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Objective: To analyze the outcomes of transperineal template-guided mapping biopsy (TTMB) in biopsy-naïve men with multiparametric magnetic resonance imaging (mpMRI) results of Prostate Imaging-Reporting and Data System (PI-RADS) 1-2. Patients and methods: We retrospectively reviewed TTMB outcomes in biopsy naïve patients with PI-RADS 1-2 at a single center from August 2018 to May 2023. The patients' clinicopathologic data were reviewed, clinically significant prostate cancer (csPCa) detection rates were identified. We determined significant predictive factors and determined those optimal cutoff point using receiver operating characteristic (ROC) curves. Results: 255 biopsy naïve patients with PI-RADS 1-2 underwent TTMB. 72 (28.2%) were diagnosed with prostate cancer and 30 (11.8%) were diagnosed with csPCa. ROC curves were used to identify predictive factors for diagnosing csPCa. Age (area under ROC curve [AUC]: 0.74, 95% CI: 0.65–0.83, P

This study aimed to assess the prognostic role of body mass index (BMI) in patients with metastatic renal cell carcinoma (mRCC) treated with first-line immune checkpoint inhibitor (ICI)-based therapy. We searched for relevant studies in the MEDLINE, Embase, and Cochrane Library databases. The initial search yielded 599 records, of which seven articles (2,517 patients) were selected for analysis. Patients with a high BMI had a favorable overall survival (OS) based on hazard ratio (HR) (crude HR 0.69, 95% confidence interval [CI] 0.57–0.83, p

Abstract TFE3-rearranged renal cell cancer (tRCC) is a rare form of RCC that involves chromosomal translocation of the Xp11.2 TFE3 gene. Despite its early onset and poor prognosis, the molecular mechanisms of the pathogenesis of tRCC remain elusive. This study aimed to identify novel therapeutic targets for patients with primary and recurrent tRCC. We collected 19 TFE3-positive RCC tissues that were diagnosed by immunohistochemistry and subjected them to genetic characterization to examine their genomic and transcriptomic features. Tumor-specific signatures were extracted using whole exome sequencing (WES) and RNA sequencing (RNA-seq) data, and the functional consequences were analyzed in a cell line with TFE3 translocation. Both a low burden of somatic single nucleotide variants (SNVs) and a positive correlation between the number of somatic variants and age of onset were observed. Transcriptome analysis revealed that four samples (21.1%) lacked the expected fusion event and clustered with the genomic profiles of clear cell RCC (ccRCC) tissues. The fusion event also demonstrated an enrichment of upregulated genes associated with mitochondrial respiration compared with ccRCC expression profiles. Comparison of the RNA expression profile with the TFE3 ChIP-seq pattern data indicated that PPARGC1A is a metabolic regulator of the oncogenic process. Cell proliferation was reduced when PPARGC1A and its related metabolic pathways were repressed by its inhibitor SR-18292. In conclusion, we demonstrate that PPARGC1A-mediated mitochondrial respiration can be considered a potential therapeutic target in tRCC. This study identifies an uncharacterized genetic profile of an RCC subtype with unique clinical features and provides therapeutic options specific to tRCC.

Abstract The COHORT trial was conducted to compare the efficacy of androgen deprivation therapy (ADT) alone versus combined with radiation therapy (ADT + RT) for clinically node-positive prostate cancer. We reported adverse events and quality of life between the two treatment groups. Fifty-nine patients were randomized to receive ADT alone or ADT + RT and analyzed as per-protocol. Patients allocated to the ADT alone arm received ADT for at least 2 years. Patients in the ADT + RT arm received additional pelvic RT. Higher rates of grade ≥ 2 acute genitourinary (0% vs. 7.1%) and late gastrointestinal adverse events (0% vs. 14.3%) were reported in the ADT + RT arm compared with the ADT alone. However, grade ≥ 2 late genitourinary toxicity was more common in the ADT alone than the ADT + RT arm (9.7% vs. 3.6%). No grade ≥ 3 adverse events were reported. There was no statistically significant difference in EPIC scores between two treatment arms. However, the urinary and bowel domains tended to decrease and recover in the ADT + RT arm. In conclusion, ADT + RT demonstrated higher rates of adverse events compared to ADT alone. However, the addition of RT did not significantly impact the quality of life.

Abstract To evaluate the recurrence rate and risk factors of recurrence after robot-assisted laparoscopic partial nephrectomy for solitary renal cell carcinoma (RCC). A total of 1265 cases of initial solitary localized RCC were analyzed. The baseline characteristics, complexity (REANL nephrometry score), intra- and peri-operative outcomes, and recurrence were evaluated. Logistic regression was performed to evaluate the factors affecting recurrence after RAPN for solitary localized RCC. Recurrence after robot-assisted partial nephrectomy (RAPN) occurred in 29 patients (2.29%). The median follow-up was 36.0 months. The N domain (nearness to collecting system/sinus) (odd ratio (OR) 3.517, 95% confidence interval (CI) 1.557–7.945, p = 0.002), operation time (OR 1.005, 95% CI 1.001–1.010, p = 0.013), and perioperative transfusion (OR 5.450, 95% CI 1.197–24.816, p = 0.028) affected recurrence. Distant metastasis among patients with recurrence was significantly associated with nearness to the collecting system/sinus (OR 2.982, 95% CI 1.162–7.656, p = 0.023) and distance between the mass and collecting system/sinus (OR 0.758, 95% CI 0.594–0.967, p = 0.026). Nearness to the collecting system/sinus, operation time, and perioperative transfusion affect recurrence after RAPN for solitary localized RCC. Moreover, the proximity to the collecting system/sinus and distance between the mass and collecting system/sinus were significantly related to distant metastasis after RAPN.

Abstract We compared the progression patterns after radical nephroureterectomy (RNU) and elective distal ureterectomy (DU) in patients with urothelial carcinoma of the distal ureter. Between Jan 2011 and Dec 2020, 127 patients who underwent RNU and 46 who underwent elective DU for distal ureteral cancer were enrolled in this study. The patterns of progression and upper tract recurrence were compared between the two groups. Progression was defined as a local recurrence and/or distant metastasis after surgery. Upper tract recurrence and subsequent treatment in patients with DU were analyzed. Progression occurred in 35 (27.6%) and 10 (21.7%) patients in the RNU and DU groups, respectively. The progression pattern was not significantly different (p = 0.441), and the most common progression site was the lymph nodes in both groups. Multivariate logistic regression analysis revealed that pT2 stage, concomitant lymphovascular invasion, and nodal stage were significant predictors of disease progression. Upper tract recurrence was observed in nine (19.6%) patients with DU, and six (66.7%) patients had a prior history of bladder tumor. All patients with upper tract recurrence after DU were managed with salvage RNU. Elective DU with or without salvage treatment was not a risk factor for disease progression (p = 0.736), overall survival (p = 0.457), cancer-specific survival (p = 0.169), or intravesical recurrence-free survival (p = 0.921). In terms of progression patterns and oncological outcomes, there was no difference between patients who underwent RNU and elective DU with/without salvage treatment. Elective DU should be considered as a therapeutic option for distal ureter tumor.

