human brain microvascular endothelial cells (BMECs) interfaced with astrocytes and pericytes, recapitulating high-level barrier function of in vivo BBB, was exploited as a screening platform. The MPS-SELEX procedure enabled robust function-based screening of the hBS candidates, which was not achievable in traditional in vitro BBB models. The identified aptamer (hBS01) through five-round of MPS-SELEX exhibited high capability to transport protein cargoes across the human BBB via clathrin-mediated endocytosis and enhanced uptake efficiency in BMECs and brain cells. The enhanced targeting specificity of hBS01 was further validated both in vitro and in vivo, confirming its powerful brain accumulation efficiency. These findings demonstrate that MPS-SELEX has potential in the discovery of aptamers with high target specificity that can be widely utilized to boost the development of drug delivery strategies.

Synthesis and anti-prion aggregation activity of acylthiosemicarbazide analogues.

Prions are infectious protein particles known to cause prion diseases. The biochemical entity of the pathogen is the misfolded prion protein (PrPSc) that forms insoluble amyloids to impair brain function. PrPSc interacts with the non-pathogenic, cellular prion protein (PrPC) and facilitates conversion into a nascent misfolded isoform. Several small molecules have been reported to inhibit the aggregation of PrPSc but no pharmacological intervention was well established thus far. We, here, report that acylthiosemicarbazides inhibit the prion aggregation. Compounds 7x and 7y showed almost perfect inhibition (EC50 = 5 µM) in prion aggregation formation assay. The activity was further confirmed by atomic force microscopy, semi-denaturing detergent agarose gel electrophoresis and real-time quaking induced conversion assay (EC50 = 0.9 and 2.8 µM, respectively). These compounds also disaggregated pre-existing aggregates in vitro and one of them decreased the level of PrPSc in cultured cells with permanent prion infection, suggesting their potential as a treatment platform. In conclusion, hydroxy-2-naphthoylthiosemicarbazides can be an excellent scaffold for the discovery of anti-prion therapeutics.

Polygenic risk score for tumor aggressiveness and early-onset prostate cancer in Asians.

We attempted to assess the performance of an ethnic-specific polygenic risk score (PRS) designed from a Korean population to predict aggressive prostate cancer (PCa) and early-onset (age < 60). A PRS score comprised of 22 SNPs was computed in 3695 patients gathered from one of 4 tertiary centers in Korea. Males with biopsy or radical prostatectomy-proven PCa were included for analysis, collecting additional clinical parameters such as age, BMI, PSA, Gleason Group (GG), and staging. Patients were divided into 4 groups of PRS quartiles. Intergroup differences were assessed, as well as risk ratio and predictive performance based on GG using logistic regression analysis and AUC. No significant intergroup differences were observed for BMI, PSA, and rate of ≥ T3a tumors on pathology. Rate of GG ≥ 2, GG ≥ 3, and GG ≥ 4 showed a significant pattern of increase by PRS quartile (p < 0.001, < 0.001, and 0.039, respectively). With the lowest PRS quartile as reference, higher PRS groups showed sequentially escalating risk for GG ≥ 2 and GG ≥ 3 pathology, with a 4.6-fold rise in GG ≥ 2 (p < 0.001) and 2.0-fold rise in GG ≥ 3 (p < 0.001) for the highest PRS quartiles. Combining PRS with PSA improved prediction of early onset csPCa (AUC 0.759) compared to PRS (AUC 0.627) and PSA alone (AUC 0.736). To conclude, an ethnic-specific PRS was found to predict susceptibility of aggressive PCa in addition to improving detection of csPCa when combined with PSA in early onset populations. PRS may have a role as a risk-stratification model in actual practice. Large scale, multi-ethnic trials are required to validate our results.

Diagnostic value of multiparametric MRI in detecting residual or recurrent prostate cancer after high-intensity focused ultrasound.

