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author:("Ahn, tanjong")
1.  Histologic Variability and Diverse Oncologic Outcomes of Prostate Sarcomas 
Korean Journal of Urology  2014;55(12):797-801.
Purpose
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).
Results
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).
Conclusions
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.
doi:10.4111/kju.2014.55.12.797
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 
Purpose
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).
Results
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).
Conclusion
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.
doi:10.4143/crt.2013.154
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.
Methods:
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.
Results:
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.
Conclusion:
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.
doi:10.4293/JSLS.2014.00335
PMCID: PMC4232409  PMID: 25408605
Benign; Nephroureterectomy; Upper urinary tract; Urothelial carcinoma
5.  Is Bladder Tumor Location Associated with Prostate Cancer Detection after Intravesical Bacillus Calmette-Guérin Instillation? 
PLoS ONE  2014;9(7):e103791.
Objectives
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1371/journal.pone.0103791
PMCID: PMC4114875  PMID: 25072158
6.  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.
Purpose
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.
Results
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).
Conclusions
Although chronic kidney disease was lower after PN, overall survival and cardiac events were similar regardless of type of nephrectomy.
doi:10.4111/kju.2014.55.7.446
PMCID: PMC4101113  PMID: 25045442
Aged; Cardiovascular diseases; Kidney; Mortality; Nephrectomy
7.  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
doi:10.3346/jkms.2014.29.5.669
PMCID: PMC4024950  PMID: 24851023
Urinary Bladder Neoplasms; Cystectomy; Prognosis
8.  Prognosis of Prostate Cancer With Other Primary Malignancies 
Korean Journal of Urology  2014;55(5):327-334.
Purpose
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).
Results
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.
Conclusions
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.
doi:10.4111/kju.2014.55.5.327
PMCID: PMC4026659  PMID: 24868337
Neoplasms; Prognosis; Prostate; Recurrence
9.  Preoperative Factors Predictive of Posterolateral Extracapsular Extension After Radical Prostatectomy 
Korean Journal of Urology  2013;54(12):824-829.
Purpose
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.
Results
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).
Conclusions
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.
doi:10.4111/kju.2013.54.12.824
PMCID: PMC3866284  PMID: 24363862
Magnetic resonance imaging; Prostatectomy; Prostatic neoplasms
10.  Whole pelvic intensity-modulated radiotherapy for high-risk prostate cancer: a preliminary report 
Radiation Oncology Journal  2013;31(4):199-205.
Purpose
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.
Results
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.
Conclusion
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.
doi:10.3857/roj.2013.31.4.199
PMCID: PMC3912233  PMID: 24501707
Prostate neoplasms; Intensity-modulated radiotherapy; Complications
11.  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.
doi:10.3346/jkms.2013.28.5.687
PMCID: PMC3653080  PMID: 23678259
Cachexia; Castration-Resistant Prostate Cancer; Docetaxel; Megestrol Acetate; Survival
12.  Nomogram using transrectal ultrasound-derived information predicting the detection of high grade prostate cancer on initial biopsy 
Prostate International  2013;1(2):69-75.
Purpose:
To develop a nomogram using transrectal ultrasound (TRUS)-derived information for predicting high grade (HG) prostate cancer (PCa) on initial biopsy.
Methods:
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.
Results:
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.
Conclusions:
The nomogram using TRUS-derived information had a high predictive accuracy for HGPCa on initial prostate biopsy.
doi:10.12954/PI.12008
PMCID: PMC3814113  PMID: 24223405
Prostatic neoplasms; Biopsy; Nomograms; Ultrasonography
13.  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.
Purpose:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
doi:10.12954/PI.13024
PMCID: PMC3814118  PMID: 24223414
Castration refractory prostate cancer; Chemotherapy; Prostate-specific antigen
14.  Changes in Prostate Cancer Aggressiveness over a 12-Year Period in Korea 
Korean Journal of Urology  2012;53(10):680-685.
