bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic significance of perirenal fat invasion and tumor size in pT1 to pT3a renal cell carcinoma: Results of a comprehensive multicenter study of the CORONA project—Can we improve prognostic discrimination of patients with stage pT3a tumors?
Authors: Brookman-May Sabine Doris , May Matthias , Zigeuner Richard , Cindolo Luca , Shariat Shahrokh F. , Wirth Manfred , Gunia Sven ,   CORONA Group
Published: February 2017

416

Background: The renal cell carcinoma (RCC) TNM system merges perirenal fat invasion (PFI) and renal vein invasion (RVI) as stage pT3a despite limited evidence concerning their prognostic equivalence. Additionally, the prognostic value of PFI compared to pT1-pT2 tumors remains controversial. Methods: Data of 7,595 pT1a-pT3a RCC patients undergoing radical nephrectomy or nephron-sparin surgery were pooled from 12 European and U.S. centers (1999-2010). Patients were grouped according to stages and presence of PFI/RVI, i.e., pT1-2N0M0 (n=6,137; 80.8%), pT3aN0M0+PFI (n=1,036; 13.6%), and pT3aN0M0 (RVI±PFI; n=422; 5.6%). Cancer-specific survival (CSS) was estimated by Kaplan-Meier method. Univariate and multivariable Cox proportional-hazards regression models, sensitivity and discrimination analyses were conducted to evaluate the impact of clinico-pathological parameters on cancer-specific mortality (CSM). Results: Compared to stage pT1-2, patients staged pT3a were significantly more frequently male (58.9 vs. 53.1%), older (65 vs. 62.1 yrs), more often had clear cell RCC (86.1 vs. 77.7%), Fuhrman grade 3-4 (30.5 vs. 13.4%), tumor size >7 cm (39.6% vs. 13%), and less often underwent NSS (7.1 vs. 36.6%; each p<0.001). On multivariable analysis, CSM of both patients with PFI and RVI±PFI was significantly enhanced compared to pT1-2 patients (HR 1.96 and 2.14, resp.; p<0.001), whereas patients featuring PFI only and RVI±PFI did not differ (HR 0.92; p=0.48). Tumor size instead significantly influenced CSM in stage pT3a (HR 1.07; p<0.001) with a 7 cm cut-off yielding the highest c-index. Conclusions: Since the prognostic impact of PFI and RVI on CSM seems to be comparable, merging both as stage pT3a might be justified. Enhanced prognostic discrimination of stage pT3a RCC patients appears to be possible by employing a 7 cm tumor size cut-off within an alternative staging system.
Patients with metastatic chromophobe renal cell carcinoma treated with sunitinib therapy: Analysis of an international database regarding outcome and comparison to clear cell histology (mccRCC).
Authors: Keizman Daniel , Sarid David , Lee Jae-Lyun , Gottfried Maya , Maimon Natalie , Hammers Hans J. , Eisenberger Mario A. , Carducci Michael Anthony , Sinibaldi Victoria J. , Neiman Victoria , Rosenbaum Eli , Gez Eli , Peer Avivit , Mermershtain Wilmosh , Rouvinov Keren , Berger Raanan , Yildiz Ibrahim
Published: February 2017

429

Background: Sunitinib (Su) is a standard therapy (tx) for mccRCC. Data on its activity in the rare variant of metastatic chromophobe renal cell carcinoma (mchRCC) are limited by very small or heterogeneous (mixed histology with papillary type, or mixed targeted therapies) studies. We analyzed the activity of Su in a relatively large and homogenous international cohort of mchRCC pts, in terms of outcome and comparison to mccRCC. Methods: Records from mchRCC pts treated with first-line Su in 9 centers across 4 countries were retrospectively reviewed. Univariate and multivariate analyses of association between clinicopathologic factors and outcome were performed. Subsequently, mchRCC pts were individually matched to mccRCC pts. We compared the response rate (RR), progression free survival (PFS), and overall survival (OS) between the groups. Results: Between 2004-2014, 33 pts (median age 64, 45% male) with mchRCC were treated with Su as first-line tx. 76% had a prior nephrectomy. HENG risk was good 27%, intermediate 55%, and poor 18%. 33% were active smokers, and 30% users of angiotensin system inhibitors (ASIs). 55%, 27%, and 33% had lung, liver, and bone metastases, respectively. 48% had a pre-tx neutrophil to lymphocyte ratio (NLR) >3. 42% had dose reduction/tx interruption (DR/TI). Su-induced hypertension (HTN) occurred in 48%. 75% achieved a clinical benefit (partial response + stable disease), while 25% had disease progression within the first 3 months of tx. Median PFS and OS were 10 and 26 months, respectively. Factors associated with PFS were the HENG risk (HR 3.8, p=0.025) and pre-tx NLR >3 (HR 0.6, p=0.012). Factors associated with OS were the HENG risk (HR 4.27, p=0.027), liver metastases (HR 4.6, p=0.029), and pre-treatment NLR <3 (HR 0.5, p=0.04). Tx outcome was not significantly different between mchRCC pts and mccRCC pts, who were individually matched by HENG risk, nephrectomy/smoking status, pre-tx NLR, use of ASIs, DR/TI, and Su induced HTN. In mccRCC pts (p value versus mchRCC), 70% achieved a clinical benefit (p=0.58), and median PFS and OS were 9 (p=0.7) and 24 (p=0.6) months, respectively. Conclusions: In mchRCC pts, Su tx may have similar outcome to mccRCC pts.
Performance of MRI-TRUS-guided fusion biopsy to detect progression on active surveillance for low- and intermediate-risk prostate cancer.
Authors: Frye Thomas P. , Shakir Nabeel Ahmad , Abboud Steven , George Arvin Koruthu , Merino Maria J , Choyke Peter L. , Turkbey Baris , Wood Bradford J. , Pinto Peter A.
Published: February 2017