PURPOSE: To evaluate the diagnostic performance of follow-up multiparametric MRI for prediction of recurrent prostate cancer after high-intensity focused ultrasound (HIFU), and to find other, if any, clinical or radiological predictors. MATERIALS AND METHODS: Post-HIFU MRIs of 110 consecutive patients who underwent follow-up biopsies between August 2019 and April 2021 were retrospectively analyzed and the likelihood of recurrence was assessed on a five-point Likert scale by two board-certified uroradiologists. Diagnostic performance of the Likert scale assigned to the post-HIFU MRI was assessed using the follow-up biopsy results as a reference standard. Among the clinical and radiological variables, predictors of the recurrence were examined through logistic regression. RESULTS: In per-patient and per-sector analyses, Likert scale on post-HIFU MRI showed a sensitivity and specificity of 0.37 and 0.97, and 0.42 and 0.87, respectively, in predicting recurrence. Two patients with high suspicion on MRI required additional treatment to regain biochemical control despite negative biopsies. High suspicion on post-HIFU MRI (odds ratio = 1.74; p < 0.01), and more cancer-positive cores on initial biopsy (odds ratio = 1.25; p = 0.03) were independent predictors of recurrence. CONCLUSION: Albeit with low sensitivity, high suspicion on post-HIFU MRI may be clinically important because of its high specificity, especially when considering the possibility of sampling error in biopsies. Patients with a high number of cancer-positive cores at diagnosis should avoid HIFU as they have an increased risk of recurrence.

The Prostate Health Index and multi-parametric MRI improve diagnostic accuracy of detecting prostate cancer in Asian populations.

PURPOSE: The aim of this study was to evaluate the effectiveness of the Prostate Health Index (PHI) and prostate multi-parametric magnetic resonance imaging (mpMRI) in predicting prostate cancer (PCa) and clinically significant prostate cancer (csPCa) during initial prostate biopsy. MATERIALS AND METHODS: In total, 343 patients underwent initial prostate biopsy and were screened by use of PHI and prostate-specific antigen (PSA) levels between April 2019 and July 2021. A subgroup of 232 patients also underwent prostate mpMRI. Logistic regression analysis was performed to evaluate the accuracies of PSA, PHI, and mpMRI as predictors of PCa or csPCa. These predictive accuracies were quantified by using the area under the receiver operating characteristic curve. The different predictive models were compared using the DeLong test. RESULTS: Logistic regression showed that age, PSA, PHI, and prostate volume were significant predictors of both PCa and csPCa. In the mpMRI subgroup, age, PSA level, PHI, prostate volume, and mpMRI were predictors of both PCa and csPCa. The PHI (area under the curve [AUC]=0.693) was superior to the PSA level (AUC=0.615) as a predictor of PCa (p=0.038). Combining PHI and mpMRI showed the most accurate prediction of both PCa and csPCa (AUC=0.833, 0.881, respectively). CONCLUSIONS: The most accurate prediction of both PCa and csPCa can be performed by combining PHI and mpMRI. In the absence of mpMRI, PHI is superior to PSA alone as a predictor of PCa, and adding PHI to PSA can increase the detection rate of both PCa and csPCa.

Clinical benefits of retrograde bladder filling method prior to catheter removal after TURP for BPH: A prospective randomized trial.

