bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of patient gender on urologist decision-making regarding treatment of the localized renal mass introduction and objective.
Authors: Shah Ankur , Ulmer William , Feustel Paul , O'Malley Rebecca Leigh
Published: February 2018

646

Background: Gender disparity in the proportion of patients receiving nephron sparing strategies (NSS) for the treatment of localized renal masses has been demonstrated in large population series as well as in single centers of excellence. Reasons for the discrepancy remain elusive. We aimed to assess urologist treatment patterns for localized renal masses in both genders to gauge the existence of provider-based gender biases. We hypothesize that female patients may be recommended more aggressive treatment due to provider biases related to patient gender. Methods: Urologists were randomly emailed 1 of 2 surveys including 6 vignettes of various patients with renal masses. Both surveys were identical other than the vignette patient gender (VPG) which was male in 50% and female in 50%. Self-selected respondents chose the single best treatment option from the following choices: active surveillance (AS), percutaneous or laparoscopic ablation (ABL), partial nephrectomy (PN), and radical nephrectomy (RN). Fisher’s exact test was used to assess differences in treatment recommended based on VPG. Nominal logistic regression was performed to assess the magnitude of differences. Results: Of the 423 urologists who completed the survey there was an even response to both surveys (210 vs. 213). Most respondents were male (93%), married (89%) and in private practice (44%). Age and time practicing were evenly distributed and median number of nephrectomies done per year was 15. There were no significant differences in demographics between the respondents of the 2 surveys. When comparing AS, ABL, PN, and RN the only vignette that differed based on VPG was question 3 (p = 0.019). Comparison of any NSS vs. RN in question 3 showed male VPG was 1.67 times more likely to be recommended RN (p = 0.040). Urologist gender had no effect on these findings. Conclusions: In this survey study of practicing urologists we found that male patient gender increased recommendations for radical surgery and less nephron sparing strategies in a hypothetical older patient with a localized renal mass. Provider biases do not appear to be solely responsible for gender disparities seen in the treatment of a localized renal mass.
Phase II study of sequential first-line pazopanib (PAZ) followed by everolimus (EVE) in patients (pts) with advanced or metastatic renal cell carcinoma (RCC) (CATChEz Study).
Authors: de Souza Paul L. , Wong Shirley , Sewak Sanjeev , Kotasek Dusan , Keam Bhumsuk , Chung Jinsoo , Erbeck Noelle , Han Jackie , Dezzani Luca , Ahmad Qasim , Mainwaring Paul N.
Published: February 2018

648

Background: EVE following failure of sorafenib or sunitinib for RCC was first approved by the FDA in 2009. CATChEz (NCT01545817) was designed to test the activity of EVE following first-line PAZ in pts with advanced or metastatic RCC who had not received prior systemic therapy. Methods: From 2012 to 2016, pts received first-line PAZ followed by EVE until progressive disease (PD), death, unacceptable toxicity, consent withdrawal, or study termination. Pts with PD during or within 6 months of stopping PAZ were eligible for EVE. Pts off study treatment were evaluated for PD, survival, and updates on anticancer treatment every 8 weeks until death or end of study. The primary efficacy endpoint was median progression-free survival (mPFS) for the second-line EVE treatment period; secondary endpoints included other survival measures, and safety evaluations were for second-line EVE and grade 3/4 toxicities attributable to PAZ and EVE. Results: Of 74 pts who started first-line PAZ, 38 received ≥1 dose of second-line EVE. The primary endpoint of mPFS from the start of second-line EVE and the secondary endpoint of mPFS with first-line PAZ (Table) were consistent with previous reports; no unexpected adverse events (AEs) were reported. All pts had ≥1 treatment-emergent AE, 83.8% had grade ≥3 AEs, and 71.6% had serious AEs. Of 34 total deaths, 29 were due to PD and 5 were due to AEs (2 related to EVE [lower respiratory tract infection; pulmonary sepsis]; 3 unrelated to study treatment). Conclusions: Efficacy and safety outcomes were consistent with published phase III data. The CATChEz study supports sequential first-line use of PAZ followed by EVE for the treatment of pts with advanced or metastatic RCC. Clinical trial information: NCT01545817. [Table: see text]
Correlation between depression/anxiety and somatic circulating tumor DNA (ctDNA) alterations in patients with metastatic renal cell carcinoma (mRCC).
Authors: Bergerot Cristiane Decat , Bergerot Paulo Gustavo , Clark Karen L. , Loscalzo Matthew J. , Lanman Richard B. , Banks Kimberly , Pal Sumanta K.
Published: February 2018

649

Background: A correlation between depression/anxiety and survival has been established in patients (pts) with mRCC (Cohen et al PLoS One 2012). We hypothesize that frequently encountered genomic alterations (GAs) in mRCC may identify pts with these psychological disorders. Methods: Data was obtained from pts with mRCC who received ctDNA profiling as a part of routine clinical care at progression using a CLIAA-certified platform evaluating 73 genes. Genomic alterations (GAs) were pooled for the entire cohort. ICD-9 diagnoses corresponding to anxiety and depression (300 and 311, respectively) were derived from detailed chart review, including review of established diagnoses and medication history. The chi-square test was used to determine the association between frequent GAs (those occurring in ≥5% of the study population) and the presence of depression and anxiety. Results: ctDNA results from 52 pts with mRCC were assessed (gender: 69.2% M, 30.8% F; average age: 58; histology: 84.6% clear cell, 15.4% non-clear cell). The most commonly used 1st-line treatment was sunitinib (46.1%). GAs were detected in 55.8% of pts. The most frequent GAs in the overall cohort included TP53 (21.1%), VHL (17.3%) and EGFR (7.7%). 5 and 8 pts were coded as having depression and anxiety, respectively. The average number (range) of ctDNA alterations detected was 1.1 (0-4) in patients with depression/anxiety and 1.6 (0-10) in those without (P = 0.001). The presence of VHL mutation was found to occur exclusively in pts with no depression/anxiety (P = 0.05), while 13 patients (25%) lacking VHL GAs had these psychological disorders. Conclusions: The absence of VHL alterations have been associated with poorer survival in pts with RCC (Patard et al Int J Cancer 2008), and our findings suggest that these patients may further have higher rates of depression/anxiety. Our data imply that patients bearing mutations in VHL may a prime target for early psychosocial interventions.
Activity of third line (3L) therapy in patients with metastatic non-clear-cell renal cell carcinoma (mnccRCC).
Authors: Guida Annalisa , Le Teuff Gwénaël , Colomba Emeline , Silva Carolina Alveosta , Salviat Flore , Baciarello Giulia , Derosa Lisa , Loriot Yohann , Fizazi Karim , Di Palma Mario , Massard Christophe , Escudier Bernard , Albiges Laurence
Published: February 2018