43

Background: Active surveillance (AS) is an established treatment option for men with low risk prostate cancer. Its role in intermediate prostate cancer is still being investigated. Recent studies have shown that multiparametric-MRI (mp-MRI) along with MRI-TRUS fusion-guided biopsy may better assess risk in patients eligible for AS, compared to 12-core biopsy, due to improved detection of clinically significant cancers. The objective is to determine the performance of MRI-TRUS guided biopsy for men on AS with both low and intermediate risk disease. Methods: Between 2007-2014 men on AS were included if they had complete mp-MRI and pathology data for 2 or more MRI-TRUS biopsy sessions. Fusion guided biopsy procedures consisted of MRI identified targeted biopsies as well as random 12 core biopsies. Men were allowed to participate in AS with low and intermediate risk prostate cancer, Gleason score ≤ 3+4=7. Progression was defined by patients with initial Gleason 3+3=6 to any Gleason 4, and Gleason 3+4=7 disease progressing to a primary Gleason 4 or higher. Results: 89 men met our study criteria with an average age of 62 years old (range 45-79). 75 men had low risk Gleason 3+3=6 at the outset of AS by 1st biopsy session with a median PSA 5.1 ng/ml. The other 14 men had intermediate risk prostate cancer Gleason 3+4=7 at the outset of AS and a median PSA 4.6 ng/ml. During follow-up, 25 (33%) low risk men progressed to 3+4 or above at a median of 20.6 months. Of these, 19 were found by targeted biopsy. 6 (43%) of the intermediate risk men progressed to Gleason 4+3=7 at a median of 36.8 months. 4 of these progressed on targeted fusion biopsy. In the intermediate risk men, 84 random biopsy cores were require to detect 1 progression versus 15 targeted biopsy cores to detect 1 progression. Conclusions: The majority of patients on AS who progressed were identified by MRI-TRUS targeted biopsy. Less biopsy cores are required to detect progression with targeted biopsy. These results are preliminary and a larger cohort with longer follow-up would be beneficial.
Comprehensive genomic profiling of 443 cases of renal cell carcinoma to reveal frequent clinically relevant genomic alterations.
Authors: Pal Sumanta Kumar , Ali Siraj M. , Chalmers Zachary , Karam Jose A. , Elvin Julia Andrea , Chmielecki Juliann , Yelensky Roman , Van Allen Eliezer Mendel , Lipson Doron , Wang Kai , Fay Andre Poisl , Choueiri Toni K. , Miller Vincent A. , Stephens Phil , Ross Jeffrey S.
Published: February 2017

433

Background: Despite the availability of targeted therapy, effective management of advanced RCC is an unmet medical need as treatment is not personalized and is not guided by patient-specific genomic alterations (GAs). To assess the spectrum of clinically relevant GAs (CRGAs) in advanced RCC, comprehensive genomic profiling (CGP) of clinical RCC samples was performed with the goal of informing use of existing and novel targeted therapies. Methods: DNA was extracted from 40 microns of FFPE sections from 443 consecutive patients with relapsed/metastatic RCC. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 646X for 3,230 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. The CGP assay included base substitutions (SUB), INDELs, copy number alterations (CNA) and fusions/rearrangements. CRGA were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: There were 73% male and 27% female patients with a mean age of 56 years, and the majority of cases were advanced stage with 198/443 specimens (44.6%) from metastatic sites. 400/443 patients (89%) had at least 1 GA on CGP with a mean 3.1 GA/case. 396/400 RCC harboring GA had at least 1 CRGA involving 111 individual genes with a mean of 1.32 CRGA/UC. The most common novel CRGA in order of frequency were: CDKN2A (21%), BAP1 (12%), ATM (11%), PTEN(8.5%), TSC1(8.3%), mTOR (7%), MET (6.5%), AR (5.3%), DNMT3A (5%) and TSC2 (5%). Moreover, VHL harbored a diversity of GA’s in in 49% of cases. Collecting duct carcinomas harbored an enrichment of NF2 truncating alterations (>40%), distinct from renal medullary carcinoma which did not harbor such GA. Multiple clinical antitumor responses to targeted therapies will be presented. Conclusions: Using a CGP assay capable of detecting all classes of GA simultaneously, a high frequency of CRGA was identified in a large series of patients with advanced RCC. The diversity of CRGA suggests opportunities for the rational application of existing and investigational targeted therapies, and for possible deeper characterization of histological types of RCC.
The risk of second primary cancers in clear cell and papillary renal cancer.
Authors: Hamid Muhammad Saad , Shameem Raji , Jain Rishi , Sullivan Kevin M.
Published: February 2017

446

Background: Renal cell carcinoma (RCC) survivors have an increased risk of developing second primary cancers. We sought to determine the role of RCC tumor histology for the risk of developing second primary solid tumors. Methods: The Surveillance Epidemiology and End Results (SEER) database was used to detect RCC cases diagnosed up to 12/31/2011. The Standardized Incidence Ratio (SIR) was calculated as the ratio of observed to expected cases of second primary malignancy based on incidence data in the general United States population. The two most common RCC histological subtypes were included; clear cell and papillary. The latency exclusion period from the date of diagnosis was 60 months. We investigated for the effect of latency period after initial diagnosis (5-10 years and >10 years) that may increase the risk for a second primary cancer. Results: A total of 2,669 patients with an initial diagnosis of RCC (clear cell: 2,368, papillary: 301) that developed second primary cancers were included in our analysis. There was a significantly increased risk of thyroid cancer (SIR: 2.30, p<0.05), prostate cancer (SIR: 1.12, p<0.05) and “all solid tumors” (SIR: 1.14, p<0.05) in clear cell RCC cases. Regarding latency period, thyroid cancer (SIR: 2.87, p<0.05) risk was increased in the 5-10 years latency period, but not in the >10 years latency period. Overall, in patients diagnosed with papillary RCC, tumors of the prostate (SIR: 1.30, p<0.05), lung (SIR: 1.78, p<0.05) and pancreas (SIR: 2.70, p<0.05) were increased. Exclusively in the 5-10 years latency period, the risk for developing lung cancer (SIR: 1.90, p<0.05) was significant. Conclusions: RCC histology may impact the risk for developing specific second primary solid tumors.
Angiogenic profile and pathological features in the prediction of clinical outcome of advanced renal cell carcinoma patients receiving sunitinib.
Authors: Bianconi Maristella , Scartozzi Mario , Faloppi Luca , Zizzi Antonio , D'Anzeo Marco , Giampieri Riccardo , Del Prete Michela , Bittoni Alessandro , Montironi Rodolfo , Cascinu Stefano
Published: February 2017

