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1.  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
2.  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
3.  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
4.  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
5.  Effect of Gleason scores of lymph node metastases on prognosis of patients with prostate cancer 
The long-term mortality risk from prostate cancer increases in lymph node (LN) positive patients. This study was done to assess the effect of lymph node Gleason score (LNGS) on prognosis in patients with LN-positive prostate cancer. Among the 1,415 patients who received pelvic lymph node dissection (PLND), 117 (8.4%) patients had a positive LN. The PGS of the prostate specimens and the LNGS of the positive LNs were assessed by uropathologists. The median age of patients at surgery was 67 years (interquartile range [IQR], 62-71 years) and the median follow-up duration was 44.3 months (IQR, 27.0-78.5 months). Pathologic Gleason scores (PGS) of 6-9 included one (0.9%), 53 (49.5%), 22 (20.6%), and 31 (29.0%) patients. The median total number of retrieved LNs was 9.0 (IQR, 5.3-12.8). The median number of positive LNs was one (IQR, 1-2). Cancer architecture with a Gleason pattern and score were observed in LNs as in ordinary prostate specimens. LNGS 6-9 included nine (8.1%), 57 (51.4%), 31 (27.9%), and 14 (12.6%) patients. The speaman’s analysis showed the meaningful correlation between PGS and LNGS (P = 0.249, P = 0.011). The univariate analysis showed that the number of positive LNs and LNGS were significantly associated with prostate cancer-specific survival (P = 0.028; P = 0.005). The same architecture that is seen in the prostate was seen in positive LNs, and LNGS may be a significant prognostic factor in patients with LN-positive prostate cancer.
PMCID: PMC4203233  PMID: 25337262
Gleason score; prognosis; lymph node metastasis; prostate cancer; radical prostatectomy
6.  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
7.  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
8.  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
9.  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
10.  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
11.  Retropubic Versus Robot-Assisted Laparoscopic Prostatectomy for Prostate Cancer: A Comparative Study of Postoperative Complications 
Korean Journal of Urology  2013;54(11):756-761.
To compare the complications of radical retropubic prostatectomy (RRP) with those of robot-assisted laparoscopic prostatectomy (RALP) performed by a single surgeon for the treatment of prostate cancer.
Materials and Methods
The postoperative complications of 341 patients who underwent RRP and 524 patients who underwent RALP for prostate cancer at the Asan Medical Center between July 2007 and August 2012 were retrospectively reviewed and compared. Complications were classified according to the modified Clavien classification system.
RALP was associated with a shorter length of hospital stay (mean, 7.9 days vs. 10.1 days, p<0.001) and duration of urethral catheterization (6.2 days vs. 7.5 days, p<0.001) than RRP. Major complications (Clavien grade III-IV) were less common in the RALP group than in the RRP group (3.4% vs. 7.6%, p=0.006). There were no significant differences in medical complications between procedures. Considering surgical complications, urinary retention (7.0% vs. 2.7%, p=0.002) and wound repair (4.1% vs. 0.2%, p<0.001) were more common after RRP than after RALP. Extravasation of contrast medium during cystography was more common in the RRP group than in the RALP group (10.0% vs. 2.1%, p<0.001).
RALP is associated with a lower complication rate than RRP.
PMCID: PMC3830968  PMID: 24255757
Complications; Prostate; Prostate neoplasms; Prostatectomy
12.  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
13.  The Establishment of K-CaP (the Multicenter Korean Prostate Cancer Database) 
Korean Journal of Urology  2013;54(4):229-233.
The purpose of this article was to announce the establishment of the multicenter Korean Prostate Cancer Database (K-CaP) and to provide urologists with details about K-CaP's methodology.
Materials and Methods
The initial participating K-CaP institutions include five medical centers in Korea. First, we registered prostate cancer patients who underwent radical prostatectomy as the basic background data. K-CaP is poised to combine these initial observational longitudinal studies with those of other eligible institutions as the database grows. All current prostate cancer patients in Korea are able to be registered into the Web-based database system and thereby have a role in several observational studies. The structure of the database for K-CaP was developed by matching it with the respective data from different studies. The operability of the K-CaP database system was verified by using the existing databases from three participating institutions.
The analysis of clinicopathologic characteristics of patients with the use of the Web-based database was successfully conducted. We confirmed the accurate operation of the Web-based database system without any difficulties.
We are announcing the establishment of K-CaP the first database of comprehensive observational longitudinal studies about prostate cancer in Korea. The database will be successfully maintained by sufficiently and continuously updating all patient data covering several treatments. Complete statistical results for registered prostate cancer patients are forthcoming for the basic background data to establish the database. Even though much trial and error are expected during the development process, we expect that K-CaP will eventually become one of the most powerful longitudinal observation databases.
