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We aimed to isolate circulating tumor cells (CTCs) using a microfluidic technique with a novel lateral magnetophoretic microseparator. Prostate cancer–specific gene expressions were evaluated using mRNA from the isolated CTCs. A CTC‐based multigene model was then developed for identifying advanced prostate cancer. Peripheral blood samples were obtained from five healthy donors and patients with localized prostate cancer (26 cases), metastatic hormone‐sensitive prostate cancer (mHSPC, 10 cases), and metastatic castration‐resistant prostate cancer (mCRPC, 28 cases). CTC recovery rate and purity (enriched CTCs/total cells) were evaluated according to cancer stage. The areas under the curves of the six gene expressions were used to evaluate whether multigene models could identify mHSPC or mCRPC. The number of CTCs and their purity increased at more advanced cancer stages. In mHSPC/mCRPC cases, the specimens had an average of 27.5 CTCs/mL blood, which was 4.2 × higher than the isolation rate for localized disease. The CTC purity increased from 2.1% for localized disease to 3.8% for mHSPC and 6.7% for mCRPC, with increased CTC expression of the genes encoding prostate‐specific antigen (PSA), prostate‐specific membrane antigen (PSMA), and cytokeratin 19 (KRT19). All disease stages exhibited expression of the genes encoding androgen receptor (AR) and epithelial cell adhesion molecule (EpCAM), although expression of the AR‐V7 variant was relatively rare. Relative to each gene alone, the multigene model had better accuracy for predicting advanced prostate cancer. Our lateral magnetophoretic microseparator can be used for identifying prostate cancer biomarkers. In addition, CTC‐based genetic signatures may guide the early diagnosis of advanced prostate cancer. CTCs have useful biological information for understanding the prostate cancer aggressiveness. CTC‐based gene signatures have potential for early diagnosis of metastatic prostate cancer. Multigene profile (AR, AR‐V7, PSA, PSMA, EpCAM, and KRT19) may guide the diagnosis and treatment of metastatic prostate cancer.

Objectives To examine the diagnostic performance of Vesical Imaging-Reporting and Data System (VIRADS) and to find a quantitative indicator for predicting muscle layer invasion of bladder cancer. Methods 3-T MRI of 82 patients performed before transurethral resection of bladder tumors or radical cystectomy between July 2018 and June 2019 were retrospectively analyzed. For one index lesion of each patient, two radiologists independently assigned VIRADS score and measured tumor-wall interface (contact length between tumor and bladder wall) on T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI. Inter-reader agreement was assessed, and logistic regression analysis was performed to find indicators of muscle layer invasion. Comparison of indicators’ diagnostic performance was done with receiver operating characteristic (ROC) curve and generalized linear model analyses. Optimal cutoff point was determined by the Youden index J . Results Inter-reader agreement was at least substantial for VIRADS categorization ( κ 0.77–0.81), and almost perfect for tumor-wall interface (intraclass correlation coefficient 0.88–0.90). Tumor-wall interface (odds ratio [OR] 1.90–2.00) and VIRADS score (OR 8.59–8.89) were independently associated with muscle layer invasion ( p  ≤ 0.02). For VIRADS, area under the ROC curve (AUROC) was 0.94, and the accuracy was 0.93 at score 3, the optimal threshold for predicting muscle layer invasion. Depending on the MRI sequence, tumor-wall interface showed AUROCs of 0.90–0.92 and accuracy of 0.84–0.90 at suggested thresholds (3 ± 0.3 cm). Tumor-wall interface showed insignificant differences in accuracy compared with VIRADS ( p > 0.10), except as measured on diffusion-weighted images ( p = 0.01). Conclusions VIRADS is a good predictor of muscle layer invasion. As an independent quantitative indicator, tumor-wall interface may complement VIRADS to enhance prediction. Key Points • Vesical Imaging-Reporting and Data System (VIRADS) is a promising predictor of muscle invasion of bladder cancer with good reproducibility, as suggested by previous studies. • VIRADS score and the tumor-wall interface (curvilinear contact length between the tumor and the bladder wall) are independent predictors of muscle layer invasion. • As an easy-to-use quantitative indicator, tumor-wall interface is expected to be used as an indicator complementary to VIRADS, a qualitative indicator.

Survival analyses for malignancies, including renal cell carcinoma (RCC), have primarily been conducted using the Cox proportional hazards (CPH) model. We compared the random survival forest (RSF) and DeepSurv models with the CPH model to predict recurrence-free survival (RFS) and cancer-specific survival (CSS) in non-metastatic clear cell RCC (nm-cRCC) patients. Our cohort included 2139 nm-cRCC patients who underwent curative-intent surgery at six Korean institutions between 2000 and 2014. The data of two largest hospitals’ patients were assigned into the training and validation dataset, and the data of the remaining hospitals were assigned into the external validation dataset. The performance of the RSF and DeepSurv models was compared with that of CPH using Harrel’s C-index. During the follow-up, recurrence and cancer-specific deaths were recorded in 190 (12.7%) and 108 (7.0%) patients, respectively, in the training-dataset. Harrel’s C-indices for RFS in the test-dataset were 0.794, 0.789, and 0.802 for CPH, RSF, and DeepSurv, respectively. Harrel’s C-indices for CSS in the test-dataset were 0.831, 0.790, and 0.834 for CPH, RSF, and DeepSurv, respectively. In predicting RFS and CSS in nm-cRCC patients, the performance of DeepSurv was superior to that of CPH and RSF. In no distant time, deep learning-based survival predictions may be useful in RCC patients.