Abstract The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1–4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1–2) or a high-grade group (WHO/ISUP grade 3–4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5–18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6–17.4) in the high-grade group and 28.0 months (21.1–34.9) in the low-grade group (p

Purpose: To create a nomogram that can predict the probability of prostate cancer using prostate health index (PHI) and clinical parameters of patients. And the optimal cut-off value of PHI for prostate cancer was also assessed. Materials and Methods: A prospective, multi-center study was conducted. PHI was evaluated prior to biopsy in patients requiring prostate biopsy due to high prostate-specific antigen (PSA). Among screened 1,010 patients, 626 patients with clinically suspected prostate cancer with aged 40 to 85 years, and with PSA levels ranging from 2.5 to 10 ng/mL were analyzed. Results: Among 626 patients, 38.82% (243/626) and 22.52% (141/626) were diagnosed with prostate cancer and clinically significant prostate cancer, respectively. In the PSA 2.5 to 4 ng/mL group, the areas under the curve (AUCs) of the nomograms for overall prostate cancer and clinically significant prostate cancer were 0.796 (0.727–0.866; p

Background The aim of this study was to evaluate the risk factors for prostate-specific antigen (PSA) persistence in pathological stage T3aN0 prostate cancer (PCa) after robot-assisted laparoscopic radical prostatectomy (RALP). Methods A retrospective study was performed on 326 patients with pT3aN0 PCa who underwent RALP between March 2020 and February 2022. PSA persistence was defined as nadir PSA of >0.1 ng/mL after RALP, and the risk factors for PSA persistence were evaluated using logistic regression analysis. Results Among 326 patients, 61 (18.71%) had PSA persistence and 265 (81.29%) had PSA of

Background: This study aimed to evaluate the treatment outcomes and define the prostate-specific antigen (PSA) kinetics as potential prognostic factors in patients with intermediate- or high-risk localized prostate cancer (PCa) who underwent moderately hypofractionated radiation therapy. Methods: The study retrospectively reviewed the medical records of 149 patients with intermediate- or high-risk localized PCa who underwent definitive radiation therapy (70 Gy in 28 fractions) without androgen deprivation therapy. Clinical outcomes were analyzed based on risk stratification (favorable-intermediate, unfavorable-intermediate, and high-risk). The biochemical failure rate (BFR) and clinical failure rate (CFR) were stratified based on the PSA nadir and the time to the PSA nadir to identify the prognostic effect of PSA kinetics. Acute and late genitourinary and gastrointestinal adverse events were analyzed. Results: Significant differences were observed in the BFR and CFR according to risk stratification. No recurrence was observed in the favorable intermediate-risk group. The 7-year BFR and CFR for the unfavorable intermediate-risk and high-risk groups were 19.2% and 9.8%, and 31.1% and 25.3%, respectively. Patients with a PSA nadir >0.33 ng/mL or a time to the PSA nadir

Nephron-sparing surgery is the standard treatment for small renal mass (SRM). Nephron-sparing surgery has evolved from an open to a minimally invasive technique. Robot-assisted partial nephrectomy (RAPN) is the latest technique in this field and is reported to be safe and feasible, showing oncologically and functionally superior or compatible results compared with open and laparoscopic partial nephrectomy for SRM. This is not limited to only SRM but also applies to large and complex renal masses and other challenging situations. RAPN showed good oncological and functional outcomes for ≥clinical T2 renal tumors, complex renal masses (PADUA score ≥10, RENAL score ≥10), hilar renal tumors, and multiple renal tumors. In addition, the outcomes of RAPN in these challenging cases were not inferior to those in conventional cases. RAPN could also be applied to a number of challenging cases in which the open technique was considered first. RAPN showed good results in patients with a solitary kidney, horseshoe kidney, and in repeat surgeries. Furthermore, RAPN could be safely performed on obese, elderly, and pediatric patients. Finally, this review evaluates efficiency and utility of RAPN based on the results of challenging cases of renal masses and to project the future of RAPN.

Purpose This study investigated whether two-dimensional shear wave elastography (2D-SWE), using a newly developed device, is useful for predicting prostate cancer (PCa). Methods In this prospective study, 38 patients with suspected PCa underwent 2D-SWE, followed by a standard systematic 12-core biopsy with and without a targeted biopsy. Tissue stiffness on SWE was measured in the target lesion and in 12 regions of the systematic biopsies, and the maximum (Emax), mean (Emean), and minimum (Emin) values of stiffness were generated. The area under the receiver operating characteristic curve (AUROC) for predicting clinically significant cancer (CSC) was calculated. Interobserver reliability and variability were evaluated using the intraclass correlation coefficient (ICC) and Bland-Altman plots, respectively. Results PCa was found in 78 of 488 regions (16%) in 17 patients. In region-based and patientbased analyses, the Emax, Emean, and Emin values of PCa were significantly higher than those of benign prostate tissue (P

ObjectiveUsing multi-parametric magnetic resonance imaging (mpMRI) to identify patients with clinical T3a (cT3a) who were overestimated on mpMRI with final pathological T2 (pT2). To suggest that the neurovascular bundle (NVB) can be preserved by evaluating the characteristics of patients according to their pathological grade among cT3a prostate cancer (PCa) patients using mpMRI.Materials and methodsPatients who underwent robot-assisted laparoscopic radical prostatectomy (RALP) were retrospectively analyzed and those patients with clinical T3aN0M0 were enrolled. These enrolled patients were divided into a localized cancer group with pT2 PCa and a locally advanced group with pT3a or higher. Factors affecting the diagnosis of localized PCa after RALP in patients with cT3a PCa were evaluated.ResultsAmong the preoperative parameters of patients with cT3a PCa, the prostate specific antigen density (PSAD) (OR: 3.76, 95% CI: 1.85–7.64, p

Key points The new transperineal ultrasound (TPUS) technique can offer an accessible route in men without an anus. A PI-RADS 5 tumor is a good indication for the new TPUS-guided biopsy technique. The TPUS-guided biopsy is difficult to target a small prostate tumor (

In chronic infections and cancer, exhausted CD8 T cells exhibit heterogeneous subpopulations. TCF1+PD-1+ progenitor exhausted CD8 T cells (Tpex) can self-renew and give rise to Tim-3+PD-1+ terminally differentiated CD8 T cells that retain their effector functions. Tpex cells are thus essential to maintaining a pool of antigen-specific CD8 T cells during persistent antigenic stimulation, and only they respond to PD-1-targeted therapy. Despite their potential as a crucial therapeutic target for immune interventions, the mechanisms controlling the maintenance of virus-specific Tpex cells remain to be determined. We observed approximately 10-fold fewer Tpex cells in the spleens of mice chronically infected with lymphocytic choriomeningitis virus (LCMV) one-year post-infection (p.i.) than at three months p.i. Similar to memory CD8 T cells, Tpex cells have been found to undergo self-renewal in the lymphoid organs, prominently the bone marrow, during chronic LCMV infection. Furthermore, ex vivo treatment with IL-15 preferentially induced the proliferation of Tpex cells rather than the terminally differentiated subsets. Interestingly, single-cell RNA sequencing analysis of LCMV-specific exhausted CD8 T cells after ex vivo IL-15 treatment compared with those before treatment revealed increased expression of ribosome-related genes and decreased expression of genes associated with the TCR signaling pathway and apoptosis in both Tpex and Ttex subsets. The exogenous administration of IL-15 to chronically LCMV-infected mice also significantly increased self-renewal of Tpex cells in the spleen and bone marrow. In addition, we assessed the responsiveness of CD8 tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma patients to IL-15. Similar to the data we obtained from chronic viral infection in mice, the expansion of the Tpex subset of PD-1+ CD8 TILs upon ex vivo IL-15 treatment was significantly higher than that of the terminally differentiated subset. These results show that IL-15 could promote self-renewal of Tpex cells, which has important therapeutic implications.

