bluuebunny/crossref_metadata_2025 huggingface dataset:
Sunitinib and pazopanib treatment patterns and cost outcomes in Medicare supplemental-covered patients with renal cell carcinoma.
Authors: Harnett James , MacLean Elizabeth A. , Bhattacharyya Helen , Cisar Laura A. , Hoang Caroline , Mardekian Jack
Published: February 2017

485

Background: Few studies compare targeted treatments for renal cell carcinoma (RCC) so understanding real world treatment patterns and healthcare utilization may inform decision making. This study evaluated treatment naïve RCC patients initiating sunitinib (SUN) or pazopanib (PAZ) and the potential impact of administration schedules on duration of therapy (persistence) assessments using claims data. Methods: This retrospective cohort analysis used de-identified Truven Marketscan Medicare Supplemental claims data. Included patients were ≥20 years, diagnosed with RCC with ≥1 prescription (Rx) for SUN or PAZ between Oct. 2009–Sept. 2013 and continuously enrolled ≥6 months prior to and 12 months after index. Patient characteristics, treatment patterns, persistence, RCC-related and all-cause costs were evaluated. Chi-square, Student t-test, or Wilcoxon signed-rank test were used to compare groups (α=0.05). A generalized linear model was used to evaluate costs controlling for patient demographics and characteristics, index medication dose, persistence and index medication. As the recommendation for most patients receiving SUN is 4 weeks on, 2 weeks off, a sensitivity analysis was conducted imputing 42 days supply (DS) for SUN Rx with 28 or 30 DS. Results: 291 patients initiated SUN (76.6%) and PAZ (23.4%). There were no significant (NS) differences between groups in demographics, Charlson Comorbidity Index scores, or proportion with pre-index inpatient admission. Mean time from earliest RCC diagnosis to index was longer for PAZ compared to SUN (518 vs. 398 days, p<0.05). There was NS difference in mean persistence in the non-imputed (154 vs. 175 days, p=0.20) and imputed DS (182 vs. 175, p=0.69) analyses for SUN and PAZ, respectively. Adjusted mean RCC-related ($65,993 vs. $65,254, p=0.68) and all-cause ($92,121 vs. 87,962, p=0.18) costs were NS different between SUN and PAZ cohorts, respectively. Conclusions: This analysis indicates NS differences in treatment persistence or costs for Medicare Supplemental patients with RCC initiating SUN or PAZ. Understanding the implications of SUN’s dosing schedule on DS values for persistence and other calculations is critical.
Lag time to adverse events after radical prostatectomy and curative radiotherapy.
Authors: Thellenberg-Karlsson Camilla , Fridriksson Jon , Folkvaljon Yasin , Nilsson Per , Robinson David , Franck Lissbrant Ingela , Ehdaie Behdar , Eastham James Andrew , Widmark Anders , Stattin Pär
Published: February 2017

49

Background: Men who are curatively treated with radiotherapy (RT) or radical prostatectomy (RP) for localized prostate cancer have long life expectancy but data on long term complications to treatment are scarce. Methods: In the nationwide, population-based Prostate Cancer data Base Sweden (PCBaSe), we identified men who underwent RT or RP between 1997 and 2012. Date of radiotherapy and dose of radiation were reassessed in an audit. For each case five controls from the background population, matched for age and county of residence, had been identified. The National Patient Register was used to identify diagnoses and surgical procedures indicating a complication to treatment, such as urinary incontinence, lower urinary tract symptoms and gastrointestinal symptoms, up to twelve years after treatment. The incidence rate ratio of complications for men who received RT and RP relative to their matched controls was calculated and relative risks (RR) were calculated for RT vs RP adjusted for treatment year, age, Charlson comorbidity index, educational level, PSA-level, clinical T stage and biopsy Gleason score. Results: In total, 37,420 men met the study criteria, of whom 12,534 had undergone RT and 24,886 had undergone RP. There were 186,624 matched controls. The risk of receiving any of the analyzed diagnoses or surgeries at 12 years after treatment was higher after RT; RT vs RP RR 1.20 (95%CI 1.08-1.34) and RT vs RP RR 1.49, (95% CI 1.36-1.64) for the diagnoses and surgical procedures respectively. At 3 years the risk of receiving any of the analyzed diagnoses was comparable between the treatments; RT vs RP RR 1.02 (95% CI 0.91-1.16) but the risk of undergoing any of the analyzed surgical procedures remained higher after RT during the entire study period. Men who underwent RP had a higher risk of being diagnosed or treated for urinary incontinence; RT vs RP RR 0.09 (95% CI 0.04-0.19) and RR 0.04 (95% CI 0.01-0.11) for the selected diagnoses and surgical procedures respectively. Conclusions: Complications after RP mostly occurred within the first 3 years after surgery whereas complications after RT were more frequent at a later date after treatment.
Can neutrophil-to-lymphocyte ratio be used to identify patients with metastatic renal cell carcinoma who may gain greater benefit from cytoreductive nephrectomy?
Authors: Dai Daphne , Kanjanapan Yada , Kwan Edmond Michael , Yip Desmond , Lawrentschuk Nathan , Davis Ian D. , Azad Arun , Rosenthal Mark , Arifeen Shams Ul , Alam Mahmood , Gibbs Peter , Tran Ben
Published: February 2017

