Sextant Systematic Biopsy Versus Extended 12-Core Systematic Biopsy in Combined Biopsy for Prostate Cancer.

BACKGROUND: This study assessed the comparative effectiveness of sextant and extended 12-core systematic biopsy within combined biopsy for the detection of prostate cancer. METHODS: Patients who underwent combined biopsy targeting lesions with a Prostate Imaging Reporting and Data System (PI-RADS) score of 3-5 were assessed. Two specialists performed all combined cognitive biopsies. Both specialists performed target biopsies with five or more cores. One performed sextant systematic biopsies, and the other performed extended 12-core systematic biopsies. A total of 550 patients were analyzed. RESULTS: Cases requiring systematic biopsy in combined biopsy exhibited a significant association with age ≥ 65 years (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.25-4.32; P = 0.008), PI-RADS score (OR, 2.32; 95% CI, 1.25-4.32; P = 0.008), and the number of systematic biopsy cores (OR, 3.69; 95% CI, 2.11-6.44; P < 0.001). In patients with an index lesion of PI-RADS 4, an extended 12-core systematic biopsy was required (target-negative/systematic-positive or a greater Gleason score in the systematic biopsy than in the targeted biopsy) (P < 0.001). CONCLUSION: During combined biopsy for prostate cancer in patients with PI-RADS 3 or 5, sextant systematic biopsy should be recommended over extended 12-core systematic biopsy when an effective targeted biopsy is performed.

Risk factors of recurrence after robot-assisted laparoscopic partial nephrectomy for solitary localized renal cell carcinoma.

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.

Nomogram Using Prostate Health Index for Predicting Prostate Cancer in the Gray Zone: Prospective, Multicenter Study.

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<0.001), and 0.697 (0.598-0.795; p=0.001), respectively. In the PSA 4 to 10 ng/mL group, the AUCs of nomograms for overall prostate cancer and clinically significant prostate cancer were 0.812 (0.783-0.842; p<0.001), and 0.839 (0.810-0.869; p<0.001), respectively. CONCLUSIONS: Even though external validations are necessary, a nomogram using PHI might improve the prediction of prostate cancer, reducing the need for prostate biopsies.

Prostate-specific antigen kinetics in hypofractionated radiation therapy alone for intermediate- and high-risk localized prostate cancer.

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 <36 months had a significantly greater BFR and CFR. The crude rate of grade 3 late adverse events was 3.4% (genitourinary: 0.7%; gastrointestinal: 2.7%). No grade 4-5 adverse event was reported. Conclusion: A significant difference in clinical outcomes was observed according to risk stratification. The PSA nadir and time to the PSA nadir were strongly associated with the BFR and CFR. Therefore, PSA kinetics during follow-up are important for predicting prognosis.

Combination of multiparametric magnetic resonance imaging and transperineal template-guided mapping prostate biopsy to determine potential candidates for focal therapy.

Background: We assessed the ability of the combination of multiparametric magnetic resonance imaging (mpMRI) and transperineal template-guided mapping biopsy (TTMB) to determine the eligibility for focal therapy (FT) (hemiablation) in men and compared it with that of histology from radical prostatectomy (RP) specimens. Materials and methods: In this study, 120 men who underwent mpMRI, TTMB, and RP in a single tertiary center from May 2017 to June 2021 were analyzed. The criteria of hemiablation eligibility were unilateral low-to intermediate-risk prostate cancer (limited to a maximum of International Society of Urological Pathology (ISUP) grade group 3 and prostate-specific antigen (PSA) <20 ng/mL) and clinical stage ≤T2. Evidence of non-organ-confined disease or contralateral Prostate Imaging Reporting and Data System (PI-RADS) v2 score ≥4 on mpMRI was classified as ineligible for hemiablation. Clinically significant cancer at RP was defined as any of the following: (1) ISUP grade group 1 with tumor volume ≥1.3 mL; (2) ISUP grade group ≥2; or (3) the presence of advanced stage (≥pT3). Results: Of the 120 men, data of 52 men who met the selection criteria for hemiablation were compared with final RP findings. Of these 52 men, 42 (80.7%) could be considered suitable for hemiablation on RP. The sensitivity, specificity, and accuracy of mpMRI and TTMB in predicting FT eligibility were 80.7%, 85.1%, and 82.5%, respectively. The rate of undetected contralateral significant cancer was 10 (19.2%) on mpMRI and TTMB. Six had bilateral significant cancer and four had small volumes of ISUP grade group ≥2. Conclusions: The combination of mpMRI and TTMB substantially improves the prediction of potential candidates for hemiablation based on consensus recommendations. Improved selection criteria and further investigative tools are required to improve patient selection for hemiablation.