Objectives: To efficiently implement artificial intelligence (AI) software for medical applications, it is crucial to understand the acceptance, expected effects, expected performance, and concerns of software users. In this study, we examine the acceptance and expectation of the Dr. Answer AI software for prostate cancer. Methods: We conducted an online survey for urologists from August 13 to September 18, 2020. The target software is an AI-based clinical software called Dr. Answer AI software, used for prostate cancer diagnosis. We collected data from 86 urologists and conducted a basic statistical and multiple regression analysis using the R package. Results: The compatibility was significantly associated with the intention to use the Dr. Answer AI software. The expected average accuracy for the software ranges from 86.91% to 87.51%, and the urologists perceived that the cloud method is suitable to introduce the software. The most desirable function of the software for the specialists is predicting the occurrence of extracapsular extension, seminal vesicle invasion, and lymph node metastasis after radical prostatectomy. Finally, the primary concerns involved the cost, compatibility with existing systems, and obtaining accurate information from the software. Conclusions: Our results present an understanding of the acceptance, expected effects, expected performance, and concerns of software users. The results provide a guide to help AI software be properly developed and implemented in medical applications.

Background: We investigated the necessity of multiple core biopsies when performing transperineal template-guided mapping biopsy (TTMB) for patients with large prostates and no suspicious lesions on multiparametric magnetic resonance imaging (mpMRI). Materials and methods: We retrospectively analyzed 304 patients on active surveillance (AS), 212 patients with previously negative transrectal ultrasound-guided biopsy (TRUS-Bx) and 67 biopsy naïve patients who underwent TTMB between May 2017 and December 2020. The number of core biopsies and acute urinary retention (AUR) rates were analyzed in relation to the prostate volume (PV). Cancer detection rate according to the prostate volume and Prostate Imaging-Reporting and Data System (PI-RADS) scores were compared using the Pearson Chi-square test. Results: AUR occurred more frequently in patients with PV over 39 cc (5.5% vs. 24.4%, P

The use of patient-derived tumor tissues and cells has led to significant advances in personalized cancer therapy and precision medicine. The advent of genomic sequencing technologies has enabled the comprehensive analysis of tumor characteristics. The three-dimensional tumor organoids derived from self-organizing cancer stem cells are valuable ex vivo models that faithfully replicate the structure, unique features, and genetic characteristics of tumors. These tumor organoids have emerged as innovative tools that are extensively employed in drug testing, genome editing, and transplantation to guide personalized therapy in clinical settings. However, a major limitation of this emerging technology is the absence of a tumor microenvironment that includes immune and stromal cells. The therapeutic efficacy of immune checkpoint inhibitors has underscored the importance of immune cells, particularly cytotoxic T cells that infiltrate the vicinity of tumors, in patient prognosis. To address this limitation, co-culture techniques combining tumor organoids and T cells have been developed, offering diverse avenues for studying individualized drug responsiveness. By integrating cellular components of the tumor microenvironment, including T cells, into tumor organoid cultures, immuno-oncology has embraced this technology, which is rapidly advancing. Recent progress in co-culture models of tumor organoids has allowed for a better understanding of the advantages and limitations of this novel model, thereby exploring its full potential. This review focuses on the current applications of organoid-T cell co-culture models in cancer research and highlights the remaining challenges that need to be addressed for its broader implementation in anti-cancer therapy.

Abstract We aimed to evaluate the detection rates of prostate cancer (PCa) and clinically significant PCa (csPCa) using magnetic resonance imaging-targeted biopsy (MRI-TBx) in men with low prostate-specific antigen (PSA) levels (2.5–4.0 ng/mL). Clinicopathologic data of 5502 men with PSA levels of 2.5–10.0 ng/mL who underwent transrectal ultrasound-guided biopsy (TRUS-Bx) or MRI-TBx were reviewed. Participants were divided into four groups: LP-T [low PSA (2.5–4.0 ng/mL) and TRUS-Bx, n = 2018], LP-M (low PSA and MRI-TBx, n = 186), HP-T [high PSA (4.0–10.0 ng/mL) and TRUS-Bx, n = 2953], and HP-M (high PSA and MRI-TBx, n = 345). The detection rates of PCa and csPCa between groups were compared, and association of biopsy modality with detection of PCa and csPCa in men with low PSA levels were analyzed. The detection rates of PCa (20.0% vs. 38.2%; P

As the incidence of prostate cancer (PCa) has increased, screening based on prostate-specific antigen (PSA) has become controversial due to the low specificity of PSA. Therefore, we investigated the diagnostic performance of prostate health index (PHI) density (PHID) for the detection of PCa and clinically significant PCa (csPCa) compared to PSA, PSA density (PSAD), and PHI as a triaging test. We retrospectively reviewed 306 men who underwent prostate biopsy for PSA levels of 2.5 to 10 ng/mL between January 2020 and April 2023. Of all cohorts, 86 (28.1%) and 48 (15.7%) men were diagnosed with PCa and csPCa, respectively. In ROC analysis, the highest AUC was identified for PHID (0.812), followed by PHI (0.791), PSAD (0.650), and PSA (0.571) for PCa. A similar trend was observed for csPCa: PHID (AUC 0.826), PHI (AUC 0.796), PSAD (AUC 0.671), and PSA (0.552). When the biopsy was restricted to men with a PHID ≥ 0.56, 26.5% of unnecessary biopsies could be avoided; however, 9.3% of PCa cases and one csPCa case (2.1%) remained undiagnosed. At approximately 90% sensitivity for csPCa, at the given cut-off values of PHI ≥ 36.4, and PHID ≥ 0.91, 48.7% and 49.3% of unnecessary biopsies could be avoided. In conclusion, PHID had a small advantage over PHI, about 3.6%, for the reduction in unnecessary biopsies for PCa. The PHID and PHI showed almost the same diagnostic performance for csPCa detection. PHID can be used as a triaging test in a clinical setting to pre-select the risk of PCa and csPCa.

Purpose: To evaluate the clinical impact of strict selection criteria for active surveillance (AS) of prostate cancer in a Korean population. Materials and Methods: A single-center, prospectively collected AS cohort from December 2016 to February 2019 was used. Following pre-determined criteria, patients were categorized into “strict AS” and “non-strict AS” groups. Clinicopathological progression-free survival (PFS) and treatment-free survival (TFS) of the two groups were compared using the Kaplan–Meier curve and log-rank test. Age-adjusted hazard ratios for clinicopathological progression was calculated using Cox proportional regression analysis. Results: Of 54 eligible patients, 25 and 29 were assigned to “strict AS” and “non-strict AS,” respectively. Clinicopathological progression and definitive treatment rates were 24.0% (6 of 25 patients) vs. 51.7% (15 of 29 patients) and 32.0% (8 of 25 patients) vs. 62.1% (18 of 29 patients) in “strict AS” and “non-strict AS” groups. Progress to high-risk cancer (pathologic T3 or surgical Gleason Grade 2 over) in radical prostatectomy was higher in “non-strict AS” than “strict AS”. PFS (mean 34.6±2.9 mo vs. 22.6±2.7 mo; p=0.025) and TFS (mean 31.8±3.2 mo vs. 19.6±2.4 mo; p=0.018) favor the “strict AS” group than “non-strict AS” group. Age-adjusted hazard ratio for clinicopathological progression of strict criteria was 0.36 (95% confidence interval, 0.14–0.94; p=0.04). Conclusions: PFS and TFS were better in the “strict AS” group than in the “non-strict AS” group. This finding should be informed to relevant patients during decision making and considered in Korean guidelines.