650

Background: Medical treatment of patients (pts) with mnccRCC remains uncertain, with no established standard treatment. In addition, no data on late line of treatment have been reported. The aim of this study was to investigate clinical outcome for patients receiving 3L therapy in mnccRCC Methods: Retrospective data analysis was performed using the IGRECC (Institut Gustave Roussy REnal Cell Carcinoma) database to describe clinical features and outcomes of 3L therapy in mnccRCC pts. Kaplan Meier estimation was applied for progression-free survival (PFS) and overall survival (OS) Results: Out of all pts with mRCC treated with a targeted therapy from 2005 to 2016, 202/1027 (20%) had mnccRCC. 117 (58%) received 2L therapy and 62 (30%) received 3L therapy. These pts had papillary RCC (61%), unclassified RCC (19), Xp11translocation renal cell carcinoma (13%) and chromophobe tumors (7%). The most common 3L therapies were: everolimus (29%), sorafenib (18%), other drugs in clinical trials (16%), sunitinib (11%), axitinib (10%) and cabozantinib (10%). Baseline characteristics are displayed in Table 1. With a median follow-up of 47 months (mo) (min: 0.7 max: 74), the median PFS is 5 mo (95%CI 2.7 - 5.8) and the median OS is 11.7 mo (95%CI 10 - 20). Pts with a favourable, intermediate and poor risk International Metastatic Renal Cell Cancer Database Consortium (IMDC) score had a median OS of 21 mo (95%CI 8 – NR), 11.9 mo (95%CI 10 – 25), and 6.2 mo (95%CI 2 – 8), respectively (p < 0.0001). One patient (2%) obtained a partial response and 26 pts (51%) achieved a stable disease, among 51 evaluable pts Conclusions: This is the first report investigating the impact of 3L systemic therapy in a rare population. Selected pts could benefit of more lines of therapy and IMDC score appears to stratify well prognostic groups, especially poor risk patients. [Table: see text]
Integrating a paradigm shift into treatment of renal cell cancer: Effect of online CME on oncologists' knowledge and competence.
Authors: Herrmann Tara , Warren Charlotte , Kadkhoda Haleh , Pacheco Erin , McDermott David F.
Published: February 2018

651

Background: The objective of this study was to determine the effect of online, case-based, continuing medical education (CME) on the knowledge and competence of oncologists regarding the management of metastatic renal cell cancer (mRCC). Methods: Oncologists participated in a text-based online CME activity composed of 2 patient cases with interactive questions. Evidence-based educational feedback was provided following each response. Three multiple-choice knowledge/competence and 1 self-efficacy question were selected from the set of intra-activity questions to be repeated after participation. These were used to assess the impact of the education in the form of a repeated pairs, in which each participant served as his/her own control. The analysis included: For all questions combined, McNemar’s chi-square test assessed the differences from pre- to post-assessment; P values <.05 are considered statistically significant; Effect size was calculated using Cramer’s V by determining the change in proportion of participants who answered questions correctly; The activity launched online 9/2016 and data collected through 10/2016. Results: Upon completion of the activity, an improvement was observed in oncologists’ ability to: Identify the most appropriate evidence-based regimen for a patient with mRCC that has progressed on a first line TKI (60% vs 18%, P =0.019); Recognize the symptoms of an irAE in a patient receiving an immune checkpoint inhibitor (55% vs 85%, P <0.001); Elicit patient preferences, goals, and values to help decide the best course of action in their care and disease management (26% vs 83%, P <0.001); Feel more confident in selecting the most appropriate option for a patient with mRCC whose disease has progressed on therapy (+17%). Conclusions: An online, interactive, case-based CME activity improved the knowledge/competence of oncologists, showing that unique educational methodologies and platforms, available on-demand, can be effective tools for advancing clinical decision making in the rapidly changing environment of mRCC disease management. Additional studies are needed to assess whether improved aptitude translates to improved performance during clinical practice.
Rheumatologic immune-related adverse events (irAE) in patients (pts) with genitourinary (GU) malignancies treated with immune checkpoint inhibitors (CPI).
Authors: Ornstein Moshe Chaim , Calabrese Cassandra , Wood Laura S. , Kirchner Elizabeth , Tyler Allison Janine , Profusek Pam , Allman Kimberly D , Kontzias Apostolos , Grivas Petros , Garcia Jorge A. , Calabrese Leonard , Rini Brian I.
Published: February 2018