490

Background: Two randomized trials demonstrated survival benefits associated with cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the interferon era. However, the role of CN in the era of targeted therapies is yet to be defined. In recent years, neutrophil-to-lymphocyte ratio (NLR) has emerged as a clinically useful prognostic marker in several cancers including mRCC. In this multi-center retrospective study, we aim to assess the impact of CN in mRCC and the value of NLR in risk stratification and patient selection. Methods: Patients with de novo mRCC diagnosed between 2006 and 2012 from three large Australian hospitals were identified using an electronic database. Data regarding clinicopathological features, MSKCC risk group, NLR at the time of metastatic diagnosis, treatments received and survival were collected. NLR ≥5 was used as the cutoff for statistical analyses. Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses used the Cox proportional hazards method. Results: Our study identified 91 de novo mRCC patients. CN was performed in 46 (51%) patients. Patients who underwent CN were more likely to be younger (median age 59.0 vs. 64.6, p=0.019), and to have received systemic therapy post CN (91% vs. 76%, p=0.043). Median overall survival (mOS) was significantly improved in patients who underwent CN (23.0 mo vs. 10.9 mo, p=0.039). Patients with NLR <5 also had superior mOS (16.7 mo vs. 6.2 mo; HR 0.53; 95% CI; 0.24-0.84; p=0.013). While CN was associated with substantially improved survival in patients with both NLR <5 (mOS 31.1 mo vs. 7.0 mo; HR 0.41; 95% CI, 0.18-0.64; p=0.0009) and NLR ≥5 (mOS 10.9 mo vs. 2.3 mo; HR 0.33; 95% CI, 0.11-0.69; p=0.009), the absolute survival difference was greater in patients with baseline NLR <5. Significant survival benefits associated with CN were maintained in multivariate analyses (HR 0.31; 95% CI, 0.18-0.55; p<0.0001). Conclusions: CN is associated with significantly improved OS in de novo mRCC. The incremental survival benefit associated with CN was seen irrespective of NLR.
Analyses of the transcriptome and metabolome to elucidate the role of HIF1α in clear cell renal cell carcinoma metabolism.
Authors: Minton Denise R. , Fu Leiping , Chen Qiuying , Robinson Brian D. , Gross Steven S. , Shevchuk Maria M. , Nanus David M. , Gudas. Lorraine J.
Published: February 2017

493

Background: Clear cell renal cell carcinoma (ccRCC) is characterized by altered metabolism, including a shift from oxidative phosphorylation to glycolysis and lactate production (the Warburg effect). Here we evaluate human ccRCC tissue samples and kidney samples from the TRACK transgenic mouse model of ccRCC (that express constitutively active HIF1α in proximal tubule cells) [1] to characterize the effect of HIF1α on the renal cancer metabolome. Methods: We performed untargeted metabolomics analyses of 12 primary human ccRCCs and 10 TRACK kidney samples. In addition, we analyzed human ccRCC mRNA expression (Oncomine database) and performed RNA sequencing (RNAseq) on six TRACK kidney samples for expression of HIF1α target genes that regulate metabolism. Results: Analysis of RNA expression of HIF1α target genes in human ccRCCs and TRACK kidneys identified significantly increased transcript levels of genes responsible for mediating glucose uptake and glycolysis and suppressing the activity of the TCA cycle and mitochondrial respiration, including glucose transporter 1 (SLC2A1), glycolytic enzyme phosphofructokinase (PFKP), TCA cycle inhibitor pyruvate dehydrogenase kinase (PDK1), oxidative phosphorylation inhibitor NADH dehydrogenase 1 alpha subcomplex, 4-like 2 (NDUFA4L2), and lactate transporter (SLC16A3). Metabolomics analysis similarly demonstrated a significant increase in glycolytic intermediates and lactate, in association with a decrease in metabolites of the TCA cycle. Conclusions: These studies show that in both human ccRCC and TRACK mice HIF1α mediates a metabolic switch to aerobic glycolysis, implicating HIF1α in RCC tumorigenesis. Additionally, these data suggest that targeting the metabolic pathway (or inhibition of HIF1α) is a novel approach to treat ccRCCs.
Comparative effectiveness of first-line VEGF TKI followed by second-line therapy with either a VEGF TKI or an mTOR inhibitor in patients with metastatic renal cell carcinoma.
Authors: Patel Shiven B. , Tantravahi Srinivas Kiran , Gill David , Poole Austin , Merriman Joseph , Batten Julia A. , Stenehjem David D. , Agarwal Neeraj
Published: February 2017

495

Background: In the INTORSECT trial, not progression-free (PFS), but overall survival (OS) was higher with sorafenib vs. temsirolimus in 2nd setting after 1st sunitinib therapy. Here, we compare the PFS and OS between any vascular endothelial growth factor inhibitor (VEGF TKI) and mTOR inhibitors (mTORi) in 2nd setting in mRCC after progression on 1st VEGF TKI. Methods: Pts were identified from an institutional database. Survival estimates of PFS and OS were assessed from initiation of 2nd therapy by Kaplan-Meier methodology and stratified by the median PFS of the 1st therapy. Results: Of 142 pts, 66 received a VEGF TKI (n=24, 36%) or an mTORi (n=42, 64%) in 2nd setting. Pts and disease characteristics with corresponding outcomes are presented in the table. Conclusions: A trend for improved PFS and OS was found with 2nd therapy with a VEGF TKI over an mTORi. Longer OS with 2nd VEGF TKI was seen in those on 1st VEGF TKI <8 months suggesting that continued VEGF inhibition may be a reasonable strategy in these pts. Data need to be validated in a larger cohort. [Table: see text]
Concordance of Gleason score on biopsy and after prostatectomy: A SEER database analysis.
Authors: Wong Andrew Thomas , Agarwal Manuj , Navo Elliot B. , Schwartz David , Schreiber David
Published: February 2017

