Binglin Yue

Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer Prevention

Preclinical, epidemiologic, and prior clinical trial data suggest that green tea catechins (GTC) may reduce prostate cancer risk. We conducted a placebo-controlled, randomized clinical trial of Polyphenon E (PolyE), a proprietary mixture of GTCs, containing 400 mg (−)-epigallocatechin-3-gallate (EGCG) per day, in 97 men with high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP). The primary study endpoint was a comparison of the cumulative one-year prostate cancer rates on the two study arms. No differences in the number of prostate cancer cases were observed: 5 of 49 (PolyE) versus 9 of 48 (placebo), P = 0.25. A secondary endpoint comparing the cumulative rate of prostate cancer plus ASAP among men with HGPIN without ASAP at baseline, revealed a decrease in this composite endpoint: 3 of 26 (PolyE) versus 10 of 25 (placebo), P < 0.024. This finding was driven by a decrease in ASAP diagnoses on the Poly E (0/26) compared with the placebo arm (5/25). A decrease in serum prostate-specific antigen (PSA) was observed on the PolyE arm [−0.87 ng/mL; 95% confidence intervals (CI), −1.66 to −0.09]. Adverse events related to the study agent did not significantly differ between the two study groups. Daily intake of a standardized, decaffeinated catechin mixture containing 400 mg EGCG per day for 1 year accumulated in plasma and was well tolerated but did not reduce the likelihood of prostate cancer in men with baseline HGPIN or ASAP. Cancer Prev Res; 8(10); 879–87. ©2015 AACR.

Is the R.E.N.A.L. Nephrometry Scoring System Predictive of the Functional Efficacy of Nephron Sparing Surgery in the Solitary Kidney

PURPOSEnWe evaluated the ability of renal tumor complexity, as assessed by the R.E.N.A.L. (radius, exophytic, nearness to collecting system, anterior/posterior and location) nephrometry scoring system, to predict the functional efficacy of nephron sparing surgery.nnnMATERIALS AND METHODSnWe evaluated 42 patients who presented with an anatomically (32) or a functionally (10) solitary kidney and underwent partial nephrectomy. Each renal unit was assigned a R.E.N.A.L. nephrometry score using preoperative imaging. The CKD-EPI equation was applied to calculate the estimated glomerular filtration rate. The difference between the estimated glomerular filtration rate at baseline and at postoperative time points served as a measurement of the renal functional loss attributable to partial nephrectomy.nnnRESULTSnIn the 42 patients who underwent partial nephrectomy the mean preoperative estimated glomerular filtration rate was 61.5 ml/minute/1.73 m(2). The median total nephrometry score was 8 (range 4 to 10). In the immediate postoperative period the cohort mean estimated glomerular filtration rate of 48.6 ml/minute/1.73 m(2) was significantly less than the preoperative value (p <0.0001). At 6-month followup the mean estimated glomerular filtration rate had recovered at 54.1 ml/minute/1.73 m(2) but it remained significantly less than the preoperative value (p = 0.0002). We noted no relationship between the postoperative decrease in the estimated glomerular filtration rate and the assigned total nephrometry score or in any individual component of the R.E.N.A.L. scoring system related to the targeted lesion.nnnCONCLUSIONSnNeither the individual components of the R.E.N.A.L. nephrometry scoring system nor the total nephrometry score predicted the realized functional loss, as assessed by the estimated glomerular filtration rate in patients with a solitary kidney treated with nephron sparing surgery. However, nephron sparing surgery was quite efficacious for preserving renal function since only a durable 11.6% decrease was noted in the estimated glomerular filtration rate.

Both tumor depth and diameter are predictive of sentinel lymph node status and survival in Merkel cell carcinoma

The purposes of this study were 1) to determine the impact of primary tumor‐related factors on the prediction of the sentinel lymph node (SLN) status and 2) to identify clinical and pathologic factors associated with survival in Merkel cell carcinoma (MCC).

A Composite Gene Expression Signature Optimizes Prediction of Colorectal Cancer Metastasis and Outcome

