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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: To assess the efficacy and safety of docetaxel rechallenge in the salvage setting in metastatic castration-resistant prostate cancer (mCRPC) patients. Materials and Methods: Clinicopathologic data from patients treated with docetaxel rechallenge were collected from a single-center cancer registry. Among 227 patients who received first-line docetaxel for mCRPC between January 2011 and June 2019, 23 undergo rechallenge docetaxel after failure to androgen receptor targeting agents and/or cabazitaxel treatment. Endpoints included radiologic progression-free survival (PFS), treatment duration, and prostate-specific antigen (PSA) response and safety. Results: Overall, 30%, 44%, 13%, and 13% of patients received docetaxel rechallenge as either the third, fourth, fifth, or sixth-line therapy, respectively, at a median of 23.6 months after stopping first-line docetaxel. With first-line docetaxel and rechallenge, median treatment duration was 6.4 and 3.3 months, respectively. With docetaxel rechallenge, PSA response was 35% (95% confidence interval [CI], 15% to 54%) and median PFS was 4.5 months (95% CI, 1.9 to 7.1 months). The median OS was 24.3 months (95% CI, 4.6 to 44.0 months). There were 7 severe adverse events (grade 3 or more) including anemia (8.7%), neutropenia, thrombocytopenia, leukopenia, diarrhea, and nausea (4.3% each). Conclusions: Docetaxel rechallenge showed meaningful anti-tumor activity with acceptable toxicity in heavily pretreated patients with mCRPC.

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

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.

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.

Purpose: This post hoc analysis evaluated treatment effects, safety, and pharmacokinetics of enzalutamide in Korean patients in the phase 3, double-blind, placebo-controlled PREVAIL trial. Materials and Methods: Asymptomatic or mildly symptomatic chemotherapy-naïve men with metastatic castration-resistant prostate cancer that progressed on androgen deprivation therapy received 160 mg/d oral enzalutamide or placebo (1:1) until death or discontinuation due to radiographic progression or skeletal-related event and initiation of subsequent therapy. Coprimary end points were centrally assessed radiographic progression-free survival (rPFS) and overall survival (OS). Secondary end points included investigator-assessed rPFS, time to initiation of chemotherapy, time to prostate-specific antigen (PSA) progression, PSA response (≥50% decline), and time to skeletal-related event. Results: Of 1,717 total patients, 78 patients were enrolled in Korea (enzalutamide, n=40; placebo, n=38). Hazard ratios (95% confidence interval) for enzalutamide versus placebo were 0.23 (0.02–2.24) for centrally assessed rPFS, 0.77 (0.28–2.15) for OS, 0.21 (0.08–0.51) for time to chemotherapy, and 0.31 (0.17–0.56) for time to PSA progression. A PSA response was observed in 70.0% of enzalutamide-treated and 10.5% of placebo-treated Korean patients. Adverse events of grade ≥3 occurred in 33% of enzalutamide- treated and 11% of placebo-treated Korean patients, with median treatment durations of 13.0 and 5.1 months, respectively. At 13 weeks, the plasma concentration of enzalutamide plus N-desmethyl enzalutamide was similar in Korean and non-Korean patients (geometric mean ratio, 1.04; 90% confidence interval, 0.97–1.10). Conclusions: In Korean patients, treatment effects and safety of enzalutamide were consistent with those observed in the overall PREVAIL study population (ClinicalTrials.gov Identifier: NCT01212991).

Purpose: Magnetic anchoring devices may reduce the number of port sites needed in laparoscopic surgery. In this study, we prospectively assessed the feasibility of using a magnetic anchoring and guidance system (MAGS) in laparoendoscopic single-site (LESS) surgery performed by novices. Materials and Methods: A total of 10 LESS simple nephrectomies were performed with or without MAGS in a nonsurvival porcine model by 6 operators with no previous LESS surgery experience. After installation of the homemade single port, an intra-abdominal magnet was fixed to the renal parenchyma with suturing and stabilized by an external magnet placed on the flank so that the position of the kidney could be easily changed by moving the external handheld magnet. The length of the procedure and any intraoperative complications were evaluated. Results: Operative time (mean±standard deviation) was shorter in the group using the magnetic anchoring device (M-LESS-N) than in the group with conventional LESS nephrectomy (C-LESS-N) (63±20.8 minutes vs. 82±40.7 minutes, respectively). Although all nephrectomies were completed uneventfully in the M-LESS-N group, renal vein injury occurred during dissection of the renal hilum in two cases of C-LESS-N and was resolved by simultaneous transection of the renal artery and vein with an Endo-GIA stapler. Conclusions: LESS-N using MAGS is a feasible technique for surgeons with no LESS surgery experience. Taking into account the 2 cases of renal vein injury in the C-LESS-N group, the application of MAGS may be beneficial for overcoming the learning curve of LESS surgery.