Comparison of Prostate-Specific Antigen and Its Density and Prostate Health Index and Its Density for Detection of Prostate Cancer.

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.

Risk factors for prostate-specific antigen persistence in pT3aN0 prostate cancer after robot-assisted laparoscopic radical prostatectomy: a retrospective study.

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 <0.1 ng/mL after RALP (successful radical prostatectomy [RP] group). In the PSA persistence group, 51 patients (83.61%) received adjuvant treatment. Biochemical recurrence occurred in 27 patients (10.19%) in the successful RP group during the mean follow-up period of 15.22 months. Multivariate analysis showed that the risk factors for PSA persistence were large prostate volume (hazard ratio [HR], 1.017; 95% confidence interval [CI], 1.002-1.036; p=0.046), lymphovascular invasion (LVI) (HR, 2.605; 95% CI, 1.022-6.643; p=0.045), and surgical margin involvement (HR, 2.220; 95% CI, 1.110-4.438; p=0.024). CONCLUSION: Adjuvant treatment may be needed for improved prognosis in patients with pT3aN0 PCa after RALP with a large prostate size, LVI, or surgical margin involvement.

New transperineal ultrasound-guided biopsy for men in whom PSA is increasing after Miles' operation.

OBJECTIVES: Currently, a prostate biopsy is guided by transrectal ultrasound (US) alone. However, this biopsy cannot be performed in men without an anus. The aim of this study was to show the outcomes of a new transperineal US (TPUS)-guided biopsy technique in patients who underwent Miles' operation. METHODS: Between April 2009 and March 2022, TPUS-guided biopsy was consecutively conducted in 9 patients (median, 71 years; range, 61-78 years) with high prostate-specific antigen values (22.60 ng/mL; 6.19-69.7 ng/mL). Their anuses were all removed due to rectal cancer. TPUS-guided biopsy was performed according to information on prostate magnetic resonance imaging. The technical success rate, cancer detection rate, and complication rate were recorded. Tumor sizes were compared between benign and cancer groups using an unpaired t-test with Welch's correction. RESULTS: The new TPUS-guided biopsy was successfully performed in all patients. Cancer was detected in 77.8% (7/9) of the patients. These were all categorized as PI-RADS 5. Among them, the detection rate of significant cancer (Gleason score 7 or higher) was 66.7% (6/9). The median tumor size was 2.4 cm (1.7-3.1 cm). However, two patients were diagnosed with benign tissue with PI-RADS 3 or PI-RADS 4. Their median tumor size was 1.0 cm (0.8-1.2 cm). There was significant difference between the cancer and benign groups (p = 0.037) in terms of tumor size. Neither post-biopsy bleeding nor infections occurred. CONCLUSIONS: New TPUS-guided biopsy technique may contribute to detecting large PI-RADS 5 prostate cancer in men after Miles' operation.

Fat Loss in Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors.

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.