458

Background: Metastatic renal cell carcinoma (mRCC) ever represented a challenge in patients’ treatment, there is a wide variability in the amount and duration of response among patients. It has been previously reported how VEGF and VEGFRs SNPs could predict response to treatment with sunitinib. Tumour heterogeinity is a matter of debate in mRCC. The aim of our study is to assess if pathological features and the expression of VEGF and VEGFRs polymorphisms in tumour, metastatic, and normal renal tissues could have a role in patients’ treatment and prognosis. Methods: We enrolled 123 patients treated at our institution. We collected histologic samples of tumour, metastatic, and normal renal tissue of 92 patients with mRCC treated with first-line sunitinib. For 21 patients, all three tissues were available. A pathological revision was conducted evaluating: granular cells percentage, grading, necrosis, regressive and sarcomatoid areas, and vascularization pattern. Histologic samples were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Polymorphisms were correlated with pathological features and PFS and OS. We then analysed concordance in SPNs expression among tissues. Results: VEGF A rs833061, VEGF A rs699947, VEGF A rs2010963, and VEGR3 rs6877011 were confirmed as significant SNPs in PFS. 19 out of 21 patients presented concordance among tissues polymorphisms expression (97%). The presence of a G allele in the rs6877011 seems to correlate with a higher percentage of granular cells. The presence of C allele in rs2010963 correlates with an alterated vascularazation. Conclusions: A preliminary analysis of our data shows the predictive and prognostic value of angiogenic polymorphisms and their concordance in tumoral, metastatic, and normal tissue. Furthermore, they are correlated with the percentage of granular cells and the vascular architecture, with possible predictive and prognostic significance. Further data will be presented at the meeting.
Evaluation of major histocompatibility complex class I expression in clear cell renal cell carcinoma as a prognostic tool.
Authors: de la Calle Claire M. , Holzman Sarah A. , Sheikh Umer , Huang Jonathan H. , Kissick Haydn T. , Osunkoya Adeboya O. , Pollack Brian P. , Patil Dattatraya , Ogan Kenneth , Master Viraj A.
Published: February 2017

469

Background: After nephrectomy for clear cell renal cell carcinoma (ccRCC) approximately one-third of patients develop metastases. Yet, with currently used prognostic tools such as the TNM staging and the Fuhrman nuclear grade (FNG) system, it is difficult to accurately assess prognosis for each patient. Here, we evaluated Major Histocompatibility Complex Class I (MHCI) expression as a potential prognostic immune marker in ccRCC. Methods: Fifty-five post-nephrectomy patients that presented with localized ccRCC were included. All patients had four or more years of follow up. MHCI was stained in the tumor sections via immunohistochemistry. Then, via an automated image analysis algorithm MHCI expression was quantitated with the Positivity score, the ratio of positively stained pixels over the total number of pixels. Results: Mean MHCI positivity score of the cohort was 0.75 (SE= ±0.20). At the end of the follow-up period, the patients who were alive had higher MHCI expression (0.80 positivity score; SE ±0.14) than those who died of disease (0.62 positivity score; SE= ±0.16; t test, p<0.0001). MHCI positivity scores above the mean were associated with increased cancer specific survival (Mantel-Cox, p=0.0021). MHCI expression was higher among patients with no recurrence (0.80; SE= ±0.16) compared to those that recurred during the study period (0.70; SE= ±0.22; t test, p=0.017); and time-to-recurrence was longer in patients with above mean MHCI positivity scores (Mantel-Cox, p=0.017). Patients who were alive with recurrence had increased MHCI expression (0.81; SE= ±0.10) compared to those who succumbed to disease recurrence (0.62; SE= ±0.25; t-test, p=0.0009). No correlation was detected between FNG and tumor expression of MHCI (ANOVA, p=0.655, F=0.423) or between stage at presentation and MHCI tumor expression (ANOVA, p=0.734, F=0.311). Conclusions: With an automated high-throughput image analysis, this cohort shows that increased MHCI expression in ccRCC is associated with improved prognosis after curative nephrectomy.
Kinase gene expression profiling of metastatic tumor tissue to prioritize therapeutic targets in clear cell renal cell carcinoma.
Authors: Ghatalia Pooja , Yang Eddy Shih-Hsin , Chen Dongquan , Wei Shi , Cooper Tiffiny , Sudarshan Sunil , Naik Gurudatta , Sonpavde Guru
Published: February 2017