PMCID: PMC3630340  PMID: 23614058
Database; K-CaP; Korea; Prostate neoplasms
14.  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
15.  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
16.  Clinical Experience with Limited Lymph Node Dissection for Prostate Cancer in Korea: Single Center Comparison of 247 Open and 354 Robot-Assisted Laparoscopic Radical Prostatectomy Series 
Korean Journal of Urology  2012;53(11):755-760.
There are limited data on the role of limited pelvic lymph node dissection (PLND) in patients with prostate cancer in Korea. The objective of this study was to demonstrate our clinical experience with limited PLND and the difference in its yield between open retropubic radical prostatectomy (RRP) and robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer patients in Korea.
Materials and Methods
We retrospectively analyzed 601 consecutive patients undergoing radical prostatectomy and bilateral limited PLND by either RRP (n=247) or RALP (n=354) in Asan Medical Center. All patients were divided into three groups according to the D'Amico's risk stratification method. Clinicopathologic data, including the yield of lymph nodes, were thoroughly reviewed and compared among the three risk groups or between the RRP and RALP subjects.
The mean patient age was 64.9 years and the mean preoperative prostate-specific antigen was 9.8 ng/ml. The median number of removed lymph nodes per patient was 5 (range, 0 to 20). The numbers of patients of each risk group were 167, 199, and 238, and the numbers of patients with tumor-positive lymph nodes were 1 (0.6%), 4 (2.0%), and 17 (7.1%) in the low-, intermediate-, and high-risk groups, respectively. In the high-risk group, the lymph node-positive ratio was higher in RRP (14.9%) than in RALP subjects (2.4%).
We speculate that limited PLND may help in prostate cancer staging in intermediate- and high-risk prostate cancer groups. RRP is a more effective surgical modality for PLND than is RALP, especially in high-risk prostate cancer groups.
PMCID: PMC3502733  PMID: 23185666
Lymph node excision; Prostatectomy; Prostatic neoplasms
17.  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
18.  Validation of the 2009 TNM Classification for Renal Cell Carcinoma: Comparison with the 2002 TNM Classification by Concordance Index 
Korean Journal of Urology  2011;52(8):524-530.
To assess the validity of the 2009 TNM classification for renal cell carcinoma (RCC) and compare its ability to predict survival relative to the 2002 classification.
Materials and Methods
We identified 1,691 patients who underwent radical nephrectomy or partial nephrectomy for unilateral, sporadic RCC between 1989 and 2007. Cancer-specific survival was estimated by the Kaplan-Meier method and was compared among groups by the log-rank test. Associations of the 2002 and 2009 TNM classifications with death from RCC were evaluated by Cox proportional hazards regression models. The predictive abilities of the two classifications were compared by using Harrell's concordance (c) index.
There were 234 deaths from RCC a mean of 38 months after nephrectomy. According to the 2002 primary tumor classification, 5-year cancer-specific survival was 97.6% in T1a, 92.0% in T1b, 83.3% in T2, 61.9% in T3a, 51.1% in T3b, 40.0% in T3c, and 33.6% in T4 (p for trend<0.001). According to the 2009 classification, 5-year cancer-specific survival was 83.2% in T2a, 83.8% in T2b, 62.6% in T3a, 41.1% in T3b, 50.0% in T3c, and 26.1% in T4 (p for trend<0.001). The c index for the 2002 primary tumor classification was 0.810 in the univariate analysis and increased to 0.906 in the multivariate analysis. The c index for the 2009 primary tumor classification was 0.808 in the univariate analysis and increased to 0.904 in the multivariate analysis.
Our data suggest that the predictive ability the 2009 TNM classification is not superior to that of the 2002 classification.
PMCID: PMC3162217  PMID: 21927698
Kidney neoplasms; Mortality; Neoplasm staging; Prognosis; Renal cell carcinoma
19.  Does Radical Cystectomy Improve Overall Survival in Octogenarians with Muscle-Invasive Bladder Cancer? 
Korean Journal of Urology  2011;52(7):446-451.
We compared the efficacy of radical cystectomy (RC) and non-RC treatment [transurethral resection of bladder tumor (TURB) only, partial cystectomy, or TURB followed by radiotherapy] in octogenarians with muscle-invasive bladder cancer (MIBC).
Materials and Methods
A total of 177 patients aged 80 years or more underwent TURB at our institute, and 41 patients had MIBC according to the histologic examination. Fourteen patients with lymph node or distant metastasis were excluded, and 27 patients were ultimately included. Patients were stratified by treatment modality (RC vs. non-RC), Charlson Comorbidity Index (low CCI vs. high CCI), and clinical tumor stage (organ-confined disease vs. extravesical disease). The effects of several variables on cancer-specific and overall survival were assessed.