Repression of SLC22A3 by the AR-V7/YAP1/TAZ axis in enzalutamide-resistant castration-resistant prostate cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive and fatal disease, with most patients succumbing within 1-2 years despite undergoing multiple treatments. Androgen-receptor (AR) inhibitors, including enzalutamide (ENZ), are used for the treatment of mCRPC; however, most patients develop resistance to ENZ. Herein, we propose that the repression of SLC22A3 by AR-V7/YAP1/TAZ conferred ENZ resistance in mCRPC. SLC22A3 expression is specifically downregulated in the ENZ-resistant C4-2B MDVR cells, and when YAP1/TAZ is hyperactivated by AR full-length or AR-V7, these proteins interact with DNMT1 to repress SLC22A3 expression. We observed low SLC22A3 expression and high levels of TAZ or YAP1 in mCRPC patient tissues harbouring AR-V7 and the opposite expression patterns in normal patient tissues. Our findings suggest a mechanism underlying ENZ resistance by providing evidence that the AR-V7/YAP1/TAZ axis represses SLC22A3, which could be a potential treatment target in prostate cancer.

Chromosomal Instability in Cell-free DNA as a Prognostic Biomarker of Metastatic Hormone-sensitive Prostate Cancer Treated with Androgen Deprivation Therapy.

BACKGROUND: Although patients with metastatic hormone-sensitive prostate cancer (mHSPC) undergo androgen deprivation therapy (ADT), the disease can progress to metastatic castration-resistant prostate cancer (mCRPC). There are no reliable biomarkers for predicting this progression. Chromosomal instability resulting in copy number alterations (CNAs) is characteristically observed in patients with various cancers. OBJECTIVE: To investigate the role of chromosomal instability in patients with mHSPC. DESIGN, SETTING, AND PARTICIPANTS: This prospective study analyzed cell-free DNA (cfDNA) in pretreatment plasma samples from 75 patients with elevated prostate-specific antigen. Low-depth whole-genome sequencing of cfDNA was performed to identify CNAs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The I score (sum of the product of the absolute Z score and the corresponding chromosome length) was used as a measure of chromosomal instability. Kaplan-Meier and Cox proportional-hazard regression analyses were performed to evaluate the association between the I score and time to progression (TTP) and the prognostic value of chromosomal instability in predicting castration resistance, respectively. RESULTS AND LIMITATIONS: Of 22 patients with a positive I score, 86.4% (19/22) had metastatic prostate cancer. Of these 19 cases, 94.7% (18/19) were mHSPC, which was high-volume mHSPC in 83.3% (15/18). None of the patients with localized prostate cancer had a positive I score. TTP in patients with mHSPC was significantly shorter in the positive than in the negative I-score group (16.4 vs 36.9 mo; p = 0.001). Only the I score could independently predict mCRPC development (hazard ratio 10.315, 95% confidence interval 1.141-93.208; p = 0.038). CONCLUSIONS: The I score could be a biomarker for ADT response and progression to mCRPC in patients with mHSPC. PATIENT SUMMARY: We investigated whether genetic changes in cell-free DNA can predict outcomes for patients with metastatic prostate cancer that still responds to hormone therapy. We found that chromosomal instability could be a potential predictor of the development of metastatic castration-resistant prostate cancer.

A Comparison of Functional and Oncologic Outcomes between Partial Nephrectomy and Radiofrequency Ablation in Patients with Chronic Kidney Disease after Propensity Score Matching.

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.

Clinical Utility of Prostate Health Index for Diagnosis of Prostate Cancer in Patients with PI-RADS 3 Lesions.