Purpose: To assess the efficacy and safety of docetaxel rechallenge in the salvage setting in metastatic castration-resistant prostate cancer (mCRPC) patients. Materials and Methods: Clinicopathologic data from patients treated with docetaxel rechallenge were collected from a singlecenter cancer registry. Among 227 patients who received first-line docetaxel for mCRPC between January 2011 and June 2019, 23 undergo rechallenge docetaxel after failure to androgen receptor targeting agents and/or cabazitaxel treatment. Endpoints included radiologic progression-free survival (PFS), treatment duration, and prostate-specific antigen (PSA) response and safety. Results: Overall, 30%, 44%, 13%, and 13% of patients received docetaxel rechallenge as either the third, fourth, fifth, or sixth-line therapy, respectively, at a median of 23.6 months after stopping first-line docetaxel. With first-line docetaxel and rechallenge, median treatment duration was 6.4 and 3.3 months, respectively. With docetaxel rechallenge, PSA response was 35% (95% confidence interval [CI], 15% to 54%) and median PFS was 4.5 months (95% CI, 1.9 to 7.1 months). The median OS was 24.3 months (95% CI, 4.6 to 44.0 months). There were 7 severe adverse events (grade 3 or more) including anemia (8.7%), neutropenia, thrombocytopenia, leukopenia, diarrhea, and nausea (4.3% each). Conclusions: Docetaxel rechallenge showed meaningful anti-tumor activity with acceptable toxicity in heavily pretreated patients with mCRPC. [ABSTRACT FROM AUTHOR]

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 TRUSguided 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. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the differences in the cancer detection rate and pathological findings on a second prostate biopsy according to benign diagnosis, high-grade prostatic intraepithelial neoplasia (HGPIN), and atypical small acinar proliferation (ASAP) on first biopsy. Materials and Methods: We retrospectively reviewed the records of 1,323 patients who underwent a second prostate biopsy between March 1995 and November 2012. We divided the patients into three groups according to the pathologic findings on the first biopsy (benign diagnosis, HGPIN, and ASAP). We compared the cancer detection rate and Gleason scores on second biopsy and the unfavorable disease rate after radical prostatectomy among the three groups. Results: A total of 214 patients (16.2%) were diagnosed with prostate cancer on a second biopsy. The rate of cancer detection was 14.6% in the benign diagnosis group, 22.1% in the HGPIN group, and 32.1% in the ASAP group, respectively (p<0.001). When patients were divided into subgroups according to the number of positive cores, the rate of cancer detection was 16.7%, 30.5%, 31.0%, and 36.4% in patients with a single core of HGPIN, more than one core of HGPIN, a single core of ASAP, and more than one core of ASAP, respectively. There were no significant differences in Gleason scores on second biopsy (p=0.324) or in the unfavorable disease rate after radical prostatectomy among the three groups (benign diagnosis vs. HGPIN, p=0.857, and benign diagnosis vs. ASAP, p=0.957, respectively). Conclusions: Patients with multiple cores of HGPIN or any core number of ASAP on a first biopsy had a significantly higher cancer detection rate on a second biopsy. Repeat biopsy should be considered and not be delayed in those patients. [ABSTRACT FROM AUTHOR]