PURPOSE: To evaluate possible benefits and clinical feasibility of retrograde bladder filling method prior to intra-vesical catheter removal after transurethral prostatectomy (TURP) for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Male patients undergoing TURP for BPH from January 2019 to October 2019 were randomized in a 1:1 ratio into either retrograde filling (RF) or spontaneous voiding (SV) methods at a single institution to determine safety and efficacy of RF (NCT04309032), with surgeons blinded to allocation. Perioperative outcomes including postoperative complications were compared between two groups. Clinician/patients' satisfaction level which was evaluated with postoperative questionnaires were also compared. RESULTS: A total of 56 patients were randomized into two groups and 56 were included in final analysis (28 men in RF group, 26 in SV group). No significant differences in baseline characteristics including age, prostate volume, or perioperative uroflowmetry were observed. However, RF significantly facilitated time to void (67.0±63.2 vs. 144.0±78.7 min; p<0.001) and time to discharge (168.4±57.2 vs. 218.9±106.9 min; p=0.046). Immediate postoperative complications were comparable in both methods with no significant difference. Overall patient and medical staff satisfaction showed tolerable and similar response by either procedure. CONCLUSIONS: RF method for intra-vesical catheter removal is a safe and satisfactory method that can facilitate early voiding detection and shorten the time to discharge. Further trials are required to further validate our results.

Defending Person Detection Against Adversarial Patch Attack by Using Universal Defensive Frame.

Person detection has attracted great attention in the computer vision area and is an imperative element in human-centric computer vision. Although the predictive performances of person detection networks have been improved dramatically, they are vulnerable to adversarial patch attacks. Changing the pixels in a restricted region can easily fool the person detection network in safety-critical applications such as autonomous driving and security systems. Despite the necessity of countering adversarial patch attacks, very few efforts have been dedicated to defending person detection against adversarial patch attack. In this paper, we propose a novel defense strategy that defends against an adversarial patch attack by optimizing a defensive frame for person detection. The defensive frame alleviates the effect of the adversarial patch while maintaining person detection performance with clean person. The proposed defensive frame in the person detection is generated with a competitive learning algorithm which makes an iterative competition between detection threatening module and detection shielding module in person detection. Comprehensive experimental results demonstrate that the proposed method effectively defends person detection against adversarial patch attacks.

Multiple primary cancers in men with sporadic or familial prostate cancer: Its clinical implications.

OBJECTIVE: To evaluate the risk of concordant cancers in patients with prostate cancer (CaP) and examine whether this risk differed according to family history of CaP. MATERIALS AND METHODS: We examined 1,102 patients with CaP , having prospectively acquired pedigrees, and analyzed information regarding multiple primary cancers. The prevalence of concordant cancers was assessed with respect to the family history of CaP . First-degree familial CaP was defined as a positive history of CaP in first-degree relatives (parents, siblings, and offspring). Odds ratios for each concordant cancer in men with first-degree familial CaP were estimated. Clinical characteristics were compared between men with and without concordant cancers. RESULTS: The prevalence of multiple primary cancers in sporadic PCa was 12.0%, similar to that of first-degree familial CaP (13.5%, P = 0.698). Gastrointestinal cancer was the most common concordant cancer (3.6%), followed by colorectal (2.9%), lung (1.5%), urothelial (1.3%), kidney (1.1%), and other cancers. Colorectal cancer was more frequent in first-degree familial CaP than in sporadic disease (6.8 vs. 2.7%, P = 0.045). However, the rates of other concordant cancers were similar between the 2 groups (P range, 0.242-0.963). Compared with sporadic disease, the age-adjusted odds ratio for concordant colorectal cancer in first-degree familial CaP was 2.930 (95% confidence interval, 1.082-7.929). Patients with concordant colorectal cancer had fewer (2.8 vs. 3.9 cores, P = 0.041) and a lower percentage of (23.5 vs. 33.1%, P = 0.030) positive biopsy cores than CaP only patients. CONCLUSIONS: A family history of CaP was significantly associated with a risk of concordant colorectal cancer. These findings imply that some CaP shares a genetic pathogenesis with colorectal cancer.

A smart, practical, deep learning-based clinical decision support tool for patients in the prostate-specific antigen gray zone: model development and validation.