476

Background: Kinase inhibitors are the mainstay of therapy for patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC). Since kinases are actionable and lethal metastatic tumor tissue has not been comprehensively studied, we hypothesized that paired intra-patient kinase gene expression analysis in primary tumor (T), matched normal kidney (N) and metastatic tumor tissue (M) may help identify drivers of metastasis and potential therapeutic targets. Methods: Total mRNA isolated from macrodissected formalin fixed paraffin embedded tissue from T, N, and M from 35 pts (total 105 samples) with ccRCC underwent expression profiling for 519 kinase genes using the nCounter System by Nanostring Technologies. Digital raw counts of mRNA abundance were normalized using internal positive and negative controls as well as 7 housekeeping genes. The mean signals from N, T, and M sites were used to calculate change in gene expression, and a p value by t test <0.05 was considered significant. To identify genes unique to metastasis, kinases with significant expression in the M compared to N or T were selected. Functional analysis was conducted to identify key signaling pathways by using Ingenuity Pathway Analysis. Results: The median age of pts was 56 years and 30 were male. Fifteen pts had metastatic disease at presentation and the remaining developed subsequent metastasis. Clustering analysis for all 105 samples separated normal tissues from tumor or metastasis. The top pathways involved in the kinases overexpressed in M compared to N or T involved Pyridoxal 5'-phosphate Salvage, Salvage Pathways of Pyrimidine Ribonucleotides, NF-kB Signaling, NGF Signaling and Cell Cycle Control of Chromosomal Replication. The top kinases over-expressed in M compared to T include: EPHB2, AURKA, GUCY2C, GSG2, IKBKE, MELK, CSK, CHEK2, CDC7, and MAP3K8. Conclusions: Multiple pathways and kinase genes wereover-expressed in metastatic ccRCC, which suggests a major role for agents targeting metabolic pathways and inhibitors of kinases not currently recognized as therapeutic targets. These data warrant validation and suggest potential drivers of metastasis and actionable therapeutic targets in metastatic ccRCC.
Percentage of sarcomatoid component as a prognostic indicator for survival in sarcomatoid renal cell carcinoma.
Authors: Adibi Mehrad , Thomas Arun Z. , Borregales Leonardo , Merrill Megan M. , Sircar Kanishka , Tamboli Pheroze , Slack Rebecca , Chen Hsiang-Chun , Tannir Nizar M. , Jonasch Eric , Matin Surena F. , Wood Christopher G. , Karam Jose A.
Published: February 2017

499

Background: Renal cell carcinoma with sarcomatoid component (sRCC) is characterized by the microscopic spectrum of spindle cells within a background of RCC. The presence of sarcomatoid elements is associated with higher stage of presentation and decreased patient survival. The objective of this study is to examine the clinicopathological characteristics associated with overall survival (OS), specifically examining the percentage of sarcomatoid component (PSC) to stratify risk. Methods: We retrospectively reviewed data for all radical nephrectomy patients with pathologically confirmed sarcomatoid component from 1987−2011. All slides were re−reviewed by a GU pathologist to ascertain PSC. Patient characteristics were tabulated overall and by disease status (metastatic vs. localized). Cutpoints in the percent sarcomatoid providing a meaningful difference in OS were identified by recursive partitioning analysis (RPA) as univariate and combined with patient characteristics. Factors selected included age, gender, race, clinical stage, tumor histology, and treatment. The Kaplan−Meier method and two−sided log−rank test was used to assess differences in OS. Results: Among 186 patients with sRCC, 64 (34%) had localized and 122 (66%) metastatic disease. Patients were primarily white (76%) males (63%) with clear cell histology (73%), and did not receive neoadjuvant or adjuvant therapy (87%). The median follow−up time was 12.1 months (range, 0.1 to 242.2 months). The median OS was 12.6 months (95% confidence interval (CI) 10.7−14.9 months). Two subgroups were identified with a cut−point of 12.5% for PSC after univariate RPA. Patients with PSC ≥ %12.5 were at higher risk of death compared to patients with <%12.5 (45% vs. 61% 1 year OS; p value=0.04). Mutlivariate RPA revealed clinical stage and percent sarcomatoid were significantly associated with OS. Patients with localized disease were most likely to be alive at 1 year (74%). Among patients with metastatic disease with PSC<%42.5 had 1−year OS of 44% vs. 27% for patients with ≥%42.5 cutoff (p<0.001). Conclusions: The PSC appears to be a prognostic factor in the OS of patients with RCC, with larger percentage of involvement portending a worse survival.
Multiplatform molecular analysis of biomarkers in renal cell carcinoma.
Authors: Ho Thai Huu , Millis Sherri Z. , Doll Nancy , Gatalica Zoran , Reddy Sandeep K. , Bryant David , Joseph Richard Wayne , Vogelzang Nicholas J.
Published: February 2017

501

Background: Predictive biomarkers of response to targeted therapy are lacking in renal cell carcinoma (RCC). We evaluated a cohort of RCC patients referred for molecular profiling to identify potentially actionable recurrent molecular aberrations. Methods: 166 consecutive renal cases referred to Caris Life Sciences over 2 yrs were evaluated with central pathology review. Cases were subtyped into clear cell (ccRCC), n=100, papillary (PRCC), n=20, sarcomatoid, n=10, translocation, n=6, medullary, n=4 or unclassified, n=26. 63% of cases were metastatic. Testing included a combination of sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]), and/or gene amplification (CISH or FISH). Results: ccRCC had a 52% loss of PTEN, while PRCC had a 21% loss (p value=0.02). 100% of ccRCC with sarcomatoid features (4) showed aberrant expression of PD-L1 and were infiltrated with PD-1+ tumor infiltrating lymphocytes; 100% of 10 non-ccRCC sarcomatoids also had aberrant expression of PD-L1. Loss of PBRM1 expression was observed in 60% of ccRCC. Loss of histone 3 lysine 36 trimethylation (H3K36me3), which is associated with SETD2 mutations, was observed in 30% of ccRCC. TOP2A was overexpressed in ccRCC at 30% and in non-ccRCC at 50%. 100% of ccRCC and PRCC overexpressed EGFR; a single unclassified renal cell carcinoma did not overexpress EGFR. 50% of cases had cMET overexpression, amplification, or mutation. HER2 was not amplified or overexpressed in any RCC; a single rare HER2 mutation (R816H) was found in a collecting duct carcinoma. VHL mutations were identified in 50% of ccRCC tumors. We observed lower rates of TP53 (14%), ATM (6%), and PIK3CA(4% ccRCC, 7% PRCC) mutations compared to other cancers. Conclusions: Multiplatform molecular profiling of renal cell carcinoma identifies potential predictive biomarkers in ccRCC. The documented activity of everolimus in ccRCC (RECORD-1 trial) may be attributable to PIK3CA pathway alterations. RCC with sarcomatoid features may respond to PD1/PD-L1 targeted immunotherapies. The impact of molecular profiling in ccRCC to predict responses to currently available targeted therapy has important implications for trial design and patient selection.
Survival comparison analysis of two historical cohorts of metastatic renal cell carcinoma patients (cytokine therapy versus targeted agents): A European single-center experience over 26 years.
Authors: Hutterer Georg C. , Golbeck Silvia V. , Mrsic Edvin , Krieger Daniel , Bezan Angelika , Jesche Johanna , Pummer Karl , Zigeuner Richard , Pichler Martin
Published: February 2017