50

Background: The Gleason score (GS) is a well-established prognostic factor and is used to guide clinical decision-making for patients with prostate cancer. Concordance between the clinical GS of the core biopsy and of the pathologic specimen after radical prostatectomy has ranged from 30% to 75% in prior single-institution studies. The objective of this study is to analyze biopsy concordance utilizing the population-based Surveillance, Epidemiology, and End Results (SEER) database. Methods: Patients diagnosed with localized prostate adenocarcinoma (cT1c-4 Nx-1 M0) who underwent prostatectomy from 2010-2011 were identified in the SEER database. Agreement between clinical and pathologic GS was analyzed using the kappa (k) statistic. Univariate and multivariate logistic regression was performed to identify factors which may impact concordance using SPSS v21. Results: A total of 34,195 patients were included in this analysis. Median age was 61 and median PSA was 5.9 ng/ml. The majority of patients had clinical GS of 6 or 7 (76.5 %) and PSA < 10 ng/ml (77.4%). Overall concordance was 55.4% with k of 0.36, indicating fair agreement. Results are summarized in the Table. Of patients with clinical GS 6, concordance was 55.3%, with 43.1% upgraded to pathologic GS 7. Among patients with clinical GS 7, concordance was 66.9% for GS 3+4 and 42.9% for GS 4+3. Concordance was 24.8% among patients with clinical GS 8, with 57.4% downgrade rate. On multivariate analysis, Black race, increasing age, higher PSA and SEER registries California, Connecticut, Hawaii and Iowa predicted for decreased likelihood of concordance. Conclusions: This is, to our knowledge, the largest contemporary study of prostate biopsy concordance. We found a substantial rate of upgrade from GS 6 or 7 as well as significant downgrade from GS 8. Further investigation is needed to determine other potential factors to predict biopsy concordance. [Table: see text]
Comparative effectiveness of everolimus (EVE) and axitinib (AXI) for second-line treatment of metastatic renal cell carcinoma (mRCC) in the United States: A retrospective chart review.
Authors: Vogelzang Nicholas J. , Pal Sumanta Kumar , Signorovitch James E. , Reichmann William M. , Chopra Pooja , Liu Zhimei , Perez Jose Ricardo , Jonasch Eric
Published: February 2017

500

Background: EVE and AXI are approved as 2nd-line TTs for mRCC. This study compares OS and PFS among mRCC patients treated with EVE and AXI following 1st TKI. The extent to which the duration of 1st TKI can inform optimal selection of a 2nd-line TT is of interest. Methods: A retrospective patient chart review study was conducted. Medical oncologists or hematologists/oncologists who treated ≥3 mRCC patients in the past year were recruited from a national panel. Patient eligibility criteria included: 1) aged ≥18 years; 2) initiated and discontinued 1st TKI (sunitinib or pazopanib) for medical reasons; 3) initiated 2nd TT between 2/1/2012 and 1/31/2013. OS was defined as time from initiation of 2nd TT to death. PFS was defined as time from initiation of 2nd TT to physician/chart reported progression or death, whichever occurred first. Multivariable Cox proportional hazards models were used to estimate the hazard ratio (HR) for OS and PFS between EVE and AXI, adjusting for age, gender, type and duration of 1st TKI, response to 1st TKI, duration of mRCC at 2nd TT, disease profile, performance status, sites of metastases, and years of physician practice. Comparative effectiveness was also analyzed by the type and duration (<6, 6-12, >12 months) of 1st TKI. Results: A total of 298 and 122 patients received 2nd TT with EVE and AXI. After adjusting for baseline characteristics, there was no statistically significant difference between EVE and AXI in OS [HR (95% CI): 1.10 (0.69-1.75)] or PFS [HR (95% CI): 1.12 (0.81-1.54)]. When stratified by subgroups defined by type and duration of 1st TKI, there was no statistically significant difference in OS between EVE and AXI in all subgroups, except for patients with <6 months on sunitinib as 1st TKI in which AXI had longer OS (HR =3.95). There was no statistically significant difference in PFS between EVE and AXI in all subgroups. Conclusions: In this large, retrospective chart review study, there was no significant difference in OS or PFS between EVE and AXI. Subgroup analyses stratified by duration of 1st TKI did not suggest that longer duration of 1st TKI was associated with better efficacy for 2nd-line AXI vs. EVE.
Association of pharmacokinetics of axitinib with treatment outcome and adverse events in advanced renal cell carcinoma patients.
Authors: Tsuchiya Norihiko , Igarashi Ryoma , Suzuki-Honma Naoko , Fujiyama Nobuhiro , Narita Shintaro , Inoue Takamitsu , Saito Mitsuru , Akihama Susumu , Tsuruta Hiroshi , Miura Masatomo , Habuchi Tomonori
Published: February 2017

506

Background: Therapeutic drug monitoring (TDM) has been recognized as a useful tool for optimizing the dose of many drugs. The effectiveness of TDM for molecular targeted agents, however, has not so far been established. In this study, we examined the associations between pharmacokinetics of axitinib (AXI) and adverse events (AEs) and clinical outcomes in patients with advanced renal cell carcinoma (aRCC). Methods: The pharmacokinetics of AXI was examined in 24 patients (18 males and 6 females) with aRCC. The plasma AXI levels were measured using high-performance liquid chromatography and a pharmacokinetic study was performed on day 7 in the first cycle. Subsequently, the associations between the pharmacokinetics of AXI and the occurrence and grade of AEs, best tumor response, and progression-free survival (PFS) were investigated. Results: All the patients were been treated with 10 mg/day of AXI at the day of pharmacokinetics and the trough levels were ranged between 1.2 and 70.97 ng/mL. The trough levels were significantly associated with the occurrence of hypertension, hyperthyroidism, and grade 1 or higher proteinuria (p=0.037, 0.024, 0.027 by Mann-Whitney test, respectively), and were associated with the best tumor response (by Mann-Whitney test, p=0.043) (Table 1). Patients with 5.0 ng/mL of higher trough levels of AXI showed a tendency toward longer PFS than those with the trough levels less than 5.0 ng/mL (Table 2). Conclusions: TDM of AXI in patients with aRCC may be useful to determine the adequate dose and prevent severe AEs. Further studies are mandatory to conclude the usefulness of TDM of AXI for the long-term clinical efficacy in patients with aRCC. [Table: see text] [Table: see text]
Outcomes and prognosticators in patients with pathologic T4 renal cell carcinoma.
Authors: Borregales Leonardo , Kim Dae Y. , Qiao Wei , Tamboli Pheroze , Jonasch Eric , Tannir Nizar M. , Matin Surena F. , Wood Christopher G. , Karam Jose A.
Published: February 2017