Due to the highly immunogenic nature of renal cell carcinoma (RCC), the tumor microenvironment (TME) is enriched with various innate and adaptive immune subsets. In particular, gamma-delta (γδ) T cells can act as potent attractive mediators of adoptive cell transfer immunotherapy because of their unique properties such as non-reliance on major histocompatibility complex expression, their ability to infiltrate human tumors and recognize tumor antigens, relative insensitivity to immune checkpoint molecules, and broad tumor cytotoxicity. Therefore, it is now critical to better characterize human γδ T-cell subsets and their mechanisms in RCCs, especially the stage of differentiation. In this study, we aimed to identify γδ T cells that might have adaptive responses against RCC progression. We characterized γδ T cells in peripheral blood and tumor-infiltrating lymphocytes (TILs) in freshly resected tumor specimens from 20 RCC patients. Furthermore, we performed a gene set enrichment analysis on RNA-sequencing data from The Cancer Genome Atlas (TCGA) derived from normal kidneys and RCC tumors to ascertain the association between γδ T-cell infiltration and anti-cancer immune activity. Notably, RCC-infiltrating CD3low Vγ9Vδ1 T cells with a terminally differentiated effector memory phenotype with up-regulated activation/exhaustion molecules were newly detected as predominant TILs, and the cytotoxic activity of these cells against RCC was confirmed in vitro. In an additional analysis of the TCGA RCC dataset, γδ T-cell enrichment scores correlated strongly with those for CTLs, Th1 cells, “exhausted” T cells, and M1 macrophages, suggesting active involvement of γδ T cells in anti-tumor rather than pro-tumor activity, and Vδ1 cells were more abundant than Vδ2 or Vδ3 cells in RCC tumor samples. Thus, we posit that Vγ9Vδ1 T cells may represent an excellent candidate for adoptive immunotherapy in RCC patients with a high risk of relapse after surgery.

Abstract This study aims to compare oncologic and functional outcomes after radical nephroureterectomy (RNU) and segmental ureterectomy (SU) in patients with upper urinary tract urothelial carcinoma (UTUC). We retrospectively collected data on patients who underwent either RNU or SU of UTUC. Propensity score matching was performed among 394 cases to yield a final cohort of 40 RNU and 40 SU cases. Kaplan–Meier analysis and the log-rank test were used to compare overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and intravesical recurrence-free survival (IVRFS) between the groups. We also compared the change in postoperative estimated glomerular filtration rate (eGFR). There was no significant difference in terms of CSS, PFS, and IVRFS between the RNU and SU groups, but the RNU group had a better OS than the SU group (p = 0.032). Postoperative eGFR was better preserved in the SU group than in the RNU group (p

Purpose: To investigate germline and somatic mutation profiles in Korean patients with prostate cancer using liquid biopsy and solid tissue testing and to evaluate the prognostic value of circulating tumor DNA (ctDNA) in predicting castration resistance in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Materials and Methods: Plasma samples from 56 prostate cancer patients were subjected to next-generation sequencing (NGS) to identify germline mutations and ctDNA analysis using liquid biopsy to detect somatic mutations. Additionally, paired solid cancer tissues from 18 patients were subject to NGS to detect somatic mutations. The clinical parameters and ctDNA profiles of patients with mHSPC were analyzed to evaluate the prognostic value of ctDNA mutations with respect to predicting castration resistance using Cox proportional hazards regression analysis. Results: Germline mutations occurred in 3.6% of the patients in this cohort, with mutations identified in RAD50 (1.8%) and BRCA1 (1.8%). Somatic mutations detected by liquid biopsy and solid tissue testing were common in TP53 (12.5%), PIK3CA (3.6%), and TMPRSS2-ERG (3.6%). Of the 18 patients with paired tissue testing, two patients had at least one identical somatic mutation in both the liquid biopsy and solid tissue testing. In patients with mHSPC, the presence of ctDNA mutations could independently predict the castration resistance development (hazard ratio, 13.048; 95% confidential interval, 1.109–153.505; p=0.041). Conclusions: Korean patients with prostate cancer showed a relatively low germline mutation rate compared to other ethnicities. The ctDNA mutations detected by liquid biopsy can predict the development of castration resistance in patients with mHSPC.

Purpose: Prostate cancer has a low mortality rate and requires persistent treatment; however, treatment decisions are challenging. Because prostate cancer is complex, the outcomes warrant thorough follow-up evaluation for appropriate treatment. Electronic health records (EHRs) do not present intuitive information. This study aimed to develop a Clinical Decision Support System (CDSS) for prognosis management of radical prostatectomy. Methods: We used data from 5,199 prostate cancer patients from three hospitals’ EHRs in South Korea, comprising laboratory results, surgery, medication, and radiation therapy. We used open source R for data preprocessing and development of web-based visualization system. We also used R for automatic calculation functionalities of two factors to visualize the data, e.g., Prostate-Specific Antigen Doubling Time (PSADT), and four Biochemical Recurrence (BCR) definitions: American Society of Therapeutic Radiology and Oncology (ASTRO), Phoenix, consecutive PSA > 0.2 ng/mL, and PSA > 0.2 ng/mL. Results: We developed the Prostate Cancer Trajectory Map (PCT-Map) as a CDSS for intuitive visualization of serial data of PSA, testosterone, surgery, medication, radiation therapy, BCR, and PSADT. Conclusions: The PCT-Map comprises functionalities for BCR and PSADT and calculates and visualizes the newly added patient data automatically in a PCT-Map data format, thus optimizing the visualization of patient data and allowing clinicians to promptly access patient data to decide the appropriate treatment.

Abstract We evaluated the predictive role of circulating tumor DNA (ctDNA) detection by targeted deep sequencing in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint blockades (ICB). To determine the feasibility of ctDNA detection in our panel encompassing 40 genes, we collected 10 ml of blood from 20 patients at the time of radical nephrectomy. We analyzed somatic mutations in primary tumors and ctDNA samples from these patients. We finally collected 10 ml of blood before and after 1 month of treatment, respectively, from four patients with mRCC who received first-line ICB treatment. Variants were detected in primary tumors of 15 patients (75%) and ctDNA was detected in the plasma of 9 patients (45%). We examined the predictive role of ctDNA in four patients who received first-line ICB therapy. In two patients showing partial response, ctDNA levels decreased after 1 month of ICB treatment. However, in one patient who showed disease progression, ctDNA levels increased after 1 month of ICB treatment. Taken together, ctDNA detection in plasma by targeted deep sequencing was feasible in patients with RCC. Moreover, the levels of ctDNA could be an early predictor of treatment response in patients with mRCC who receive ICB therapy.

The purpose of this study was to determine the prognostic impact of fat loss after immune checkpoint inhibitor (ICI) treatment in patients with metastatic clear cell renal cell carcinoma (ccRCC). Data from 60 patients treated with ICI therapy for metastatic ccRCC were retrospectively analyzed. Changes in cross-sectional areas of subcutaneous fat (SF) between the pre-treatment and post-treatment abdominal computed tomography (CT) images were expressed as percentages and were divided by the interval between the CT scans to calculate ΔSF (%/month). SF loss was defined as ΔSF < −5%/month. Survival analyses for overall survival (OS) and progression-free survival (PFS) were performed. Patients with SF loss had shorter OS (median, 9.5 months vs. not reached; p < 0.001) and PFS (median, 2.6 months vs. 33.5 months; p < 0.001) than patients without SF loss. ΔSF was independently associated with OS (adjusted hazard ratio (HR), 1.49; 95% confidence interval (CI), 1.07–2.07; p = 0.020) and PFS (adjusted HR, 1.57; 95% CI, 1.17–2.12; p = 0.003), with a 5%/month decrease in SF increasing the risk of death and progression by 49% and 57%, respectively. In conclusion, Loss of SF after treatment initiation is a significant and independent poor prognostic factor for OS and PFS in patients with metastatic ccRCC who receive ICI therapy.