652

Background: Rheumatologic irAEs in pts treated with CPIs present a clinical challenge. We describe the clinical characteristics, treatment, and outcomes of rheumatologic irAEs in CPI-treated GU malignancy pts. Methods: Pts with GU malignancies who were treated with CPIs and developed grade ≥ 2 (per CTCAEv4) rheumatologic irAEs (i.e., arthralgias and myalgias) were retrospectively reviewed. Patient-, disease-, and rheumatologic-related data were collected and analyzed. Results: Twenty-three pts were identified; 19 (83%) had renal cell carcinoma (RCC) and 4 (17%) had urothelial carcinoma (UC). The majority (70%) were male; median age at diagnosis was 56 (range, 36-78). All RCC pts had clear cell histology and all had prior nephrectomy; 1 UC pt had prior cystectomy. Most RCC pts (58%) received antiangiogenic therapy prior to CPI treatment and 50% of UC pts received prior chemotherapy. CPI therapy included anti-PD-L1 (30%), anti-PD-1 (43%), and combined PD-1 / CTLA-4 antibodies (26%). Median time from CPI initiation to rheumatologic irAE was 5.1 months (range, 0.23 – 51.3). Most (74%) patients had 2-4 muscle or joint groups involved. CPI was held in in 20 (87%) pts who developed rheumatologic irAEs. Most (96%) pts were treated with prednisone. Median initial prednisone dose was 40mg/d (range, 10-90mg/d) and median duration of prednisone therapy was 43.6 weeks (range, 2.5–206). Treatment intensification with methotrexate (14%), infliximab (14%), tocilizumab (9%), and etanercept (9%) was required in some pts for rheumatologic symptom control. Of the patients whose CPI was held for rheumatologic irAEs, 30% restarted CPI therapy following symptoms improvement, 15% switched to a subsequent therapy, and 55% have an ongoing sustained response to therapy (median 9.1 months; range, 0.63 - 46.1) despite no subsequent anti-cancer therapy. Conclusions: Rheumatologic irAEs in CPI-treated GU malignancy pts vary in timing of presentation, severity, and treatment. Multidisciplinary teams that include a rheumatologist are critical for optimal pt management. Larger pt populations are needed to assess the predictive/prognostic impact of these irAEs on outcome.
A cost-benefit analysis for sonographic screening for renal tumors.
Authors: Roizman Shmuel , Leshno Moshe , Haifler Miki , Rappaport Yishai Hode , Zisman Amnon
Published: February 2018

665

Background: In the last 2 decades, the rates of metastatic Renal Cell Carcinoma (RCC) at diagnosis declined from 33% to 17%This fact is attributed to massive penetration of cross sectional imaging leading to a marked stage migration. The cost of targeted therapy for metastatic RCC patients is very high. These trends led us to hypothesize that screening for RCC with ultrasound may be cost effective. Objective: To assess the cost effectiveness of screening with ultrasound for renal tumors in the general population over 60 years of age. Methods: Using the Markov model, a mathematical framework was set up describing the course of disease with and without screening for RCC using abdominal ultrasonography. Quality Adjusted Life Year (QALY) and financial costs were the outputs of the model. Results: Average costs for the screening strategy was 137.4 U$ and for non-screening was 31.4 U$. Screening and non-screening strategy would add an average of 21.7396 and 21.7385 QALY, respectively. An increase of 0.001 QALY equates to Incremental Cost Effectiveness Ratio (ICER) of 86,4 U$ per QALY, Currently, the cost which is considered cost effective for 1 QALY point is approximately 27,548.21 U$. The two variables most influential on the model output were prevalence of RCC and US cost. Conclusions: To our knowledge, this is the sole cost benefit screening study performed for RCC in the targeted therapy era. Screening for renal tumors using abdominal ultrasonography at a cost of 35.81 U$ per exam is cost effective. Our findings are highly suggestive that early screening for RCC may be cost effective for preventing RCC metastatic disease and nevertheless will save lives.
A biopsy-based genomic classifier to predict biochemical failure after definitive radiation without hormone therapy in a prospective cohort of intermediate risk prostate cancer.
Authors: Chua Melvin , Murgic Jure , Hosni Ali , Salcedo Adriana , Kamel-Reid Suzanne , Berlin Alejandro , Pintile Melania , Fraser Michael , Van Der Kwast Theodorus , Boutros Paul Christopher , Bristow Robert G.
Published: February 2018

68

Background: Recently, NCCN adopted the Zumsteg-Spratt subclassification to define NCCN favorable and unfavorable intermediate-risk prostate cancer (IR-PCa). NCCN unfavorable disease is recommended to receive combination androgen deprivation therapy (ADT) and radiotherapy. To determine if genomics could help identify a subset who may safely avoid ADT, we evaluated the Decipher genomic classifier (GC) in IR-PCa treated with dose-escalated image-guided radiotherapy (DE-IGRT) alone. Methods: Our cohort comprised of 121 patients with NCCN favorable (N = 49, 40%) and unfavorable (N = 74, 60%) IR-PCa, who received 78 Gy without ADT. Diagnostic needle biopsies with the highest Gleason score (GS) and %tumor involvement were macrodissected for RNA extraction. GC scores were determined from the Decipher prostate cancer classifier assay (GenomeDx Biosciences, San Diego, CA). Primary clinical endpoint was biochemical relapse ([BCR], PSA nadir + 2ng/ml) post-DE-IGRT. We compared association with BCR against known clinicopathologic prognostic indices and the NCCN risk strata. Results: With a median follow up of 7.5y, 24 (19%) patients experienced BCR. Individual clinical indices did not predict BCR-free survival rate (BFS). NCCN risk strata was however associated with a small but significant difference in BFS (5-y 93%, favorable vs 88%, unfavourable, P = 0.046). GC scores stratified 85 (70%), 19 (16%), and 17 (14%) men into low, intermediate, and high risk of recurrence; 5-y BFS were 95%, 89%, and 59%, respectively (P < 0.001). On multivariable analysis, a hazard ratio of 4.71 (95% CI 1.81-12.28, P = 0.0015) for BCR was observed for the GC high risk group compared to low/intermediate; NCCN risk strata and intraductal variant did not achieve significance. Conclusions: In IR-PCa men treated with DE-IGRT monotherapy, Decipher GC was an independent predictor of BCR. While most men in this our cohort were stratified as NCCN unfavorable IR-PCa, the majority were GC low risk with excellent outcomes from DE-IGRT alone. In contrast, a minority with GC high risk had suboptimal outcomes, and may benefit from ADT intensification.
Outcomes of patients (pts) with metastatic clear-cell renal cell carcinoma (mCCRCC) treated with second-line (2L) vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) after first-line (1L) immune checkpoint inhibitors (ICI).
Authors: Shah Amishi Yogesh , Lemke Emily , Gao Jianjun , Chandramohan Anuradha , Campbell Matthew T. , Zurita Amado J. , Xiao Lianchun , Wang Jennifer , Corn Paul Gettys , Jonasch Eric , Sharma Padmanee , Tannir Nizar M.
Published: February 2018