Purpose
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.
Results
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.
Conclusions
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.
doi:10.4111/kju.2012.53.10.680
PMCID: PMC3490087  PMID: 23136627
Korea; Neoplasm grading; Prostatic neoplasms
15.  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.
Purpose
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.
Results
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.
Conclusion
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.
doi:10.3349/ymj.2012.53.3.543
PMCID: PMC3343449  PMID: 22476998
Prostate neoplasms; prostatectomy; treatment outcome; ethnic groups
16.  Treatment outcome of postoperative radiotherapy for retroperitoneal sarcoma 
Radiation Oncology Journal  2011;29(4):260-268.
Purpose
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.
Results
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.
Conclusion
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.
doi:10.3857/roj.2011.29.4.260
PMCID: PMC3429911  PMID: 22984679
Sarcoma; Retroperitoneal; Radiotherapy; Postoperative; Outcome
17.  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.
Purpose
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.
Results
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.
Conclusions
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.
doi:10.4111/kju.2011.52.11.741
PMCID: PMC3242986  PMID: 22195262
Androgens; Lymph nodes; Prostatectomy
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.
Purpose
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.
Results
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.
Conclusions
Our data suggest that the predictive ability the 2009 TNM classification is not superior to that of the 2002 classification.
doi:10.4111/kju.2011.52.8.524
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.
Purpose
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.
Results
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.
Conclusions
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.
doi:10.4111/kju.2011.52.7.446
PMCID: PMC3151630  PMID: 21860763
Aged; Comorbidity; Cystectomy; Urinary bladder neoplasms
20.  Clinical Significance of a Large Difference (≥ 2 points) between Biopsy and Post-prostatectomy Pathological Gleason Scores in Patients with Prostate Cancer 
Journal of Korean Medical Science  2011;26(4):507-512.
We investigated the clinical significance of large difference (≥ 2 points) between biopsy-derived (bGS) and post-prostatectomy Gleason scores (pGS). At 14 medical centers in Korea, 1,582 men who underwent radical prostatectomy for prostate cancer were included. According to the difference between bGS and pGS, the patients were divided into three groups: A (decreased in pGS ≥ 2, n = 30), B (changed in pGS ≤ 1, n = 1,361; control group), and C (increased in pGS ≥ 2, n = 55). We evaluated various clinicopathological factors of prostate cancer and hazards for biochemical failure. Group A showed significantly higher mean maximal percentage of cancer in the positive cores (max%) and pathological T stage than control. In group C, the number of biopsy core was significantly smaller, however, tumor volume and max% were significantly higher and more positive biopsy cores were presented than control. Worse pathological stage and more margin-positive were observed in group A and C than in control. Hazard ratio for biochemical failure was also higher in group A and C (P = 0.001). However, the groups were not independent factors in multivariate analysis. In conclusion, large difference between bGS and pGS shows poor prognosis even in the decreased group. However it is not an independent prognostic factor for biochemical failure.
doi:10.3346/jkms.2011.26.4.507
PMCID: PMC3069569  PMID: 21468257
Prostatic Neoplasms; Gleason Score; Prognosis
21.  Radical Cystectomy and Orthotopic Bladder Substitution Using Ileum 
Korean Journal of Urology  2011;52(4):233-240.
Over the past decade, continent urinary diversion, especially orthotopic bladder substitutions, has become increasingly popular following radical cystectomy for bladder cancer. The ultimate goal of orthotopic bladder substitution is to offer patients the best quality of life, similar to that of patients with native bladders. To achieve that purpose, surgeons should be familiar with the characteristics of good candidates for neobladders, the possible intraoperative and postoperative problems related to the surgery, and the solutions to these problems. Postoperative surveillance and instructions given to the patients also contribute to successful, functional results. Here, we reviewed the indications, pitfalls, and solutions for orthotopic bladder substitutions and the patients' quality of life after surgery. When performed properly, orthotopic continent diversion offers good quality of life with few long-term complications. Therefore, we believe it is the best option for the majority of patients requiring cystectomy.
doi:10.4111/kju.2011.52.4.233
PMCID: PMC3085614  PMID: 21556208
Cystectomy; Quality of life; Urinary bladder; Urinary bladder neoplasms; Urinary diversion
22.  Predictive Characteristics of Malignant Pheochromocytoma 
Korean Journal of Urology  2011;52(4):241-246.