Purpose: To determine the clinical significance and correlation between the Prostate Health Index (PHI) and Gleason score in patients with a prostate-specific antigen (PSA) value of 2.5–10 ng/mL. Materials and Methods: This retrospective analysis included 114 patients who underwent biopsy after completion of the PHI from November 2018 to July 2019. Various parameters such as PSA, PHI, PSA density, free PSA, p2PSA, and %free PSA were collected, and correlations with biopsy Gleason score and cancer detection rates were investigated. Results: Baseline characteristics were comparable between PHI groups (0–26.9 [n=11], 27.0–35.9 [n=17], 36.0–54.9 [n=50], and ≥55.0 [n=36]). A total of 37 patients (32.5%) were diagnosed with prostate cancer, and 28 (24.6%) were diagnosed with clinically significant prostate cancer (CSPC, Gleason score ≥7) after prostate biopsy. The cancer detection rate gradually increased with a corresponding increase in the PHI (18%, 24%, 30%, and 44%, respectively). The same pattern was observed with detecting CSPC (0%, 18%, 26%, and 33%, respectively). There was no CSPC in the groups with PHI

PurposePatients with International Metastatic RCC Database Consortium (IMDC) poor risk metastatic renal cell carcinoma (mRCC) rarely respond to first-line tyrosine kinase inhibitors (TKIs) including sunitinib, and carries a very poor prognosis. In recent years, combination therapy involving immune checkpoint inhibitors (ICIs) have demonstrated superior efficacy to sunitinib in poor risk disease.Materials and MethodsIn a retrospective study using a cancer chemotherapy registry, 206 consecutive patients with mRCC in the first-line setting were identified between Oct 2019 and Dec 2020. Sixty-one patients had a poor risk mRCC, and were treated with TKI monotherapy (n=36), nivolumab plus ipilimumab (n=16), or pembrolizumab plus axitinib (n=9). Endpoints included overall survival (OS), progression-free survival (PFS), response rate (RR), and safety.ResultsPatients’ median age was 61 years and the median number of risk factors was 3 (range, 3-5). During a median 23.0 months of follow-up, the median OS was 24.3 months with ICI-based combinations and 14.8 months with TKI monotherapy, and the median PFS periods were 9.3 months and 3.4 months, respectively. An objective response occurred in 60% of the patients receiving ICI-based combinations and in 19% of those receiving TKI monotherapy (P=0.001). In the multivariate regression model, number of IMDC risk factors and the ICI-based combination therapy were independent prognostic factors for PFS. All-causality grade 3 or 4 adverse events were 44% for ICI-based combinations and 50% for TKI monotherapy.ConclusionsAmong patients with poor risk mRCC, first-line ICI-based therapy showed significantly longer OS and PFS, as well as a higher RR, than TKI monotherapy.

Purpose: The clinical impact of the platelet-to-lymphocyte ratio (PLR) on the prognosis of patients with metastatic renal cell carcinoma (mRCC) remains controversial. We investigated the associations between elevation of the PLR and disease prognosis in patients with synchronous mRCC. Materials and Methods: The data of 1,505 patients with synchronous mRCC were retrospectively analyzed. The entire cohort was stratified into two subgroups according to PLR. Kaplan–Meier and Cox proportional analyses were performed to investigate the possible associations between the PLR and disease prognosis. Results: There were 921 patients with a high PLR and 584 patients with a low PLR by use of the cutoff of 146. The patients with a high PLR had worse clinical characteristics in terms of advanced clinical stage (p

Purpose: This study aimed to evaluate the clinical efficacy of enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients using real-world data from Korean patients. Materials and Methods: We retrospectively reviewed the medical records of 199 chemotherapy-naïve patients with mCRPC at 13 tertiary centers in Korea between 2014 and 2017. All patients received enzalutamide daily and 89 patients received concurrent androgen deprivation therapy (ADT). Results: The median age of the patients was 74 years. Initial results showed that 81.5% of the patients had Gleason score ≥8 and 33.3% of the patients had European Cooperative Oncology Group Performance Status 0. The overall mortality rate was 12%. The median OS was not archieved and 76.7% of patients were alive at 30 months. Median time until PSA progression was 6 months. The overall survival rate at 2 years was significantly higher (84.6% vs. 71.7%, p=0.015) and the duration of PSA progression-free survival was significantly longer (8.0 vs. 4.6 months, p=0.008) in patients receiving concurrent ADT than in those receiving enzalutamide alone. The incidence of adverse events of grade 3 or higher was 1.7%. Multivariate Cox proportional hazard analysis indicated that ADT administered concurrently with enzalutamide significantly improved the overall survival (hazard ratio, 0.346; 95% confidence interval, 0.125–0.958). Conclusions: Enzalutamide is effective and safe for chemotherapy-naïve patients with mCRPC. Furthermore, the overall survival was significantly higher in patients receiving enzalutamide and concurrent ADT than in patients receiving enzalutamide alone.

[This corrects the article DOI: 10.1371/journal.pone.0249709.].

BackgroundMagnetic resonance imaging (MRI) and transrectal ultrasound (TRUS)-guided cognitive or image fusion biopsy is performed to target a prostate imaging reporting and data system (PI-RADS) 3–5 lesion. Biopsy Gleason score (GS) is frequently underestimated compared to prostatectomy GS. However, it is still unclear about how many cores on target are necessary to reduce undergrading and if additional cores around the target may improve grade prediction on surgical specimen.PurposeTo determine the number of target cores and targeting strategy to reduce GS underestimation.Materials and MethodsBetween May 2017 and April 2020, a total of 385 patients undergoing target cognitive or image fusion biopsy of PI-RADS 3–5 index lesions and radical prostatectomies (RP) were 2:1 matched with propensity score using multiple variables and divided into the 1–4 core (n = 242) and 5–6 core (n = 143) groups, which were obtained with multiple logistic regression with restricted cubic spline curve. Target cores of 1–3 and 4–6 were sampled from central and peripheral areas, respectively. Pathologic outcomes and target cores were retrospectively assessed to analyze the GS difference or changes between biopsy and RP with Wilcoxon signed-rank test.ResultsThe median of target cores was 3 and 6 in the 1–4 core and 5–6 core groups, respectively (p < 0.001). Restricted cubic spline curve showed that GS upgrade was significantly reduced from the 5th core and there was no difference between 5th and 6th cores. Among the matched patients, 35.4% (136/385; 95% confidence interval, 0.305–0.403) had a GS upgrade after RP. The GS upgrades in the 1–4 core and 5–6 core groups were observed in 40.6% (98/242, 0.343–0.470) and 26.6% (38/143, 0.195–0.346), respectively (p = 0.023). Although there was no statistical difference between the matched groups in terms of RP GS (p = 0.092), the 5–6 core group had significantly higher biopsy GS (p = 0.006) and lower GS change from biopsy to RP (p = 0.027).ConclusionFive or more target cores sampling from both periphery and center of an index tumor contribute to reduce GS upgrade.

