Cheryn Song

Factors Influencing Renal Function Reduction After Partial Nephrectomy

PURPOSE We investigated factors determining the degree of functional reduction by measuring changes in individual renal function before and after partial nephrectomy. MATERIALS AND METHODS In 117 patients who underwent elective partial nephrectomy the glomerular filtration rate of the renal units with tumor from the diethylenetetramine pentaacetic acid renal scan was measured before and at a mean of 6.5 months after surgery. Kidney volume was calculated using computerized tomography. Of these patients 52 and 65 underwent open and laparoscopic partial nephrectomy, respectively. Satinsky clamps were used for renal artery-vein clamping in all patients. We analyzed patient, tumor and perioperative characteristics including surgical method with respect to changes in glomerular filtration rate. RESULTS Renal cell carcinoma was diagnosed in 101 (86.3%) patients. Between the laparoscopic and open partial nephrectomy groups significant differences were noted in tumor size (2.14 vs 3.72 cm, p <0.001) and warm ischemia time (33.5 vs 20.5 minutes, p <0.001). Reduction and percent reduction in glomerular filtration rate (13.3 vs 12.6 ml per minute per m(2), p = 0.662; 29.9% vs 33.2%, p = 0.337), and reduction and percent reduction in kidney volume (35.8 vs 36.4 cm(3), p = 0.886; 20.4% vs 24.0%, p = 0.151), respectively, were similar between the groups. On multivariate analysis renal volume reduction (%, p <0.0001) was the most significant, independent prognosticator for glomerular filtration rate reduction followed by polar location of the tumor (upper vs mid-lower pole, p = 0.012) and increasing age (p = 0.041). CONCLUSIONS Renal volume reduction, tumor location and patient age determine renal function after partial nephrectomy. In appropriate cases the laparoscopic method can show surgical and functional outcomes equivalent to those of the open method.

Factors Determining Functional Outcomes After Radical Prostatectomy: Robot-Assisted Versus Retropubic

BACKGROUND Early studies reported comparative results of functional outcomes between robot-assisted (RARP) and retropubic radical prostatectomy (RRP). However, well-controlled single-surgeon prospective studies comparing the outcomes are rare. OBJECTIVE To compare functional outcomes after RARP and RRP performed by a single surgeon, and to identify factors predictive of early return of continence and potency. DESIGN, SETTING, AND PARTICIPANTS A total of 763 consecutive patients undergoing RP between 2007 and 2010 were prospectively included and serially followed postoperatively for comparative analysis. INTERVENTION RARP was performed in 528 patients, and 235 underwent RRP. MEASUREMENTS Continence was defined as being completely pad free. Potency was defined as having erection sufficient for intercourse with or without a phosphodiesterase type 5 inhibitor. Continence and potency recovery were checked serially by interview and questionnaire at 1, 3, 6, 9, 12, 18, and 24 mo postoperatively. Cox proportional hazards method analyses was performed to determine predictive factors for early recovery. RESULTS AND LIMITATIONS After the initial 132 cases, patients who underwent RARP demonstrated faster recovery of urinary continence compared to RRP patients. Potency recovery was more rapid in the RARP group at all evaluation time points, beginning from the initial cases. In multivariate analysis, younger age and longer preoperative membranous urethral length seen by prostate magnetic resonance imaging (MRI) demonstrated statistical significance as independent prognostic factors for continence recovery; younger age, surgical method (RARP vs RRP), and higher preoperative serum testosterone were independent prognostic factors for potency recovery. The limitations of the present study were that it was nonrandomized and used interview to evaluate potency recovery. CONCLUSIONS Patients after RARP demonstrated superior functional recovery. Moreover, membranous urethral length on preoperative MRI and patient age were factors independently predictive of continence recovery, while patient age and higher preoperative serum testosterone were independent prognostic factors for potency recovery.

The Efficacy and Safety of Sunitinib in Korean Patients with Advanced Renal Cell Carcinoma: High Incidence of Toxicity Leads to Frequent Dose Reduction