682

Background: Little data exists on objective response rates (ORR), progression-free survival (PFS), and safety of 2L VEGFR-TKI after 1L ICI therapy in pts with mCCRCC. Methods: This is a retrospective study of pts with mCCRCC who received 2L VEGFR-TKI after progressive disease (PD) with 1L ICI. Tumor response was assessed by a blinded radiologist using RECIST 1.1. Descriptive statistics, the Fisher’s test, and Kaplan-Meier method were used. Results: We report on 43 pts who were treated at MDACC from 2015 till present. Median age at mCCRCC diagnosis was 59 years (range: 43-72). 33 pts had lung mets, 20 had LN mets, 14 had bone mets, and 3 had liver mets. As 1L therapy, 20 pts received nivolumab + ipilimumab, 14 received nivolumab + bevacizumab, and 9 received nivolumab. Median time on ICI therapy was 29.4 weeks. All pts had resolution of Grade 3/4 AEs from ICI and PD before initiation of VEGFR-TKI. One patient (2%) had CR, 17 pts (40%) had PR, and 25 pts (58%) had SD, leading to 100% disease control rate (DCR) as best response to 2L VEGFR-TKI. Median PFS was 10.0 months (95% CI: 7.4, NA). Estimated 1-yr overall survival (OS) was 87.5% (95% CI: 74.6 - 100). Seven pts (16%) discontinued VEGFR-TKI therapy because of AEs: Gr 3 transaminitis (3 on pazopanib), Gr 3 hand-foot skin reaction (1 on axitinib), impaired wound healing (1 on axitinib), and Gr 3 pancreatitis (1 on pazopanib, 1 on axitinib). Conclusions: In this retrospective study, we observed a 42% ORR, a 10-month median PFS, and a 100% DCR in pts with mCCRCC who received VEGFR-TKI after PD with ICI. These results inform the design of trials with 2L VEGFR-TKI after failure of ICI therapy. [Table: see text]
Oncologic and functional outcomes of radical and partial nephrecotmy in PT3A patholigically upstaged renal cell carcinoma: A multi-instituitional analysis.
Authors: Reddy Madhumitha , Bindayi Ahmet , Hamilton Zachary , Ryan Stephen , Yim Kendrick , Nasseri Ryan , Joshi Shreyas , Peyronnet Benoit , Bensalah Karim , Pruthi Deepak Kumar , Montorsi Francesco , Capitanio Umberto , Lane Brian R. , Uzzo Robert , Derweesh Ithaar
Published: February 2018

685

Background: Radical Nephrectomy (RN) has been the standard of care for complex and locally advanced renal cell carcinoma (RCC). Efficacy of PN in the setting of pT3a pathologic upstaged disease is controversial. We compared oncologic and functional outcomes of RN and PN in patients with upstaged pT3a RCC. Methods: Multicenter retrospective analysis of patients with cT1−2N0M0 RCC undergoing RN or PN upstaged to pT3a postoperatively. Primary outcome was Overall Survival (OS), with secondary outcomes being Recurrence Free Survival (RFS) and eGFR < 60 at last follow-up. Results: 8185 patients were analyzed (mean follow up 48 months). 945 (11.5%) were upstaged to pT3a [686 (72.6%) RN, 243 (25.7%) PN]. Logistic regression analysis showed that increasing age, decreasing BMI, increasing intraoperative EBL, and positive margin increased the OR of all-cause mortality (all p < 0.05, Table). Kaplan Meier analysis (KMA) revealed 5−year OS for PN cT1→pT3a, RN cT1→pT3a, PN cT2→pT3a, RN cT2→pT3a of 64%, 65.2%, 56.4% and 55.2% respectively (p = 0.059). KMA revealed 5−year RFS for PN cT1→pT3a, RN cT1→pT3a, PN cT2→pT3a, RN cT2→pT3a of 79%, 74%, 70% and 51% respectively (p < 0.001). PN was associated with a decreased risk of GFR < 60 at follow up (39.6% vs. 59.5% for RN, p = 0.008) Conclusions: PN did not adversely affect oncologic outcomes in select patients who are upstaged to pT3a RCC from cT1 or cT2 disease, and may provide renal functional benefit. Improvements with respect to RFS for PN are most likely driven by selection bias. [Table: see text]
Level of preoperative CRP as an independent predictor of survival in patients after nephrectomy for renal cell carcinoma: Long-term outcomes.
Authors: Saon Md , Patil Dattatraya H , Ding Tiffany , Kim Frances Y , Torlak Mersiha , Ogan Kenneth , Master Viraj A.
Published: February 2018