To compare the oncological and perioperative outcomes of different nephroureterectomy approaches in patients with non-metastatic upper tract urothelial carcinoma (UTUC). We retrospectively analyzed the data of 422 patients who underwent open, laparoscopic, or robotic nephroureterectomy for non-metastatic UTUC. Perioperative and postoperative survival outcomes were compared using Kaplan-Meier analyses and Cox-proportional hazard models. Of the patients, 161, 137, and 124 were treated with an open, laparoscopic, and robotic approach, respectively. Laparoscopic and robotic approaches involved significantly less blood loss (p = 0.001), shorter hospital stay (p < 0.001), and longer operation time (p < 0.001) compared with the open approach. There were no significant differences in intraoperative complications (open, 8.1%; laparoscopic, 5.1%; robotic, 7.3%; p = 0.363) or early postoperative complications (open, 14.9%; laparoscopic, 14.6%; robotic, 13.7%; p = 0.880). The laparoscopic and robotic groups showed significantly less postoperative analgesic use (p = 0.015). The robotic group showed significantly longer progression-free, cancer-specific, and overall survivals than the open approach group on univariate Kaplan-Meier analysis, but surgery type was not significantly associated with survival outcomes per multivariate Cox proportional tests (all p-values > 0.05). The laparoscopic and robotic approaches yielded better perioperative outcomes, such as less intraoperative bleeding, shorter hospital stays, less analgesic usage, and non-inferior oncological outcomes, compared with the open approach. Further prospective studies are needed to compare these surgical techniques.

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.

We evaluated the role of prostate health index (PHI) in predicting Gleason score (GS) upgrading in International Society of Urological Pathology Grade Group (ISUP GG) 1 & 2 prostate cancer (PCa) or adverse pathologic outcomes at radical prostatectomy (RP). A total of 300 patients with prostate specific antigen ≥ 3 ng/mL, PHI and prostate biopsy (71 patients with RP included) were retrospectively included in the study. The primary study outcomes are PCa and clinically significant PCa (csPCa, defined as ISUP GG ≥ 2) diagnostic rate of PHI, and GS upgrading rate at RP specimen. The secondary outcomes are the comparison between GS upgrading and non-upgrading group, GS upgrading and high-risk PCa (ISUP GG ≥ 3 or ≥ pT3a) predictability of preoperative clinical factors. Overall, 139 (46.3%) and 92 (30.7%) were diagnosed with PCa and csPCa, respectively. GS upgrading rate was 34.3% in all patients with RP. Significant differences were shown in the total prostate volume (p = 0.047), the distribution of ISUP GG at biopsy (p = 0.001) and RP (p = 0.032), respectively. PHI values ≥ 55 [Odds ratio (OR): 3.64 (95% confidence interval (CI) = 1.05–12.68, p = 0.042] and presence of PI-RADS lesion ≥ 4 (OR: 7.03, 95% CI = 1.68–29.51, p = 0.018) were the significant predictors of GS upgrading in RP specimens (AUC = 0.737). PHI values ≥ 55 (OR: 9.05, 5% CI = 1.04–78.52, p = 0.046) is a significant factor for predicting adverse pathologic features in RP specimens (AUC = 0.781). PHI could predict GS upgrading in combination with PIRADS lesions ≥ 4 in ISUP GG 1 & 2. PHI alone could evaluate the possibility of high-risk PCa after surgery as well.

We evaluated the recurrence after radical and partial nephrectomy in patients with RENAL nephrometry score [RENAL] ≥ 10. A total of 474 patients (radical nephrectomy [RN, n = 236] & partial nephrectomy [PN, n = 238]) in a single tertiary referral institution from December 2003 to December 2019 were assessed. Functional outcomes, defined as estimated glomerular filtration rate changes, relapse pattern, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were evaluated using propensity score-matched analysis. The predictors of recurrence and survival were assessed by Cox-regression analysis. 44 patients in the RN group and 88 in the PN group were included without significant differences in preoperative clinical factors after matching. The PN patients achieved significantly higher renal function preservation rates (p < 0.001). There were five recurrences in RN and six in PN. The PN patients revealed 5-year RFS rate (86.8%), 5-year CSS rate (98.5%), and 5-year OS rate (98.5%) comparable to the RN patients (RFS: 88.7% [p = 0.780], CSS: 96.7% [p = 0.375], and OS: 94.3% [p = 0.248]). Patients with a body mass index (BMI) ≥ 23 had lower 5-year RFS rates (85.5%) and OS rates (95.6%) than those with BMI < 23 (RFS: 90.0% [p = 0.195], OS: 100% [p = 0.117]) without significance. The significant predictor of recurrence was the pathologic T stage (hazard ratio [HR] 3.99, 95% confidence [CI] 1.10–14.50, p = 0.036). The significant predictor of death was the R domain of the RENAL (HR 3.80, 95% CI 1.03–14.11, p = 0.046). PN, if technically feasible, could be considered to preserve renal function in patients with RENAL ≥ 10. Nonetheless, PN needs to be implemented with caution in some patients due to the higher potentiality for recurrence and poor survival.

