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author:("Ahn, tanjong")
1.  Oncologic outcomes in men with metastasis to the prostatic anterior fat pad lymph nodes: a multi-institution international study 
BMC Urology  2015;15:79.
The presence of lymph nodes (LN) within the prostatic anterior fat pad (PAFP) has been reported in several recent reports. These PAFP LNs rarely harbor metastatic disease, and the characteristics of patients with PAFP LN metastasis are not well-described in the literature. Our previous study suggested that metastatic disease to the PAFP LN was associated with less severe oncologic outcomes than those that involve the pelvic lymph node (PLN). Therefore, the objective of this study is to assess the oncologic outcome of prostate cancer (PCa) patients with PAFP LN metastasis in a larger patient population.
Data were analyzed on 8800 patients from eleven international centers in three countries. Eighty-eight patients were found to have metastatic disease to the PAFP LNs (PAFP+) and 206 men had isolated metastasis to the pelvic LNs (PLN+). Clinicopathologic features were compared using ANOVA and Chi square tests. The Kaplan-Meier method was used to calculate the time to biochemical recurrence (BCR).
Of the eighty-eight patients with PAFP LN metastasis, sixty-three (71.6 %) were up-staged based on the pathologic analysis of PAFP and eight (9.1 %) had a low-risk disease. Patients with LNs present in the PAFP had a higher incidence of biopsy Gleason score (GS) 8–10, pathologic N1 disease, and positive surgical margin in prostatectomy specimens than those with no LNs detected in the PAFP. Men who were PAFP+ with or without PLN involvement had more aggressive pathologic features than those with PLN disease only. However, there was no significant difference in BCR-free survival regardless of adjuvant therapy. In 300 patients who underwent PAFP LN mapping, 65 LNs were detected. It was also found that 44 out of 65 (67.7 %) nodes were located in the middle portion of the PAFP.
There was no significant difference in the rate of BCR between the PAFP LN+ and PLN+ groups. The PAFP likely represents a landing zone that is different from the PLNs for PCa metastasis. Therefore, the removal and pathologic analysis of PAFP should be adopted as a standard procedure in all patients undergoing radical prostatectomy.
Electronic supplementary material
The online version of this article (doi:10.1186/s12894-015-0070-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4521494  PMID: 26231860
Lymph node metastases; Prostate anterior fat pad; Prostate cancer
2.  Prognostic impact of preoperative statin use after radical nephroureterectomy for upper urinary tract urothelial carcinoma 
Korean Journal of Urology  2015;56(7):498-504.
The objective was to investigate the impact of statin use on prognosis after radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC).
Materials and Methods
A retrospective review of medical records identified 277 patients who underwent radical nephroureterectomy for primary UTUC at Asan Medical Center between January 2006 and December 2011. Information on preoperative statin use was obtained from patient charts in an electronic database. We assessed the impact of statin use on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS).
Of these 277 patients, 62 (22.4%) were taking statin medications. Compared to the statin nonusers, the statin users were older, had a higher body mass index, and had higher rates of cardiovascular disease and diabetes. The 5-year RFS rates of statin users and nonusers were 78.5% and 72.5%, respectively (p=0.528); the 5-year CSS rates were 85.6% and 77.7%, respectively (p=0.516); and the 5-year OS rates were 74.5% and 71.4%, respectively (p=0.945). In the multivariate analysis, statin use was not an independent prognostic factor for RFS (hazard ratio, 0.47; p=0.056), CSS (hazard ratio, 0.46; p=0.093), or OS (hazard ratio, 0.59; p=0.144) in patients who underwent radical nephroureterectomy for UTUC.
Statin use was not associated with improved RFS, CSS, or OS in the sample population of patients with UTUC.
PMCID: PMC4500806  PMID: 26175868
Carcinoma; Hydroxymethylglutaryl-CoA reductase inhibitors; Transitional cell carcinoma
3.  Antibiotic prophylaxis with intravenous ceftriaxone and fluoroquinolone reduces infectious complications after transrectal ultrasound-guided prostatic biopsy 
Korean Journal of Urology  2015;56(6):466-472.
To assess the rates of infectious complications before and after the change of prophylactic antibiotic regimens in prostate needle biopsy.
Materials and Methods
The records of 5,577 patients who underwent prostate needle biopsy at Asan Medical Center between August 2005 and July 2012 were retrospectively reviewed. Group 1 (n=1,743) included patients treated between 2005 and 2009 with fluoroquinolone for 3 days, group 2 (n=2,723) included those treated between 2009 and 2012 with ceftriaxone once before the biopsy and fluoroquinolone before biopsy and continue therapy for 3 days, and group 3 (n=1,111) received the same treatment for more than 7 days after the biopsy. Univariable and multivariable logistic regression models addressed risk factors associated with infectious complication after prostate needle biopsy.
Infectious complication after prostate needle biopsy developed in 18 (group 1), seven (group 2), and two patients (group 3) (p=0.001). In group 1, seven patients with infectious complication had positive blood cultures and harbored fluoroquinolone-resistant Escherichia coli, four had ceftriaxone susceptible isolates, and three had extended spectrum beta-lactamase-positive E. coli. Two patients in group 1 required intensive care because of septic shock. In multivariable analysis, the patients with combination of fluoroquinolone and ceftriaxone had significantly lower infectious complication rate than the fluoroquinolon alone (p=0.003).
Antibiotic prophylaxis with ceftriaxone and fluoroquinolone before prostate needle biopsy decreased the risk of potentially serious infectious complications.
