Risk Factors and Patterns of Locoregional Recurrence after Radical Nephrectomy for Locally Advanced Renal Cell Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to investigate the risk factors and patterns of locoregional recurrence (LRR) after radical nephrectomy (RN) in patients with locally advanced renal cell carcinoma (RCC). @*Materials and Methods@#We retrospectively analyzed 245 patients who underwent RN for non-metastatic pT3-4 RCC from January 2006 to January 2016. We analyzed the risk factors associated with poor locoregional control using Cox regression. Anatomical mapping was performed on reference computed tomography scans showing intact kidneys. @*Results@#The median follow-up duration was 56 months (range, 1 to 128 months). Tumor extension to renal vessels or the inferior vena cava (IVC) and Fuhrman’s nuclear grade IV were identified as independent risk factors of LRR. The 5-year actuarial LRR rates in groups with no risk factor, one risk factor, and two risk factors were 2.3%, 19.8%, and 30.8%, respectively (p < 0.001). The locations of LRR were distributed as follows: aortocaval area (n=2), paraaortic area (n=4), retrocaval area (n=5), and tumor bed (n=11). No LRR was observed above the celiac axis (CA) or under the inferior mesenteric artery (IMA). @*Conclusion@#Tumor extension to renal vessels or the IVC and Fuhrman’s nuclear grade IV were the independent risk factors associated with LRR after RN for pT3-4 RCC. The locations of LRR after RN for RCC were distributed in the tumor bed and regional lymphatic area from the bifurcation of the CA to that of the IMA.

Node-Positive Bladder Cancer After Neoadjuvant Chemotherapy Followed by Radical Cystectomy: A Single-Center Retrospective Study

Purpose@#There remains a lot of unmet need to increase understanding of node-positive (ypN+) muscle invasive bladder cancer (MIBC) after neoadjuvant chemotherapy and radical cystectomy to decide the appropriate therapeutics. @*Materials and Methods@#In a retrospective study using the center cancer chemotherapy registry, we found 113 MIBC patients who were treated with neoadjuvant chemotherapy involving gemcitabine and cisplatin (GP) followed by radical cystectomy between 2010 and 2014. Disease-free survival (DFS) and overall survival (OS) were compared according to the pathologic node positivity (ypN- vs. ypN+). Among a total of 165 patients with MIBC who received neoadjuvant chemotherapy involving GP, 118 underwent radical cystectomy. In 46 patients with ypN+ disease, DFS and OS were evaluated according to administration of adjuvant GP. @*Results@#After neoadjuvant chemotherapy and radical cystectomy, 41% of patients had ypN+ disease, which showed significantly shorter DFS (median, 7.4 months; 95% confidence interval [CI], 5.3–9.6 months) and OS (median, 20.0 months; 95% CI, 13.4–26.6 months) compared to those with ypN- disease. The patients with ypN+ disease had a high risk of recurrence or death, regardless of the administration of adjuvant chemotherapy or adjuvant regimen. @*Conclusions@#Within the limitations of this retrospective study, MIBC patients with ypN+ disease despite neoadjuvant chemotherapy and radical cystectomy had a poor prognosis. Further studies involving novel, effective adjuvant treatment including immunotherapy agents are needed to reduce the high risk of recurrence or death in these patients.

Node-Positive Bladder Cancer After Neoadjuvant Chemotherapy Followed by Radical Cystectomy: A Single-Center Retrospective Study

Purpose@#There remains a lot of unmet need to increase understanding of node-positive (ypN+) muscle invasive bladder cancer (MIBC) after neoadjuvant chemotherapy and radical cystectomy to decide the appropriate therapeutics. @*Materials and Methods@#In a retrospective study using the center cancer chemotherapy registry, we found 113 MIBC patients who were treated with neoadjuvant chemotherapy involving gemcitabine and cisplatin (GP) followed by radical cystectomy between 2010 and 2014. Disease-free survival (DFS) and overall survival (OS) were compared according to the pathologic node positivity (ypN- vs. ypN+). Among a total of 165 patients with MIBC who received neoadjuvant chemotherapy involving GP, 118 underwent radical cystectomy. In 46 patients with ypN+ disease, DFS and OS were evaluated according to administration of adjuvant GP. @*Results@#After neoadjuvant chemotherapy and radical cystectomy, 41% of patients had ypN+ disease, which showed significantly shorter DFS (median, 7.4 months; 95% confidence interval [CI], 5.3–9.6 months) and OS (median, 20.0 months; 95% CI, 13.4–26.6 months) compared to those with ypN- disease. The patients with ypN+ disease had a high risk of recurrence or death, regardless of the administration of adjuvant chemotherapy or adjuvant regimen. @*Conclusions@#Within the limitations of this retrospective study, MIBC patients with ypN+ disease despite neoadjuvant chemotherapy and radical cystectomy had a poor prognosis. Further studies involving novel, effective adjuvant treatment including immunotherapy agents are needed to reduce the high risk of recurrence or death in these patients.

