1.Determinant of Aggressive Phenotype in Metastatic Hormone-Sensitive Prostate Cancer Depends on an Intrinsic, Highly Aggressive Cell Cluster: Integrated Single-Cell RNA and Whole Transcriptomic Sequencing Analyses
Minyong KANG ; ByulA JEE ; Jiwoong YU ; Soohyun HWANG ; Kyunghee PARK ; Kyung Yeon HAN ; Wan SONG ; Hyun Hwan SUNG ; Hwang Gyun JEON ; Byong Chang JEONG ; Seong Il SEO ; Se Hoon PARK ; Woong-Yang PARK ; Seong Soo JEON
Journal of Urologic Oncology 2025;23(2):98-111
Purpose:
Although the combination of androgen deprivation therapy with docetaxel or abiraterone acetate and prednisone has become a standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC) and has shown improved overall survival, a subset of patients still progress to castration-resistant disease. However, the underlying molecular features in these patients remain poorly understood.
Materials and Methods:
We performed single-cell RNA sequencing (scRNA-seq) on 12 tissue samples, including 2 mHSPC samples, 7 primary prostate cancer (PCa) samples, and 3 matched normal samples from 7 patients. Raw sequencing data was processed by Cell Ranger software (10X Genomics) and aligned to the human reference genome (GRCh38). A comprehensive analysis of samples from patients with mHSPC was also conducted and validated using a cohort of 52 patients with mHSPC.
Results:
Our results identified distinct subpopulations within luminal and mononuclear phagocyte (MNP) clusters characterized by proliferative activation associated with unfavorable clinical outcomes. Furthermore, we observed that the MNP cluster exhibited significant proliferation activity. To understand the underlying mechanisms associated with aggressiveness, we conducted cell-cell interaction, copy number variation and pseudotime analysis. Utilizing 87 network genes from scRNA-seq, we classified 52 mHSPC patients into 2 molecular subtypes and demonstrated their correlation with distinct transcriptomic profiles and survival outcomes. Importantly, a 14-gene signature derived from 3 distinct gene sets exhibited a strong association with patient survival and drug response. The prognostic value of our findings was further validated in large-scale cohorts comprising localized PCa, metastatic PCa, mHSPC, and metastatic castration-resistant PCa patients.
Conclusion
This study provides valuable insights into the identification of high-risk patients, novel biomarkers, and potential therapeutic targets for individuals with mHSPC. Furthermore, the results in this study can serve as a basis for future investigations aimed at refining prognostic strategies and developing targeted therapies for patients with mHSPC.
2.Gender and Menopause Impact on Recurrence and Cancer-Specific Mortality in Bladder Cancer After Radical Cystectomy: A Retrospective Cohort Study
Jee Soo PARK ; Won Sik JANG ; Jieun HEO ; Won Sik HAM ; Kyung Hwan KIM ; Jong Kil NAM ; Bum-Jin LIM ; Bum Sik HONG ; Wook NAM ; Sangchul LEE ; Jong Jin OH ; Seung Hwan JEONG ; Ja Hyeon KU ; Tae Il NOH ; Sung Gu KANG ; Seok Ho KANG ; Yun-Sok HA ; Tae Gyun KWON ; Tae‑Hwan KIM ; Jongchan KIM ; Geehyun SONG ; Ho Kyung SEO ; Wan SONG ; Hyun Hwan SUNG ; Byong Chang JEONG
Journal of Urologic Oncology 2025;23(1):88-93
Purpose:
Although bladder cancer occurs three to 4 times more frequently in men than in women, the relative number of deaths compared to incidence is higher in women, suggesting that women have a worse prognosis than men. Emerging evidence indicates that the activity of the sex steroid hormone pathway may play a role in bladder cancer development, with demonstrations that both androgens and estrogens have biological effects on bladder cancer in vitro and in vivo. This study investigates the influence of sex and menopausal status on recurrence and cancer-specific death (CSD) in bladder cancer patients undergoing radical cystectomy (RC).
Materials and Methods:
This retrospective analysis included 3,913 patients from the Korean Bladder Cancer Study Group Database who underwent RC between 2010 and 2019. Patients were categorized based on gender and menopausal status (≤50 years: premenopausal; >50 years: postmenopausal). Pathological factors, neoadjuvant chemotherapy, recurrence, and CSD rates were analyzed using chi-square and Fisher exact tests.