OBJECTIVE: Despite efforts to improve screening and early detection of prostate cancer (PC), no available biomarker has shown acceptable performance in patients with prostate-specific antigen (PSA) gray zones. We aimed to develop a deep learning-based prediction model with minimized parameters and missing value handling algorithms for PC and clinically significant PC (CSPC). MATERIALS AND METHODS: We retrospectively analyzed data from 18 824 prostate biopsies collected between March 2003 and December 2020 from 2 databases, resulting in 12 739 cases in the PSA gray zone of 2.0-10.0 ng/mL. Dense neural network (DNN) and extreme gradient boosting (XGBoost) models for PC and CSPC were developed with 5-fold cross-validation. The area under the curve of the receiver operating characteristic (AUROC) was compared with that of serum PSA, PSA density, free PSA (fPSA) portion, and prostate health index (PHI). RESULTS: The AUROC values in the DNN model with the imputation of missing values were 0.739 and 0.708 (PC) and 0.769 and 0.742 (CSPC) in internal and external validation, whereas those of the non-imputed dataset were 0.740 and 0.771 (PC) and 0.807 and 0.771 (CSPC), respectively. The performance of the DNN model was like that of the XGBoost model, but better than all tested clinical biomarkers for both PC and CSPC. The developed DNN model outperformed PHI, serum PSA, and percent-fPSA with or without missing value imputation. DISCUSSION: DNN models for missing value imputation can be used to predict PC and CSPC. Further validation in real-life scenarios are need to recommend for actual implementation, but the results from our study support the increasing role of deep learning analytics in the clinical setting. CONCLUSIONS: A deep learning model for PC and CSPC in PSA gray zones using minimal, routinely used clinical parameter variables and data imputation of missing values was successfully developed and validated.

Diagnostic accuracy of prostate-specific antigen below 4 ng/mL as a cutoff for diagnosing prostate cancer in a hospital setting: A systematic review and meta-analysis.

PURPOSE: A prostate-specific antigen (PSA) cutoff of 4 ng/mL has been widely used for prostate cancer screening in population-based settings. However, the accuracy of PSA below 4 ng/mL as a cutoff for diagnosing prostate cancer in a hospital setting is inconclusive. We systematically reviewed the accuracy of PSA below 4 ng/mL cutoff in a hospital setting. MATERIALS AND METHODS: We systematically reviewed the literature by searching major databases until March 2020, and a meta-analysis and quality assessment were performed. RESULTS: A total of 11 studies were included at the completion of the screening process. The meta-analysis showed a sensitivity of 0.92 and a specificity of 0.16 for a PSA cutoff below 4 ng/mL. The area under the hierarchical summary receiver operating characteristic curve was 0.87, the positive likelihood ratio was 1.23, the negative likelihood ratio was 0.46, and the diagnostic odds ratio was 2.64. PSA sensitivities and specificities varied according to the cutoff range: 0.94 and 0.17 for 2 to 2.99 ng/mL, and 0.92 and 0.16 for 3 to 3.99 ng/mL, respectively. No significant differences in the sensitivity and specificity of PSA cutoffs in the range of 2 to 2.99 ng/mL and 3 to 3.99 ng/mL were found. CONCLUSIONS: Although a PSA cutoff <3 ng/mL is relatively more sensitive and specific than PSA ≥3 ng/mL, no significant differences in sensitivity and specificity were found in the diagnosis of prostate cancer. Therefore, clinicians should choose an appropriate PSA cutoff on the basis of clinical circumstances and patients' characteristics.

Outcomes of partial gland ablation using high intensity focused ultrasound for prostate cancer.