514

Background: The 2010 American Joint Committee on Cancer (AJCC) TNM staging system defines pathological T4 renal cell carcinoma (RCC) as extension of tumor beyond Gerota’s fascia and/or invading contiguously into the adrenal gland. This subset of patients with the highest stage and locally advanced disease demonstrate poor outcomes with an estimated 5 year-survival rate of 20-30%. For this high-risk population, patient selection is imperative for proper patient counseling and to identify patients who would benefit from surgical intervention. Our objective was to study patient outcomes and determine prognostic variables predicting survival in pT4 RCC. Methods: From July 1992 to January 2012, we identified 64 patients at our institution who underwent radical nephrectomy and were found to have pT4 disease. The clinical and pathological variables were studied using univariate analysis to identify prognostic variables predicting survival using the Cox proportional hazards model. Survival plots were estimated using Kaplan-Meier method and survival analysis was performed using log-rank test. Results: Median patient age was 56 years (35-82), and 46 (68.7%) were male. Fifty-two (83%) patients had ECOG Performance Status 0 or 1. At diagnosis, 20 (32%) patients were M0 and 42 (68%) were M1. Median tumor size was 13 cm (5.5-25). Forty-nine (76%) patients had clear cell RCC and 26 (40%) had sarcomatoid features. Forty-seven (73.4%) patients had Fuhrman grade 3 or 4. Twenty-eight (44%) patients were pN0, 16 (25%) were pN1, and 20 (31%) were pNx. On multivariate analysis, the significant predictors of survival (p < 0.05) were M stage at time of nephrectomy, pN stage, performing LN dissection, Fuhrman grade, and presence of sarcomatoid features. Conclusions: Survival in patients with pT4 remains poor. Predictors of survival in pT4 RCC patients include M stage, N stage, LN dissection, Fuhrman grade, and sarcomatoid features. Preoperative identification of patients with pT4 needs refinement, and could help improve patient management and selection for inclusion in neoadjuvant trials.
Validation of an active surveillance threshold for the CCP score in conservatively managed men with localized prostate cancer.
Authors: Stone Steven , Cuzick Jack M. , Fisher Gabrielle , Yang Zi Hua , North Bernard , Berney Daniel M. , Beltran Luis , Greenberg David , Møller Henrik , Reid Julia E. , Gutin Alexander , Lanchbury Jerry S. , Brawer Michael K. , Scardino Peter T.
Published: February 2017

54

Background: Active surveillance (AS) is an increasingly popular treatment modality for men with localized prostate cancer. However, better risk stratification is needed to appropriately select men for AS. The cell cycle progression (CCP) score has proven to be a robust predictor of prostate cancer outcomes in various clinical settings, including conservatively managed cohorts. Here, we present a validation of an AS threshold for a predefined score that combines CCP with CAPRA (combined clinical CCP risk (CCR) score) for predicting prostate cancer mortality (PCM) in conservatively managed patients. Methods: We determined the CCR score distribution in 505 men who were tested in our clinical laboratory and, based on their clinical characteristics, might typically be considered for AS. Specifically, the training cohort consisted of men who had Gleason score ≤ 3+4; PSA < 10 ng/ml; < 25% cores positive; and clinical stage ≤ T2a. A threshold CCR score of 0.80 was selected such that 90% of the men in the training cohort had scores below the threshold. The performance characteristics of the threshold were then evaluated in two independent cohorts of conservatively managed men (TAPG1 [N= 180] and TAPG2 [N=585]). Survival data were censored at 10 years. Results: The primary pre−planned analysis called for evaluating the CCR threshold on TAPG2. There were 60 men (of 585) below the threshold in the validation cohort and the threshold validated, dichotomizing the cohort into high and low risk groups (log rank P−value = 0.0008). There were no deaths in patients below the threshold and the Cox proportional hazard estimate of 10−year PCM associated with the CCR threshold was 3.3%. The 10−year risk of PCM associated with the threshold in the combined cohort (TAPG1 and TAPG2) was 3.2% and there were no observed prostate cancer deaths in patients below the threshold. Conclusions: For patients considering deferred treatment, the CCR score provides significant prognostic information at disease diagnosis. The threshold presented here was derived from the ‘typical’ risk of PSM for AS patients and can be used to guide patient selection for AS based on an integrated view of risk assessment.
Use of multiparametric MRI to alter management pathways: Treatment patterns of prostate cancer in the targeted biopsy era.
Authors: Chelluri Raju , Frye Thomas P , George Arvin , Fascelli Michele , Ho Richard , Abboud Steven , Walton-Diaz Annerleim , Sankineni Sandeep , Turkbey Baris , Wood Bradford J. , Pinto Peter A.
Published: February 2017