PMCID: PMC4462638  PMID: 26078845
Antibiotic prophylaxis; Biopsy; Ceftriaxone; Infection; Prostate
4.  Prognostic Significance of CREB-Binding Protein and CD81 Expression in Primary High Grade Non-Muscle Invasive Bladder Cancer: Identification of Novel Biomarkers for Bladder Cancer Using Antibody Microarray 
PLoS ONE  2015;10(4):e0125405.
High-grade (HG) bladder cancers (BCs) are genetically unstable and have an unpredictable course. The identification of prognostic factors in HG non-muscle invasive BC (NMIBC) is crucial for improving patients’ quality of life and preventing BC-specific mortality. Here, we used an antibody microarray (AbM) to identify novel candidate biomarkers in primary HG NMIBC and validated the prognostic significance of the candidate biomarkers. Three pairs of tissue samples from primary HG NMIBC and normal urothelium were analyzed using an AbM kit containing 656 antibodies, and differentially expressed proteins were identified. Among the 42 upregulated and 14 downregulated proteins with statistical significance in BC tissues, CREB-binding protein and CD81 were selected as representative upregulated and downregulated candidate biomarkers, respectively. We then validated the expression of these candidate biomarkers in primary human urothelial cells and BC cell lines by western blotting and immunofluorescence assays, and the results were consistent with the AbM expression profiles. Additionally, Kaplan-Meier survival using immunohistochemical data from an independent primary HG NMIBC cohort comprising 113 patients showed that expression of the 2 biomarkers was significantly associated with recurrence-free and progression-free survival. In multivariate analysis, the 2 biomarkers remained significant predictors for recurrence-free survival. Taken together, our findings suggest that expression of CREB-binding protein and CD81 in BC tissue specimens may have prognostic value in patients with primary HG NMIBC.
PMCID: PMC4411067  PMID: 25915404
5.  Clinicopathological Features of Prostate Ductal Carcinoma: Matching Analysis and Comparison with Prostate Acinar Carcinoma 
Journal of Korean Medical Science  2015;30(4):385-389.
We evaluated the clinicopathological features and prognosis of 29 cases of prostate ductal carcinoma was considered to be an aggressive subtype of prostate acinar carcinoma. We selected 29 cases who were diagnosed prostate ductal carcinoma and had a radical prostatectomy (RP). The acinar group (n = 116) was selected among 3,980 patients who underwent a prostatectomy. The acinar group was matched to the ductal group for prostate specific antigen (PSA), clinical stage, Gleason score, and age. The mean (range) of the follow-up periods for the ductal and acinar group was 23.8 ± 20.6 and 58 ± 10.5 months, respectively. The mean age of the prostate ductal and acinar carcinoma patients was 67.3 and 67.0 yr and the mean PSA level was 14.7 and 16.2 ng/mL, respectively. No statistical differences were evident between groups in terms of the final pathologic stage or positive resection margin rate other than the postoperative Gleason score. A greater proportion of the ductal group demonstrated a postoperative Gleason score ≥ 8 in comparison with the acinar group (P = 0.024). Additionally, we observed significant prognostic difference in our patient series in biochemical recurrence. The ductal group showed a poorer prognosis than the acinar group (P = 0.016). There were no differences significantly in terms of final pathology and rate of positive resection margin, but a greater proportion of the ductal group demonstrated a Gleason score ≥ 8 than the acinar group after matching for PSA, Gleason score in biopsy and clinical stage. The ductal group also showed a poorer prognosis.
Graphical Abstract
PMCID: PMC4366958  PMID: 25829805
Prostate Neoplasms; Prostatectomy; Disease Progression; Recurrence
6.  Prevalence and clinical significance of incidental 18F-fluoro-2-deoxyglucose uptake in prostate 
Korean Journal of Urology  2015;56(4):288-294.
To investigate the prevalence and clinical significance of incidental prostate fluoro-2-deoxyglucose (FDG) uptake and to evaluate its impact on patient management.
Materials and Methods
Of 47,109 men who underwent FDG positron emission tomography between 2004 and 2014, 1,335 (2.83%) demonstrated incidental FDG uptake in the prostate, with 99 of the latter undergoing prostate biopsy. The primary end point was the histological presence of prostate adenocarcinoma in the biopsy specimen. Outcomes, including treatment methods, survival, and causes of death, were also assessed. Factors associated with the diagnosis of prostate cancer were evaluated by using logistic regression analysis.
Patients with prostate cancer were more likely to have higher serum prostate-specific antigen (PSA) (p=0.001) and focal FDG uptake (p=0.036) than were those without. Prostate cancer occurred in 1 of 26 patients (3.8%) with serum PSA<2.5 ng/mL, compared with 40 of 67 patients (59.7%) with serum PSA≥2.5 ng/mL. Multivariable analysis showed that focal lesions (odds ratio [OR], 5.50; p=0.038), age (OR, 1.06; p=0.031), and serum PSA (OR, 1.28; p=0.001) were independent predictors of prostate cancer diagnosis. Most patients with prostate cancer had organ-confined tumors. Of these, 12 (29.3%) underwent radical prostatectomy and 25 (60.9%) received hormone therapy. Of the 11 patients who died, 9 died of primary cancer progression, with only 1 patient dying from prostate cancer.
The prevalence of incidental FDG uptake in the prostate was not high, although patients with elevated serum PSA had a higher incidence of prostate cancer. Patients with FDG uptake in the prostate should be secondarily evaluated by measuring serum PSA, with those having high serum PSA undergoing prostate biopsy.
PMCID: PMC4392028  PMID: 25874042
Incidental findings; Positron-emission tomography; Prostate neoplasms
7.  Is Intravesical Bacillus Calmette-Guérin Therapy Superior to Chemotherapy for Intermediate-risk Non-muscle-invasive Bladder Cancer?: An Ongoing Debate 
Journal of Korean Medical Science  2015;30(3):252-258.