687

Background: Preoperative C- Reactive Protein (CRP) has predictive value for metastasis development and mortality in renal cell carcinoma (RCC). However, the predictive potential of preoperative CRP at presentation on survival after nephrectomy remains unclear. This study investigates the prognostic value of preoperative CRP on overall long term survival in RCC patients post-nephrectomy. Methods: 683 post-nephrectomy patients for localized clear cell RCC were evaluated from 2005-2017 to investigate preoperative CRP’s prognostic value on overall survival. Cohort was divided into 3 groups based on preoperative CRP (≤ 10, 10-100, > 100 mg/L). Kaplan-Meier curve and Cox proportional hazards models evaluated the predictive value of preoperative CRP in addition to established covariates. Results: Mean age was 59±12 years. 81 (11.6%) patients were deceased at the end of follow-up. T-stage distribution of cohort as follows: T1 = 444 (65%), T2 = 38 (6%), T3 = 197 (29%), and T4 = 4 (1%). Log Rank test of the Kaplan–Meier estimates of survival probability in RCC patients stratified by preoperative CRP revealed significant difference (p-value < 0.001). Per Cox models, high preoperative CRP values were associated with higher mortality (P < 0.001), higher T Stage (P < 0.001), Fuhrman Grade (P < 0.001), fat invasion (P < 0.001), and necrosis (P < 0.001). Multivariable model identified high preoperative CRP ( > 100) as an independent predictor of survival compared to low-to-normal (HR: 2.1, 95%CI: 1.00-4.23, p-value-0.05). 5-year survival of patients with CRP > 100 was 43%. Conclusions: Preoperative CRP could potentially be used as an independent predictor of overall survival post nephrectomy in patients with RCC. Higher CRP values are associated with higher mortality in such patients.
Association of preoperative neutrophil-to-lymphocyte ratio with immune populations in the tumor microenvironment of patients with clear cell renal cell carcinoma.
Authors: Sanchez Alejandro , Liu Ming , Nixon Briana , Ghanaat Mazyar , DiNatale Renzo , Blum Kyle A , Russo Paul , Reuter Victor E. , Li Ming , Hakimi A. Ari
Published: February 2018

688

Background: Currently, there are no blood biomarkers that reflect the composition of immune cells in the tumor microenvironment (TME) of patients with clear cell renal cell carcinoma (ccRCC). High pre-operative neutrophil-to-lymphocyte ratio (NLR) is associated with adverse oncologic outcomes in ccRCC. However, how NLR relates to the immune cell composition in the TME is not well understood. Methods: We performed flow cytometry on tumor and adjacent normal renal tissue from a prospective cohort of patients who underwent surgery from 6/2015-7/2017. Immune cell populations, as a percent of total CD45+, were compared to baseline age, sex, body mass index (BMI), SSIGN score, sarcomatoid differentiation, and AJCC stage (I-IV). NLR was calculated using pre-operative absolute neutrophil-to-lymphocyte counts and further categorized as inflamed if NLR was ≥ 3. Correlations between continuous variables were performed using Spearman’s rank correlation. Comparisons of means were made using the Wilcoxon signed-rank test. Results: Among 48 patients, 32 (71%) were male, median age was 59 (IQR 52-66), BMI of 38.5 (IQR 26-32.6), SSIGN score of 8 (IQR 5-12), 9 (20%) had sarcomatoid differentiation, and 20 (44%) had metastases at presentation. No correlations were found between age, BMI, and different immune cell populations or NLR. A higher ratio of tissue resident (CD8a+CD49a+CD103+) to circulating (CD8a+CD49a-CD103-) CD8+ T-cells in the TME was associated with increasing stage at presentation (p = 0.02). Inflamed patients had similar total CD45+, CD8+ T cell, CD4+ T cell, and macrophage immune infiltration. However, inflamed patients had a higher proportion of CD8+ Tres infiltration (p = 0.04) and a trend towards higher neutrophil infiltration (p = 0.15). Conclusions: A higher proportion of resident CD8+T-cells correlated with advanced disease at presentation. NLR may reflect a change in the type of CD8+T cell population found in the TME. This population of CD8+ T-cells, and NLR as a possible biomarker should be validated and further investigated in a larger cohort of patients. Funding: Ruth L. Kirschstein Research Service Award T32CA082088 (A.S., M.G.)
Evaluation of preoperative C-reactive protein: Albumin ratio in patients with clear cell renal cell carcinoma.
Authors: Patil Dattatraya H , Williams Sierra , Torlak Mersiha , Alemozaffar Mehrdad , Lay Aaron , Pattaras John , Kucuk Omer , Carthon Bradley Curtis , Bilen Mehmet Asim , Ogan Kenneth , Master Viraj A.
Published: February 2018

690

Background: Multiple inflammatory markers have been evaluated in predicting preoperative risk in patient’s undergoing curative nephrectomy for Clear cell renal cell carcinoma. We propose that ratio of C-Reactive Protein to albumin (CA-ratio) would prove to be a good prognostic indicator for assessment of overall survival and comparable to established nomograms in clear call RCC. Methods: Patients that underwent nephrectomy for localized clear cell RCC between 2007 and 2016 were retrospectively identified. The optimal threshold for individual biomarkers among the panel was determined using grid search methodology, receiver operating characteristic (ROC) analysis, and sensitivity-specificity trade-off analysis. Prognostic value of CA-ratio was analyzed using the Kaplan-Meier method and Cox proportional regression models. ROC and chi-square analyses were performed to compare the predictive ability of CA-ratio to SSIGN, and UISS. Results: Among the 433 clear cell RCC patients treated with nephrectomy, mean age at surgery was 58.4±12, and mean BMI was 30.6±6.8. 158 (36.5%) had CA-ratio < 0.1, while 164 (37.9%) were between 0.1-0.2, and 111 (25.6%) were 0.2+. Pathological T-stage was distributed as follows: T1: 294 (67.9%), T2: 29 (6.7%), T3: 106 (24.5%), and T4: 4 (0.9%). Overall, 60 (13.9%) patients died before end of the follow-up. Area under the curve (AUC) for CA-ratio was 0.72, comparable to SSIGN (AUC 0.73, p = 0.12). On multivariate COX proportional hazards analysis, patients with ratio 0.2 or more were more likely to die compared to patients with ratio < 0.1 [HR:3.45 95%CI:1.68-7.10, p = < 0.001], while adjusting for T-stage, grade, necrosis, and age. Conclusions: CA-ratio is an cost-effective , independent and significant predictor of overall survival in clear cell RCC with accuracy at least as good as other established prognostic tools including SSIGN and UISS. [Table: see text]
National determinants of active surveillance among patients with clinical stage 1A kidney tumors.
Authors: Lu Amanda , Nguyen Kevin , Nolte Adam C , Alimi Oriyomo , Hsiang Walter , Ghabili Kamyar , Syed Jamil , Shuch Brian M. , Leapman Michael
Published: February 2018