56

Background: As the use of multiparametric MRI (mpMRI) to diagnose prostate cancer (PCa) becomes established, better knowledge of treatment patterns is needed to counsel patients. Prior studies have shown 40-55% undergo Radical Prostatectomy (RP), while only 6% prefer Active Surveillance (AS), and that stratification by risk does not greatly alter treatment pathways. We aim to delineate the distribution of PCa treatment modalities in the MRI/US fusion-guided prostate biopsy (FB) era. Methods: A retrospective review was performed of all patients who underwent FB at the NIH from 2010 to present. Demographics, Gleason scores, MRI Suspicion scores and treatment outcomes were recorded. Patients were stratified according to D’Amico Risk Criteria, and outcomes were coded into four categories: AS; RP; Radiation (XRT, Brachytherapy); and Other (Systemic or Focal therapy). Results: 839 men were reviewed. Mean age was 62.6 years old and mean PSA was 9.7 ng/mL. Total cancer detection rate was 70% (n = 589). Of FB positive men, 474 had treatment information available. Overall 225 (47.5%) entered AS, 158 (33.3%) underwent RP, 61 (12.9%) received XRT, and 30 (6.3%) received other intervention. Subgroup analysis by MRI suspicion score (Table) showed 47.4% frequency of RP in the high vs. 30.9% and 19.4% for moderate and low suspicion groups, respectively. Analysis by D’Amico Risk (Table) showed 86% of low risk men chose AS vs. 0% of high risk men. Conversely 9.7% of low, 44.5% of intermediate and 55.7% of high risk men underwent RP. Conclusions: FB was associated with a higher rate of AS choice as a treatment modality for low risk disease. However most patients with clinically significant PCa still chose RP as their treatment. FB is an additional tool that allows the urologist to better counsel patients and provides individualized treatment for PCa. [Table: see text]
Oncological outcomes in high-risk prostate cancer after radical prostatectomy based on Gleason score: USC experience with 3,755 cases.
Authors: Djaladat Hooman , Xu Weichen , Cai Jie , Lieskovsky Gary , Daneshmand Siamak
Published: February 2017

60

Background: Gleason score is an important predictor of oncological outcomes after radical prostatectomy. However, it remains unclear whether there is a difference in outcomes between Gleason score (GS) 8 and 9-10 disease. We compare oncological outcomes after open radical prostatectomy for prostate cancer patients with GS of 8 versus 9-10. Methods: Of 3,755 radical prostatectomy patients (1987-2008), 360 patients with final pathology of GS 8, 9 or 10 and N0M0 were included. No significant differences between age, race and surgical margins between the two groups. Impact of GS on outcomes was controlled for preoperative PSA, pathological stage, use of adjuvant radiation therapy and use of neoadjuvant/adjuvant hormone deprivation therapy in multivariable analyses. Outcomes of interest were biochemical recurrence free survival (BCRFS), clinical recurrence free survival (CRFS) and overall survival (OS). Kaplan Meier plots, log rank tests and multivariable Cox regression model were used to analyze the data. Results: Median follow-up for GS 8 and GS 9-10 were 10.0 years and 8.6 years, respectively (p=0.43). Conclusions: Long term follow up after radical prostatectomy reveals significant differences in BCRFS and CRFS but not OS between patients with GS 8 vs. 9-10 prostate cancers. Further studies may examine sub-stratification of GS 8 tumors into a lower risk category than GS 9-10 tumors. [Table: see text] [Table: see text]
The association of very low PSA with increased cancer-specific death in men with high-grade prostate cancer.
Authors: Mahal Brandon Arvin Virgil , Aizer Ayal Aaron , Efstathiou Jason Alexander , Nguyen Paul Linh
Published: February 2017

62

Background: It has been hypothesized that very low PSAs in men with high-grade prostate cancer could reflect dedifferentiation and a poorer prognosis, but clinical evidence to support this is limited. We sought to determine whether a very low-presenting PSA was associated with greater prostate cancer-specific mortality (PCSM) among men with Gleason score (GS) 8-10 disease. Methods: The Surveillance, Epidemiology and End Results Program was used to identify a national cohort of 328,904 men diagnosed with cT1-4N0M0 prostate cancer between 2004 and 2010. Multivariable Fine-Gray competing-risks regression analysis was used to determine PCSM as a function of PSA level (<2.5 ng/mL, 2.6-4 ng/mL, 4.1-10 ng/mL, 10.1-20 ng/mL, 20.1-40 ng/mL, or >40ng/mL) and GS (8-10 vs. <=7). Results: Median follow-up was 38 months. Among men with GS 8-10 disease, using PSA 4.1-10 as the reference group, the Adjusted HR (AHR) for PCSM for men with PSA level <2.5 was 1.86 (95% CI 1.51-2.29; P<0.001), PSA 2.6-4 was1.44 (1.17-1.78; P<0.001), PSA 10.1-20 was 1.58 (1.39-1.78; P<0.001), PSA 20.1-40 was 2.04 (1.78-2.33; P<0.001), and PSA>40 was 3.19 (2.83-3.59; P<0.001), suggesting a U-shaped distribution. There was a significant interaction between PSA level and GS (Pinteraction<0.001) such that PSA <2.5 only significantly predicted for poorer PCSM among patients with high grade GS 8-10 disease. Conclusions: Among patients with high grade GS 8-10 disease, patients with PSA <2.5 and 2.6-4 appear to have a higher risk for cancer-specific death compared to patients with a 10.1-20 PSA level, supporting the notion that low PSA in GS 8-10 disease may be a sign of underlying aggressive and extremely poorly differentiated or anaplastic low PSA-producing tumors. Patients with low PSA GS 8-10 disease should be considered for clinical trials studying the use of chemotherapy and other novel agents in very-high risk prostate cancers.
Quality of life (QOL) and acute toxicities of a pilot study of focal salvage high-dose rate (HDR) prostate brachytherapy in patients with local recurrence after definitive external-beam radiotherapy (XRT).
Authors: Chung Hans T. , D'Alimonte Laura , Loblaw D. Andrew , Ravi Ananth , Wronski Matthew , Davidson Melanie , Haider Masoom A. , Morton Gerard
Published: February 2017