The objective of this study was to evaluate the risk of recurrence in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) after intravesical instillation with chemotherapeutic agents or Bacillus Calmette-Guérin (BCG) therapy. A cohort of 746 patients with intermediate-risk NMIBC comprised the study group. The primary outcome was time to first recurrence. The recurrence rates of the transurethral resection (TUR) alone, chemotherapy, and BCG groups were determined using Kaplan-Meier analysis. Risk factors for recurrence were identified using Cox regression analysis. In total, 507 patients (68.1%), 78 patients (10.5%), and 160 (21.4%) underwent TUR, TUR+BCG, or TUR+chemotherapy, respectively. After a median follow-up period of 51.7 months (interquartile range=33.1-77.8 months), 286 patients (38.5%) developed tumor recurrence. The 5-yr recurrence rates for the TUR, chemotherapy, and BCG groups were 53.6%±2.7%, 30.8%±5.7%, and 33.6%±4.7%, respectively (P<0.001). Chemotherapy and BCG treatment were found to be predictors of reduced recurrence. Cox-regression analysis showed that TUR+BCG did not differ from TUR+chemotherapy in terms of recurrence risk. Adjuvant intravesical instillation is an effective prophylactic that prevents tumor recurrence in intermediate-risk NMIBC patients following TUR. In addition, both chemotherapeutic agents and BCG demonstrate comparable efficacies for preventing recurrence.
Graphical Abstract
PMCID: PMC4330478  PMID: 25729246
Urinary Bladder Neoplasm; BCG Vaccine; Transurethral Resection; Chemotherapy
8.  Clinicopathological features of Xp11.2 translocation renal cell carcinoma 
Korean Journal of Urology  2015;56(3):212-217.
Xp11.2 translocation renal cell carcinoma (RCC) is characterized by various translocations of the TFE3 transcription factor gene. These rare cancers occur predominantly in children and young adults. Here, we review the clinicopathological features of Xp11.2 translocation RCC.
Materials and Methods
We identified 21 patients with Xp11.2 translocation RCC. We retrospectively analyzed patient characteristics, clinical manifestations, and specific pathological features to assess definitive diagnosis, surgical and systemic treatments, and clinical outcomes.
The mean age at diagnosis was 43.4±20.0 years (range, 8-80 years; 8 males and 13 females). Eleven patients were incidentally diagnosed, nine patients presented with local symptoms, and one patient presented with systemic symptoms. The mean tumor size was 6.2±3.8 cm (range, 1.9-14 cm). At the time of diagnosis, 11, 1, and 5 patients showed stage I, II, and III, respectively. Four patients showed distant metastasis. At analysis, 15 patients were disease-free after a median follow-up period of 30.0 months. Four patients received target therapy but not effectively.
Xp11 translocation RCC tends to develop in young patients with lymph node metastasis. Targeted therapy did not effectively treat our patients. Surgery is the only effective therapy for Xp11 translocation RCC, and further studies are needed to assess systemic therapy and long-term prognosis.
PMCID: PMC4355432  PMID: 25763125
Angiogenesis inducing agents; Genetic translocation; Renal cell carcinoma
9.  Histologic Variability and Diverse Oncologic Outcomes of Prostate Sarcomas 
Korean Journal of Urology  2014;55(12):797-801.
Primary prostate sarcomas are a rare type of prostate cancer that account for less than 0.1% of primary prostate malignancies. We analyzed the experience of a single institution with prostate sarcoma over 20 years.
Materials and Methods
In this case series, the medical records of 20 patients with prostate sarcoma were reviewed from June 1990 to December 2013 to identify symptoms at presentation, diagnostic procedures, metastasis presence and development, histologic subtype, French Fédération Nationale des Centres de Lutte Contre le Cancer grade, primary tumor grade and size, and treatment sequence, including surgery and preoperative and postoperative therapies. The average follow-up period was 23.6 months (range, 1.4-83.3 months).
The average patient age was 46.3±16.7 years. Most patients presented with lower urinary tract symptoms (55%). The histologic subtype was spindle cell sarcoma in five patients (25%), rhabdomyosarcoma in three patients (15%), synovial sarcoma in three patients (15%), liposarcoma in three patients (15%), stromal sarcoma in three patients (15%), and Ewing sarcoma, nerve sheath tumor, and adenocarcinoma with sarcomatoid component (5% each). For liposarcoma, two patients were alive after complete surgical resection and had a good prognosis. At last follow-up, 15 patients had died of sarcoma. The 2- and 5-year actuarial survival rates for all 20 patients were 53% and 12%, respectively (medial survival, 20 months).
The disease-specific survival rate of prostate sarcoma is poor. However, sarcoma that is detected early shows a better result with proper management including surgical intervention with radio-chemotherapy than with no treatment. Early diagnosis and complete surgical resection offer patients the best curative chance.