Prognostic Significance of Systemic Inflammatory Response in Patients with Synchronous and Metachronous Metastatic Renal Cell Carcinoma Receiving First-Line Tyrosine Kinase Inhibitors

PURPOSE@#To determine whether systemic inflammatory response (SIR), particularly platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR), has different prognostic role between patients with metastatic renal cell carcinoma (mRCC) receiving first-line tyrosine kinase inhibitors (TKI).@*MATERIALS AND METHODS@#We retrospectively reviewed 547 patients with mRCC who were diagnosed and treated with a first-line TKI between 2007 and 2015. The primary endpoint was overall survival (OS) and secondary endpoint was progression-free survival (PFS). We evaluated differences in survival outcomes according to SIR and identified predictors of OS and PFS.@*RESULTS@#In synchronous mRCC, patients with a higher PLR had significantly worse OS and PFS. Moreover, a higher NLR was also associated with both worse OS and PFS in these patients. However, PLR was not associated with either OS or PFS in metachronous mRCC patients. While metachronous mRCC patients with a higher NLR had worse OS compared to those with lower NLR, there was no difference in PFS according to the status of NLR. On multivariate analysis, PLR was identified as predictive factor for OS (hazard ratio [HR], 1.55) as well as PFS (HR, 1.39) in patients with synchronous mRCC, but not in patients with metachronous mRCC. Additionally, higher NLR was also remained as predictive factor of both OS (HR, 1.83) and PFS (HR, 1.57) in patients with synchronous mRCC.@*CONCLUSIONS@#Our study indicates that simple biomarkers of SIR, particularly PLR and NLR, can be more useful predictors of survival outcomes in patients with synchronous mRCC rather than metachronous mRCC.

Role of Magnetic Resonance Imaging Using Prostate Imaging-Reporting and Data System Version 2 to Predict Clinically Significant Cancer After Radical Prostatectomy in Very Low-Risk or Low-Risk Prostate Cancer

PURPOSE: To determine the negative predictive value (NPV) of multiparametric magnetic resonance imaging (mp-MRI) for clinically significant cancer (CSC) based on the Prostate Imaging-Reporting and Data System (PI-RADS) version 2 in very low-risk or low-risk prostate cancer patients. MATERIALS AND METHODS: We retrospectively analyzed 380 patients with low risk of prostate cancer who underwent mp-MRI before radical prostatectomy (RP) from 2011 to 2013. Of the 380 patients, 142 patients were in the very low risk group. CSC at RP was defined as follows: any T3−4, G3+4 with tumor volume>15%, G4+3 or higher. In the very low risk and low risk groups, we analyzed the rate of CSC according to PI-RADS score and calculated the NPV of mp-MRI for detection of CSC. RESULTS: In the low risk group, 20.8% (n=79) of patients had PI-RADS version 2 score 1–2 and 17.4% (n=66) of patients had PI-RADS version 2 score 3. In the very low risk group, 26.8% (n=38) of patients had PI-RADS version 2 score 1–2 and 17.6% (n=25) of patients had PI-RADS version 2 score 3 in the very low risk group. Rates of CSC were 33.7% (n=128) and 16.9% (n=24) in the low risk and very low risk groups, respectively. The NPV of MRI was 93.7% in the very low risk group and 78.6% in the low risk group. CONCLUSIONS: The NPV of PI-RADS for CSC is high in the very low risk group, but not in the low risk group. Further multicenter studies are needed to investigate the utility of PI-RADS version 2 for NPV.