694

Background: Active surveillance (AS) has been increasingly recognized as a viable management strategy for patients with small renal masses (SRM). To better understand the contemporary management landscape of SRMs we examined practice patterns in a nationally representative cancer database. Methods: We identified patients with clinical T1a renal masses within the National Cancer Database (NCDB) between 2010 to 2014. Patients were classified according to initial management received including AS, surgery, ablation, or other treatment. We characterized time trends in the use of surveillance versus definitive therapy and examined clinical and socio-demographic determinants of AS among patients with small renal masses using multivariate logistic regression models. Results: We identified 59,189 patients who satisfied the inclusion criteria. Of the total cohort, 1,733 (2.9%) individuals received initial management with AS, while 57,456 (97.1%) received definitive treatment. There was a slight increase in initial management with surveillance however rates remained less than 5% in all years. On multivariate analysis, patient age (OR: 1.08, 95% CI 1.08-1.09), treatment at an academic center vs. community center (OR: 2.05, 95% CI: 1.83-2.29), and African American vs. Caucasian race (OR: 1.56, 95% CI:1.35-1.80) were independently associated with use of active surveillance. Moreover, regional-level differences were observed with the highest utilization of AS in the West North Central census division. Conclusions: Based on cancer registry data, national utilization of AS for SRMs remains very low, and we observed clinical and facility-level differences. Further investigation is warranted to better understand the factors underlying management for patients with SRMs.
Single center validation of neutrophil-to-lymphocyte ratio in localized and metastatic clear cell renal cell carcinoma.
Authors: Melnick Kevin Richard , Patil Dattatraya H , Khan Amir Ishaq , Kim Frances Y , Torlak Mersiha , Bilen Mehmet Asim , Kucuk Omer , Carthon Bradley Curtis , Filson Christopher Paul , Ogan Kenneth , Kissick Haydn T. , Master Viraj A.
Published: February 2018

696

Background: The neutrophil-to-lymphocyte ratio (NLR) has been evaluated as a serum marker of inflammation and oncologic prognosis. In renal cell carcinoma (RCC), a higher preoperative NLR is associated with aggressive clinicopathologic features and is an independent predictor of poor survival. This study builds upon our institution’s prior work with the NLR in metastatic RCC and examines a larger validation cohort that includes localized disease. It also compares the predictive power of the NLR to established kidney cancer prognostic scores. Methods: Our kidney cancer database provided patients with clear cell RCC who underwent nephrectomy from January 2001 to June 2017 and had a documented preoperative NLR within 15 days prior to surgery. The optimal threshold of NLR was determined using receiver operating characteristic (ROC) curve and sensitivity-specificity trade-off analysis. Kaplan-Meier curves and logistic regression analysis were performed to assess the significance and independence of preoperative NLR in predicting OS. Finally, the prognostic ability of NLR was compared to current prognostic scores through chi-square analysis of their respective c-indices. Results: The 441 patient cohort was comprised of 361 patients with localized and/or regional disease and 80 patients with distant metastases. NLR values among all participants ranged from 0.4 to 74.0 (median 3.1). ROC analysis defined an optimal preoperative NLR threshold of 3.5. On multivariate analysis, after adjusting for clinicopathologic features and distant metastatic disease, a NLR ≥ 3.5 was found to be a significant and independent predictor of overall survival (HR = 1.41, 95% CI 1.05-1.91 & p value = 0.024). Our data also revealed no statistically significant difference between the c-indices of NLR and the UISS, SSIGN, or Leibovich scores in predicting survival. Conclusions: In our validation cohort of patients with both metastatic and non-metastatic clear cell RCC, our data show that a preoperative NLR ≥ 3.5 is a significant and independent predictor of overall survival in patients undergoing nephrectomy and is comparable to other established prognostic tools in RCC.
Validation of a novel preoperative inflammatory score in localized, clear cell RCC.
Authors: Melnick Kevin Richard , Patil Dattatraya H , Khan Amir Ishaq , Kim Frances Y , Bilen Mehmet Asim , Carthon Bradley Curtis , Kucuk Omer , Filson Christopher Paul , Ogan Kenneth , Kissick Haydn T. , Master Viraj A.
Published: February 2018