Purpose: To investigate the clinical utility of transperineal template-guided saturation prostate biopsy (TPB) for risk stratification after transrectal ultrasound (TRUS)-guided biopsy. Materials and Methods: We retrospectively reviewed 155 patients who underwent TPB after previously negative results on TRUS-guided biopsy (n=58) or who were candidates for active surveillance (n=97) fulfilling the PRIAS criteria between May 2017 and November 2018. The patients' clinicopathologic data were reviewed, and the detection of clinically significant cancer (CSC) and upgrading of Gleason grade were identified. Results: The patients' median age and pre-TPB prostate-specific antigen (PSA) value were 65.0 years and 5.74 ng/mL, respectively. A median of 36 biopsy cores was obtained in each patient, with a median TPB core density of 0.88 cores/cm3. Of the 58 males with a previous negative result on TRUS-guided biopsy, prostate cancer (PCa) was detected in 17 males (29.3%), including 8 with CSC. Of the 97 patient candidates for active surveillance, upgrading of the Gleason grade was identified in 31 males (32.0%), 20 with a Gleason grade of 7 (3+4), 6 with a Gleason grade of 7 (4+3), and 5 with a Gleason grade of 8 (4+4). The overall complication rate was 14.8% (23/155), and there were no Clavien–Dindo grade 3 to 5 complications. Conclusions: TPB helps to stratify the risk of PCa that was previously missed or underdiagnosed by TRUS-guided biopsy. TPB might be used as a diagnostic tool to determine risk classification and to help counsel patients with regard to treatment decisions.

BackgroundTo evaluate the conditional intravesical recurrence (IVR)–free (IVRF) survival rate in patients with upper tract urothelial carcinoma (UTUC) who had no history of bladder cancer and no concomitant bladder cancer. Hence, we aimed to analyze a relatively large number of patients with UTUC who underwent radical nephroureterectomy with bladder cuff excision (RNUx).MethodsWe retrospectively analyzed the data of 1,095 patients with UTUC who underwent RNUx. Their baseline characteristics, bladder tumor history, and UTUC features were analyzed to evaluate oncological outcomes. To determine the factors affecting IVR, surgical modality, use of preoperative ureteroscopy, TNM stage, and pathological outcomes were evaluated. Multivariable Cox regression analyses were performed to evaluate the factors affecting IVR. Conditional IVRF survival rate was analyzed using Kaplan–Meier curves.ResultsAmong the 1,095 patients, 462 patients developed IVR, and the mean time to the development of IVR was 13.08 ± 0.84 months after RNUx. A total of 30.74% of patients with IVR and 15.32% of those without IVR had a history of bladder cancer (p < 0.001). Multivariable analysis showed that a history of bladder cancer, multifocal tumors, use of preoperative ureteroscopy, extravesical bladder cuffing method, lymph node involvement, positive surgical margins, and use of adjuvant chemotherapy were determined to be risk factors for IVR. The conditional IVRF rate was 74.0% at 12 months after RNUx, 87.1% at 24 months after RNUx, 93.6% at 36 months after RNUx, and 97.3% at 60 months after RNUx. The median IVRF survival period was 133.00 months for all patients. In patients with IVRF at 24 months after RNUx, only ureteroscopy was an independent risk factor for IVR [hazard ratio (HR) 1.945, p = 0.040]. In patients with IVRF at ≥36 months, there was no significant factor affecting IVR.ConclusionsActive IVR assessment is required until 36 months after RNUx. In addition, patient education and regular screening tests, such as urine analysis and cytology, are required for patients with IVRF for ≥36 months.

Purpose: This study aimed to compare functional and oncological outcomes between partial nephrectomy (PN) and radiofrequency ablation (RFA) for a small renal mass (SRM, ≤4 cm) in patients with chronic kidney disease (CKD). Materials and Methods: Patients with CKD who underwent either PN or RFA for SRM between 2005 and 2019 were included. Patients were stratified into two categories: CKD stage 2 and CKD stage 3 or higher. We performed propensity score matching (PSM) analysis in patients with CKD stage 2 and CKD stage 3 or higher. We compared the functional and oncological outcomes between two groups according to CKD stage before and after PSM. Results: Among 1332 patients, 1195 patients were CKD stage 2 and 137 patients were CKD stage 3 or higher. After PSM analysis using age, pre-treatment eGFR, and clinical tumor size as matching variables, the PN and RFA groups had 270 and 135 CKD stage 2 patients, respectively, and both had 53 patients each with CKD stage 3 or higher. There were no significant differences in percent change in eGFR at 1 year post-operation between groups in patients with CKD stage 2 and stage 3 or higher. Among all patients with tissue-proven malignancy, the 5-year recurrence-free survival (RFS), cancer-specific survival, and overall survival were significantly higher in the PN group. However, only the 5-year RFS was significantly higher in the PN group after matching. Conclusion: Mortality is low in patients with SRM, and functional outcomes were not significantly different between the two treatments. RFA could be an alternative treatment modality in patients who are poor candidates for surgery.

Objectives: To develop a model to predict biochemical recurrence (BCR) after radical prostatectomy (RP), using artificial intelligence (AI) techniques. Patients and Methods: This study collected data from 7,128 patients with prostate cancer (PCa) who received RP at 3 tertiary hospitals. After preprocessing, we used the data of 6,755 cases to generate the BCR prediction model. There were 16 input variables with BCR as the outcome variable. We used a random forest to develop the model. Several sampling techniques were used to address class imbalances. Results: We achieved good performance using a random forest with synthetic minority oversampling technique (SMOTE) using Tomek links, edited nearest neighbors (ENN), and random oversampling: accuracy = 96.59%, recall = 95.49%, precision = 97.66%, F1 score = 96.59%, and ROC AUC = 98.83%. Conclusion: We developed a BCR prediction model for RP. The Dr. Answer AI project, which was developed based on our BCR prediction model, helps physicians and patients to make treatment decisions in the clinical follow-up process as a clinical decision support system.

Purpose: To analyze the characteristics of somatic mutations and copy number alterations (CNAs) in Korean patients with advanced prostate cancer (PCa) by use of the Oncomine Comprehensive Panel (ThermoFisher Scientific) and low-coverage, whole-genome sequencing (LC-WGS). Materials and Methods: We retrospectively analyzed PCa tissues obtained from 14 patients with advanced PCa (metastatic tumor, 12 [85.7%]; nonmetastatic castration-resistant PCa, 1 [7.1%]; pT3b, 1 [7.1%]) from 2009 to 2017. The Oncomine Comprehensive Panel included a total of 143 genes. Moreover, LC-WGS was performed to detect CNAs of the entire genome. Two plasma samples matched with tumor tissues were analyzed using LC-WGS to compare the chromosomal aberration patterns between circulating tumor DNA and tumor tissue. Results: Genetic alterations were most frequently observed in the androgen receptor (AR) (42.9%, n=6/14), TP53 (14.3%, n=2/14), and PTEN (14.3%, n=2/14) genes in the Oncomine panel. AR amplification was the most common CNA (35.7%, n=5/14). As a result of LC-WGS, CNAs were confirmed in about 92.9% (n=13/14) of the samples in regions Xq12, 8q24.21, and 11q13.3 (gains) and in regions 6q16.1, 8p23.1, 10q25.1, 16q24.2, 18q12.3, Xq25, and Xq26.3 (losses). All CNAs identified in the Oncomine panel matched the results of LC-WGS. Additionally, LC-WGS of two plasma samples that matched tumor tissues revealed that CNA patterns of plasma samples (circulating tumor DNA) were very similar to those detected in tumor samples. Conclusions: Our data showed that the characteristics of mutations and CNAs in Korean patients with advanced PCa were similar to those observed in previous studies.