Purpose: We previously found that an epithelial-to-mesenchymal transition (EMT)–based gene expression signature was highly correlated with the first principal component (PC1) of 326 colorectal cancer tumors and was prognostic. This study was designed to improve these signatures for better prediction of metastasis and outcome. Experimental Design: A total of 468 colorectal cancer tumors including all stages (I–IV) and metastatic lesions were used to develop a new prognostic score (ΔPC1.EMT) by subtracting the EMT signature score from its correlated PC1 signature score. The score was validated on six other independent datasets with a total of 3,697 tumors. Results: ΔPC1.EMT was found to be far more predictive of metastasis and outcome than its parent scores. It performed well in stages I to III, among microsatellite instability subtypes, and across multiple mutation-based subclasses, demonstrating a refined capacity to predict distant metastatic potential even in tumors with a “good” prognosis. For example, in the PETACC-3 clinical trial dataset, it predicted worse overall survival in an adjusted multivariable model for stage III patients (HR standardized by interquartile range [IQR] = 1.50; 95% confidence interval, 1.25–1.81; P = 0.000016, N = 644). The improved performance of ΔPC1.EMT was related to its propensity to identify epithelial-like subpopulations as well as mesenchymal-like subpopulations. Biologically, the signature was correlated positively with RAS signaling but negatively with mitochondrial metabolism. ΔPC1.EMT was a “best of assessed” prognostic score when compared with 10 other known prognostic signatures. Conclusions: The study developed a prognostic signature score with a propensity to detect non-EMT features, including epithelial cancer stem cell–related properties, thereby improving its potential to predict metastasis and poorer outcome in stage I–III patients. Clin Cancer Res; 22(3); 734–45. ©2015 AACR.

Using Percentage of Sarcomatoid Differentiation as a Prognostic Factor in Renal Cell Carcinoma

BACKGROUNDnThe objective of this study was to determine if the percentage of sarcomatoid differentiation (%Sarc) in renal cell carcinoma (RCC) can be used for prognostic risk stratification, because sarcomatoid RCC (sRCC) is an aggressive variant of kidney cancer.nnnPATIENTS AND METHODSnWe performed a retrospective analysis of patients who underwent surgery for RCC at our institution between 1999 and 2012. Pathology slides for all sRCC cases were reexamined by a single pathologist and %Sarc was calculated. %Sarc was analyzed as a continuous variable and as a categorical variable at cut points of 5%, 10%, and 25%. Potential prognostic factors associated with overall survival (OS) were determined using the Cox regression model. OS curves were generated using Kaplan-Meier methods and survival differences compared using the log-rank test.nnnRESULTSnOne thousand three hundred seven consecutive cases of RCC were identified, of which 59 patients had sRCC (4.5%). As a continuous variable %Sarc was inversely associated with OS (Pxa0= .023). Predictors of survival on multivariable analysis included pathologic (p) T status, tumor size, clinical (c) M status and %Sarc at the 25% level. OS was most dependent on the presence of metastatic disease (4 months vs. 21.2 months; Pxa0= .001). In cM0 patients with locally advanced (≥ pT3) tumors, OS was significantly diminished in patients with > 25 %Sarc (Pxa0= .045). However, %Sarc did not influence OS in patients with cM1 disease.nnnCONCLUSIONnPatients with sRCC have a poor overall outcome as evidenced by high rates of recurrence and death, indicating the need for more effective systemic therapies. In nonmetastatic patients, the incorporation of %Sarc in predictive nomograms might further improve risk stratification.

Implications of Definitive Prostate Cancer Therapy on Soft Tissue Margins and Survival in Patients Undergoing Radical Cystectomy for Bladder Urothelial Cancer

PURPOSEnWe evaluated the possibility of an existing link between definitive prostate cancer treatment and its effect on positive soft tissue surgical margins at radical cystectomy. A secondary objective was to determine whether definitive prostate cancer treatment was associated with bladder cancer survival end points.nnnMATERIALS AND METHODSnThere were 749 patients who underwent radical cystectomy between 2000 and 2013. After excluding females and patients with nonurothelial histologies 561 men were identified, of whom 69 (12.3%) received single or multimodal definitive prostate cancer treatment. Univariate and multivariable logistic regression was used to determine an association between clinical and pathological features such as definitive prostate cancer treatment and positive soft tissue surgical margins. Cox regression models and competing risk regression were used to investigate the impact of definitive prostate cancer treatment and positive surgical margins on survival.nnnRESULTSnThe median age of the male population was 70.0 years. There were 57xa0cases of positive soft tissue surgical margins in our cohort of 561 men (10.2%). Of men who underwent previous definitive prostate cancer treatment 20 of 69xa0(29.0%) had positive surgical margins compared to 37 of 492 (7.5%) who never received definitive prostate cancer treatment (p <0.0001). Brachytherapy, radiotherapy, hormonal therapy and radical prostatectomy significantly increased the rate of positive margins. Brachytherapy (OR 5.8), radiotherapy (OR 2.7) and hormonal therapy (OR 5.1) remained independent predictors of positive margins on multivariate analysis. Positive margins were associated with negative effects on recurrence-free (HR 3.1), cancer specific (HR 4.1) and overall survival (HR 2.8).nnnCONCLUSIONSnPatients with a history of definitive prostate cancer treatment are at increased risk for positive soft tissue surgical margins. Positive margins significantly impact bladder cancer recurrence-free, cancer specific and overall survival following radical cystectomy. Careful patient counseling and surgical planning are crucial when treating patients undergoing radical cystectomy who have axa0history of definitive prostate cancer treatment.