79

Background: Despite dose-escalated radiotherapy, studies of post-treatment biopsies of the prostate for intermediate-risk prostate cancer suggest that approximately 20% will be positive. Salvage options include surgery, brachytherapy, cryotherapy or high-frequency ultrasound. However, the risk of significant complications (e.g. fistula, incontinence, bladder neck contracture), is not insignificant. The objective of this pilot study is to explore the QOL, toxicities and efficacy of focal salvage HDR prostate brachytherapy. Methods: This study was approved by the institution’s research ethics board. Eligible patients included: biopsy-confirmed local recurrence >30 months after XRT, MRI demonstrating solitary recurrence confined to the prostate, negative metastatic workup, IPSS <15, post-XRT PSA <10ng/mL, prostate volume ≤50cc. Salvage ultrasound-based HDR brachytherapy was performed with a prescription dose of 27Gy divided over two implants separated by 1 week to the target volume (TV) as seen on MRI with dose constraints to the urethra and rectum. Results: Eleven patients (mean age 73 years) have been enrolled in the study. At initial presentation, there were 4, 6 and 1 low-, intermediate- and high-risk disease, and initial XRT received was 70-78Gy. The Gleason score of the local recurrence was 7 and 8-10 in 6 and 5 patients, respectively. The pre-HDR mean PSA was 5.0 (range 1.3 – 9.29). The median size of the recurrence on MRI was 10mm and median volume of the TV was 5.9cc (2.2-16.1), TV V100 96.0%, urethral D10 64.5% and rectal D1cc 42.9%. Ten patients have at least 6 months of follow-up (median 10 months), and no acute GU/GI grade 3-5 toxicities were observed, including urinary retention. The most common acute toxicity was frequency and nocturia. Mean IPSS at baseline, 1-, 3- and 6-months was 6, 8, 7 and 5. At 6-months, 9 of 10 patients had a lower PSA (mean 1.78) than baseline. There was no significant change in EPIC urinary, bowel and sexual domains within the first 6-months. Conclusions: Preliminary data suggests that focal salvage HDR brachytherapy was technically feasible with minimal acute toxicities. Clinical trial information: NCT01583920.
Are men with favorable intermediate-risk prostate cancer candidates for active surveillance?
Authors: Raldow Ann Caroline , Zhang Danjie , Chen Ming-Hui , Braccioforte Michelle H. , Moran Brian Joseph , D'Amico Anthony Victor
Published: February 2017

82

Background: Active surveillance (AS) is considered appropriate for patients with low-risk prostate cancer (PC) and a life expectancy of at least 10 years. However, with grade migration following the 2005 International Society of Urologic Pathology consensus conference, AS may also be an initial option for men with favorable intermediate-risk PC. We estimated and compared the risk of PC-specific mortality (PCSM) following high dose radiation therapy and androgen deprivation therapy as appropriate amongst men with low, favorable intermediate, unfavorable intermediate, and high-risk PC. Methods: The study consisted of 6,595 consecutively treated men (median age: 68 years) with localized or locally advanced PC at the Chicago PC Center between 1997 and 2013. Fine and Gray competing risks regression analyses (table) were used to assess the risk of PCSM in men with favorable intermediate, unfavorable intermediate or high-risk compared to low-risk PC, adjusting for age at and year of treatment. Results: After median follow-up of 7.76 years, 820 men died: 72 of PC. While men with favorable intermediate-risk did not have significantly increased risk of PCSM as compared to low-risk PC (adjusted hazard ratio (HR) 1.28, 0.63-2.62 95% confidence interval (CI), p-value 0.49), men with high (adjusted HR 9.91, 5.48-17.94 95% CI, p-value <0.0001) or unfavorable intermediate-risk PC (adjusted HR 3.17, 1.60-6.30, p-value 0.001) did. Eight-year point estimates of PCSM were low: 0.68% [0.32-1.31% 95% CI] and 0.44% [0.25-0.75% 95% CI] for men with favorable intermediate and low-risk PC, respectively. Conclusions: Men with low and favorable intermediate-risk PC have similar and low estimates of PCSM during the first decade following standard management. These results provide evidence to support AS as an initial approach for men with favorable intermediate-risk PC. [Table: see text]
Evaluation of the economic impact of the CCP assay in localized prostate cancer.
Authors: Crawford E. David , Cole Doria , Lewine Nicolas , Gustavsen Gary
Published: February 2017