Purpose
The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. We aimed to identify the clinical characteristics predictive of malignancy after initial surgical removal in patients with pheochromocytoma.
Materials and Methods
We retrospectively reviewed the records of 152 patients diagnosed with pheochromocytoma, including 5 (3.3%) with metastasis at the time of the initial surgical excision and 12 (7.9%) who developed metastasis during follow-up. To determine the factors predictive of malignancy, we compared clinical, radiographical, and urinary chemical findings between patients with benign and malignant disease. Mean follow-up was 41.5 months (range, 0.9-298 months) after surgery.
Results
Malignant tumors were significantly larger than benign tumors (11.1±4.0 cm vs. 6.2±3.4 cm, p<0.001), and postoperative persistence of arterial hypertension was more frequent after removal of malignant than benign tumors (p=0.001). Among the 147 patients without metastatic disease at diagnosis, those who developed metastasis had significantly lower concentrations of urinary catecholamine metabolites per unit of tumor, including vanillylmandelic acid (1.2 vs. 3.7 mg/day/cm, p=0.049), epinephrine (4.5 vs. 168.9 µg/day/cm, p=0.008), and norepinephrine (13.1 vs. 121.8 mg/day/cm, p<0.001). The overall 5-year metastasis-free survival rate was 84.4% and was significantly higher in patients with smaller tumors (≤5.5 vs. >5.5 cm; 90.6% vs. 81.2%, p=0.025) and higher 24-hour secretion of vanillylmandelic acid (>2.1 vs. ≤2.1 mg/day/cm; 94.9% vs. 70.9%, p=0.019).
Conclusions
Large tumor size (>5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (≤2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery.
doi:10.4111/kju.2011.52.4.241
PMCID: PMC3085615  PMID: 21556209
Adrenal gland neoplasms; Catecholamines; Pheochromocytoma; Tumor burden
23.  Nomogram to Predict Insignificant Prostate Cancer at Radical Prostatectomy in Korean Men: A Multi-Center Study 
Yonsei Medical Journal  2010;52(1):74-80.
Purpose
Due to the availability of serum prostate specific antigen (PSA) testing, the detection rate of insignificant prostate cancer (IPC) is increasing. To ensure better treatment decisions, we developed a nomogram to predict the probability of IPC.
Materials and Methods
The study population consisted of 1,471 patients who were treated at multiple institutions by radical prostatectomy without neoadjuvant therapy from 1995 to 2008. We obtained nonrandom samples of n = 1,031 for nomogram development, leaving n = 440 for nomogram validation. IPC was defined as pathologic organ-confined disease and a tumor volume of 0.5 cc or less without Gleason grade 4 or 5. Multivariate logistic regression model (MLRM) coefficients were used to construct a nomogram to predict IPC from five variables, including serum prostate specific antigen, clinical stage, biopsy Gleason score, positive cores ratio and maximum % of tumor in any core. The performance characteristics were internally validated from 200 bootstrap resamples to reduce overfit bias. External validation was also performed in another cohort.
Results
Overall, 67 (6.5%) patients had a so-called "insignificant" tumor in nomogram development cohort. PSA, clinical stage, biopsy Gleason score, positive core ratio and maximum % of biopsy tumor represented significant predictors of the presence of IPC. The resulting nomogram had excellent discrimination accuracy, with a bootstrapped concordance index of 0.827.