Comparison of Biopsy Results and Surgical Outcomes of Magnetic Resonance Imaging-Guided and Transrectal Ultrasonography-Guided Repeat Biopsy

PURPOSE: We compared biopsy results and surgical outcomes of magnetic resonance imaging (MRI)-guided biopsy with transrectal ultrasonography (TRUS)-guided biopsy to demonstrate efficacy of MRI-guided biopsy on previous biopsy negative patients. MATERIALS AND METHODS: We retrospectively reviewed data of 120 patients who were categorized into MRI-guided biopsy groups (n=20) and TRUS-guided biopsy groups (n=100). All patients were diagnosed with prostate cancer (PCa) and had undergone radical prostatectomy (RP) after MRI-guided or TRUS-guided repeat biopsy between January 2010 and March 2016. Detection rate of significant cancer and Gleason score upgrading and downgrading were examined, in addition to biopsy results and subsequent RP outcomes. RESULTS: Median values for prostate-specific antigen level of the TRUS-guided biopsy group and the MRI-guided biopsy group were 6.67 and 5.86 ng/mL (p=0.303), respectively. Median prostate volume of each group (34.1 mL vs. 23.5 mL, p=0.007), number of positive cores (2.0 vs. 3.0, p=0.001) and maximum cancer/core rate (30.0% vs. 60.0%, p<0.001) were statistically different. Positive core rates of each group were 21.9% and 87.1%, respectively. Pathologic T stage was the only variable that showed difference in surgical outcomes (p=0.002). Most of PCa was confirmed as clinically significant PCa after RP in MRI-guided biopsy group (95%). CONCLUSIONS: MRI-guided biopsy showed higher positive core rate and detection rate of clinically significant PCa than TRUS-guided biopsy in repeat biopsy setting. Prospective multicenter large-scale study and accumulation of data is expected to further define superiority of the MRI-guided biopsy.

Incidence of Pathological Downgrading and Treatment Outcome After Radical Prostatectomy in Patients With Biopsy Confirmed High Gleason Score Prostate Cancer

PURPOSE: High Gleason score (8 to 10) is a poor prognostic factor regardless of treatment. Pathological downgrading sometimes occurs in high grade prostate cancer. The aim of this study is to evaluate treatment outcomes in patients with high grade prostate cancer on biopsy who were pathological downgrading after radical prostatectomy (RP). The impact on outcomes according to changes in the Gleason score after RP was evaluated. MATERIALS AND METHODS: Of 3,236 men who underwent RP between September 1995 and December 2014, 541 patients with biopsy Gleason score 8 to 10 were retrospectively reviewed. We analyzed incidence and biochemical recurrence (BCR) free probability in this downgraded group according to the Gleason grade of cancer in the RP specimen. RESULTS: Of 541 patients had a prostate biopsy Gleason score of 8 to 10. Two hundred ten patients showed pathological downgrading after RP (38.8%). Five-year BCR-free probability of patients who had Gleason score of 7 or less after RP was 46.8%. However, 5-year BCR-free probability of patients who remained Gleason scores 8 to 10 after RP was 28.5%. There was a significantly higher BCR-free probability in pathological downgrading group (p<0.001). On multivariate analysis, biopsy Gleason 8, lower PSA, clinical T2 stage was a significant predictor of downgrading. CONCLUSIONS: In this study, 38.8% of patients with high grade prostate cancer had a Gleason score of 7 or less in the RP specimen. Downgraded prostate cancer had more favorable treatment outcome. Serum PSA, clinical stage and biopsy Gleason score were the predictive factors for pathological downgrading.

Comparison of 5-Year Outcomes of Robot-Assisted Laparoscopic and Laparoscopic Partial Nephrectomy in Patients With Localized Renal Cell Carcinoma