PMCID: PMC4265713  PMID: 25512813
Liposarcoma; Prostate; Rhabdomyosarcoma; Sarcoma
10.  VEGF/VEGFR2 and PDGF-B/PDGFR-β expression in non-metastatic renal cell carcinoma: a retrospective study in 1,091 consecutive patients 
Purpose: We aimed to investigate the correlations between the expression of VEGF, PDGF-B, and their receptors (VEGFR2 and PDGFR-β) with pathologic stage or cell type in non-metastatic renal cell carcinoma. Materials and methods: VEGF, VEGFR2, PDGF-B, and PDGFR-β protein expression were evaluated immunohistochemically in prospectively collected 1,423 tumour samples obtained during radical or partial nephrectomy at a tertiary referral center. Intensity of expression was quantified on a scale of 0 to 3, and was compared among renal cell carcinoma cell types. Results: The study cohort consisted of 1,091 patients, of mean age 54 years, including 968 (88.7%) with clear cell, 82 (7.5%) with papillary, 31 (2.8%) with chromophobe, 4 (0.4%) with unclassified, and 6 (0.5%) with other types of renal cell carcinoma. VEGF expression increased with higher T and N stage and Fuhrman nuclear grade. PDGFR-β expression was highest in clear cell renal cell carcinoma, whereas VEGF and PDGF-B expression were highest in papillary renal cell carcinoma. After adjusting for T stage and Fuhrman nuclear grade using multivariate logistic regression analysis, VEGF (OR = 3.57, P < 0.001), VEGFR2 (OR = 1.82, P = 0.017), and PDGF-B (OR = 2.46, P = 0.019) expression were significantly greater in papillary than in clear cell type. Conclusions: Our results indicate that the cytoplasmic expression of VEGF, VEGFR2, PDGF-B, and PDGFR-β in RCC tumour cells is different in various pathologic stage and cell type. Notably, VEGF and PDGF-B expression are higher in papillary than in clear cell renal cell carcinoma. Further studies using quantitative measurement of proangiogenic factors in tumour cell are needed.
PMCID: PMC4270555  PMID: 25550804
Carcinoma; renal cell; vascular endothelial growth factor A; vascular endothelial growth factor receptor-2
11.  Efficacy and Safety of Everolimus in Korean Patients with Metastatic Renal Cell Carcinoma Following Treatment Failure with a Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor 
The purpose of this study is to assess the efficacy and safety of everolimus in Korean patients with metastatic renal cell carcinoma (mRCC) for whom initial treatment with a vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) has failed.
Materials and Methods
Eligible patients with mRCC (any histology) who had progressed on or were intolerant of VEGFr-TKI therapy received oral everolimus (10 mg dose once daily). Tumor response was reassessed according to Response Evaluation Criteria in Solid Tumors (RECIST).
This study included 100 patientswith a median follow-up duration of 10.2 months, a median progression-free survival (PFS) of 4.2 months (95% confidence interval [CI], 3.4 to 5.0 months), and an overall survival of 10.1 months (95% CI, 6.9 to 13.3 months). The most common grade 3 or greater adverse events (AEs) overall were anemia (13%), pneumonitis (9%), hyperglycemia (8%), and stomatitis (6%). While the incidence of pneumonitis was similar (26 cases, 26%) to the reported incidence in Western patients, the Korean presentations were more severe: 10 patients permanently discontinued everolimus due to pneumonitis, including two deaths on treatment. Statistically significant relationships were established between biologic toxicities, hyperglycemia and anemia, and PFS (hyperglycemia vs. non-hyperglycemia: hazard ratio [HR], 0.61; p=0.055 and anemia vs. non-anemia: HR, 0.51; p=0.021).
Everolimus was effective in Korean patients with mRCC who had failed initial VEGFr-TKI therapy. While everolimus was well tolerated in general and the AE incidence of this study was similar to those of previous reports, severe pneumonitis was common. Hyperglycemia and anemia showed significant correlation with PFS and thus may be potentially useful as prognostic indicators.
PMCID: PMC4206076  PMID: 25036572
Renal cell carcinoma; Everolimus; Treatment outcome; Safety
12.  Incidence of Benign Results After Laparoscopic Radical Nephroureterectomy 
Background and Objectives:
Studies of patients with benign pathologic lesions who underwent laparoscopic radical nephroureterectomy (RNU) with preoperative suspicion of upper urinary tract urothelial carcinoma are lacking. The aim of this retrospective cross-sectional study was to evaluate the incidence of benign pathologic lesions on laparoscopic RNU for upper urinary tract tumors that are presumed to be urothelial carcinoma. The clinicopathologic characteristics of these lesions were also determined.
Between January 2004 and December 2010, 244 patients underwent laparoscopic RNU for possible upper urinary tract urothelial carcinoma at our institute. Seven (2.9%) had benign lesions at the final pathologic examination. The preoperative features of these patients were investigated, including imaging findings, urine cytologic results, and ureteroscopic findings.
The 7 patients comprised 5 men and 2 women. The lesions were located in the ureter in 5 patients and in the renal pelvis in 2. All patients underwent preoperative voided urine cytology and cystoscopy. Two patients underwent preoperative ureteroscopy. In 1 patient, definite pathologic lesions were not identified in the surgical specimen. Urinary tract tuberculosis was diagnosed in 1 patient, inflammatory pseudotumor in 2, and fibroepithelial polyps in 1. In 2 patients, stones were detected (stone with atypical papillary urothelial hyperplasia and polypoid ureteritis with ureter stone, respectively) after laparoscopic RNU.
Benign pathologic lesions were detected in 7 patients (2.9%) who had undergone laparoscopic RNU for upper urinary tract tumors that were presumed to be urothelial carcinoma. The description of these false-positive cases will help improve the preoperative counseling of these patients.
PMCID: PMC4232409  PMID: 25408605
Benign; Nephroureterectomy; Upper urinary tract; Urothelial carcinoma
13.  Is Bladder Tumor Location Associated with Prostate Cancer Detection after Intravesical Bacillus Calmette-Guérin Instillation? 
PLoS ONE  2014;9(7):e103791.
The aim of this study was to evaluate the effect of bladder tumor (BT) location on prostate cancer (PCa) detection in patients with elevated PSA levels after intravesical BCG instillation.
Between February 2004 and January 2013 prostate biopsies were performed in 59 non-muscle invasive bladder cancer (NMIBC) patients whose PSA level were elevated (≥3 ng/ml) after a 6 week course of intravesical BCG (Oncotice, 12.5 mg in 50 ml normal saline). Differences in PCa detection according to the BT location [bladder neck and/or trigone (Group 1, n = 22) vs. other locations (Group 2, n = 37)] were evaluated. The Fisher's exact test and the Mann-Whitney U test were used to evaluate the association between categorical and continuous variables, respectively.