Of the 27 patients, 11 (41%) underwent RC and 16 (59%) underwent non-RC treatment. Patients in the RC group were younger and more likely to have low CCI scores. There were no significant differences in overall or cancer-specific survival in the RC and non-RC groups. Patients with clinically organ-confined disease had better survival outcomes than did those with extravesical disease. Stratification of patients by CCI indicated that overall survival was better in patients with low CCI scores (p=0.013), although cancer-specific survival was similar in the two CCI groups. Univariate and multivariate analysis indicated that clinical tumor stage and CCI were independently associated with overall survival.
RC in octogenarians with MIBC does not improve overall survival compared with other treatment modalities. However, clinically organ-confined disease and low CCI score were associated with better overall survival.
PMCID: PMC3151630  PMID: 21860763
Aged; Comorbidity; Cystectomy; Urinary bladder neoplasms
20.  Efficacy of Dendritic Cells Matured Early with OK-432 (Picibanil®), Prostaglandin E2, and Interferon-α as a Vaccine for a Hormone Refractory Prostate Cancer Cell Line 
Journal of Korean Medical Science  2010;25(9):1284-1290.
Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil®) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-α. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-α (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-α (T), TNF-α and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.
PMCID: PMC2923792  PMID: 20808670
Dendritic Cells; Prostatic Neoplasms; Cancer Vaccines; Immunotherapy
21.  Role of Radical Prostatectomy for High-Risk Prostate Cancer 
Korean Journal of Urology  2010;51(9):589-595.
High-risk localized prostate cancer traditionally includes patients with clinical T3 disease but also includes those with apparently localized disease but with adverse prognostic factors such as a Gleason score of 8 to 10, prostate-specific antigen of more than 20 ng/ml, or extensive disease on biopsy. In the past, these patients were treated primarily with radiation therapy due to concerns that surgery was not likely to be curative and was associated with a high incidence of side-effects. In addition, the lack of randomized trials comparing curative treatments for high-risk prostate cancer makes treatment decisions in this patient population difficult. Several retrospective series have reported the long-term efficacy of radical prostatectomy monotherapy in a high-risk population, showing that the 5-year cancer-specific survival rate was more than 80% and the 5-year biochemical recurrence-free survival rate was about 50%. In addition, comparisons of different treatment options by means of nonrandomized trials have shown improved outcomes with surgery compared with radiation therapy or observation. Thus, there is renewed interest in radical prostatectomy as the primary treatment for patients with high-risk prostate cancer. Here, we reviewed the outcomes of radical prostatectomy, with or without neoadjuvant or adjuvant therapies, in high-risk patients and what is known about the choice and timing of adjuvant therapies.
PMCID: PMC2941806  PMID: 20856642
Prostatectomy; Prostatic neoplasms; Risk assessment
22.  Preoperative Clinical and Pathological Characteristics of pT0 Prostate Cancer in Radical Prostatectomy 
Korean Journal of Urology  2010;51(6):386-390.
To analyze the preoperative clinical and pathological characteristics of patients with pT0 prostate cancer.
Materials and Methods
We retrospectively reviewed the records of 702 patients who underwent radical prostatectomy (RP) at our institution between January 2004 and July 2008 for clinically localized prostate cancer. If there was no evidence of residual tumor in the pathological specimen of the prostate, a patient was staged as pT0. Patients with pT0 disease were compared with a control group of patients who were operated on during the same period.
Overall, 9 (1.3%) patients were staged as pT0 on the pathologic examination. Significant differences were observed between the pT0 group and the control patients in the biopsy Gleason score (p=0.004), the number of positive cores on biopsy (p=0.018), the tumor length of positive cores (p<0.001), and prostate volume (p=0.015). Cutoff values predictive of pT0 tumor status were defined as a biopsy Gleason score sum ≤6, 2 or fewer positive biopsy cores, tumor length on biopsy ≤2 mm, and prostate volume >30 cm3. Whereas 8 of the 9 (88.9%) pT0 patients showed all of these characteristics, only 55 of the 693 (7.9%) control patients fulfilled the criteria. The combination suggested above afforded a sensitivity of 88.8% and a specificity of 92.1% for the prediction of pT0 status.
The frequency of pT0 prostate cancer seen on RP was 1.3%. A combination of clinicopathological features, incorporating a biopsy Gleason score, the number of positive biopsy cores, tumor length on biopsy, and prostate volume, was useful to predict pT0 stage on RP.
PMCID: PMC2890054  PMID: 20577604
Biopsy; Neoplasm staging; Prostatectomy; Prostatic neoplasms
23.  A Prospective Multi-center Trial of Escherichia coli Extract for the Prophylactic Treatment of Patients with Chronically Recurrent Cystitis 
Journal of Korean Medical Science  2010;25(3):435-439.