PURPOSE: To compare the 5-year oncologic and functional outcomes of robot-assisted laparoscopic partial nephrectomy (RALPN) and laparoscopic partial nephrectomy (LPN) as treatment for localized renal cell carcinoma (RCC). MATERIALS AND METHODS: We analyzed the records of 181 patients with localized RCC who underwent RALPN (n=97) or LPN (n=84) between 2007 and 2011. Demographic and preoperative data with estimated glomerular filtration rate (eGFR), intraoperative data including warm ischemic time (WIT) and complications, oncologic outcomes (recurrence, metastasis), and rate of eGFR preservation at most recent follow-up were examined. RESULTS: WIT was shorter in the RALPN group (27±9.1 minutes) than the LPN group (31±10 minutes, p=0.019). Intraoperative complication rates were also lower in RALPN patients than LPN patients (4.1% vs. 14.3%). The eGFR preservation rate was higher in the RALPN group (84.6%) than in the LPN group (81.5%, p=0.049). Particularly, a relatively high difference in the eGFR preservation rate was observed in the RALPN group compared with the LPN group according to R.E.N.A.L. score 7–10 values (RALPN, 86.5±12.9 vs. LPN, 76.7±16.0; p=0.003). During the follow-up period, there was no local recurrence in either group and distant metastases only occurred in one patient in the RALPN group and in 2 patients in the LPN group. CONCLUSIONS: RALPN and LPN showed similar 5-year oncologic outcomes, but RALPN was superior to LPN in terms of WIT, intraoperative complications, and long-term eGFR preservation rate, especially in complex cases.

Comparisons between Standard and Extended Pelvic Lymph Node Dissections During Radical Cystectomy in Patients with Bladder Cancer: Emphasis on Staging Ability and Perioperative Complications

PURPOSE: We compared the staging ability and early complications of standard and extended pelvic lymph node dissection (sPLND and ePLND, respectively) in patients with localized bladder cancer during radical cystectomy. MATERIALS AND METHODS: We prospectively collected and analyzed the data of 261 patients who underwent radical cystectomy for localized bladder cancer. The resected lymph nodes were categorized according to anatomic locations and were carefully inspected by an experienced pathologist. The perioperative complications were classified using the Clavien-Dindo classification system. RESULTS: The 2 groups showed no significant differences in preoperative characteristics except for preoperative clinical stage (p=0.015). There were no significant differences in pathologic outcomes including pathologic stage, positive surgical margin, and lymphovascular invasion (all p>0.05), but the sPLND group showed a significantly higher cellular grade (p<0.001). The ePLND group showed a higher number of removed lymph nodes than the sPLND group (p=0.015) and a higher rate of positive lymph node invasion (35.8% vs. 28.9%). There were no significant differences in complication rates according to the extent of lymph dissection and urinary diversion type, respectively (p=0.063 and p=0.486). CONCLUSIONS: The ePLND showed more accurate nodal staging ability with comparable complication rates when compared to sPLND in patients who underwent radical cystectomy for localized bladder cancer. A further, larger prospective study is needed to confirm the result of the present study.

Twenty-Year Single Surgeon Experience with Radical Perineal Prostatectomy: Oncologic, Functional Outcomes and Perioperative Complications

PURPOSE: To evaluate oncologic, functional outcomes and complications in patients with prostate cancer (PCa) who underwent radical perineal prostatectomy (RPP). MATERIALS AND METHODS: A retrospective review of patients who underwent RPP by a single surgeon between 1995 and 2014 was performed. We analyze clinicopathologic characteristics and postoperative complications including urinary continence and erectile function. Kaplan-Meier survival analysis was used to access biochemical recurrence (BCR)-free survival (BFS) and cancer-specific survival (CSS) and log-rank test was applied. Complications were stratified by the Clavien-Dindo classification system. RESULTS: A total of 816 patients were included in this study. The mean prostate-specific antigen and prostate volume was 8.89 ng/mL and 30.8 mL. Positive surgical margin was identified in 174 patients (21.3%) after RPP. During a mean follow-up of 58.7 months, 173 patients (21.2%) experienced BCR. Overall, 44 patients (5.4%) died, of which 15 (1.8%) died from PCa. The 5-year BFS in patients with T2, T3a, and T3b were 84.8%, 69.7%, and 46.7% (p<0.001), respectively. The 10-year CSS in patients with same groups were 98.9%, 98.2%, and 79.5% (p<0.001), respectively. At 12 months after RPP, recovery of urinary continence and erectile function was identified in 88.3% and 63.7% of patients. Wound dehiscence (8.9%) was the most common complication. However, approximately 78% of complications were grade I or II. CONCLUSIONS: Our study indicates that RPP shows acceptable outcomes in terms of oncologic results and complications in patients with PCa. Careful attention is required to prevent wound dehiscence.