A total of 14 patients (23.7%) were diagnosed with PCa. The mean ± standard deviation (SD) PSA before intravesical BCG instillation and prostate biopsy were 1.36±1.04 ng/ml in Group 1 and 1.09±1.12 ng/ml in Group 2 (P = 0.633), and 6.05±3.57 ng/ml in Group 1 and 5.13±3.88 ng/ml in Group 2 (P = 0.378), respectively. Interestingly, whereas PCa was detected upon biopsy in only one patient in Group 1 (4.5%), 13 cases were detected in Group 2 (35.1%) (P = 0.009).
PCa detection after intravesical BCG was highly associated with BT location. Prostate biopsy should therefore be considered when PSA level is elevated after BCG instillation and his BT is located far from the bladder neck.
PMCID: PMC4114875  PMID: 25072158
14.  The Type of Nephrectomy Has Little Effect on Overall Survival or Cardiac Events in Patients of 70 Years and Older With Localized Clinical T1 Stage Renal Masses 
Korean Journal of Urology  2014;55(7):446-452.
To compare the outcomes of nephron-sparing options (e.g., partial nephrectomy [PN]) and low-surgical-morbidity options (e.g., radical nephrectomy [RN]) in elderly patients with limited life expectancy.
Materials and Methods
We retrospectively reviewed 135 patients aged 70 years or older who underwent RN (n=82) or PN (n=53) for clinical T1 stage renal masses between January 2000 and December 2012. Clinicopathologic data were thoroughly analyzed and compared between the RN and PN groups. The modification of diet in renal disease equation was used to estimate glomerular filtration. Overall survival and cardiac events were assessed by using Kaplan-Meier survival analysis and Cox proportional-hazards regression modeling.
Over a median follow-up period of 59.72 months, 17 patients (20.7%) in the RN group and 3 patients (5.7%) in the PN group died. Chronic kidney disease (<60 mL/min/1.73 m2) developed more frequently in RN patients than in PN patients (75.6% vs. 41.5%, p<0.001). The 5-year overall survival rate did not differ significantly between the RN and PN groups (90.7% vs. 93.8%; p=0.158). According to the multivariate analysis, the Charlson comorbidity index score was an independent predictor of overall survival (hazard ratio [HR], 2.679, p=0.037). Type of nephrectomy was not significantly associated with overall survival (HR, 2.447; p=0.167) or cardiac events (HR, 1.147; p=0.718).
Although chronic kidney disease was lower after PN, overall survival and cardiac events were similar regardless of type of nephrectomy.
PMCID: PMC4101113  PMID: 25045442
Aged; Cardiovascular diseases; Kidney; Mortality; Nephrectomy
15.  Long-Term Oncologic Outcomes after Radical Cystectomy for Bladder Cancer at a Single Institution 
Journal of Korean Medical Science  2014;29(5):669-675.
The aim of this study was to evaluate our experience using radical cystectomy to treat patients with bladder cancer and to describe the associations between pathologic features and clinical outcomes. All 701 patients who underwent radical cystectomy for bladder cancer were evaluated. The patient population consisted of 623 men and 78 women. The overall 5 and 10 yr recurrence-free survival (RFS) rates were 61.8% and 57.7%, respectively, and the 5 and 10 yr cancer-specific survival (CSS) rates were 70.8% and 65.1%, respectively. Multivariate analysis showed that factors significantly predictive of RFS and CSS included extravesical extension (P = 0.001), lymph node metastasis (P = 0.001), and lymphovascular invasion (P < 0.001 and P = 0.007). The 5 and 10 yr RFS rates for patients with lymph node metastasis were 25.6% and 20.8%, respectively, and the 5 and 10 yr CSS rates were 38.6% and 30.9%, respectively. Adjuvant chemotherapy significantly improved RFS (P = 0.002) and CSS (P = 0.001) in patients with lymph node metastasis. Radical cystectomy provides good survival results in patients with invasive bladder cancer. Pathologic features significantly associated with prognosis include extravesical extension, node metastasis, and lymphovascular invasion. Adjuvant chemotherapy improves survival in patients with advanced stage disease.
Graphical Abstract
PMCID: PMC4024950  PMID: 24851023
Urinary Bladder Neoplasms; Cystectomy; Prognosis
16.  Prognosis of Prostate Cancer With Other Primary Malignancies 
Korean Journal of Urology  2014;55(5):327-334.
The objective was to investigate the clinicopathological characteristics and the prognosis of prostate cancer patients affected by other primary malignancies.
Materials and Methods
From 1990 to 2008, we retrospectively reviewed the medical records of 1,317 patients who underwent radical prostatectomy (RP) for prostate cancer. We assessed the effect of other primary malignancies on clinicopathological features, biochemical recurrence (BCR)-free survival, cancer-specific survival (CSS), and overall survival (OS).
Of 1,317 patients, at least one additional other primary malignancy was detected in 187 patients (14.2%). A comparison of patient groups according to the presence or absence of other primary malignancies showed no significant differences in preoperative serum prostate-specific antigen concentrations, pathological Gleason scores, or pathological staging. Prostate cancer patients with other primary malignancies were older than patients without other primary malignancies (p<0.001). No significant differences in 5-year BCR-free survival (80.2% compared with 77.7%; p=0.656) or CSS (98.9% compared with 98.5%; p=0.733) were found between these groups, respectively. Five-year OS was significantly lower in prostate cancer patients with than in those without other primary malignancies (89.3% compared with 95.4%; p<0.001). Multivariate analysis showed that other primary malignancies diagnosed after RP for prostate cancer were independent predictors of OS (hazard ratio, 4.10; p<0.001) but not of BCR-free survival or CSS. Conversely, other primary malignancies diagnosed before RP for prostate cancer did not independently predict BCR-free survival, OS, or CSS.