The risk of prostate cancer (PCa) in prostate imaging reporting and data system version 2 (PI-RADSv2) score-3 lesions is equivocal; it is regarded as an intermediate status of presented PCa. In this study, we evaluated the clinical utility of the prostate health index (PHI) for the diagnosis of PCa and clinically significant PCa (csPCa) in patients with PI-RADSv2 score-3 lesions. The study cohort included patients who underwent a transrectal ultrasound (TRUS)-guided, cognitive-targeted biopsy for PI-RADSv2 score-3 lesions between November 2018 and April 2021. Before prostate biopsy, the prostate-specific antigen (PSA) derivatives, such as total PSA (tPSA), [-2] proPSA (p2PSA) and free PSA (fPSA) were determined. The calculation equation of PHI is as follows: [(p2PSA/fPSA) × tPSA ½]. Using a receiver operating characteristic (ROC) curve analysis, the values of PSA derivatives measured by the area under the ROC curve (AUC) were compared. For this study, csPCa was defined as Gleason grade 2 or higher. Of the 392 patients with PI-RADSv2 score-3 lesions, PCa was confirmed in 121 (30.9%) patients, including 59 (15.1%) confirmed to have csPCa. Of all the PSA derivatives, PHI and PSA density (PSAD) showed better performance in predicting overall PCa and csPCa, compared with PSA (all p < 0.05). The AUC of the PHI for predicting overall PCa and csPCa were 0.807 (95% confidence interval (CI): 0.710−0.906, p = 0.001) and 0.819 (95% CI: 0.723−0.922, p < 0.001), respectively. By the threshold of 30, PHI was 91.7% sensitive and 46.1% specific for overall PCa, and was 100% sensitive for csPCa. Using 30 as a threshold for PHI, 34.4% of unnecessary biopsies could have been avoided, at the cost of 8.3% of overall PCa, but would include all csPCa.

Correction: Biochemical recurrence after radical prostatectomy according to nadir prostate specific antigen value.

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

Utility of multiple core biopsies during transperineal template-guided mapping biopsy for patients with large prostates and PI-RADS 1-2 on multiparametric magnetic resonance imaging.

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 < 0.001). In addition, incidence of AUR was more in patients with PV over 39 cc and PI-RADS score of 1-2 on mpMRI (3.7% vs. 22.2%, P < 0.001). There was no significant difference in the detection rates of any prostate cancer or clinically significant prostate cancer (csPCA) between the patients on AS with PV < 39 cc and PV ≥ 39 cc and PI-RADS score 1-2 (57.4% vs. 50%, P = 0.507; 17% vs. 8.8%, P = 0.412, respectively). Additionally, no significant difference was found in the detection rates of any prostate cancer or csPCA between the patients with PV < 39 cc and PV ≥ 39 cc and PI-RADS score 1-2 who either had a previously negative TRUS-Bx or were biopsy naïve (27.9% vs. 16.2%, P = 0.101, 8.2% vs. 4.1%, P = 0.31, respectively). Conclusion: Increasing the number of core biopsies of prostates measuring ≥39 cc with PI-RADS 1-2 on mpMRI does not significantly increase the detection rates of any prostate cancer or csPCA.

A Retrospective Study of First-Line Therapy Involving Immune Checkpoint Inhibitors in Patients With Poor Risk Metastatic Renal Cell Carcinoma.

Purpose: Patients 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 Methods: In 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. Results: Patients' 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. Conclusions: Among 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.

Molecular Subtypes Based on Genomic and Transcriptomic Features Correlate with the Responsiveness to Immune Checkpoint Inhibitors in Metastatic Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) has been reported to be highly immune to and infiltrated by T cells and has angiogenesis features, but the effect of given features on clinical outcomes followed by immune checkpoint inhibitors (ICIs) in ccRCC has not been fully characterized. Currently, loss of function mutation in PBRM1, a PBAF-complex gene frequently mutated in ccRCC, is associated with clinical benefit from ICIs, and is considered as a predictive biomarker for response to anti-PD-1 therapy. However, functional mechanisms of PBRM1 mutation regarding immunotherapy responsiveness are still poorly understood. Here, we performed targeted sequencing (n = 60) and whole transcriptomic sequencing (WTS) (n = 61) of patients with metastatic ccRCC treated by ICIs. By integrating WTS data from the CheckMate 025 trial, we obtained WTS data of 177 tumors and finally identified three molecular subtypes that are characterized by distinct molecular phenotypes and frequency of PBRM1 mutations. Patient clustered subtypes 1 and 3 demonstrated worse responses and survival after ICIs treatment, with a low proportion of PBRM1 mutation and angiogenesis-poor, but were immune-rich and cell-cycle enriched. Notably, patients clustered in the subtype 2 showed a better response and survival after ICIs treatment, with enrichment of PBRM1 mutation and metabolic programs and a low exhausted immune phenotype. Further analysis of the subtype 2 population demonstrated that GATM (glycine amidinotransferase), as a novel gene associated with PBRM1 mutation, plays a pivotal role in ccRCC by using a cell culture model, revealing tumor, suppressive-like features in reducing proliferation and migration. In summary, we identified that metastatic ccRCC treated by ICIs have distinct genomic and transcriptomic features that may account for their responsiveness to ICIs. We also revealed that the novel gene GATM can be a potential tumor suppressor and/or can be associated with therapeutic efficacy in metastatic ccRCC treated by ICIs.