697

Background: A previously created and analyzed composite renal cell carcinoma (RCC) inflammatory score composed of preoperative serum markers was found to be a significant and independent predictor of overall survival in RCC with accuracy at least as good as other established prognostic tools. The aim of our study was therefore to validate the prognostic significance of this novel score in a new, independent cohort of localized clear cell RCC patients. Methods: A new cohort was randomly selected out of our nephrectomy database from a group of patients with localized clear cell RCC, who underwent nephrectomy from March 2007 to June 2017. Biomarker composition, cutoffs, and calculations of the RCC inflammatory score were accurately recreated from the previous publication. The final score was the sum of points accrued for each biomarker, ranging from 0-10, followed by stratification into baseline (0), low (1-3), intermediate (4-6), and high-risk (7-10) groups. ROC and chi-square analysis were performed to compare the prognostic ability of this novel score to SSIGN, UISS, mGPS, and Leibovich Scores. Impact on overall survival was analyzed with multivariate logistic regression analysis. Results: 252 patients were included in the study. On multivariate analysis, after adjusting for confounding variables, a “high-risk” RCC inflammatory score proved to be an independent and significant predictor of increased mortality (HR = 9.65, 95%CI 1.06-87.79, p = 0.044). At median follow up time, only 45% of high-risk score patients were alive compared with 89-98% of all other patients. Chi-square analysis of c-indices for the RCC inflammatory score and current prognostic scores revealed no statistically significant difference in prognostication of overall survival. Conclusions: Concordant with our previous data, this study reveals that a high-risk RCC inflammatory score is an independent and significant predictor of overall survival in localized clear cell RCC with comparable accuracy to accepted prognostic tools. Distinct from the original study, the high-risk group displayed an even greater association than previously shown, but the intermediate-risk group was no longer significantly different from baseline risk.
Clinical features, treatment, prognosis, and outcome of 47 patients with pure squamous cell carcinoma of the prostate.
Authors: Brunnhoelzl Daniel , Wang Jue
Published: February 2018

7

Background: Pure squamous cell carcinoma of the prostate is a rare entity. Data regarding clinical features, management, and treatment outcomes are limited. As such, management of this cancer has been variable throughout the reported literature, and with limited success. Methods: A systematic review of the literature and secondary data analysis was performed to characterize clinical features, management, and survival outcomes. Results: In total, 47 cases of histologically-confirmed pure squamous cell carcinoma of the prostate were included in analysis. Pure squamous cell carcinoma of the prostate is a disease of older males with mean age at diagnosis of 68.5 years (range 42-85). Urinary obstruction was reported as a presenting symptom in 60% of cases. PSA was usually normal with a mean value of 1.6 (n = 11). The disease was metastatic at diagnosis in 32% of patients among cases that stage was reported (n = 31). The most common sites ( > 30%) of distant metastases are bone and lymph nodes. Metastasis to lung, liver, and brain were 20%, 7%, and 7%, respectively. In terms of management, chemotherapy was given in 28% of cases, radiation in 30%, and prostatectomy in 25.5%. Hormone therapy was rarely attempted (4%). Metastatic disease was associated with a significant decrease in survival when compared to localized disease, p = 0.006. Surgical management was associated with significantly increased survival, p = 0.041. Overall 1-year survival was 32%, while 3-year survival was 9%. Conclusions: Squamous cell carcinoma of the prostate has an aggressive clinical course and is associated with poor prognosis. There is urgent need for early detection and the development of novel treatment options.[Table: see text]
Multivitamin use and risk of prostate cancer recurrence: Data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE).
Authors: Van Blarigan Erin , Kenfield Stacey A. , Cedars Benjamin E , Broering Jenny , Cowan Janet E. , Carroll Peter , Chan June M.
Published: February 2018

70

Background: Multivitamin (MV) use is common among men with prostate cancer (PCa). Yet, data on MV use and risk of PCa recurrence are limited. Methods: We conducted a prospective study among 1,373 men with non-metastatic PCa to examine whether MV use after diagnosis was associated with risk of recurrence. Participants completed a comprehensive lifestyle survey a median of 2 y after diagnosis and were followed through 2016. We defined an event of recurrence as the first of the following: PCa death, bone metastasis from PCa, biochemical recurrence, or initiation of secondary treatment. Multivariate Cox Proportional Hazards regression models were used to calculate hazards ratios (HRs) and 95% confidence intervals (CI) for the association between MV use and PCa recurrence. We adjusted for time between diagnosis and the survey, age at diagnosis, Gleason grade, clinical T-stage, PSA at diagnosis, smoking, BMI, walking pace, and primary treatment. We also explored whether age at diagnosis, BMI, time since diagnosis, smoking, or clinical features (grade, stage, treatment) modified the association between MV use and recurrence. Results: We observed 142 events of PCa recurrence over a median follow-up of 10 y; 858 (62%) men were current MV users, 216 (16%) were past users, and 299 (22%) were never users. Overall, MV use was not associated with risk of PCa recurrence (current vs. never HR: 0.69; 95% CI: 0.45, 1.07; p-trend: 0.09). However, long-term MV users (≥10 y; n = 396) had a 56% lower risk of PCa recurrence compared to never users (HR: 0.44; 95% CI: 0.25, 0.78; p-trend: 0.006). Additionally, treatment modified the association between MV use and risk of PCa recurrence ( p-interaction: 0.02). Among the 845 men who had a radical prostatectomy (RP), current MV users had a 44% lower risk of PCa recurrence compared to past/never users (HR: 0.56; 95% CI: 0.34, 0.91; p-value: 0.02). MV use was not associated with risk of PCa recurrence among the 441 men who did not have a RP. Conclusions: Long-term MV use may be associated with lower risk of PCa recurrence.
What is the most important predictor of renal function after opened and robotic partial nephrectomy? A propensity score matched study.
Authors: Nguyen Ngoc Ha , Joung Jae Young , Lee Sangchul , Lee Hakmin , Yu Young Dong , Jeong Chang Wook , Hong Sung Kyu , Lee Sang Eun , Byun Seok-Soo
Published: February 2018