Purpose: To compare the perioperative outcomes of laparoscopic partial nephrectomy (LPN) and robotic partial nephrectomy (RPN) for moderately or highly complex tumors (RENAL nephrometry score≥7). Materials and Methods: A retrospective analysis was performed for 127 consecutive patients who underwent either LPN (n=38) or RPN (n=89) between 2007 and 2013. Perioperative outcomes were compared. Results: There were no significant differences between the two groups with respect to patient gender, laterality, RENAL nephrometry score, or body mass index. The RPN group had a slightly higher RENAL nephrometry score (7.8 vs. 7.5, p=0.061) and larger tumor size (3.0 cm vs. 2.5 cm, p=0.044) but had a lower Charlson comorbidity index (3.7 vs. 4.4, p=0.017) than did the LPN group. There were no significant differences with respect to warm ischemia time, estimated blood loss, intraoperative complications, or operative time. Only one patient who underwent LPN had a positive surgical margin. There were statistically significant differences in surgical marginal width between the LPN and RPN groups (0.6 cm vs. 0.4 cm, p=0.001). No significant differences in postoperative complications were found between the two groups. Owing to potential baseline differences between the two groups, we performed a propensity-based matching analysis, in which differences in surgical margin width between the LPN and RPN groups remained statistically significant (0.6 cm vs. 0.4 cm, p=0.029). Conclusions: RPN provides perioperative outcomes comparable to those of LPN and has the advantage of healthy parenchymal preservation for complex renal tumors (RENAL score≥7). [ABSTRACT FROM AUTHOR]

Purpose: To analyze the location of the positive surgical margin (PSM) and its association with the biochemical recurrence (BCR) rate in cases of radical prostatectomy (RP) according to the type of surgery. Materials and Methods: We retrospectively analyzed 1,880 cases of RP. Baseline characteristics were analyzed. Locations of the PSM were recorded in the four surgery groups as apex, anterior, posterolateral, and base and were analyzed by using chi-square test. The association of the location of the PSM with the BCR rate was analyzed by using Kaplan-Meier survival analysis according to the type of surgery, which included radical perineal prostatectomy (RPP, n=633), radical retroperitoneal prostatectomy (RRP, n=309), laparoscopic radical prostatectomy (LRP, n=164), and robot-assisted laparoscopic radical prostatectomy (RALRP, n=774). Results: A PSM was found in a total of 336 cases (18%): 122 cases of RPP (18%), 67 cases of RRP (17%), 29 cases of LRP (17%), and 119 cases of RALRP (15%). The PSM rate did not differ significantly by surgical type (p=0.142). The location of the PSM was the apex in 136 cases (7.2%), anterior in 67 cases (3.5%), posterolateral in 139 cases (7.3%), and base in 95 cases (5.0%), and showed no significant difference according to surgical type (p=0.536, p=0.557, p=0.062, and p=0.109, respectively). The BCR rate according to the location of the PSM did not differ significantly for the four types of surgery (p= 0.694, p=0.301, p=0.445, and p=0.309 for RPP, RRP, LRP, and RALRP, respectively). Conclusions: The location of the PSM seemed to be unrelated to type of RP. There was no significant correlation between the BCR rate and the location of the PSM for any of the RP types. [ABSTRACT FROM AUTHOR]

To evaluate the oncologic outcomes and postoperative complications of high-intensity focused ultrasound (HIFU) as a salvage therapy after external-beam radiotherapy (EBRT) failure in patients with prostate cancer. Materials and Methods: Between February 2002 and August 2010, we retrospectively reviewed the medical records of all patients who underwent salvage HIFU for transrectal ultrasound-guided, biopsy-proven locally recurred prostate cancer after EBRT failure (by ASTRO definition: prostate-specific antigen [PSA] failure after three consecutive PSA increases after a nadir, with the date of failure as the point halfway between the nadir date and the first increase or any increase great enough to provoke initiation of therapy). All patients underwent prostate magnetic resonance imaging and bone scintigraphy and had no evidence of distant metastasis. Biochemical recurrence (BCR) was defined according to the Stuttgart definition (PSA nadir plus 1.2 ng/mL). Results: A total of 13 patients with a median age of 68 years (range, 60-76 years) were included. The median pre-EBRT PSA was 21.12 ng/mL, the pre-HIFU PSA was 4.63 ng/mL, and the period of salvage HIFU after EBRT was 32.7 months. The median follow- up after salvage HIFU was 44.5 months. The overall BCR-free rate was 53.8%. In the univariate analysis, predictive factors for BCR after salvage HIFU were higher pre-EBRT PSA (p=0.037), pre-HIFU PSA (p=0.015), and short time to nadir (p=0.036). In the multivariate analysis, there were no significant predictive factors for BCR. The complication rate requiring intervention was 38.5%. Conclusions: Salvage HIFU for prostate cancer provides effective oncologic outcomes for local recurrence after EBRT failure. However, salvage HIFU had a relatively high rate of complications. [ABSTRACT FROM AUTHOR]