Surveillance Following Nephron-Sparing Surgery: An Assessment of Recurrence Patterns and Surveillance Costs.

OBJECTIVEnTo assess the pattern of renal cell carcinoma (RCC) recurrences in nephron-sparing surgery (NSS) patients, and to determine whether current guidelines for surveillance could be modified based on such patterns.nnnMETHODSnRetrospective review of a single-institution NSS database. Pattern of RCC recurrences and factors associated with recurrence were analyzed using univariate and multivariable competing risk regression analyses. Cost of surveillance was estimated based on Medicare charges.nnnRESULTSnA total of 505 patients underwent elective NSS for RCC. Pathologic T stage included 394 pT1a and 79 pT1b lesions. Median follow-up was 38.3 (6-88) months. Recurrence was detected in 26 patients (5.1%) at a median of 18.9xa0months (2.7% pT1a and 12.7% pT1b). The estimated 5-year cumulative incidence of recurrence for unifocal pT1a lesions was 2.7%. On multivariable analysis, stage higher than pT1a (HR, 5.56 [CI. 2.57-12.0]) and the presence of multifocal or bilateral tumors (HR, 3.32 [CI, 1.45-7.61]) were independent predictors of disease recurrence. For the entire cohort, recurrence was observed in only 10 patients beyond 24xa0months including only 2xa0cases with pT1a.nnnCONCLUSIONnCurrent guidelines adequately capture most clinically significant recurrences, and with longer follow-up, it may be possible to confirm that routine surveillance beyond 2xa0years may have little clinical significance for patients with asymptomatic unifocal pT1a.

Behavior of Cutaneous Adnexal Malignancies: a Single Institution Experience

Cutaneous adnexal malignancies are biologically and pathologically diverse, and associated with a range of clinical outcomes. Given their rarity, the prognosis and optimal treatment of these neoplasms remains unclear. A single institution database from a tertiary care cancer center of patients treated for malignant cutaneous adnexal tumors was retrospectively analyzed. Clinicopathologic variables and outcome measures were analyzed in patients undergoing wide excision with or without sentinel node biopsy. 103 patients were analyzed; the majority of tumors were of eccrine sweat gland derivation ( n u2009=u200969, 70%), and these exhibited a higher rate of nodal involvement and overall worse outcome. Sixteen patients (16%) demonstrated nodal metastasis, which included 10 (10%) with nodal disease at presentation and 6 who developed nodal metastasis during followup. 20 patients underwent sentinel node biopsy, and 2 (10%) had a positive sentinel node. 62% of nodal metastases occurred in patients with porocarcinoma. Seven patients died of disease (7%) with a median time from diagnosis to death of 48xa0months (range, 10–174). After a median follow up of 44.7xa0months, ageu2009>u200970xa0years and larger tumor size were significantly associated with worse overall survival. Adnexal malignancies are rare tumors, and there is a paucity of information to guide the clinician in determining optimum surgical and medical treatment. Tumors of eccrine derivation, especially porocarcinomas, have a high risk of nodal involvement and may be considered for sentinel node biopsy.

MP50-19 CHRONIC KIDNEY DISEASE IN PATIENTS UNDERGOING RADICAL CYSTECTOMY FOR BLADDER CANCER: TRENDS IN CHEMOTHERAPY USAGE AND EFFECTS ON SURVIVAL

CONCLUSIONS: Using standardized reporting methodology the incidence of early complications (<30 days) in patients receiving neoadjuvant chemotherapy followed by RC is similar to previous reports in the literature. Carboplatin based chemotherapy regimen and operative time were associated with developing major complications. Patients receiving carboplatin based chemotherapy may have medical comorbidities not identified by CCI and ASA score that lead to early complications.

Utilizing percentage of sarcomatoid differentiation as a prognostic factor in renal cell carcinoma.

507 Background: Sarcomatoid renal cell carcinoma (sRCC) is a histologic feature that denotes an aggressive variant of kidney cancer and worse overall outcomes. Our aim was to determine if the percentage of sarcomatoid differentiation (% Sarc) could be used for prognostic risk stratification. Methods: We performed a retrospective analysis of patients who underwent surgery at our center and found to have sRCC. A single genitourinary pathologist reviewed each specimen for %Sarc and other pathologic variables of interest. %Sarc was analyzed as a continuous variable and as a binary variable using cut-points of 5%, 10%, and 25%. Potential prognostic factors associated with overall survival (OS) were determined using the Cox regression model. OS curves were generated with Kaplan-Meier methods and survival differences compared using the log-rank test. Results: Between 1998 and 2012, 1,307 consecutive cases of RCC were identified, of which 59 patients were confirmed to have sRCC (4.5%). As a continuous variable %S...