701

Background: This study was designed to investigate the parameters that predict the short term and long term renal function after opened partial nephrectomy (OPN) and robot-assisted partial nephrectomy (RPN). Methods: Medical records of 896 patients who underwent OPN and RPN between Feb 2004 to Apr 2017 at our institution were retrospectively reviewed. The propensity scores matching between of OPN and RPN group were performed with a ratio of 1:1. Postoperative outcomes were compared and multivariate logistic regression was performed to identify the parameters influencing acute kidney injury (AKI) and chronic kidney disease (CKD) progression. Results: No significant differences of preoperative characteristics were observed between two study groups after propensity score matching. RPN was significantly associated with longer warm ischemic time (WIT) (p < 0.001); yet, estimated blood loss (EBL), positive surgical margin (PSM) rate, major postoperative complication and CKD progression were significantly lower in RPN group (p values were < 0.001; 0.033; < 0.001; < 0.001 and 0.005 respectively). Multivariate analysis exhibited RPN is more favorable than OPN in terms of preserving renal function. Patients with a higher baseline estimated glomerular filtration rate (eGFR) were significantly associated with greater risk of AKI (OR = 1.036; 95% CI of OR 1.021-1.052; p < 0.001), but reduced risk of CKD progression (OR = 0.975; 95% CI of OR 0.955-0.994; p = 0.011). Other independent predictors of CKD progression included WIT (p = 0.025), age (p = 0.035), higher BMI (0.041) and diabetes mellitus history (p = 0.035). Conclusions: Age, BMI, diabetes mellitus history, baseline eGFR and WIT were the independent predictors of CKD progression after PN. RPN is more favorable than OPN for reducing EBL, PSM, major postoperative complication and renal function preservation.
Creation of a tissue expression biomarker-augmented prognostic model for patients with metastatic renal cell carcinoma.
Authors: Bhindi Bimal , Lohse Christine M. , Cheville John C. , Mason Ross , Tollefson Matthew K. , Harrington Susan , Dong Haidong , Parker Alexander S. , Boorjian Stephen A. , Thompson Robert Houston , Leibovich Bradley C.
Published: February 2018

703

Background: Clinical and pathologic factors alone have limited prognostic ability in patients with metastatic clear cell renal cell carcinoma (ccRCC). We sought to determine if tissue biomarkers, along with our previously reported clinical metastases score, can be used to predict cancer specific survival (CSS) in patients with metastatic ccRCC. Methods: Patients with metastatic ccRCC who underwent nephrectomy between 1990-2004 were identified using the Mayo Clinic Nephrectomy Registry. Sections from paraffin-embedded primary tumor tissue blocks were used for immunohistochemistry staining for PD-1, B7-H1 (PD-L1), B7-H3, Bim (downstream pro-apoptotic signaling molecule in PD-1 pathway), CA-IX, IMP3, Ki67, and survivin. CSS was the primary outcome. Biomarkers that were significantly associated with CSS after adjusting for the metastases score were used to develop a biomarker-specific multivariable model using a bootstrap resampling approach and forward selection. Predictive ability was summarized using a bootstrap-corrected c-index. Results: The cohort included 602 patients, 192 (32%) with metastases at diagnosis and 410 (68%) who developed metastases after nephrectomy. Median follow-up among survivors was 9.6 years (IQR 4.2,12.8) and 504 patients died of RCC. Bim, IMP3, Ki67, and survivin expression were significantly associated with CSS after adjusting for the metastases score and were used to develop a biomarker-specific model. High Bim (HR 1.44; 95%CI 1.16-1.78; p < 0.001), high survivin (HR 1.35; 95%CI 1.08-1.68; p = 0.008), and the metastases score (HR 1.13 per one point; 95%CI 1.10-1.16; p < 0.001) were retained as independent predictors in the final multivariable model (c-index 0.69). Conclusions: We created a prognostic model combining the clinical metastases score and two primary tissue expression biomarkers, Bim and survivin, for patients with metastatic RCC who underwent nephrectomy. External validation will be required prior to clinical use.
The diverse genomic landscape of low−risk prostate cancer.
Authors: Cooperberg Matthew R. , Erho Nicholas , Chan June M. , Feng Felix Y , Zhao Shuang , Simko Jeff , Cowan Janet E. , Lehrer Jonathan , Fishbane Nick , Alshalalfa Mohammed , Kolisnik Tyler , Chelliserry Jijumon , Margrave Jennifer , Aranes Maria , Du Plessis Marguerite , Buerki Christine , Tenggara Imelda , Davicioni Elai , Carroll Peter
Published: February 2018

74

Background: Among men with clinically low-risk prostate cancer, we have previously documented heterogeneity in terms of clinical characteristics and genomic risk scores. In this study, we aimed to study the underlying tumor biology of this patient population, by interrogating patterns of gene expression among men with clinically low-risk tumors. Methods: Prostate biopsies from 427 patients considered potentially suitable for active surveillance underwent central pathology review and genome-wide expression profiling. These cases were compared to 1290 higher-risk biopsy cases with diverse clinical features from a prospective genomic registry. Average genomic risk (AGR) was determined from 18 published prognostic signatures, and MSigDB Hallmark gene sets were analyzed using bootstrapped clustering methods. These sets were examined in relation to clinical variables and pathologic and biochemical outcomes using multivariable regression analysis. Results: 408 (96%) of biopsies passed RNA quality control. Based on average genomic risk quartiles defined by the high-risk multicenter cases, the UCSF low-risk patients were distributed across the quartiles as 219 (54%), 107 (26%), 61 (15%), and 21 (5%). Unsupervised clustering analysis of the Hallmark gene set scores revealed 3 clusters, which were enriched for the previously described PAM50 luminal A, luminal B and basal subtypes. These three clusters did not associate with existing clinical or known genomic risk characteristics, suggesting a novel and independent classification for low-risk prostate cancer. AGR was associated with both pathological (OR: 1.3, p < 0.001) and biochemical outcomes (OR: 1.5, p = 0.001 ) but the clusters were not. Conclusions: Prostate cancers that are largely homogeneously low-risk by traditional characteristics demonstrate substantial diversity at the level of genomic expression. Molecular sub-stratification of low-risk prostate cancer may facilitate better decision-making with respect to both timing and intensity of cancer surveillance and treatment.