Results:
Among the 3,913 patients, 400 (10.2%) were female. Premenopausal females exhibited significantly lower recurrence rates (28.6%) compared to postmenopausal females (45.7%). CSD rates were similarly reduced in premenopausal females (12.0% vs. 22.2% in postmenopausal females). No significant sex differences in recurrence or CSD were observed among premenopausal patients. Pathological T stage, nodal status, and lymphovascular invasion were significantly associated with recurrence in males, while nodal status alone was significant in females. Neoadjuvant chemotherapy was significantly more frequently administered to male patients under the age of 50, while no difference was observed in the administration of neoadjuvant chemotherapy among female patients based on menopausal status.
Conclusion
Hormonal changes associated with menopause significantly influence bladder cancer outcomes in women. Premenopausal hormonal environments seem protective, underscoring the need for further research into hormone-driven mechanisms in bladder cancer.
3.Impact of Extended Lymph Node Dissection on Survival Outcomes in Patients With Bladder Cancer and Upper Tract Urothelial Carcinoma: A Multicenter Retrospective Study
Jiwoong YU ; Wook NAM ; Kyung Hwan KIM ; Yun-Sok HA ; Geehyun SONG ; Ho Kyung SEO ; Jong Kil NAM ; Tae Il NOH ; Seok Ho KANG ; Seung-Hwan JEONG ; Ja Hyeon KU ; Jong Jin OH ; Ji Eun HEO ; Won Sik HAM ; Joongwon CHOI ; Bumjin LIM ; Bumsik HONG ; Wan SONG ; Minyong KANG ; Hwang Gyun JEON ; Seong Il SEO ; Seong Soo JEON ; Hyun Hwan SUNG ; Byong Chang JEONG ;
Journal of Urologic Oncology 2025;23(1):79-87
Purpose:
To evaluate whether extended pelvic lymph node dissection (PLND) improves survival outcomes compared with standard PLND in patients with bladder cancer (BCa) undergoing radical cystectomy (RC), and to assess its potential benefits in patients with prior or concurrent radical nephroureterectomy (p/cRNU).
Materials and Methods:
A multicenter analysis included 2202 patients with BCa undergoing RC with standard or extended PLND at 11 tertiary centers from 2003 to 2023. Following propensity score matching, 659 pairs (n=1,318), including 128 patients with p/cRNU, were analyzed. Recurrence-free survival (RFS) was the primary outcome, while overall survival (OS), cancer-specific survival (CSS), and readmission rates were secondary outcomes. Survival analyses performed using Kaplan-Meier methods and clustered Cox models.
Results:
Extended PLND yielded significantly more lymph nodes than standard PLND (median: 27.0 vs. 17.0, p<0.001) but did not improve RFS, CSS, or OS in the overall cohort (all p>0.05). Extended PLND increased readmission rates (28.4% vs. 20.2%, p=0.001) and readmission risk (odds ratio, 1.57; 95% confidence interval [CI], 1.15–2.16, p=0.005). However, subgroup analysis revealed extended PLND significantly improved RFS in patients with p/cRNU (hazard ratio, 0.54; 95% CI, 0.38–0.77; p<0.001).
Conclusion
Extended PLND does not provide survival benefits for overall patient population and increases readmission risk but significantly improves RFS in patients with p/cRNU. Tailoring PLND extent based on upper tract disease status is recommended.
4.Effectiveness of Guardix-SG in Preventing Postoperative Bowel Complications After Radical Cystectomy: A Single-Arm Prospective Observational Study
Jiwoong YU ; Wan SONG ; Minyong KANG ; Hyun Hwan SUNG ; Hwang Gyun JEON ; Seong Il SEO ; Seong Soo JEON ; Byong Chang JEONG
Journal of Urologic Oncology 2025;23(3):253-259
Purpose:
This study aimed to evaluate the effectiveness of intraoperative Guardix-SG application in reducing postoperative ileus (POI) and preventing adhesive small bowel obstruction (SBO) following radical cystectomy (RC) for bladder cancer.
Materials and Methods:
A single-arm, prospective observational study was conducted from April 2022 to February 2025. Sixty-seven patients undergoing RC with pelvic lymph node dissection received intraoperative Guardix-SG application after urinary reconstruction. Patients with prior abdominal surgery or pelvic radiotherapy were excluded. POI was defined as (1) the absence of flatus or stool by postoperative day (POD) 6 (definition 1) or (2) intolerance to oral intake by POD 5 requiring nasogastric decompression or intravenous support (definition 2). Adhesive SBO was defined as radiologic or clinical bowel obstruction without a mechanical cause. Outcomes were monitored for 3 months. Predictors of POI (definition 2) were identified using multivariable logistic regression.