513

Background: By the approval of new targeted agents in 2006, the standard of therapy in metastatic renal cell carcinoma (mRCC) changed, since they demonstrated significantly improved progression-free survival (PFS) rates compared with interferon in phase III clinical trials. Differences in overall survival (OS) could not be proven since many patients switched to another effective substance after progression of the disease. Thus, we compared two mRCC patient cohorts in order to detect OS differences between immunotherapy and targeted therapies in a real-life population outside controlled clinical trials. Methods: Clinico-pathological data from 594 mRCC patients, operated between 1984 and 2010 at a single tertiary academic center, were evaluated retrospectively with the null hypothesis, that there is no statistically significant difference in OS of patients treated either with interferon or targeted agents. Using electronical patient records, all data regarding the beginning, duration, lines, and different forms of therapies were assessed. Patients’ cancer-specific survival (CSS), as well as OS, were assessed using the Kaplan-Meier method, compared with the log-rank test. A first analysis revealed results for the entire study cohort. Subsequently, outcome analyses were restricted to mRCC patients with clear cell histology only. Results: With respect to the complete follow-up period, our results in both analyses did not show a statistically significant OS difference between the two therapy modalities. By limiting the observation period to 5 years after treatment initiation, a statistically significantly improved median five-year OS rate (26 mo.) for clear cell mRCC patients treated with targeted agents was observed, compared with 21 mo. in the interferon group (p=0.028). Conclusions: Our results confirm the presumption of an improved OS in mRCC attributable to treatments with targeted agents compared with previous cytokine therapies.
Subcapsular prostate cancer: Identification with mpMRI and MRI/TRUS fusion-guided biopsy.
Authors: Brown Anna Mary , Sankineni Sandeep , George Arvin Koruthu , Rais-Bahrami Soroush , Wood Bradford J. , Merino Maria J , Pinto Peter A. , Choyke Peter L. , Turkbey Baris
Published: February 2017

52

Background: The subcapsular region is often under-sampled by standard 12-core transrectal ultrasound (TRUS) prostate biopsy. We retrospectively evaluated multi-parametric MRI (mpMRI) features of subcapsular prostate cancers (PCa) and their detection on MRI/TRUS fusion-guided biopsy (FgBx). Methods: All patients referred for 3T mpMRI and subsequent FgBx under an IRB-approved protocol from Jan 2010 to July 2014 were reviewed. Histologically confirmed subcapsular lesions (just inside the prostate capsule with capsular border length >> width) were identified. Impact of the FgBx on clinical management according to current National Comprehensive Cancer Network (NCCN) guidelines was evaluated, with prior status based on outside TRUS biopsy results. Results: Of 992 eligible patients, 33 had subcapsular prostate lesions on mpMRI. In this subpopulation, mean age, PSA, and prostate volume were 63 years (range 52-76), 8.4ng/mL (1.2-63), and 53 mL (12-125). The FgBx, consisting of targeted (TBx) and systematic (SBx) portions, confirmed PCa in 24 of 33 patients. Five cancers (21%) were only detected by TBx. The remaining 19 were diagnosed on both TBx and SBx, but in 5 of these 19 (26%), higher Gleason scores were found on TBx cores. The FgBx results more accurately classified patients’ NCCN risk scores, with 17 prior unknown or low risk PCa upgraded to higher risk scores (Table). Conclusions: Subcapsular lesions on mpMRI are rare but largely malignant. Most are found on 12-core SBx, but ~20% require TBx for diagnosis, and TBx more accurately grades >25% of the lesions. The FgBx may improve clinical management of patients with subcapsular PCa, since more aggressive cancer was found in 17 of 24 patients. [Table: see text] [Table: see text] [Table: see text]
Impact of timing of biochemical failure on the eventual development of clinical failure after definitive treatment with brachytherapy or external beam radiotherapy for prostate cancer.
Authors: Ciezki Jay P. , Reddy Chandana A. , Klein Eric A. , Ulchaker James , Angermeier Kenneth , Tendulkar Rahul D. , Stephans Kevin L. , Campbell Steven C. , Stephenson Andrew J.
Published: February 2017