A Prospective Multicenter Trial of the Efficacy and Tolerability of Neoadjuvant Sunitinib for Inoperable Metastatic Renal Cell Carcinoma

This study aimed to evaluate the efficacy, safety, and tolerability of 2-cycled neoadjuvant sunitinib therapy (NST) in patients with inoperable metastatic renal cell carcinoma (mRCC). Between 2009 and 2012, 14 patients with inoperable mRCC from 5 Korean academic centers were prospectively enrolled after collecting their clinicopathological data and completing health-related questionnaires. The best overall response (BOR), safety profile, and changes in quality of life during NST were assessed using the RECIST criteria (version 1.0), CTCAE criteria (version 4.0), and the Cancer Quality of Life Questionnaire (QLQ-C30). Among the 14 patients, 9 patients (64.3%) experienced partial response or stable disease state, and 5 patients (35.7%) did not complete treatment, with 1 case of disease progression (7.1%), 3 grade 3 adverse events (21.4%), and 1 voluntary withdrawal (7.1%). Four patients (28.6%) were successfully converted to an operable state and underwent surgery after NST. The BOR for the primary renal lesions was 22.2%, with a median 1.3-cm diameter reduction (range: 0–2.8 cm) from a baseline diameter of 10.3 cm (range: 6.6–15.8 cm). The other 18 measurable metastatic lesions exhibited a BOR of 55.6%. The QLQ-C30 questionnaire results revealed significant improvements in the quality of life domain, although we observed significant increases in the scores for fatigue, nausea and vomiting, and the financial effects of NST (P < 0.05). Two-cycle NST provided limited efficacy for resectability of inoperable mRCC, despite mild improvements in the BOR of the primary lesion and quality of life (Clinical Trial Registry 1041140-1).

Comparison of Pathological and Biochemical Outcomes after Radical Prostatectomy in Korean Patients with Serum PSA Ranges

The aim of this study was to assess surgical outcome at radical prostatectomy (RP) in Korean men with a serum prostate-specific antigen (PSA) level of 2.5 to 3.0 ng/mL and compared with those of patients who had a PSA level of 3.0-4.0 and 4.0-10.0 ng/mL. We retrospectively compared clinico-pathological characteristics and biochemical recurrence (BCR) risk in patients with PSA level of 2.5-3.0 (group 1, n = 92, 5.7%), 3.0-4.0 (group 2, n = 283, 17.5%), or 4.0-10.0 ng/mL (group 3, n = 1,242, 76.8%) who underwent RP between 1995 and 2013. The pathologic characteristics including Gleason score, pathologic stage, and percentage of significant cancer in group 1 were similar to those in group 2 and group 3. Furthermore, pathological upgrading and upstaging were found in 23 (30.7%) and 10 (14.7%) in group 1, 84 (33.9%) and 19 (8.8%) in group 2, and 321 (32.8%) and 113 (12.8%) in group 3, respectively, with no significant differences among the three groups (all P > 0.05). In multivariate analysis, PSA grouping was not an independent predictor of BCR. Within the population with PSA lower than 10 ng/mL, substratification of PSA is not a significant predictor for upgrading, upstaging, or adverse prognosis.

Comparison of Pathological and Biochemical Outcomes after Radical Prostatectomy in Korean Patients with Serum PSA Ranges

The aim of this study was to assess surgical outcome at radical prostatectomy (RP) in Korean men with a serum prostate-specific antigen (PSA) level of 2.5 to 3.0 ng/mL and compared with those of patients who had a PSA level of 3.0-4.0 and 4.0-10.0 ng/mL. We retrospectively compared clinico-pathological characteristics and biochemical recurrence (BCR) risk in patients with PSA level of 2.5-3.0 (group 1, n = 92, 5.7%), 3.0-4.0 (group 2, n = 283, 17.5%), or 4.0-10.0 ng/mL (group 3, n = 1,242, 76.8%) who underwent RP between 1995 and 2013. The pathologic characteristics including Gleason score, pathologic stage, and percentage of significant cancer in group 1 were similar to those in group 2 and group 3. Furthermore, pathological upgrading and upstaging were found in 23 (30.7%) and 10 (14.7%) in group 1, 84 (33.9%) and 19 (8.8%) in group 2, and 321 (32.8%) and 113 (12.8%) in group 3, respectively, with no significant differences among the three groups (all P > 0.05). In multivariate analysis, PSA grouping was not an independent predictor of BCR. Within the population with PSA lower than 10 ng/mL, substratification of PSA is not a significant predictor for upgrading, upstaging, or adverse prognosis.