85

Background: Stratification of localized prostate cancer based on disease aggressiveness remains challenging, resulting in overtreatment of low-risk patients and under treatment of high-risk patients. A biopsy-based, cell cycle progression (CCP) gene expression assay can aid physicians in predicting prostate cancer aggressiveness, leading to more appropriate patient management. This study quantifies the economic impact of the CCP assay on a US commercial health plan. Methods: A fact-based economic model was developed for a hypothetical cohort of prostate cancer patients with localized disease. Patients were followed in the model for 10 years with management and progression assumptions based on published clinical data and interviews with board-certified physicians. Total cost of care was calculated for a reference scenario (current clinical practice) and a test scenario where patient management was altered based on CCP test results. Cost inputs were set for each unit of care that a patient might undergo (diagnostic/surgical/radiotherapy procedures and pharmacological therapy); costs were assigned based on published costs of care. Total cost of care was compared between the two scenarios to determine overall system economic impact. Results: The CCP test reduced costs by $2,850/patient tested over 10 years after accounting for test cost. For a health plan with 10 million members, this would translate to over $16 million in savings with two-thirds of those savings achieved in the first year after testing. The majority of savings came from increased use of active surveillance in AUA low- and intermediate-risk patients. No single model input, when changed within a range of values, caused the model to show that the test was no longer cost saving. Costs of the test scenario were never greater than the reference scenario, resulting in cost savings over the 10 years modeled. Conclusions: Use of the CCP test in a US commercial health plan has the potential to result in cost savings to payers. Savings are due to increased use of active surveillance in low- and intermediate-risk patients with less aggressive disease, but also from reduced progression rates in high-risk patients with more aggressive disease who transition to multi−modality therapy.
Impact of the 18F- PET/CT scan in the management of patients with high-risk or intermediate-risk prostate cancer at initial diagnosis or at recurrence.
Authors: Pasticier Gilles , Chicart Marine , Gross-Goupil Marine , Donon Laurence , Robert Gregoire , Ferriere Jean-Marie , Ballanger Philippe , Bernhard Jean-Christophe , Cornelis Francois , Lebras Yann , Grenier Nicolas , Ravaud Alain , Haaser Thibaut , Fernandez Philippe , De Clermont-Gallerande Henri
Published: February 2017

87

Background: It is reported that a Fcholine Positron Emission Tomography (PET/CT) scan can change the management of the patients with prostate cancer up to 20% of the cases. The aim of this study was to evaluate the impact of 18FCholine PET/CT when its indication was taken by a multi-disciplinary staff in case of initial diagnosis or in case of recurrence. Methods: This retrospective study involved 84 patients between May 2013 and July 2014. After a selective approach 86 18F-PET/CT were performed consecutively: 37 (43%) for the initial staging and 49 (57%) in biochemical failure. The acquisition protocol included a pelvic dynamic scan after injection of 4 MBq/kg of 18FCholine followed by a whole-body scan. Mean age, PSA level and Gleason score were respectively in relapse and initial staging: 71 years (59-82), 4.9 (0.12-32.8), 7 (6-9) and 63 years (48-76), 16 (2.42-55) and 8 (6-10). Results: In initial diagnosis, prostate cancer was identified in all the patients on PET/CT. Local disease was seen in 23/37 scans (62.2%); loco-regional node involvement in 8 (21.6%) and metastatic disease in 6 (16.2%). PET/CT confirmed the therapeutic decision in 48.6% of cases and led to a therapeutic modification in 43.2% of cases,avoiding radical prostatectomy and lymphadenectomy in 25% of cases or modifying the extend of radiotherapy (25%) . In biochemical recurrence, PET/CT showed relapse in the prostatic area in 14 patients (28.6%); abnormal pelvic lymph nodes in 10 cases (20.4%) and distant metastases in 18 patients (36.7%). It failed to identify the cause of relapse in 7 cases (14.3%). PET/CT confirmed the therapeutic approach in 24.5% and led to a therapeutic change in 61.2% of cases The diagnostic performance of the FCholine PET/CT scan on nodes, according to the pathological results were: sensitivity 80 %, specificity 84.6%, positive predictive value 66.7% and negative predictive value 91.7 % Conclusions: A rigorous selection of the patients before the realization of a FCholine PET/CT scan in the management of a prostate cancer can increase the diagnostic performance and provide a better impact. In this study the treatment modification affected 54.8% of the patients.
Association between provider-level factors and lymph node dissection outcomes during radical prostatectomy: A national cancer database analysis.
Authors: Kiechle Jonathan E , Wang Elyn , Yu James B. , Gross Cary Philip , Abouassaly Robert , Cherullo Edward E , Smaldone Marc C. , Shah Nilay , Trinh Quoc-Dien , Sun Maxine , Kim Simon P.
Published: February 2017

89

Background: Lymph node counts have been proposed as a quality metric for patients undergoing radical prostatectomy (RP) and pelvic lymph node dissection (PLND). It is unclear whether surgical approach and hospital characteristics independently determine the number of lymph nodes removed at PLND. Therefore, we assessed the variation in lymph node counts from a population-based cohort of patients undergoing surgery for intermediate and high-risk prostate cancer. Methods: Using the National Cancer Database, we identified all surgically treated patients diagnosed with pre-treatment intermediate or high-risk prostate cancer from 2010 to 2011. The primary outcome was the number of lymph nodes retrieved at the time of RP. Generalized estimating equations were used to assess for differences in the adjusted number of lymph nodes retrieved after accounting for patient and hospital characteristics and surgical approach. Results: Overall, 35,876 patients were diagnosed with intermediate (61.2%) and high-risk (38.8%) prostate cancer and underwent RP and PLND. On multivariable analysis, open radical prostatectomy (ORP) and high volume and academic hospitals were independently associated with greater lymph node counts compared to robotic-assisted radical prostatectomy (RARP) and medium/low and community hospitals, respectively (all p<0.001). After adjusting for patient and hospital variables, higher adjusted lymph nodes counts were observed for ORP compared to RARP (7.1 vs. 6.1; p<0.001). Adjusted counts were also higher for high volume compared to medium/low volume hospitals (7.8 vs. 5.9; p<0.001), and academic compared to community hospitals (7.3 vs. 5.6; p<0.001). Conclusions: Among patients with aggressive prostate cancer treated with RP and PLND, lymph node counts varied by surgical approach and hospital characteristics.
Molecular and clinical characterization of 1,577 primary prostate cancer tumors to reveal novel clinical and biological insights into its subtypes.
Authors: Feng Felix Yi-Chung , Tomlins Scott , Alshalalfa Mohammed , Erho Nicholas , Yousefi Kasra , Zhao Shuang , Den Robert Benjamin , Dicker Adam , Schaeffer Edward M. , Klein Eric A. , Magi-Galluzzi Cristina , Karnes R. Jeffrey , Jenkins Robert B. , Trock Bruce J. , Demarzo Angelo , Davicioni Elai
Published: February 2017