53

Background: Late treatment failure is often considered to be a rare event. We will assess the influence of the timing of biochemical failure (bF) after definitive brachytherapy (BT) or external beam radiotherapy (EBRT) for prostate cancer on its frequency and association with clinical failure (cF). Methods: Patients with prostate cancer treated between 1996 and 2009 with at least 5 years of follow-up (N= 2,293; 1,060 EBRT, 1,233 BT) were studied in the context of an IRB-approved inception cohort study. Those with a bF were reviewed to determine the timing of bF [< 5 years after treatment (bF<5) vs. > 5 years after treatment (bF>5)] and occurrence of cF post-bF. The bF definition used was the nadir + 2.0 ng/mL version. Results: Of the total patient population, 477 (21%) were noted to have bF- 244 (11%) bF<5 vs. 233 (10%) bF>5. The median follow-up after bF for the bF< 5 group is 41 months while in the bF> 5 group it is 22 months. In the BT group, 94 (8%) failed < 5 years and 87 (7%) failed > 5 years. In the EBRT group, 150 (14%) failed < 5 years and 146 (14%) failed > 5 years. The median PSA value (ng/mL) at the time of bF for all patients, EBRT, and BT in the bF<5 group was 3.70, 3.65, and 3.80, respectively (p=not significant). The median PSA value (ng/mL) at the time of bF for all patients, EBRT, and BT in the bF>5 group was 3.01, 3.01, and 3.04, respectively (p=not significant). Overall, 53.3% of patients in the bF<5 group developed cF while 27% of patients in the bF>5 group developed a cF. The actuarial five year rate of cF for the bF <5 group was 50% vs. 38% for the bF>5 group (p= 0.028). The detection of bF and cF was closely linked to PSA testing frequency ( p < 0.0001). Conclusions: The risk of bF does not appear to decrease >5 years post treatment. Late bF (i.e. >5 years after treatment) may still result in eventual cF. While cF is less common after bF > 5 years post definitive therapy, it still affects 27% of those with bF and is strongly associated with PSA testing frequency. The lower rate of cF after 5 years may relate to the shorter follow-up time for this group.
5α-reductase from radical prostatectomy tissue and utilization of testosterone and androstenedione to produce DHT: A dual isotope method and preliminary results.
Authors: Kovac Evan , Chang Kai-Hsiung , Klein Eric A. , Sharifi Nima
Published: February 2017

58

Background: Previous work has shown that 5α-reductase prefers androstenedione (AD) in favor of testosterone (T) for dihydrotestosterone (DHT) synthesis in castration-resistant prostate cancer. Yet, 5α-reductase substrate preference in the setting of localized prostate tissue has yet to be fully elucidated. We propose a novel ex-vivo method for tracking steroid handling by the prostate and report our preliminary findings. Methods: Prostate tissue from the peripheral and transitional zones of patients who underwent radical prostatectomy (RP) for localized prostate cancer were incubated in media, along with (3H)-labeled AD and (14C)-labeled T. Media was collected after 7, 24 and 48 hours of incubation, treated with glucuronidase and high performance liquid chromatography (HPLC) was used to identify steroids tagged with either 3H or 14C. Results: In total, 11 patients were consented for tissue procurement at the time of RP. Qualitatively, both AD and T are utilized by the prostate to produce DHT. Over time, concentrations of tritiated AD decreased, while concentrations of tritiated T, 5α-androstanedione and DHT rose. Similarly, concentrations of 14C-T decreased over a 48-hour period, while AD, 5α-androstanedione and DHT increased. Conclusions: We describe a dual isotope method for characterizing androgen handling by prostate tissue from patients with localized prostate cancer, using 2-channel radiolabel detection. Preliminary results show that both AD and T can be utilized by localized prostate cancer tissue. Future work will focus on determining if different phenotypes of androgen handling exist among various patient genotypes and cancer risk groups.
18F-choline PET/CT for the assesment of pelvic lymph node metastases in high-risk prostate cancer patients.
Authors: Pinto Ivan Federico , Sandoval Camilo , Diaz Jorge Gonzalo , Vidal Alvaro Daniel , Altamirano Jaime Antonio , Vilches Roberto Mauricio
Published: February 2017

61

Background: Assesment of pelvic lymph node involvement is a major dilemma due to poor diagnostic accuracy of conventional imaging such as computed tomography of the pelvis or magnetic resonance of the pelvis. Recently incorporation of new tools such as 18F-choline PET/CT address this issue, although there are few studies in this set of patients. To evaluate the 18-choline PET/CT diagnostic accuracy for staging of pelvic lymph node involvement in patients with high risk prostate cancer. Methods: Patients with diagnosis of high risk prostate cancer according to D’Amico risk assessment criteria where staged with a 18F-choline PET/CT prior to treatment with retropubic radical prostatectomy plus superextended bilateral lymph node dissection at our institution. 18F-choline PET/CT was compared with the results of pathological analisys of lymph nodes. We calculated sensitivity, specificity, positive and negative predictive value for 18F-choline PET/CT. Results: Between January 2012 and August 2014 a total of 36 patients met the following inclusion criteria: diagnosis of high prostate cancer (cT2c or more or PSA above 20 ng/ml or a gleason score 8-10), good performance status (ECOG 0-2) and a 18F-choline PET/CT as a preoperative staging procedure. Sensitivity, specificity, positive and negative predictive value were 64%, 92%, 77% and 85% respectively. Conclusions: 18F-choline PET/CT is a non invasive procedure that provides good information regarding pelvic lymph node involvement status that is better than the results of other techniques in published series, with a higher sensitivity in our group of patients. It is highly specific which means there is a very good chance that a patient with a normal study does not have lymph node metastases when analyzed.
Radical prostatectomy versus high intensity-focused ultrasound for localized prostate cancer: A matched-pair comparison.
Authors: Pasticier Gilles , Crouzet Sebastien , Colombel Marc , Rouviere Olivier , Rabilloud Muriel , Chapelon Jean-Yves , Mege-Lechevallier Florence , Tonoli-Catez Helene , Martin Xavier , Gelet Albert
Published: February 2017