Results:
The median age was 69.0 (interquartile range, 62.5–75.0) years, and 88.1% of participants were male. Robot-assisted surgery was performed in 62.7% of cases, and ileal conduit diversion was most common (64.2%). The incidence of POI was 3.0% (2 of 67) by definition 1 and 19.4% (13/67) by definition 2. Nasogastric tube placement was required in 6.0% (4 of 67). No cases of adhesive SBO or gastrointestinal reoperation were observed. Multivariable analysis identified lower body mass index as an independent predictor of POI (odds ratio, 0.74; 95% confidence interval, 0.57–0.96; p=0.023). No significant associations were found with surgical approach, diversion type, or operative time. Compared with previous studies reporting SBO rates of 3%–5% and POI rates of 14%–27%, the observed complication rates were lower or comparable.
Conclusion
Intraoperative Guardix-SG application resulted in favorable bowel outcomes after radical cystectomy, with no observed SBO and a reduced incidence of POI.
5.Impact of pretreatment body mass index on clinical outcomes in patients with metastatic renal cell carcinoma receiving first-line immune checkpoint inhibitor-based therapy: A systematic review and meta-analysis
Kunwoo LEE ; Jiwoong YU ; Wan SONG ; Hyun Hwan SUNG ; Hwang Gyun JEON ; Byong Chang JEONG ; Seong Il SEO ; Seong Soo JEON ; Minyong KANG
Investigative and Clinical Urology 2024;65(5):423-434
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<0.0001; adjusted (a)HR 0.75, 95% CI 0.59–0.95, p=0.02), but not relative risk (RR 0.88, 95% CI 0.67–1.16, p=0.37). In the subgroup analysis, patients with a high BMI had better OS in the ICI with tyrosine kinase inhibitor (TKI) subgroup (aHR 0.71, 95% CI 0.55–0.92, p=0.01), while no significant difference was found in the ICI-only subgroup (aHR 1.02, 95% CI 0.56–1.87, p=0.95). Adjusted statistics for progression-free survival (PFS) were assessable in predominantly ICI-only studies and demonstrated a favorable outcome for patients with a low BMI (aHR 1.67, 95% CI 1.14–2.45, p=0.01). In conclusion, the impact of high BMI varies depending on the treatment type, exhibiting a favorable correlation with OS within ICI with TKI subgroup, but indicating an adverse association with PFS in the ICI-only subgroup. Further research is needed to clarify the influence of BMI by stratifying patients into ICI-only and ICI with TKI treatment to provide more insights.
6.Hypofractionated radiation therapy combined with androgen deprivation therapy for clinically node-positive prostate cancer
Tae Hoon LEE ; Hongryull PYO ; Gyu Sang YOO ; Seong Soo JEON ; Seong Il SEO ; Byong Chang JEONG ; Hwang Gyun JEON ; Hyun Hwan SUNG ; Minyong KANG ; Wan SONG ; Jae Hoon CHUNG ; Bong Kyung BAE ; Won PARK
Radiation Oncology Journal 2024;42(2):139-147
Purpose:
This study aimed to analyze the treatment outcomes of combined definitive radiation therapy (RT) and androgen deprivation therapy (ADT) for clinically node-positive prostate cancer.
Materials and Methods:
Medical records of 60 patients with clinically suspected metastatic lymph nodes on radiological examination were retrospectively analyzed. Eight patients (13.3%) were suspected to have metastatic common iliac or para-aortic lymph nodes. All patients underwent definitive RT with a dose fractionation of 70 Gy in 28 fractions. ADT was initiated 2–3 months before RT and continued for at least 2 years. Biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS), and prostate cancer-specific survival (PCSS) were calculated, and genitourinary and gastrointestinal adverse events were recorded.
Results:
The median follow-up period was 5.47 years. The 5-year BFR, CFR, OS, and PCSS rates were 19.1%, 11.3%, 89.0%, and 98.2%, respectively. The median duration of ADT was 2.30 years. BFR and CFR increased after 3 years, and 11 out of 14 biochemical failures occurred after the cessation of ADT. Grade 2 and beyond late genitourinary and gastrointestinal toxicity rates were 5.0% and 13.3%, respectively. However, only two grade 3 adverse events were reported, and no grade 4–5 adverse events were reported. Patients with non-regional lymph node metastases did not have worse BFR, CFR, or adverse event rates.
Conclusion
This study reported the efficacy and tolerable toxicity of hypofractionated definitive RT combined with ADT for clinically node-positive prostate cancer. Additionally, selected patients with adjacent non-regional lymph node metastases might be able to undergo definitive RT combined with ADT.
7.Nomogram Using Prostate Health Index for Predicting Prostate Cancer in the Gray Zone:Prospective, Multicenter Study
Jae Hoon CHUNG ; Jeong Hyun KIM ; Sang Wook LEE ; Hongzoo PARK ; Geehyun SONG ; Wan SONG ; Minyong KANG ; Hyun Hwan SUNG ; Hwang Gyun JEON ; Byong Chang JEONG ; Seong IL SEO ; Hyun Moo LEE ; Seong Soo JEON
The World Journal of Men's Health 2024;42(1):168-177
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.