Abstract Background Results from randomized phase III trials have shown that thrice-weekly docetaxel added to androgen-deprivation therapy (ADT) has a significant impact on the survival of patients with metastatic castration-naïve prostate cancer (mCNPC) and established early chemotherapy as part of the standard of care for high-risk disease. Controversy remains, however, because some patients experience critical toxicities related to docetaxel. The purpose of the current study was to evaluate the feasibility and adverse events of biweekly-administered docetaxel in patients with previously-untreated, high-risk mCNPC. Methods The study included 35 consecutive patients with high-risk mCNPC who received ADT plus docetaxel 40 mg/m2. Oral prednisone 5 mg twice daily was also given. Treatment was repeated every two weeks for up to 12 cycles or until disease progression or unacceptable toxicity occurred. High-risk was defined as bone metastases beyond axial skeleton and/or visceral disease. Results The included patients’ median age was 68 years (range: 31–86 years) and 17 (49%) had visceral metastases. Biweekly docetaxel was generally well-tolerated; the most commonly observed adverse events, considering those of all grades, included alopecia (74%), nail changes (42%), and constipation (31%). Hematologic adverse events were infrequent, and no patient received hematopoietic growth factors. One patient died after the fourth cycle due to respiratory failure, which occurred as a complication of pneumonia. Among the 35 patients, 28 completed the planned 12 cycles of biweekly docetaxel. Prostate-specific antigen response (> 50% decrease from baseline) was recorded in 33 patients (94%), and the radiologic response rate was 49%. Median progression-free survival was 13.6 months (95% confidence interval: 6.7–20.4). Conclusion ADT plus biweekly-administered docetaxel appeared to be tolerated and effective in patients with high-risk mCNPC.

Patients with brain metastasis (BM) have a better prognosis when it is detected early. However, current guidelines recommend brain imaging only when there are central nervous system symptoms or abnormal experimental values. Therefore, metastases are discovered later in asymptomatic patients. As a result, there is a need for an algorithm that predicts the possibility of BM using clinical data and machine learning (ML). Data from 3153 patients with renal cell carcinoma (RCC) were collected from the 11-institution Korean Renal Cancer Study group (KRoCS) database. To predict BM, clinical information of 1282 patients was extracted from the database and used to compare the performance of six ML algorithms. The final model selection was based on the area under the receiver operating characteristic (AUROC) curve. After optimizing the hyperparameters for each model, the adaptive boosting (AdaBoost) model outperformed the others, with an AUROC of 0.716. We developed an algorithm to predict the probability of BM in patients with RCC. Using the developed predictive model, it is possible to avoid detection delays by performing computed tomography scans on potentially asymptomatic patients.

The hypersensitive prostate specific antigen (PSA) test can measure in 0.01 ng/mL units, and its efficacy for screening after radical prostatectomy (RP) has been reported. In this study, we assessed patients who underwent RP to evaluate whether the nadir value affects biochemical recurrence (BCR). From 1995 to 2014, patients classified as N0 who had negative resection margins and a nadir PSA of less than 0.2 ng/mL were evaluated. The characteristics, pathological outcomes, PSA after RP, and BCR were assessed. A total of 1483 patients were enrolled. Among them, 323 (21.78%) patients showed BCR after RP. The mean age of the BCR group was 63.86±7.31 years, and while that of the no-recurrence group was 64.06±6.82 years (P = 0.645). The mean preoperative PSA of the BCR group was 9.75±6.92 ng/mL and that of the no-recurrence group was 6.71±5.19 ng/mL (P < 0.001). The mean time to nadir (TTN) in the BCR group was 4.64±7.65 months, while that in the no-recurrence group was 7.43±12.46 months (P < 0.001). The mean PSA nadir value was 0.035±0.034 ng/mL in the BCR group and 0.014±0.009 ng/mL in the no-recurrence group (P < 0.001). In multivariable Cox regression analyses, Gleason score, positive biopsy core percentages, minimal invasive surgery, nadir PSA value, and TTN were independently associated with BCR. The mean BCR occurred at 48.23±2.01 months after RP, and there was a significant difference in BCR occurrence according to the nadir PSA value (P < 0.001). A high PSA nadir value and short TTN may predict the risk of BCR after successful RP, aiding the identification of candidates for adjuvant or salvage therapies after RP.

Background: To evaluate the utility of contemporary health screening (HS) in the diagnosis of bladder cancer (BCa). Methods: We retrospectively reviewed 279,683 individuals who underwent HS between February 1995 and April 2015. Among these individuals, 74 were diagnosed with BCa within a year after the HS and were included in the analysis. Screen-detected BCa was defined as when a referral was made to a urologist due to microscopic hematuria (MH) on urinalysis, abnormal imaging, or any urological symptoms observed at the HS. Screen-undetected BCa was defined as when no referral was made to a urologist because of no abnormality observed at the HS, but a visit to a urological outpatient clinic later was followed by a BCa diagnosis. The incidences of screen-detected BCa and BCa in the Korean population were compared. Clinicopathological characteristics were compared between the screen-detected BCa and screen-undetected BCa groups. Results: The detection rate of BCa was 17.2 per 100,000, which exceeded the 2020 estimated national crude incidence rate of 9.3 per 100,000 by approximately 1.7 times. Among the 74 patients diagnosed with BCa within a year after HS, 48 (64.9%) had screen-detected BCa. The screen-detected BCa group had a higher T stage (p = 0.009) and grade (p = 0.019) than the screen-undetected BCa group. However, the overall survival was not significantly different between the two groups (p = 0.677). A positive correlation between the MH grade and the T stage was identified (p = 0.001). Conclusion: Although HS is not focused on BCa screening, contemporary HS can contribute to the detection of BCa.

Background: Polycystic kidney disease (PKD) involves renal cysts arising from proliferating tubular cells. Autophagy has been recently suggested as a potential therapeutic target in PKD, and mammalian target of rapamycin (mTOR) is a key negative regulator of autophagy. However, the effect of autophagy regulation on cystogenesis has not been elucidated in PKD mice. Methods: Clinical validation was performed using GEO datasets and autosomal dominant polycystic kidney disease (ADPKD) patient samples. Newly established PKD and LC3 transgenic mice were used for in vivo verifications, and additional tests were performed in vitro and in vivo using multiple autophagy drugs. Findings: Neither autophagy stimulation nor LC3 overexpression alleviated PKD. Furthermore, we observed the inhibitory effect of an autophagy inhibitor on cysts, indicating its possible therapeutic use in a specific group of patients with ADPKD. Interpretation: Our findings provide a novel insight into the pathogenesis related to autophagy in PKD, suggesting that drugs related to autophagy regulation should be considered with caution for treating PKD. Funding Sources: This work was supported by grants from the Bio & Medical Technology Development Program; the Collaborative Genome Program for Fostering New Post-Genome Industry of the NRF; the Basic Science Program.