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Background: Radical prostatectomy is the gold standard treatment for localized prostate cancer. HIFU is a treatment option with promising outcomes. No randomized study is available to compare those techniques. The goal of the study was to evaluate the oncologic outcome of patients treated with HIFU and radical prostatectomy by using a matched pair analysis to compare the 2 groups. Methods: A total of 710 patients treated between 2000 and 2005 were prospectively followed in our institutional database and matched to a 1:1 basis following know prognostic variables: prostate-specific antigen (PSA) level, Gleason score, and clinical stage. After matching, 588 patients (294 in each group) were further analysed. The starts of salvage external beam radiotherapy (S-EBRT) or definitive palliative androgen deprivation therapy (ADT) were primary endpoints. Other endpoints were overall, cancer specific and metastasis free survival rates: The survival rates were calculated with Kaplan-Meier estimate Results: The seven years S-EBRT free survival rate was significantly lower after HIFU than after RP (62% versus 78%, p=0.001). The palliative androgen deprivation free rate at nine years was not significantly different between HIFU and RP (86% versus 87%, p=0.271). At nine years the overall, cancer specific and metastasis free survival rates were similar: 89%, 97%, 94 % and 89%, 97% and 97% for HIFU and RP respectively (p=0.186, 0.312, 0.107). Conclusions: Matched pair comparison of HIFU and RP has shown a higher rate of S-EBRT for HIFU. At 9 years, the rate of patients who need palliative ADT, the overall cancer specific and metastasis free survival rates were not significantly different between HIFU and RP.
Results of an online survey of physical, emotional, and practical concerns for prostate cancer survivors in the United States.
Authors: Darwish Oussama M. , Adsul Prajakta , Siddiqui Sameer
Published: February 2017

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Background: Prostate cancer survivors face numerous health concerns after treatment. The type of treatment received may have a significant impact on the physical, emotional and practical concerns of the patient. Methods: We analyzed self-reported data from the 2010 LIVESTRONG survey for people affected by prostate cancer. Survey questions were divided into 3 sections including physical, emotional, and practical concerns in the survivorship period. Survey was administered online between June 20, 2010 and March 31, 2011 on the LIVESTRONG.org website. Results: Of the 12,307 respondents, 281 males were included in the analysis based on a primary diagnosis of prostate cancer and US residency status. Mean age was 60 years (range, 41-94) and the majority were white men (90%). The 3 most common physical concerns were decrease in sexual function (70%), urinary frequency (54%) and fatigue (35%). The leading emotional concerns were fear of cancer recurrence (61%), grief about death of other cancer patients (52%) and worry about cancer genes in family members (51%). Practical concerns were cost beyond insurance coverage (90%), financial debt (40%), and inability to continue previous work (6%). One way ANOVA was conducted to detect differences in number of physical, emotional and practical concerns across types of treatment received (surgery, radiation, hormonal and combination). Significant differences were seen in number of physical (p=0.02), emotional (p=0.04) and practical (p<0.001) concerns for patients receiving different treatments (Table 1). Patient concerns also varied based on length of follow-up after treatment. Conclusions: Based on treatment type, hormonal patients have the greatest physical and emotional concerns compared to other treatment options, while surgery patients demonstrate the most practical concerns. The results of the survey illuminate the principal physical, emotional and practical concerns of prostate cancer survivors, and can assist in prioritizing and addressing major patient concerns after prostate cancer treatment.
Surgical margins and biochemical recurrence risk at 2 years for robotic prostatectomy: Comprehensive evaluation and CUSUM analysis of oncological outcomes.
Authors: Sivaraman Arjun , Sanchez-Salas Rafael , Prapotnich Dominic , Yu Kaixin , Olivier Fabien , Doudeau Christian , David Stephane , Barret Eric , Secin Fernando P. , Ingels Alexandre , Rozet Francois , Galiano Marc , Mombet Annick , Cathala Nathalia , Cathelineau Xavier
Published: February 2017

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Background: To evaluate the learning curve of Minimally Invasive Radical Prostatectomy (MIRP) in our institution and apply the cumulative summation (CUSUM) analytical technique to identify salient learning curve transition points in terms of oncological outcomes. Methods: Clinical, pathologic, and oncological outcome data were collected from our prospectively collected MIRP database to estimate Positive Surgical margin (PSM) and Biochemical Recurrence (BCR) trends during a 15 year period from 1998 to 2013. All the RPs (laparoscopic (LRP) / Robotic Assisted [RARP]) were performed by 9 surgeons. PSM was defined as presence of cancer cells at inked margins. BCR was defined as serum Prostate Specific Antigen (PSA) >0.2 ng/ml and rising or start of secondary therapy. Surgical learning curve was assessed with the application of Kaplan-Meier curves, Cox regression model, CUSUM and logistic model in order to define the “transition point” of surgical improvement. Results: We identified 5,547 patients with localized prostate cancer treated with MIRP (3,846 - LRP and 1,701 – RARP). Patient characteristics of LRP and RARP were similar. The overall risk of PSM in LRP was 25%, 20% and 17% for the first 50, 50 to 350 and >350 cases, respectively. For the same population, the 5-year BCR rate decreased from 21.5% to 16.7%. RARP started 3 years after the LRP program (after approximately 250 LRP). The PSM rate for RARP decreased from 21.8% to 20.4% and the corresponding 5-year BCR rate decreased from 17.6% to 7.9%. The CUSUM analysis showed significantly lower PSM and BCR at 2 years occurred at the transition point of 350 cases for LRP and 100 cases for RARP. In multivariable analysis, predictors of BCR were PSA, Gleason score, extra prostatic disease, seminal vesicle invasion and number of operations (p < 0.05). Patients harboring PSM showed higher BCR risk (23% vs. 8%, p < 0.05). Conclusions: Learning curve trends of MIRP in our large, single center experience showed significant reduction in PSM and BCR risk at 2 years are noted after the initial 350 cases and 100 cases of LRP and RARP, respectively.
The association of a 17-gene genomic prostate score with adverse surgical pathology and recurrence following surgery for localized prostate cancer (PCa): A comparison of African American and Caucasian patients.
Authors: Cullen Jennifer , Rosner Inger L. , Brand Timothy C. , Ali Amina , Chen Yongmei , Zhang Nan , Tsiatis Athanasios C. , Knezevic Dejan , Maddala Tara , Lawrence H. Jeffrey , Febbo Phillip G. , Srivastava Shiv , Sesterhenn Isabell , Mcleod David G.
Published: February 2017