OBJECTIVE The effects of sunitinib in a broad patient population, especially those of Asian ethnicity, have been rarely investigated. Here, we assessed the efficacy and safety of sunitinib in Korean patients with advanced renal cell carcinoma. METHODS Between April 2006 and August 2008, 77 Korean patients with advanced renal cell carcinoma were treated with sunitinib. We performed retrospective analysis for efficacy in terms of survival outcomes and response rate. Toxicity profiles were also assessed. RESULTS A total of 65 patients, including 39 (60%) patients without previous cytotoxic or immunotherapy, were eligible for the analysis. In 53 patients with measurable lesions, the objective response rate was 43% and disease control was achieved in 46 (86%) patients. The median time to treatment failure, time to progression and overall survival were 7.0, 11.8 and 22.8 months, respectively, with a median follow-up of 26.8 months in surviving patients. The most common treatment-related adverse events were fatigue (81%) and stomatitis (60%). The most common Grade 3 or 4 adverse events were hand-foot syndrome (16%), thrombocytopenia (16%) and stomatitis (10%). Dose reduction was required in 46% of patients. CONCLUSIONS The efficacy was similar to a previous Phase III trial and a safety profile of sunitinib was manageable in Korean patients with advanced renal cell carcinoma, although the incidence of dose reduction and Grade 3 or 4 adverse events were higher than those of western reports. Future studies should investigate the ethnic differences in toxicity profiles of sunitinib.

Multicenter phase II study of sunitinib in patients with non-clear cell renal cell carcinoma

BACKGROUND Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma (nccRCC). PATIENTS AND METHODS Eligibility criteria included advanced nccRCC except for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes. Patients were treated with 50 mg/day oral sunitinib for 4 weeks, followed by 2 weeks of rest. The primary end point was overall response rate (RR). RESULTS Thirty-one eligible patients were enrolled. Twenty-four patients (77%) had prior nephrectomy. By Memorial Sloan-Kettering Cancer Center criteria, 8 patients (26%) had poor risk and 14 (45%) had intermediate risk. Twenty-two patients had papillary renal cell carcinoma (RCC), and three had chromophobe RCC. Eleven patients had partial response with a RR of 36% (95% confidence interval (CI) 19% to 52%) and an additional 17 patients (55%) had stable disease. Median duration of response was 12.7 months (95% CI 6.3-19.1 months), and median progression-free survival was 6.4 months (95% CI 4.2-8.6 months). At a median follow-up duration of 18.7 months (95% CI 13.7-23.7 months), 13 patients (42%) had died, resulting in an estimated median survival of 25.6 months (95% CI 8.4-42.9 months). Toxicity profiles were commensurate with prior reports. CONCLUSIONS Sunitinib has promising activity in patients with nccRCC (NCT01219751).BACKGROUND Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma (nccRCC). PATIENTS AND METHODS Eligibility criteria included advanced nccRCC except for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes. Patients were treated with 50 mg/day oral sunitinib for 4 weeks, followed by 2 weeks of rest. The primary end point was overall response rate (RR). RESULTS Thirty-one eligible patients were enrolled. Twenty-four patients (77%) had prior nephrectomy. By Memorial Sloan-Kettering Cancer Center criteria, 8 patients (26%) had poor risk and 14 (45%) had intermediate risk. Twenty-two patients had papillary renal cell carcinoma (RCC), and three had chromophobe RCC. Eleven patients had partial response with a RR of 36% (95% confidence interval (CI) 19% to 52%) and an additional 17 patients (55%) had stable disease. Median duration of response was 12.7 months (95% CI 6.3-19.1 months), and median progression-free survival was 6.4 months (95% CI 4.2-8.6 months). At a median follow-up duration of 18.7 months (95% CI 13.7-23.7 months), 13 patients (42%) had died, resulting in an estimated median survival of 25.6 months (95% CI 8.4-42.9 months). Toxicity profiles were commensurate with prior reports. CONCLUSIONS Sunitinib has promising activity in patients with nccRCC (NCT01219751).

The Protective Role of Renal Parenchyma as a Barrier to Local Tumor Spread of Upper Tract Transitional Cell Carcinoma and its Impact on Patient Survival

PURPOSE We investigated whether tumor location has independent prognostic significance in upper tract transitional cell carcinoma cases and which factor determines it. MATERIALS AND METHODS We reviewed data on 122 renal pelvis and 102 ureteral tumor cases, including the recurrence pattern. Tumor location and other clinicopathological variables were evaluated regarding cancer specific and recurrence-free survival. Stage pT3 tumors were stratified into those invading renal parenchyma or peripelvic/periureteral fat. RESULTS Overall 5-year cancer specific survival and recurrence-free survival rates were 77.0% and 71.6%, respectively, at a mean followup of 60.7 months. Of the clinicopathological parameters T stage was the most significant prognosticator of the survival rate, while nodal involvement, high grade and ureteral tumor location were also significant for lower survival rates. Stratification analysis for matching pathological stage revealed that, while survival rates were similar in the renal pelvis and ureteral tumor groups at stage pT2 or less, renal pelvic tumors were associated with significantly higher survival rates than ureteral tumors for stage pT3. Specifically renal pelvic tumors invading the renal parenchyma were associated with a lower local failure rate, and higher cancer specific and recurrence-free survival rates than tumors invading peripelvic or periureteral fat, ie 77.5% vs 49.7% 5-year cancer specific survival and 75.6% vs 32.0% 5-year recurrence-free survival (p = 0.014 and 0.003, respectively). CONCLUSIONS Tumor location is an independent prognostic factor for pT3 upper tract transitional cell carcinoma. The overall better prognosis of renal pelvic tumors was mainly attributable to pT3 tumor outcomes, specifically lesions invading the renal parenchyma. These findings may be due to the protective role of thick renal parenchyma against local tumor spread.