Prostate cancer prognosis after RP is not dependent on the presence or absence of other primary malignancies. However, other primary malignancies diagnosed after RP for prostate cancer negatively affect OS.
PMCID: PMC4026659  PMID: 24868337
Neoplasms; Prognosis; Prostate; Recurrence
17.  Preoperative Factors Predictive of Posterolateral Extracapsular Extension After Radical Prostatectomy 
Korean Journal of Urology  2013;54(12):824-829.
In radical prostatectomy (RP) procedures, sparing the neurovascular bundles adjacent to the posterolateral aspect of the prostatic fascia has often been suggested as a possible risk factor for positive surgical margins. Here we aimed to quantify the probability of extracapsular extension (ECE) at the posterolateral side of the prostate to aid in nerve-sparing decision making.
Materials and Methods
We evaluated 472 patients who underwent RP between July 2007 and January 2012. All patients underwent preoperative magnetic resonance imaging (MRI) with diffusion-weighted imaging and apparent diffusion coefficient mapping. We analyzed 944 side-specific prostate lobes with preoperative variables. To quantify the risk of side-specific posterolateral ECE after RP, we developed a risk-stratification scoring system through logistic regression analysis.
Overall, 20.6% of 944 prostate lobes had ECE. In the multivariate analysis, prostate-specific antigen (PSA), biopsy Gleason score ≥7, percentage of side-specific cores with tumor, and posterolateral ECE on MRI were independent predictive factors of posterolateral ECE. On internal and external validation to calculate the predicted risk, the Hosmer-Lemeshow goodness-of-fit test showed good calibration (p=0.396).
PSA, biopsy Gleason score, percentage of side-specific cores with tumor, and posterolateral ECE on MRI are independent predictors of posterolateral ECE. The scoring system derived from this study will provide objective parameters for use when deciding if the neurovascular bundle can be safely spared.
PMCID: PMC3866284  PMID: 24363862
Magnetic resonance imaging; Prostatectomy; Prostatic neoplasms
18.  Whole pelvic intensity-modulated radiotherapy for high-risk prostate cancer: a preliminary report 
Radiation Oncology Journal  2013;31(4):199-205.
To assess the clinical efficacy and toxicity of whole pelvic intensity-modulated radiotherapy (WP-IMRT) for high-risk prostate cancer.
Materials and Methods
Patients with high-risk prostate cancer treated between 2008 and 2013 were reviewed. The study included patients who had undergone WP-IMRT with image guidance using electronic portal imaging devices and/or cone-beam computed tomography. The endorectal balloon was used in 93% of patients. Patients received either 46 Gy to the whole pelvis plus a boost of up to 76 Gy to the prostate in 2 Gy daily fractions, or 44 Gy to the whole pelvis plus a boost of up to 72.6 Gy to the prostate in 2.2 Gy fractions.
The study cohort included 70 patients, of whom 55 (78%) had a Gleason score of 8 to 10 and 50 (71%) had a prostate-specific antigen level > 20 ng/mL. The androgen deprivation therapy was combined in 62 patients. The biochemical failure-free survival rate was 86.7% at 2 years. Acute any grade gastrointestinal (GI) and genitourinary (GU) toxicity rates were 47% and 73%, respectively. The actuarial rate of late grade 2 or worse toxicity at 2 years was 12.9% for GI, and 5.7% for GU with no late grade 4 toxicity.
WP-IMRT was well tolerated with no severe acute or late toxicities, resulting in at least similar biochemical control to that of the historic control group with a small field. The long-term efficacy and toxicity will be assessed in the future, and a prospective randomized trial is needed to verify these findings.
PMCID: PMC3912233  PMID: 24501707
Prostate neoplasms; Intensity-modulated radiotherapy; Complications
19.  Safety of Megestrol Acetate in Palliating Anorexia-Cachexia Syndrome in Patients with Castration-Resistant Prostate Cancer 
Journal of Korean Medical Science  2013;28(5):687-692.
There are concerns whether megestrol acetate (MA) stimulates the growth of prostate cancer in castration-resistant prostate cancer (CRPC). We evaluated the effect of cumulative doses of MA on the disease-specific survival (DSS) in patients with CRPC who were receiving Docetaxel-based chemotherapy. From July 2003 through June 2009, we identified 109 consecutive patients with CRPC and who had received docetaxel-based chemotherapy. Of these patients, 68 (62.4%) have not received MA, whereas 21 patients (19.3%) and 20 patients (18.3%) had received low dose MA (total ≤ 18,400 mg) and high dose MA (total > 18,400 mg), respectively. We assessed the effect of several variables on DSS. None of the clinicopathological variables differed among the three groups. When comparing DSS using Kaplan-Meier analysis, there was no statistically significant survival differences among the three groups (P = 0.546). Using multivariate Cox proportional analyses with backward elimination, the number of docetaxel cycles was only significant factor predicting DSS (HR: 0.578, 95% CI: 0.318-0.923, P = 0.016). Cumulative doses of MA as adjuvant treatment for patients with CRPC and who are receiving docetaxel-based chemotherapy, did not affect their DSS. Therefore, MA can be safely administered in cachexic patients with CRPC.
PMCID: PMC3653080  PMID: 23678259
Cachexia; Castration-Resistant Prostate Cancer; Docetaxel; Megestrol Acetate; Survival
20.  Nomogram using transrectal ultrasound-derived information predicting the detection of high grade prostate cancer on initial biopsy 
Prostate International  2013;1(2):69-75.