To evaluate the clinical impact of preoperative glycemic status upon oncological and functional outcomes after radical prostatectomy in patients with localized prostate cancer, we analyzed the data of 2664 subjects who underwent radical prostatectomy with preoperative measurement of hemoglobin A1c within 6 months before surgery. The possible association between high hemoglobin A1c (≥ 6.5 ng/dL) and oncological/functional outcomes was evaluated. Among all subjects, 449 (16.9%) were categorized as the high hemoglobin A1c group and 2215 (83.1%) as the low hemoglobin A1c group. High hemoglobin A1c was associated with worse pathological outcomes including extra-capsular extension (HR 1.277, 95% CI 1.000–1.630, p  = 0.050) and positive surgical margin (HR 1.302, 95% CI 1.012–1.674, p  = 0.040) in multi-variate regression tests. Kaplan–Meier analysis showed statistically shorter biochemical recurrence-free survival in the high hemoglobin A1c group ( p  < 0.001), and subsequent multivariate Cox proportional analyses revealed that high hemoglobin A1c is an independent predictor for shorter BCR-free survival (HR 1.135, 95% CI 1.016–1.267, p  = 0.024). Moreover, the high hemoglobin A1c group showed a significantly longer incontinence-free survival than the low hemoglobin A1c group ( p  = 0.001), and high preoperative hemoglobin A1c was also an independent predictor for longer incontinence-free survival in multivariate Cox analyses (HR 0.929, 95% CI 0.879–0.981, p  = 0.008). The high preoperative hemoglobin A1c level was independently associated with worse oncological outcomes and also with inferior recovery of urinary continence after radical prostatectomy.

PurposeMetastatic prostate cancer (mPCa) rarely occurs under the age of 60, and we aim to evaluate the clinical outcomes and prognosis of mPCa patients ≤ 60-year-old.MethodsTwo thousand and eighty-three patients were treated with mPCa between April 2003 and May 2020. Clinicopathological characteristics between groups, biochemical recurrence (BCR)-free survival, and overall survival (OS) were assessed. Subgroup analysis was performed on patients ≤ 60 years. Multivariable cox regression was used for survival analysis.ResultsThree hundred and seventy-five patients (> 60 years: older) and 115 patients (≤ 60 years: young) were identified. 5-year BCR-free survival rates were 38.8% in young and 74.1% in older group (p < 0.001). 5-year OS were 88.1% in young and 96.5% in older group (p = 0.006). The significant factor associated with BCR was age > 60 (hazard ratio [HR] = 0.67, 95% confidence [CI]: 0.36–0.94, p = 0.017). The significant predictors of OS were age > 60 (HR 0.40, CI 0.18–0.91, p = 0.028) and local definitive treatment (HR 0.29, CI 0.13–0.64, p = 0.002). For the subgroup analysis, median BCR-free survival was significantly shorter in younger (≤ 56) group (14 mo vs. 27 mo, p = 0.026), and the median OS was significantly different (p = 0.048).ConclusionsIn mPCa patients ≤ 60-year-old, BCR occurs earlier and OS is significantly reduced than older patients. Therefore, special caution is mandatory when treating these mPCa patients.

Diffusion-weighted imaging (DWI) has been shown to be an important component of multiparametric magnetic resonance imaging (mpMRI). We compared performance of DWI for detection of prostate cancer (PCa) in peripheral zone (PZ) and transition zone (TZ) of prostate. We reviewed data of 460 subjects who underwent preoperative 3.0-Tesla mpMRI and subsequently radical prostatectomy. Level of suspicion for PCa was graded using 5-grade Likert-scale from DWI. Topographic analyses were performed for location of tumor foci at each surgical specimen. Among those with DWI grade ≥ III, we analyzed concordance rate on the location of radiologic and pathologic index lesions between DWI and surgical specimens. Among 460 patients, 351 (76.3%) patients showed suspicious DWI lesions (57.5% in PZ, 42.5% in TZ). Multivariates regression analyses revealed significant associations between high DWI grade and adverse pathologic outcomes including pathologic stage, Gleason score, tumor volume and extracapsular extension (all p < 0.05). Overall concordance rates between DWI and surgical specimen were 75.8%, significantly higher in PZ than TZ (82.2% vs. 67.1% p = 0.002). Such concordance rate showed a positive linear association with increase in DWI grading (p < 0.001). Among 109 patients with DWI grade I-II, 28 (25.7%) harbored high grade disease (pathologic Gleason score ≥ 4 + 3). DWI detects tumors in PZ of prostate more accurately than those in TZ. Such accuracy of DWI was shown to be more evident with higher DWI grade. Meanwhile, a negative DWI did not guarantee absence of high grade PCa.