Conclusion
Our current nomogram provides sufficiently accurate information in clinical practice that may be useful to patients and clinicians when various treatment options for screen-detected prostate cancer are considered.
doi:10.3349/ymj.2011.52.1.74
PMCID: PMC3017711  PMID: 21155038
Prostatic neoplasms; nomograms; insignificant
24.  Biochemical Recurrence-Free and Cancer-Specific Survival after Radical Prostatectomy at a Single Institution 
Korean Journal of Urology  2010;51(12):836-842.
Purpose
To analyze the biochemical recurrence-free and cancer-specific survival after radical prostatectomy in a consecutive series of patients with prostate cancer.
Materials and Methods
We retrospectively reviewed data for 1,822 patients who underwent radical prostatectomy with pelvic lymph node dissection at our institution between 1990 and 2009. After excluding 498 patients who were treated with neoadjuvant androgen deprivation therapy or who were followed up for ≤6 months, we included 1324 patients (mean age, 64.4 years; mean prostate-specific antigen [PSA] level, 12.3 ng/ml). We assessed patient age at the time of surgery, preoperative PSA concentration, biopsy and pathologic Gleason scores, pathologic stage, surgical margin status, disease progression, and survival.
Results
The mean follow-up time was 40 months (range, 6-193 months). The 5- and 10-year biochemical recurrence-free survival rates were 73.2% and 66.2%, respectively, and the 10-year cancer-specific survival rate was 92.4%. The mean time from surgery to biochemical recurrence was 18 months. In the multivariate analysis, Gleason score (4+3 vs. 2-6, p=0.004; 8-10 vs. 2-6, p<0.001), pathologic stage (pT3a vs. pT2, p=0.001; pT3b-4 vs. pT2, p<0.001; pN1 vs. pT2, p<0.001), and resection margin status (p<0.001) were statistically significant predictors of biochemical recurrence, with only pathologic stage (pT3b-4 vs. pT2, p=0.006; pN1 vs. pT2, p=0.010) being a statistically significant predictor of cancer-specific survival.
Conclusions
Radical prostatectomy resulted in favorable cancer control in more than 70% of patients after 5 years and a low (<10%) cancer-specific mortality rate after 10 years. The factors predictive of biochemical recurrence were Gleason score, pathologic stage, and resection margin status.
doi:10.4111/kju.2010.51.12.836
PMCID: PMC3016429  PMID: 21221203
Prostatectomy; Prostatic neoplasms
25.  Preoperative Nomograms for Predicting Extracapsular Extension in Korean Men with Localized Prostate Cancer: A Multi-institutional Clinicopathologic Study 
Journal of Korean Medical Science  2010;25(10):1443-1448.
We developed a nomogram to predict the probability of extracapsular extension (ECE) in localized prostate cancer and to determine when the neurovascular bundle (NVB) may be spared. Total 1,471 Korean men who underwent radical prostatectomy for prostate cancer between 1995 and 2008 were included. We drew nonrandom samples of 1,031 for nomogram development, leaving 440 samples for nomogram validation. With multivariate logistic regression analyses, we made a nomogram to predicts the ECE probability at radical prostatectomy. Receiver operating characteristic (ROC) analyses were also performed to assess the predictive value of each variable alone and in combination. The internal validation was performed from 200 bootstrap re-samples and the external validation was also performed from the another cohort. Overall, 314 patients (30.5%) had ECE. Age, Prostate specific antigen (PSA), biopsy Gleason score, positive core ratio, and maximum percentage of biopsy tumor were independent predictors of the presence of ECE (all P values <0.05). The nomogram predicted ECE with good discrimination (an area under the ROC curve of 0.777). Our nomogram allows for the preoperative identification of patients with an ECE and may prove useful in selecting patients to receive nerve sparing radical prostatectomy.
doi:10.3346/jkms.2010.25.10.1443
PMCID: PMC2946653  PMID: 20890424
Nomograms; Patient Selection; Prostatic neoplasms; Prostatectomy

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