To develop a nomogram using transrectal ultrasound (TRUS)-derived information for predicting high grade (HG) prostate cancer (PCa) on initial biopsy.
Data were collected on 1,048 men with serum prostate-specific antigen (PSA) levels 4.0 to 9.9 ng/mL who underwent an initial prostate biopsy. Two logistic regression-based nomograms were constructed to predict the detection of PCa. Nomogram-1 incorporated age, digital rectal examination, PSA and percent free PSA data, whereas nomogram-2 incorporated those factors plus TRUS-derived information (i.e., prostate volume and the presence of hypoechoic lesions). The prediction of any PCa and HGPCa (Gleason score≥7) were determined. Twenty percent of the data were randomly reserved for study validation, and the predictive accuracies of the two nomograms were directly compared.
Of the 1,048 men who underwent biopsy, 216 (20.6%) were found to have any PCa, and 97 (9.3%) were found to have HGPCa. All six risk factors were found to be independent predictors for both any PCa and HGPCa. The area under curve (AUC) for nomogram-2 was 0.76 (95% confidence interval [CI], 0.72 to 0.81) for predicting any PCa, and 0.83 (95% CI, 0.79 to 0.88) for predicting HGPCa. These AUCs were greater than those for nomogram-1 (0.72 [95% CI, 0.68 to 0.76 for any PCa; P<0.001], 0.78 [95% CI, 0.72 to 0.83 for HGPCa; P<0.001]). Removing the TRUS-derived information from nomogram-2 resulted in an incremental AUC decrease of 0.052 for any PCa and 0.063 for HGPCa.
The nomogram using TRUS-derived information had a high predictive accuracy for HGPCa on initial prostate biopsy.
PMCID: PMC3814113  PMID: 24223405
Prostatic neoplasms; Biopsy; Nomograms; Ultrasonography
21.  Prostate-specific antigen response rate of sequential chemotherapy in castration-resistant prostate cancer: the results of real life practice 
Prostate International  2013;1(3):125-132.
Prostate-specific antigen (PSA) response rate (>50% PSA decline in pretreatment PSA following chemotherapy) carries a significant survival advantage in castration-resistant prostate cancer (CRPC). We compared PSA response rates in first-, second- and third-line chemotherapy after failure of previous chemotherapy according to chemotherapeutic agents.
We retrospectively evaluated the oncological outcomes and PSA response rates of 384 patients with CRPC, who were treated with chemotherapy and had histologically proven adenocarcinoma of the prostate with failure after androgen ablation therapy between 1991 and 2012, at Asan Medical Center.
In 384 eligible patients, the median age was 67.5 years. The median pretreatment PSA and initial Gleason scores at baseline were 92.4 ng/mL (range, 2.0 to 6,370 ng/mL) and 9 (range, 6 to 10), respectively. The time from first diagnosis of prostate cancer to CRPC was 23 months (range, 1 to 164 months). As first-line chemotherapy, 245 patients (63.8%) received estramustine, 91 (23.7%) received docetaxel, and 39 (10.2%) received mitoxantrone. The PSA response rates were 39.6%, 51.6%, and 46.2%, respectively. Of 169 patients with second-line chemotherapy, estramustine was 15 (8.9%), docetaxel was 84 (49.7%), and mitoxantrone was 52 (30.8%). PSA response rates were 57.1%, 52%, and 28.0%, respectively. Of 81 patients with third-line chemotherapy, estramustine was 18 (22.2%), docetaxel was 16 (19.8%), and mitoxantrone was 28 (34.6%). The PSA response rates were 41.2%, 53.8%, and 11.1%, respectively. Declines in serum PSA levels of at least 50% occurred more frequently after treatment with docetaxel than with other chemo-agents regardless of second-and third-line chemotherapy. Even in third-line chemothrapy, docetaxel maintained the PSA response rate, whereas the PSA response rate of other agents, including mitoxantrone, decreased in patients in whom prior therapy failed.
Docetacel was the most effective chemotherapeutic agent in second- and third-line trials of chemotherapy in Korean CRPC patients. Although docetaxel is not used as first-line chemotherapy, and new agents are not available for therapy in CRPC patients, we can consider docetaxel a second- or third-line chemotherapy in CRPC.
PMCID: PMC3814118  PMID: 24223414
Castration refractory prostate cancer; Chemotherapy; Prostate-specific antigen
22.  Changes in Prostate Cancer Aggressiveness over a 12-Year Period in Korea 
Korean Journal of Urology  2012;53(10):680-685.
To investigate whether tumor aggressiveness in patients with prostate cancer has changed in Korea since the introduction of prostate-specific antigen (PSA) testing.
Materials and Methods
The data from 2,508 patients with pathologically confirmed prostate cancer who underwent radical prostatectomy at Asan Medical Center between 2000 and 2011 were reviewed. The patients were divided into four 3-year time series, and the changes between the groups in terms of serum PSA levels, pathological Gleason score (GS), and pathological stage were assessed. The change in GS over time in organ-confined disease and in patients whose PSA was below 10 ng/ml was also analyzed.
The mean PSA levels dropped significantly over the 12-year period (p<0.001). The frequency of organ-confined disease increased (55.7% vs. 64.7% vs. 62.9% vs. 63.5%, p=0.043). The frequency of patients with a GS of 8 or more decreased (38.9% vs. 25.7% vs. 18.2% vs. 19.7%) and the frequency of patients with a GS of 6 or less increased (15.0% vs. 18.9% vs. 26.7% vs. 18.2%, p=0.003). However, the vast majority (more than 70%) of all cases had a high GS (7 or greater) at all time points. The GS distribution did not change over time in patients whose PSA levels were below 10 ng/ml or in those who had organ-confined disease.