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Background: Molecular assays can improve risk assessment for newly diagnosed PCa, but it is imperative to characterize assay performance in different racial groups, since tumor biology and clinical outcomes may vary. A racially diverse cohort of men (20% AA) with PCa in the Center for Prostate Disease Research multi-center national database was used to determine the association of GPS with outcomes in men treated with radical prostatectomy (RP) for localized PCa. Methods: Biopsy specimens from 431 men treated with RP for NCCN very low, low or intermediate risk PCa at 2 U.S. military medical centers were tested with a 17-gene RT-PCR assay to validate the association between GPS (scale 0-100) and 1) biochemical recurrence (BCR) following RP, and 2) adverse pathology (AP) at RP. BCR was defined as 2 successive PSA levels > 0.2 ng/mL. AP was defined as high-grade (primary Gleason pattern 4 or any pattern 5) and/or pT3 disease. Cox proportional hazards and logistic regression models were used. Results: GPS was obtained in 402 cases (93%), including 82 AA men. A broad range of GPS results was observed in both AA and CA men; GPS distributions were similar between AA (median GPS = 30.3; inter-quartile range (IQR): 23-38) and CA (median GPS = 30.3; IQR: 23-40); no correlation was observed between GPS and race (r = -0.04, p = 0.45). No differences in expression of individual genes or gene groups in the assay were observed between the two groups. In univariable analysis, PSA, biopsy GS and NCCN risk group were associated with BCR and AP, but race was not. The associations between GPS and clinical outcomes were similarly strong and statistically significant in both AA and CA men - BCR HR/20 GPS units = 3.0 (95% CI: 2.0-4.3) for CA vs. 3.5 (95% CI: 1.0-11.7) for AA; AP OR/20 units = 4.0 (95% CI: 2.6-6.6) for CA vs. 2.9 (95% CI: 1.2-7.6) for AA (p < 0.05 for all). Conclusions: In this cohort of patients treated in a health care system with equal access, clinical outcomes and the tumor biology measured by GPS were similar between AA and CA patients. GPS is a significant predictor of BCR and AP in men treated with RP for localized PCa in both AA and CA men.
Early radiation response between GnRH agonist versus antagonist combined with radiotherapy in high-risk prostate cancer.
Authors: Crehange Gilles , Cochet Alexandre , Cueff Adele , Martin Etienne , Maingon Philippe , Brunotte Francois , Walker Paul M
Published: February 2017

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Background: Degarelix, a GnRH antagonist, provides a very rapid and sustained testosterone suppression alongside with the VEGF pathway inhibition through the FSH receptors. This raises the question as to whether high risk localized prostate cancer (HRPCa) could respond differently to radiotherapy (RT) + Degarelix when compared with RT + GnRH agonist. Methods: 30 HRPCa patients were treated with exclusive RT combined with a GnRH agonist (n= 19) or Degarelix (n= 11). MRSI was performed before the start of hormones and 3 months after the end of RT. Choline (tumor metabolism) and citrate (healthy prostate metabolism) were quantified with MR spectroscopy and the slopes of gadolinium wash-in (SWI) and wash-out (SWO) were assessed in the peripheral zone (PZ), the central gland (CG) and the tumor with DCE-MRI. Results: At baseline, 14 patients had a T3 (46.7%) and 9 patients (30%) had a GS≥8. The median PSA values were 12.7 ng/mL [3.0-153.7] for agonists and 14.0 ng/mL [6.8-23.6] for Degarelix (p=ns). The mean prostate volumes (Pvol) were 32.0±15.5 mL for agonist and 33.0±10.0 mL for Degarelix (p=ns). The median dose of RT was 78Gy in each group, [72.0-80.0] with agonist and [70.2-80.0] with Degarelix. There were no significant differences in choline, citrate, SWI and SWO in the PZ, the CG and the tumor. At 3 months, Pvol were 20.8±8.0 mL for agonist and 21.4±6.2 mL for Degarelix (p=0.71) and the mean and median PSA values for agonist vs Degarelix were 0.5±0.8 ng/mL vs 0.1±0.1 ng/mL and 0.1 ng/mL [0.02-2.8] vs 0.1 ng/mL [0.005-0.3], respectively. Citrate was significantly decreased with Degarelix in the PZ (4.3±4.4 vs 1.1±0.8, p=0.0142), in the CG (4.0±4.0 vs 1.1±1.0, p=0.009) but not in the tumor (2.5±2.6 vs 1.7±1.9, p=0.23). Choline concentrations were similar between both groups in the PZ, the CG and the tumor. There was a trend towards a lower contrast uptake in the tumor with Degarelix (mean SWI and SWO: 134.6±56.2 s-1 vs 104.1±36.3 s-1, p=0.13 and 259.6±103.1 s-1 vs 306.1±70.4 s-1, p=0.15). Conclusions: Degarelix combined with RT offers a significant early, more profound metabolic atrophy in the prostate, but not in the tumor. There is a trend towards a lower tumor vascularization with Degarelix compared with GnRH agonists.