Robotic Radical Nephroureterectomy with Bladder Cuff Excision for Upper Tract Urothelial Carcinoma: A Trend Analysis of Utilization and a Comparative Study.

Purpose: To compare the perioperative outcomes and oncological results of open, laparoscopic, and robotic radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) and to analyze trends in the utilization of RNU. Methods: From 2017 to 2020, the records of 61, 185, and 119 patients who underwent open, laparoscopic, and robotic RNU, respectively, were reviewed. Results: Baseline characteristics were not significantly different among the three groups. Robotic RNU has recently started to increase from 9% in 2017 to 67% in 2021. Operation time, blood loss, length of hospital stay, and 90-day complications were not different between the three groups. The three-year overall survival (OS) rates for open, laparoscopic, and robotic RNU were 91.8%, 90.4%, and 92.1%, respectively (p > 0.05). No differences in the progression-free survival (PFS), cancer-specific survival (CSS), and OS were observed according to the surgical approach in the Kaplan−Meier survival analysis. Multivariate analysis showed that surgical approach was not an independent predictor of PFS, CSS, and OS. Conclusion: The use of robotic RNU in patients with UTUC has been starting to increase and replace open and laparoscopic RNU. Perioperative outcomes, 90-day complications, and oncological outcomes of robotic RNU were not inferior to those of open and laparoscopic RNU.

Utility of Contemporary Health Screening in the Diagnosis of Bladder Cancer.

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.

Risk Factors and Patterns of Locoregional Recurrence after Radical Nephrectomy for Locally Advanced Renal Cell Carcinoma.

PURPOSE: We aimed to investigate the risk factors and patterns of locoregional recurrence (LRR) after radical nephrectomy (RN) in patients with locally advanced renal cell carcinoma (RCC). MATERIALS AND METHODS: We retrospectively analyzed 245 patients who underwent RN for non-metastatic pT3-4 RCC from January 2006 to January 2016. We analyzed the risk factors associated with poor locoregional control using Cox regression. Anatomical mapping was performed on reference computed tomography scans showing intact kidneys. RESULTS: The median follow-up duration was 56 months (range, 1 to 128 months). Tumor extension to renal vessels or the inferior vena cava (IVC) and Fuhrman's nuclear grade IV were identified as independent risk factors of LRR. The 5-year actuarial LRR rates in groups with no risk factor, one risk factor, and two risk factors were 2.3%, 19.8%, and 30.8%, respectively (p < 0.001). The locations of LRR were distributed as follows: aortocaval area (n=2), paraaortic area (n=4), retrocaval area (n=5), and tumor bed (n=11). No LRR was observed above the celiac axis (CA) or under the inferior mesenteric artery (IMA). CONCLUSION: Tumor extension to renal vessels or the IVC and Fuhrman's nuclear grade IV were the independent risk factors associated with LRR after RN for pT3-4 RCC. The locations of LRR after RN for RCC were distributed in the tumor bed and regional lymphatic area from the bifurcation of the CA to that of the IMA.