We have assessed the efficacy and safety of Escherichia coli extract (ECE; Uro-Vaxom®) which contains active immunostimulating fractions, in the prophylactic treatment of chronically recurrent cystitis. Forty-two patients with more than 2 episodes of cystitis in the proceeding 6 months were treated for 3 months with one capsule daily of ECE and observed for a further 6 months. The primary efficacy criterion was the number of episodes of recurrent cystitis during the 6 months after treatment compared to those during the 6 months before treatment. At the end of the 9-month trial, 34 patients (all women) were eligible for statistical analysis. Their mean age was 56.4 yr (range, 34-75 yr), and they had experienced recurrent urinary tract infections for 7.2±5.2 yr. The number of recurrences was significantly lower during the 6-month follow-up period than during the 6 months preceding the trial (0.35 vs. 4.26, P<0.001). During the follow-up, 28 (82.4%) patients had no recurrences and 4 (11.8%) had 1 each. In patients who relapsed, ECE alleviated cystitis symptoms, including painful voiding, frequency and urgency. There were no serious adverse events related to the study drug. Our study demonstrates the efficacy and safety of ECE in the prophylactic treatment of chronically recurrent cystitis.
PMCID: PMC2826739  PMID: 20191044
Cystitis; Immunization; Escherichia coli; OM-8930; Prevention and Control
24.  Docetaxel Chemotherapy of Korean Patients with Hormone-refractory Prostate Cancer : Comparative Analysis between 1st-line and 2nd-line Docetaxel 
Yonsei Medical Journal  2008;49(5):775-782.
This study was undertaken to investigate the outcomes associated with docetaxel treatment of Korean patients with hormone-refractory prostate cancer (HRPC) and to compare its clinical efficacies in 1st and 2nd-line settings.
Materials and Methods
This study was retrospectively performed and included 47 patients with HRPC. The 1st-line group consisted of 19 patients who had not undergone prior chemotherapy, and the 2nd-line group consisted of 28 patients who underwent prior chemotherapy. All patients were treated with 75 mg/m2 IV docetaxel every 3 weeks and 5 mg of prednisone twice daily with a continuous androgen blockade.
Of 47 study subjects, 14 patients (29.8%) had ≥ 50% PSA decline from baseline. PSA response was more common in the 1st-line group, but this was not statistically different (42.1% vs. 21.4%, p = 0.114). After a median follow up of 11 months (range, 6 - 24 months), the 1st-line group showed a longer time to PSA progression (4 vs. 2 months, p = 0.015) and survival (17 vs. 10 months, p = 0.037) than the 2nd-line group. In terms of toxicities, no difference was apparent between the 2 groups.
In a 1st-line setting, docetaxel is an effective and tolerable agent for Korean HRPC patients, and that its efficacy is limited, although 2nd-line docetaxel is tolerable.
PMCID: PMC2615369  PMID: 18972598
Prostate neoplasm; chemotherapy; docetaxel
25.  Analysis of Changes in the Total Lymphocyte and Eosinophil Count during Immunotherapy for Metastatic Renal Cell Carcinoma: Correlation with Response and Survival 
Journal of Korean Medical Science  2007;22(Suppl):S122-S128.
The aims of this study were to analyze lymphocyte and eosinophil counts in consecutive peripheral blood samples taken during immunotherapy for metastatic renal cell carcinoma (mRCC) and to correlate the findings with objective response and survival. A total of 40 patients with mRCC who received immunotherapy with interleukin-2, interferon-α, and 5-fluorouracil were analyzed. Objective responses were observed in 14 patients, including 2 (5%) who showed a complete response (CR) and 12 (30%) who showed a partial response (PR). Eleven patients (27%) achieved stable disease (SD), and 15 patients (38%) had progressive disease (PD). Changes from baseline in the total lymphocyte counts were significantly higher in the responding patients (CR+PR+SD) than in the non-responding patients (PD) (p=0.017), but no difference was seen in the total eosinophil counts (p=0.275). Univariate analysis identified the Eastern Cooperative Oncology Group (ECOG) performance status (p=0.017), the presence of a primary renal tumor (p<0.001) and the peripheral lymphocyte counts at week 4 (p=0.034) as prognostic factors, but a low ECOG performance status (p=0.003) and the presence of a primary renal tumor (p=0.001) were identified as independent poor prognostic factors by multivariate analysis. This study provides further evidence that changes in blood lymphocyte counts may serve as an objective indicator of objective responses.
PMCID: PMC2694375  PMID: 17923738
Renal Cell Carcinoma; Interleukin-2; Interferon-alpha; Lymphocytes; Eosinophils

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