Utilization Trend of Partial Nephrectomy for the Treatment of Renal Cell Carcinoma in Korea: An Multicenter study using URO-PDS

PURPOSE: Partial nephrectomy has a similar oncologic outcome to radical nephrectomy while reducing cardiac and metabolic morbidity. However, previous studies reported that partial nephrectomy had been underutilized. The purpose of this study is to analyze trends in the use of partial nephrectomy in Korea and evaluate which individual factors and hospital factor influenced the operative approach. MATERIALS AND METHODS: Using URO-PDS database, 11560 patients underwent nephrectomy for renal cell carcinoma between 2006 and 2010 were identified. International Classification of Disease (ICD-9) diagnosis codes were applied to target subject of interest. Logistic regression was applied to identify determinants of partial nephrectomy. RESULTS: Over the study period, the proportion of partial nephrectomies has steadily increased from 9.4% in 2006 to 30.4% in 2010 (p<0.001). Deviation of utilization in partial nephrectomy has been observed based on the area (p<0.001) and type of surgery (p<0.001). Individual of younger age, as well as male, were more likely to be treated with partial nephrectomy (p<0.001 for each). Furthermore, Patient treated at hospitals with higher nephrectomy volume were more prone to be treated with partial nephrectomy (p<0.001 for each). CONCLUSIONS: Partial nephrectomies have been increasingly performed over the study period but are still underutilized.

Laparoscopic Partial Nephrectomy Using a Water (Hydro)-Jet System: A Case Report

The water-jet system (WJS) can be used for selective dissection of kidney parenchyma without renal artery clamping in laparoscopic partial nephrectomy (LPN). We report our experiences regarding LPN with a WJS. The first case was a 59 year old male with a 1.8 cm solid mass in the Rt. mid-lateral area (R.E.N.A.L score: 5a). The second case was a 24 year old female with a 2.3cm solid mass in the Lt. mid-lateral area (R.E.N.A.L score: 7x). We successfully finished non-clamping LPN using a WJS without perioperative complications. Surgical margins were negative (7mm and 1mm for cases 1 and 2, respectively). Post-operative renal function was not decreased significantly. LPN using a WJS is a feasible and safe technique which can be performed for small renal masses without ischemic damage.

Multiple cores of high grade prostatic intraepithelial neoplasia and any core of atypia on first biopsy are significant predictor for cancer detection at a repeat biopsy

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

Effect of curcumin on the interaction between androgen receptor and Wnt/beta-catenin in LNCaP xenografts

PURPOSE: Curcumin is a nontoxic, chemopreventive agent possessing multifaceted functions. Our previous study showed that curcumin inhibits androgen receptor (AR) through modulation of Wnt/beta-catenin signaling in LNCaP cells. Therefore, we investigated the in vivo effects of curcumin by using LNCaP xenografts. MATERIALS AND METHODS: LNCaP cells were subcutaneously inoculated in Balb/c nude mice. When the tumor volume reached greater than 100 mm3, either curcumin (500 mg/kg body weight) or vehicle was administered through oral gavage three times weekly for 4 weeks. The expression of AR and intermediate products of Wnt/beta-catenin were assessed. RESULTS: Curcumin had an inhibitory effect on tumor growth during the early period, which was followed by a slow increase in growth over time. Tumor growth was delayed about 27% in the curcumin group. The mean prostate-specific antigen (PSA) doubling time in the curcumin group was approximately twice that in the untreated group. Curcumin significantly decreased AR expression at both the mRNA and protein level. The PSA levels tended to be reduced in the curcumin group. However, there were no significant changes in expression of Wnt/beta-catenin pathway intermediates. CONCLUSIONS: This study revealed that curcumin initially interferes with prostate cancer growth by inhibiting AR activity and possibly by reducing PSA expression. Further research is needed to investigate the plausible mechanism of the antiandrogenic action of curcumin.

Is Radical Perineal Prostatectomy a Viable Therapeutic Option for Intermediate- and High-risk Prostate Cancer?