In 2000 to 2011, the preoperative PSA, pathological stage, and pathological GS dropped. However, the majority of the prostate cancers in Korean men were poorly differentiated, even when the patients had organ-confined disease or their PSA levels were less than 10 ng/ml.
PMCID: PMC3490087  PMID: 23136627
Korea; Neoplasm grading; Prostatic neoplasms
23.  Recent Changes in the Clinicopathologic Features of Korean Men with Prostate Cancer: A Comparison with Western Populations 
Yonsei Medical Journal  2012;53(3):543-549.
The aim of this study was to evaluate the recent changes in the clinicopathologic features of prostate cancer in Korea and to compare these features with those of Western populations.
Materials and Methods
We retrospectively reviewed the data of 1582 men undergoing radical prostatectomy for clinically localized prostate cancer between 1995 and 2007 at 10 institutions in Korea for comparison with Western studies. The patients were divided into two groups in order to evaluate the recent clinicopathological changes in prostate cancer: Group 1 had surgery between 1995 and 2003 (n=280) and Group 2 had surgery between 2004 and 2007 (n=1302). The mean follow-up period was 24 months.
Group 1 had a higher prostate-specific antigen level than Group 2 (10.0 ng/mL vs. 7.5 ng/mL, respectively; p<0.001) and a lower proportion of biopsy Gleason scores ≤6 (35.0% vs. 48.1%, respectively; p<0.001). The proportion of patients with clinical T1 stage was higher in Group 2 than in Group 1. Group 1 had a lower proportion of organ-confined disease (59.6% vs. 68.6%; p<0.001) and a lower proportion of Gleason scores ≤6 (21.3% vs. 33.0%; p<0.001), compared to Group 2. However, the relatively higher proportion of pathologic Gleason scores ≤6 in Group 2 was still lower than those of Western men, even though the proportion of organ-confined disease reached to that of Western series.
Korean men with prostate cancer currently present better clinicopathologic parameters. However, in comparison, Korean men still show relatively worse pathologic Gleason scores than Western men.
PMCID: PMC3343449  PMID: 22476998
Prostate neoplasms; prostatectomy; treatment outcome; ethnic groups
24.  Treatment outcome of postoperative radiotherapy for retroperitoneal sarcoma 
Radiation Oncology Journal  2011;29(4):260-268.
To evaluate the treatment outcome and prognostic factor after postoperative radiotherapy in retroperitoneal sarcoma.
Materials and Methods
Forty patients were treated with surgical resection and postoperative radiotherapy for retroperitoneal sarcoma from August 1990 to August 2008. Treatment volume was judged by the location of initial tumor and surgical field, and 45-50 Gy of radiation was basically delivered and additional dose was considered to the high-risk area.
The median follow-up period was 41.4 months (range, 3.9 to 140.6 months). The 5-year overall survival (OS) was 51.8% and disease free survival was 31.5%. The 5-year locoregional recurrence free survival was 61.9% and distant metastasis free survival was 50.6%. In univariate analysis, histologic type (p = 0.006) was the strongest prognostic factor for the OS and histologic grade (p = 0.044) or resection margin (p = 0.032) had also effect on the OS. Histologic type (p = 0.004) was unique significant prognostic factor for the actuarial local control.
Retroperitoneal sarcoma still remains as a poor prognostic disease despite the combined modality treatment including surgery and postoperative radiotherapy. Selective dose-escalation of radiotherapy or combination of effective chemotherapeutic agent must be considered to improve the treatment result especially for the histopathologic type showing poor prognosis.
PMCID: PMC3429911  PMID: 22984679
Sarcoma; Retroperitoneal; Radiotherapy; Postoperative; Outcome
25.  Impact of Adjuvant Androgen-Deprivation Therapy on Disease Progression in Patients with Node-Positive Prostate Cancer 
Korean Journal of Urology  2011;52(11):741-745.
The survival benefits of adjuvant androgen-deprivation therapy (ADT) in prostate cancer and lymph node metastasis remain unclear. We assessed the role of ADT in disease progression after radical prostatectomy (RP).
Materials and Methods
Of 937 patients who underwent RP, we identified 40 (4.2%) who had lymph node metastasis. A total of 18 received adjuvant ADT (ADT group) and 22 were observed (observation group). Clinical progression-free survival (PFS), cancer- specific survival (CSS), and overall survival (OS) were compared in the 2 groups. Prognostic factors for clinical progression and biochemical recurrence (BCR) were analyzed.
The 5-year PFS, CSS, and OS of the entire cohort were 75.0%, 85.0%, and 72.5%, respectively. In the ADT group, 6 patients (33.3%) showed clinical progression at a median 42.7 months. The 5-year PFS, CSS, and OS rates of this group were 72.2%, 83.3%, and 72.2%, respectively. In the observation group, 14 patients (63.6%) received salvage therapy owing to BCR. Nine patients (40.9%) with BCR in the observation group showed clinical progression at a median 43.4 months after RP. The 5-year PFS, CSS, and OS rates of this group were 77.2%, 86.4%, and 72.8%, respectively. In the observation group, the BCR rate was lower in patients with pT3a or less disease than in those with pT3b disease.
Adjuvant ADT in node-positive prostate cancer did not reduce or delay disease progression or improve survival. Because a substantial number of untreated patients with pT3a or less disease did not experience recurrence, administration of ADT should be initiated carefully. However, in patients with pT3b disease, adjuvant ADT and radiotherapy could be considered.
PMCID: PMC3242986  PMID: 22195262
Androgens; Lymph nodes; Prostatectomy

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