Prognostic Significance of Perinephric Fat Infiltration and Tumor Size in Renal Cell Carcinoma

PURPOSES It is controversial that perinephric fat infiltration has an impact on survival in patients with renal cell carcinoma. Therefore, we evaluated the influence of perinephric fat infiltration and tumor size on patient survival. MATERIALS AND METHODS We retrospectively reviewed the medical records of 783 and 77 patients with pT1-2 (cN0M0) and pT3a (cN0M0) renal cell carcinoma, respectively. Sporadic unilocular noncystic renal cell carcinoma was included. Univariate and multivariate analyses of prognostic factors, including perinephric fat infiltration, on cancer specific and disease-free survival were performed. Median followup was 56.0 months after surgery. RESULTS Patients with pT1-2 and pT3a tumors had a 5-year cancer specific survival rate of 96.1% and 84.9%, and a 5-year disease-free survival rate of 93.4% and 74.7%, respectively (each p <0.01). Age, tumor size and Fuhrman nuclear grade were independent prognostic factors for cancer specific and disease-free survival, whereas perinephric fat infiltration was significant only for disease-free survival. However, perinephric fat infiltration had a significant effect on cancer specific survival in patients with pT3a tumors more than 7 cm (p = 0.001). In contrast, patients with pT3a tumors 7 cm or less had cancer specific and disease-free survival similar to that of patients with pT2 tumors. Recurrence of pT3a tumors greater than 7 cm was observed in 44% of patients but in only 14.6% of those with pT3a tumors 7 cm or less (p = 0.029). In contrast to the recurrence of tumors 7 cm or less, recurrence of pT3a tumors more than 7 cm usually developed at multiple sites with a large tumor burden and it progressed rapidly. Consequently 85% of patients with recurrence of pT3a tumors larger than 7 cm died of renal cell carcinoma compared with 33% of those with recurrence of pT3a tumors 7 cm or less (p = 0.001). CONCLUSIONS In pT3a renal cell carcinoma tumor size was the strongest prognostic factor of disease-free and cancer specific survival. Perinephric fat infiltration was an independent prognostic factor for disease-free survival but not for cancer specific survival due to the less aggressive behavior of small (7 cm or less) pT3a tumors after recurrence. Tumor size and perinephric fat infiltration should be included in T3a renal cell carcinoma staging.

Urodynamic interpretation of changing bladder function and voiding pattern after radical prostatectomy: a long-term follow-up

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b

RandomizEd phase II trial of Sunitinib four weeks on and two weeks off versus Two weeks on and One week off in metastatic clear-cell type REnal cell carcinoma: RESTORE trial

BACKGROUND The standard sunitinib schedule, 4 weeks on, followed by 2 weeks off (4/2 schedule), is associated with troublesome toxicities, and maintenance of adequate sunitinib dosing and drug levels, which are essential for achieving an optimal treatment outcome, is challenging. The objective of this study was to investigate the efficacy and safety of an alternative sunitinib dosing schedule of 2 weeks on and 1 week off (2/1 schedule) compared with the standard sunitinib schedule of 4 weeks on and 2 weeks off (4/2 schedule). PATIENTS AND METHODS In this multicenter, randomized, open-label, phase II trial, treatment-naïve patients with clear-cell type metastatic renal cell carcinoma (mRCC) were randomly assigned to 4/2 or 2/1 schedules after stratification by Memorial Sloan Kettering Cancer Center risk group and the presence or absence of measurable lesions. The primary end point was the 6-month failure-free survival (FFS) rate, determined by intention-to-treat analysis. RESULTS From November 2007 to February 2014, 76 patients were accrued, and 74 were eligible. FFS rates at 6 months were 44% with the 4/2 schedule (N = 36) and 63% with the 2/1 schedule (N = 38). Neutropenia (all grades, 61% versus 37%; grade 3-4, 28% versus 11%) and fatigue (all grades, 83% versus 58%) were more frequently observed with schedule 4/2. There was a strong tendency toward a lower incidence of stomatitis, hand-foot syndrome, and rash with schedule 2/1. Objective response rates (ORRs) were 47% in schedule 2/1 and 36% in schedule 4/2. With a median follow-up of 30.0 months, the median time to progression (TTP) was 12.1 months in schedule 2/1 and 10.1 months in schedule 4/2. CONCLUSION Sunitinib administered with a 2/1 schedule is associated with less toxicity and higher FFS at 6 months than a 4/2 schedule, without compromising the efficacy in terms of ORR and TTP (NCT00570882).