The aim of this study was to investigate a single-institution experience with radical perineal prostatectomy (RPP), radical retropubic prostatectomy (RRP) and minimally invasive radical prostatectomy (MIRP) with respect to onco-surgical outcomes in patients with intermediate-risk (IR; PSA 10-20 ng/mL, biopsy Gleason score bGS 7 or cT2b-2c) and high-risk (HR; PSA >20 ng/mL, bGS > or =8, or > or =cT3) prostate cancer (PCa). We retrospectively reviewed data from 2,581 men who underwent radical prostatectomy for IR and HR PCa (RPP, n = 689; RRP, n = 402; MIRP, n = 1,490 [laparoscopic, n = 206; robot-assisted laparoscopic, n = 1,284]). The proportion of HR PCa was 40.3%, 46.8%, and 49.5% in RPP, RRP, and MIRP (P < 0.001), respectively. The positive surgical margin rate was 23.8%, 26.1%, and 18.7% (P = 0.002) overall, 17.5%, 17.8%, and 8.8% (P < 0.001) for pT2 disease and 41.9%, 44.4%, and 40.0% (P = 0.55) for pT3 disease in men undergoing RPP, RRP, and MIRP, respectively. Biochemical recurrence-free survival rates among RPP, RRP, and MIRP were 73.0%, 70.1%, and 76.8%, respectively, at 5 yr (RPP vs. RPP, P = 0.02; RPP vs. MIRP, P = 0.23). Furthermore, comparable 5-yr metastases-free survival rates were demonstrated for specific surgical approaches (RPP vs. RPP, P = 0.26; RPP vs. MIRP, P = 0.06). RPP achieved acceptable oncological control for IR and HR PCa.

Diagnostic and Prognostic Significance of Radiologic Node-positive Renal Cell Carcinoma in the Absence of Distant Metastases: A Retrospective Analysis of Patients Undergoing Nephrectomy and Lymph Node Dissection

The aim of this study was to evaluate the diagnostic and prognostic value of clinical-positive nodes at preoperative imaging (cN1) in patients with non-metastatic renal cell carcinoma (RCC) treated with lymph node dissection (LND). We retrospectively reviewed data for a cohort of 440 consecutive patients (cN0, 76.8%; cN1, 23.2%) with cTanyNanyM0 RCC who underwent nephrectomy and LND from 1994 to 2013. Metastasis-free survival (MFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine significant predictors of MFS and CSS. The mean number of lymph nodes (LNs) examined for all patients was 8.3, and pN1 disease was identified in 31 (7.0%). LN staging by preoperative imaging had a sensitivity of 65%, a specificity of 80%, and an accuracy of 77%. During a median follow-up of 69 months, 5-yr MFS and CSS were 83.6% and 91.3% in patients with cN0 and 49.2% and 70.1% in patients with cN1, demonstrating a trend toward worse prognosis with radiologic lymphadenopathy (all P < 0.001). Furthermore, differences in MFS and CSS between the cN0pN0 and cN1pN0 groups were significant (all P < 0.001). Clinical nodal involvement is an important determinant of adverse prognosis in patients with non-metastatic RCC who undergo LND.

Interval from Prostate Biopsy to Radical Prostatectomy Does Not Affect Immediate Operative Outcomes for Open or Minimally Invasive Approach

Traditionally, urologists recommend an interval of at least 4 weeks after prostate biopsy before radical prostatectomy. The aim of our study was to evaluate whether the interval from prostate biopsy to radical prostatectomy affects immediate operative outcomes, with a focus on differences in surgical approach. The study population of 1,848 radical prostatectomy patients was divided into two groups according to the surgical approach: open or minimally invasive. Open group included perineal and retropubic approach, and minimally invasive group included laparoscopic and robotic approach. The cut-off of the biopsy-to-surgery interval was 4 weeks. Positive surgical margin status, operative time and estimated blood loss were evaluated as endpoint parameters. In the open group, there were significant differences in operative time and estimated blood loss between the or =4-week interval subgroups, but there was no difference in positive margin rate. In the minimally invasive group, there were no differences in the three outcome parameters between the two subgroups. Multivariate analysis revealed that the biopsy-to-surgery interval was not a significant factor affecting immediate operative outcomes in both open and minimally invasive groups, with the exception of the interval > or =4 weeks as a significant factor decreasing operative time in the minimally invasive group. In conclusion, performing open or minimally invasive radical prostatectomy within 4 weeks of prostate biopsy is feasible for both approaches, and is even beneficial for minimally invasive radical prostatectomy to reduce operative time.