9

Background: Prostate cancer molecular subtypes based on ETS gene fusions and SPINK1 were originally identified through outlier gene expression profiling analysis. Such molecular subtypes may have utility in disease stratification and clonality assessment, complementing available purely prognostic tests. Hence, we determined the analytical validity of molecular subtyping in a large sample of PCa treated with radical prostatectomy. Methods: We analyzed Affymetrix Human Exon 1.0ST GeneChip expression profiles for 1,577 patients from 8 radical prostatectomy (RP) cohorts. Multi-feature random forest classifiers and outlier analysis were used to define microarray-based molecular subtypes. Results: A random forest (RF) classifier was trained and validated to predict ERG fusion status using a subset with known ERG rearrangement status defined by FISH, achieving >95% sensitivity and specificity in the validation subset. Less frequent rearrangements involving other ETS genes or SPINK1 over-expression were predicted based on gene expression outlier analysis. Across cohorts, 45%, 9% 8% and 38% of PCa were classified as ERG+, ETS+, SPINK+, and Triple Negative, respectively. Global gene expression analysis shows that the four subtypes could be collapsed into three entities (ERG+, ETS+ and SPINK+/Triple Negative) based on expression patterns and clinical characteristics similarity. A series of multivariable analyses further revealed, ERG+ to be associated with lower pre PSA and Gleason scores but more likely to have EPE and occur in patients with European American ancestry compared to the ETS+, SPINK+/Triple Negative tumors (p<0.001). In contrast, patients with ETS+ were more likely to have SVI compared to both ERG+ and SPINK/Triple Negative (p=0.01), while SPINK+/Triple Negative had higher Gleason scores and were more likely to occur in African Americans (p<0.001). Conclusions: The Decipher platform can accurately determine ERG rearrangement status and PCa molecular subtypes. Inclusion of molecular subtyping, such as m-ERG status, may enable additional precision medicine opportunities in prognostic tests
Multi-institutional registry for prostate cancer radiosurgery: An observational clinical trial.
Authors: Freeman Debra
Published: February 2017

98

Background: To report on the design, methodology and early outcome results of a multi-institutional registry study of prostate cancer radiosurgery. Methods: The Registry for Prostate Cancer Radiosurgery (RPCR) was established in 2010 to further evaluate the efficacy and toxicity of prostate radiosurgery (SBRT) for the treatment of clinically localized prostate cancer. Men with prostate cancer were asked to voluntarily participate in the Registry. Demographic, baseline medical and treatment-related data were collected and stored electronically in a HIPAA-compliant database, maintained by Advertek, Inc. Enrolled men were asked to complete short, multiple choice questionnaires regarding their bowel, bladder and sexual function. Patient-reported outcome forms were collected at baseline and at regular intervals (every 3-6 months) following treatment. Serial PSA measurements were obtained at each visit and included in the collected data. Results: From July 2010 to July 2013, nearly 2,000 men from 45 participating sites were enrolled in the registry. The majority (86%) received radiosurgery as monotherapy. At 2 years follow-up, biochemical disease free survival was 92%. No Grade 3 late urinary toxicity was reported. One patient developed Grade 3 gastrointestinal toxicity (rectal bleeding). Erectile function was preserved in 80% of men <70 yeats old. Overall compliance with data entry was 64%. Conclusions: Stereotactic radiosurgery is an alternative option to conventional radiotherapy for the treatment of organ-confined prostate cancer. The Registry for Prostate Cancer Radiosurgery represents the collective experience of multiple institutions, including community-based cancer centers, with outcome results in keeping with published, prospective trials of prostate SBRT.
In search of the optimal outcome measure for patients with advanced cancer and gastrointestinal obstruction: A qualitative research study.
Authors: Badgwell Brian D. , Williams Loretta A. , Bruera Eduardo
Published: February 2017

100

Background: Gastrointestinal obstruction (GIO) is the most common indication for palliative surgical consultation in patients with advanced cancer. The purpose of this study was to delineate the symptom burden and experience of patients with GIO. Methods: Twenty patients with advanced cancer and GIO described symptoms at the time of surgical consultation. We used content analysis of interview transcripts and symptoms were ranked by frequency and compared to a general symptom assessment survey (MD Anderson Symptom Inventory). Results: Malignancy type included colorectal (N = 9), gastric (N = 4), urothelial/renal (N = 3), and other (N = 4), while site of obstruction was small bowel in 11 (55%), gastric outlet in 3 (15%), and large bowel in 6 (30%). Thirteen patients (65%) had received chemotherapy within 6 weeks. Imaging evidence of a primary/recurrent tumor, carcinomatosis, or ascites was documented in 13 (65%), 11 (55%), and 16 (80%) patients, respectively. Thirty symptoms were identified on qualitative interviewing. MD Anderson Symptom Inventory symptoms of pain, nausea, and vomiting were frequently noted. Frequently mentioned GIO-specific symptoms included bloating, cramping, not having a bowel movement, and inability to eat. Conclusions: Qualitative research methodology can identify symptoms of importance to patients which can be used to assess improvement after treatment of GIO. Expert panel rating will be used to develop the final symptom item list prior to psychometric testing of the survey.