Differential Diagnosis of Complex Cystic Renal Mass Using Multiphase Computerized Tomography

PURPOSE We evaluated the additional usefulness of multiphase computerized tomography for improving the differential diagnosis of cystic renal masses by the Bosniak classification. MATERIALS AND METHODS We reviewed the records of 104 patients with Bosniak class II (29 or 27.8%), III (38 or 36.5%) and IV (37 or 35.7%) cystic renal masses managed surgically between 1997 and 2007. On preoperative multiphase computerized tomography enhancement differences in HU between the precontrast and corticomedullary phases were measured at the highest enhancement area to correlate with pathological findings. RESULTS Renal cell carcinoma was diagnosed in 56 patients (53.8%). Of the tumors 35 (62.5%) showed clear cell histology. According to Bosniak class 3 (11.5%), 21 (55.2%) and 32 (86.4%) class II to IV lesions, respectively, were diagnosed as renal cell carcinoma. For renal cell carcinoma and benign cysts mean HU at the precontrast phase was similar (31.5 and 32.4 HU, respectively), while renal cell carcinoma showed a significantly higher measurement at the corticomedullary phase (112.9 vs 59.8 HU, p <0.0001). To differentiate renal cell carcinoma a corticomedullary phase minus precontrast phase value of greater than 42 HU was predictive with 97.1% sensitivity and 85.7% specificity (area under the ROC curve 0.966). In a multiple regression model the corticomedullary phase minus precontrast phase value and the Bosniak classification independently determined malignant pathological findings (corticomedullary phase minus precontrast phase greater than 42 HU HR 31.541, 95% CI 8.320-119.563 and Bosniak class HR 5.545, 95% CI 2.153-14.279, each p <0.0001). CONCLUSIONS In cases of complex cystic renal masses diagnostic accuracy can be improved to differentiate renal cell carcinoma by combining Bosniak class and enhancement differences measured on multiphase computerized tomography between precontrast and maximal enhancement phases. This would help determine the need for and the method of surgical treatment.

Do molecular biomarkers have prognostic value in primary T1G3 bladder cancer treated with bacillus Calmette-Guerin intravesical therapy?

OBJECTIVES We examined whether altered protein expression for 7 potential biomarkers, including p53, pRb, PTEN, Ki-67, p27, FGFR3, and CD9, could predict tumor recurrence and progression in patients treated with bacillus Calmette-Guerin (BCG) therapy for primary stage T1 grade 3 (T1G3) bladder cancer (BC). MATERIALS AND METHODS The study included 61 patients with primary T1G3 BC who were treated with 6 weekly intravesical BCG instillations after clinically complete transurethral resection of bladder tumor between 1990 and 2007. All patients had proper muscle tissue in their specimen. Protein expression for 7 molecular biomarkers before BCG therapy was analyzed by immunohistochemistry based on tissue microarray methodology, and the percentage of positive cells was determined quantitatively in a blind fashion. Survival analysis was performed using Kaplan-Meier curves and Cox regression to determine the effect of each marker on recurrence-free survival (RFS) and progression-free survival (PFS) after BCG therapy. RESULTS Overall 5-year RFS and PFS rates were 56.0% and 84.5%, respectively, with a median follow-up of 60.0 months (range 6-217). The altered expression for each marker were noted in 53.3% for p53, 73.3% for pRb, 63.8% for PTEN, 40.0% for Ki-67, 66.1% for p27, 37.3% for FGFR3, and 47.5% for CD9, respectively. No significant association was found between altered marker status and clinicopathologic characteristics. While increased p53 expression was associated with progression after BCG therapy (5-year PFS rates: 90.7% in p53 < 10% vs. 78.7% in p53 ≥ 10%, P = 0.0495), no single marker was associated with RFS and PFS after BCG therapy in univariate and multivariate Cox regression analysis. Similarly, in subgroup analysis according to tumor size, multiplicity, and morphology, no single marker was associated with RFS and PFS. No difference was noted in molecular marker status between BCG responders and nonresponders. CONCLUSIONS Our findings indicate that immunohistochemical analysis for 7 potential molecular markers has no predictive value for recurrence and progression in primary T1G3 BC treated with BCG therapy. Large prospective studies are needed to validate the prognostic molecular markers in primary T1G3 BC.