ObjectivesThe importance of clinical outcome prediction models using artificial intelligence (AI) is being emphasized owing to the increasing necessity of developing a clinical decision support system (CDSS) employing AI. Therefore, in this study, we proposed a "Dr. Answer" AI software based on the clinical outcome prediction model for prostate cancer treated with radical prostatectomy.MethodsThe Dr. Answer AI was developed based on a clinical outcome prediction model, with a user-friendly interface. We used 7,128 clinical data of prostate cancer treated with radical prostatectomy from three hospitals. An outcome prediction model was developed to calculate the probability of occurrence of 1) tumor, node, and metastasis (TNM) staging, 2) extracapsular extension, 3) seminal vesicle invasion, and 4) lymph node metastasis. Random forest and k-nearest neighbors algorithms were used, and the proposed system was compared with previous algorithms.ResultsRandom forest exhibited good performance for TNM staging (recall value: 76.98%), while k-nearest neighbors exhibited good performance for extracapsular extension, seminal vesicle invasion, and lymph node metastasis (80.24%, 98.67%, and 95.45%, respectively). The Dr. Answer AI software consisted of three primary service structures: 1) patient information, 2) clinical outcome prediction, and outcomes according to the National Comprehensive Cancer Network guideline.ConclusionThe proposed clinical outcome prediction model could function as an effective CDSS, supporting the decisions of the physicians, while enabling the patients to understand their treatment outcomes. The Dr. Answer AI software for prostate cancer helps the doctors to explain the treatment outcomes to the patients, allowing the patients to be more confident about their treatment plans.

Objectives: The objectives of the current study were to determine long-term biochemical recurrence rates stratified by adverse pathologic features and to identify predictive factors of biochemical recurrence rates following radical prostatectomy performed by either retropubic prostatectomy or robot-assisted laparoscopic prostatectomy from single tertiary center prostate cancer database. Material and Methods: The Seoul National University Hospital prostate cancer database was queried for all patients treated with radical prostatectomy from 1999 to 2015. Among the 2680 patients who underwent radical prostatectomy, 331 patients with seminal vesicle invasion (pathologic T3bN0-1M0 stage) were identified. The primary endpoint was biochemical recurrence, defined as two consecutive postoperative prostate specific antigen values ≥0.2 ng/ml. Comparative analysis based on adverse pathologic characteristics and operation type was performed. Results: Five and 10-year biochemical recurrence-free survival in the entire cohort was 59.0% and 42.9%. The Kaplan-Meier survival analysis demonstrated 5-year biochemical recurrence free survival rates differences in patients with different lymph node involvement (70.6% vs. 52.4%, log-rank, p=0.01). Variables including age, extracapsular extension, lymph node invasion, surgical margin, perineural invasion, multicentricity and Capra-S score were similar between the groups of patients who underwent either retropubic or robot-assisted laparoscopic radical prostatectomy. The mean prostate specific antigen level, seminal vesicle invasion laterality, tumor volume, and pathologic Gleason score were lower in the cohort of patients who underwent robot-assisted laparoscopic prostatectomy. No statistically significant differences were found in 5-year biochemical recurrence-free survival rates stratified by operation type (58.1% vs. 65%, log-rank, p=0.8), by Capra-S score (72.5% vs. 56.8%, log rank, p=0.1), or by surgical margin status (69.4% vs. 59.3%, log-rank, p=0.8). In univariate and multivariate Cox proportional regression analysis lymph node involvement (p=0.01) was found to be a statistically significant predictor of biochemical recurrence. Conclusion: Patients with positive lymph node involvement have a poor prognosis. Capra-S score was unable to predict biochemical recurrence in patients with pathologic T3b stage prostate cancer. Robot-assisted laparoscopic prostatectomy is comparable to retropubic radical prostatectomy in terms of the biochemical progression of prostate cancer with seminal vesicle invasion.

Purpose: The aim of this study was to investigate the clinical significance of 7 circulating adipokines according to body mass index (BMI) in Korean men with localized prostate cancer (PCa) undergoing radical prostatectomy (RP). Materials and Methods: Sixty-two of 65 prospectively enrolled patients with clinically localized PCa who underwent RP between 2015 and 2016 were evaluated. Patients were classified into 2 groups according to their BMI: non-obese (＜25 kg/m2) and obese (≥25 kg/m2). The adipokines evaluated were interleukin-2, insulin-like growth factor 1 (IGF-1), chemerin, C-X-C motif chemokine 10, adiponectin, leptin, and resistin. Multivariate logistic regression analysis was used to identify the independent predictors of advanced tumor stage. Results: We found that obese patients with PCa who underwent RP had a higher incidence of tumors with a high Gleason score (≥8), pathological T3 (pT3) stage, and positive extraprostatic extension than patients with a normal BMI. Additionally, patients with obesity showed significantly lower serum adiponectin and higher serum leptin levels, but did not show differences in other adipokines. Multivariate analysis demonstrated that IGF-1 (odds ratio [OR]=1.03) was identified as a predictor of advanced tumor stage (≥pT3) in the overall population. However, only leptin remained an independent predictive factor for advanced tumor stage (≥pT3) (OR=1.15) in patients with obesity. Conclusions: In conclusion, our results indicate that a higher leptin level in obese men can be considered a risk factor for aggressive PCa. This prospective study provides greater insight into the role of circulating adipokines in Korean patients with PCa undergoing RP, particularly in patients with obesity.

Intraductal carcinoma of the prostate (IDC-P) is a rare and unique form of aggressive prostate carcinoma, which is characterized by an expansile proliferation of malignant prostatic epithelial cells within prostatic ducts or acini and the preservation of basal cell layers around the involved glands. The vast majority of IDC-P tumors result from adjacent high-grade invasive cancer via the retrograde spreading of tumor cells into normal prostatic ducts or acini. A subset of IDC-P tumors is rarely derived from the de novo intraductal proliferation of premalignant cells. The presence of IDC-P in biopsy or surgical specimens is significantly associated with aggressive pathologic features, such as high Gleason grade, large tumor volume, and advanced tumor stage, and with poor clinical courses, including earlier biochemical recurrence, distant metastasis, and worse survival outcomes. These architectural and behavioral features of IDC-P may be driven by specific molecular properties. Notably, IDC-P possesses distinct genomic profiles, including higher rates of TMPRSS2–ERG gene fusions and PTEN loss, increased percentage of genomic instability, and higher prevalence of germline BRCA2 mutations. Considering that IDC-P tumors are usually resistant to conventional therapies for prostate cancer, further studies should be performed to develop optimal therapeutic strategies based on distinct genomic features, such as treatment with immune checkpoint blockades or poly (adenosine diphosphate–ribose) polymerase inhibitors for patients harboring increased genomic instability or BRCA2 mutations, as well as genetic counseling with genetic testing. Patient-derived xenografts and tumor organoid models can be the promising in vitro platforms for investigating the molecular features of IDC-P tumor.

Abstract To evaluate the influence of patient-associated parameters and comorbities, with a special focus on renal function after intravesical adjuvant bacillus Calmette-Gue´rin (BCG) immunotherapy in patients with non–muscle-invasive bladder cancer (NMIBC). We retrospectively reviewed the medical records of patients treated from October, 1991 to December, 2013 at Seoul National University who were diagnosed with NMIBC and treated with intravesical BCG. A total of 344 patients who were diagnosed with NMIBC and treated with intravesical BCG were enrolled in this study. Tumor recurrence was observed in 171 patients (49.3%); progression to higher pT category or grade was found in 68 patients (15.1%). Multivariate analysis demonstrated that recurrent tumors and the presence of multiple tumors increased the risk of recurrence. However, other factors also appeared to predict recurrence, such as impaired renal function (