BACKGROUND: To evaluate the clinical and oncological outcomes of partial gland ablation (PGA) using high intensity focused ultrasound (HIFU) technique for the clinically unilateral prostate cancer. METHODS: We performed a retrospective analysis for the 163 patients who treated by PGA for clinically unilateral prostate cancer. The PGA was performed using Focal one system with concurrent trans-urethral prostatectomy. The oncological and functional outcomes were evaluated as well as risk factors for remnant disease after PGA. Clinically significant cancer was defined as grade group ≥2. RESULTS: Among the entire subjects, grade group 2 or greater was present at pre-treatment biopsy in 76.7%. Median follow-up time was 17 months and 60.1% of total subjects had follow-up biopsy at postoperative 1 year. There were 25 subjects (24.2%) with any cancer and 13 subjects (12.6%) with CS cancer at the follow-up biopsy. The preoperative age and number of positive cores at preoperative biopsy were significantly associated with positive results at follow-up biopsy. Incontinence which requires 2 or more pads per day was observed at 4 subjects (2.5%) postoperatively. There were no subjects who needed intensive care or experienced rectal complications. CONCLUSION: The PGA with HIFU was safe and showed good preservation of functional outcomes as well as satisfactory oncological control. The remnant disease was observed in the 24.5% of patients who underwent follow-up biopsy in the present study. Thus, further prospective study is needed to evaluate oncological and functional outcomes of PGA with HIFU more accurately.

The tumor volume after radical prostatectomy and its clinical impact on the prognosis of patients with localized prostate cancer.

We evaluated the contribution of tumor volume (TV) to localized prostate cancer (PCa) patients' prognosis. We retrospectively analyzed the data of 2394 patients who underwent radical prostatectomy (RP) for localized PCa. The effect of TV and tumor prostate ratio (TV/PV) on PCa patients' prognosis was analyzed through Kaplan-Meier and Cox-proportional analysis. The mean prostate volume for all patients was 36.5 ± 15.4 cc, and the mean TV was 5.9 ± 8.3 cc. A significant positive relationship was observed between the classification by risk group in D' Amico risk classification and the National Comprehensive Cancer Network risk group (P < 0.001). The high TV showed significantly worse pathologic outcomes than the low TV in terms of high rates of extra-capsular extension, seminal vesicle invasion, and positive surgical margin (P < 0.05). The patients with high TV and TV/PV had significantly shorter biochemical recurrence-free survivals than those with low TV and TV/PV (P < 0.001). Finally, based on multivariate Cox-proportional analyses, TV and TV/PV was an independent predictor to predict shorter biochemical recurrence-free survival as both a TV (HR: 1.04, 95% CI 1.04-1.05, P < 0.001) and TV/PV (HR: 1.42, 95% CI 1.13-1.78, P = 0.003). TV was revealed to be an independent prognostic factor in the postoperative biochemical recurrence. Patients with a high number of positive core and longer tumor length were significantly related to higher TV.

Prediction of clinically significant prostate cancer using polygenic risk models in Asians.

PURPOSE: To develop and evaluate the performance of a polygenic risk score (PRS) constructed in a Korean male population to predict clinically significant prostate cancer (csPCa). MATERIALS AND METHODS: Total 2,702 PCa samples and 7,485 controls were used to discover csPCa susceptible single nucleotide polymorphisms (SNPs). Males with biopsy-proven or post-radical prostatectomy Gleason score 7 or higher were included for analysis. After genotype imputation for quality control, logistic regression models were applied to test association and calculate effect size. Extracted candidate SNPs were further tested to compare predictive performance according to number of SNPs included in the PRS. The best-fit model was validated in an independent cohort of 311 cases and 822 controls. RESULTS: Of the 83 candidate SNPs with significant PCa association reported in previous literature, rs72725879 located in PRNCR1 showed the highest significance for PCa risk (odds ratio, 0.597; 95% confidence interval [CI], 0.555-0.641; p=4.3×10-45). Thirty-two SNPs within 26 distinct loci were further selected for PRS construction. Best performance was found with the top 29 SNPs, with AUC found to be 0.700 (95% CI, 0.667-0.734). Males with very-high PRS (above the 95th percentile) had a 4.92-fold increased risk for csPCa. CONCLUSIONS: Ethnic-specific PRS was developed and validated in Korean males to predict csPCa susceptibility using the largest csPCa sample size in Asia. PRS can be a potential biomarker to predict individual risk. Future multi-ethnic trials are required to further validate our results.