8.Single Early Intravesical Instillation of Epirubicin for Preventing Bladder Recurrence after Nephroureterectomy in Upper Urinary Tract Urothelial Carcinoma
Jong Hoon LEE ; Chung Un LEE ; Jae Hoon CHUNG ; Wan SONG ; Minyong KANG ; Hwang Gyun JEON ; Byong Chang JEONG ; Seong Il SEO ; Seong Soo JEON ; Hyun Hwan SUNG
Cancer Research and Treatment 2024;56(3):877-884
Purpose:
We aimed to assess the effectiveness of early single intravesical administration of epirubicin in preventing intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.
Materials and Methods:
Patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy between November 2018 and May 2022 were retrospectively reviewed. Intravesical epirubicin was administered within 48 hours if no evidence of leakage was observed. Epirubicin (50 mg) in 50 mL normal saline solution was introduced into the bladder via a catheter and maintained for 60 minutes. The severity of adverse events was graded using the Clavien-Dindo classification. We compared intravesical recurrence rate between the two groups. Multivariate analyses were performed to identify the independent predictors of bladder recurrence following radical nephroureterectomy.
Results:
Epirubicin (n=55) and control (n=116) groups were included in the analysis. No grade 1 or higher bladder symptoms have been reported. A statistically significant difference in the intravesical recurrence rate was observed between the two groups (11.8% at 1 year in the epirubicin group vs. 28.4% at 1 year in the control group; log-rank p=0.039). In multivariate analysis, epirubicin instillation (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20 to 0.93; p=0.033) and adjuvant chemotherapy (HR, 0.29; 95% CI, 0.13 to 0.65; p=0.003) were independently predictive of a reduced incidence of bladder recurrence.
Conclusion
This retrospective review revealed that a single immediate intravesical instillation of epirubicin is safe and can reduce the incidence of intravesical recurrence after radical nephroureterectomy. However, further prospective trials are required to confirm these findings.
9.Sextant Systematic Biopsy Versus Extended 12-Core Systematic Biopsy in Combined Biopsy for Prostate Cancer
Jae Hoon CHUNG ; Wan SONG ; Minyong KANG ; Hyun Hwan SUNG ; Hwang Gyun JEON ; Byong Chang JEONG ; Seong IL SEO ; Seong Soo JEON ; Hyun Moo LEE ; Byung Kwan PARK
Journal of Korean Medical Science 2024;39(7):e63-
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.
10.Enzalutamide Maintenance Following Docetaxel in Metastatic Castration-Naive Prostate Cancer: A Pilot Feasibility Study
Sung Hee LIM ; Sung Wook CHO ; Jae Hoon CHUNG ; Wan SONG ; Minyong KANG ; Hyun Hwan SUNG ; Hwang Gyun JEON ; Byong Chang JEONG ; Seong Il SEO ; Seong Soo JEON ; Se Hoon PARK
Journal of Urologic Oncology 2024;22(1):29-33
Purpose:
To assess the feasibility and short-term efficacy of maintenance enzalutamide following first-line docetaxel plus androgen deprivation therapy (ADT) in patients with high-volume, metastatic castration-naive prostate cancer (mCNPC).
Materials and Methods:
The present study included 38 consecutive patients with mCNPC who did not have disease progression with ADT plus docetaxel between October 2022 and October 2023. Patients received a switch maintenance therapy with enzalutamide until progression, unacceptable toxicity, or patient withdrawal. Endpoints included time to prostate-specific antigen (PSA) progression and safety.
Results:
Among the 38 patients, the median age was 68 years, and the most frequently observed metastatic site was bone (n=36), followed by lymph nodes (n=28), lung (n=8), and liver (n=1). The median duration of firstline docetaxel was 2.8 months (range, 2.7–5.0 months). At the time of commencing maintenance enzalutamide, the median PSA was 3.2 ng/mL (range, 0.01–258 ng/mL). Maintenance enzalutamide was generally welltolerated. A total of 11 patients (28%) discontinued enzalutamide, and the main reasons included adverse events (prolonged fatigue of grade 1 or 2, n=6), disease progression (n=3) and financial burdens (n=2). Median time to PSA progression was not reached, and 93% were PSA progression-free at 12 months.
Conclusions
Maintenance enzalutamide is a feasible treatment option with potential clinical benefit for patients with high-volume mCNPC who were progression-free after first-line ADT+docetaxel.

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