bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicity, quality of life outcomes, and dosimetric impact in phase III trial of hypofractionated or standard fractionated proton therapy for low-risk prostate cancer patients: PCG GU 002.
Authors: Schmidt Matthew Q. , Vargas Carlos E. , Hartsell William F. , Dunn Megan , Keole Sameer R. , Doh Lucius , Chang John Han-Chih , Sinesi Christopher , Larson Gary L.
Published: March 2017

48

Background: The purpose of this study is to identify differences in toxicity, quality of life (QOL), and dosimetric endpoints among patients with low-risk prostate adenocarcinoma treated with either standard fractionation or hypofractionation proton-beam therapy. Methods: We analyzed the results of the first 75 patients treated in our phase III trial comparing 38Gy relative biological effectiveness (RBE) in 5 fractions (fx) (n = 46) vs. 79.2Gy (RBE) in 44 fx. (n = 29). All patients had low-risk prostate cancer and were treated with proton radiation using fiducial markers and daily image guidance. We evaluated American Urological Association (AUA) Symptom Index, adverse events (AEs), and Expanded Prostate Index Composite (EPIC) domains at pretreatment and 3, 6, 12, 18, 24, 36 and 48 months. Doses to the prostate were selected based on similar long term effects to normal tissue based on an α/β = 3.5 for an EQD2 of 76Gy. Results: The median follow-up was 36 months for both groups; 23 (30%) patients reached a follow-up of 48 months. We observed a small difference in AUA score (3.2 vs. 8.6, p = 0.002) at 1-year favoring the 79.2Gy arm. AUA scores were not statistically different at 18 months and after. Similarly, EPIC Urinary symptoms favored the 79.2Gy arm at 1 year (92.3 vs. 84.5, p = 0.009) and 18 months (92.3 vs. 85.3, p = 0.03); bother scores were not significantly different at any other time points. G2 or higher GU toxicity was similar between arms (p = 0.8). No differences in EPIC Bowel symptoms, EPIC Sexual symptoms, or bowel G2 or higher toxicities were seen. One death was observed in the 38Gy arm due to an unrelated case of multiple myeloma. The bladder V80 (79.2Gy arm, p = 0.04) and V39 (38Gy arm, p = 0.05) were predictive for G2 or higher GU AE. There was no association observed between rectal dose and G2 or higher rectal toxicity. Conclusions: Patients treated in the hypofractionated and standard arms tolerated treatment well. A small and temporary difference in the GU domain was seen favoring the standard arm. As predicted long term effects on the GU domain and bowel were similar for both arms, suggesting that the α/β is similar to 3.5 for long term effects. Clinical trial information: 01230866.
Effect of nivolumab on tumor growth rate (TGR) in metastatic renal cell carcinoma (mRCC).
Authors: Mazza Camille , Arfi-Rouche Julia , Koscielny Serge , Caramella Caroline , Lahmar Jihene , Escudier Bernard J. , Albiges Laurence
Published: March 2017

481

Background: Response assessment under immune checkpoint inhibitors is a challenge that RECIST criteria may not adequately reflect. TGR takes into account the pretreatment kinetics and allows dynamic assessments. How TGR varies under nivolumab remains unknown. We aim at describing the pattern of TGR changes during nivolumab treatment. Methods: We performed a central radiological review of all consecutive patients treated with nivolumab at Gustave Roussy within the GETUG-AFU 26 NIVOREN (EudraCT 2015-004117). Tumor response was assessed at week 8 and every 8-12 weeks subsequently using RECIST 1.1. TGR was computed for the pre nivolumab treatment (TGR pre) and at first (TGR N1) and second assessment (TGR N2) under nivolumab. Results: A total of 45 patients treated with nivolumab between Feb and Jul 2016 were reviewed. Median age at nivolumab start was 60 years-old, 74 % were male. Median number of prior lines of systemic therapies was 2. Median follow-up from nivolumab start was 6 months. TGR pre and TGR N1 were available in 39 patients. Overall, mean decrease in TGR N1 compared to TGR pre was 26%. Among 39 evaluable patients, 23 (59%) patients had a decrease in TGR N1 compared with TGR pre; while an increase was described in 16 (41%) patients. Only one patient out of 39 (2.5%) had a major increase of more than 50% in TGR N1 compared with TGR pre, and could be defined as a hyper-progressor. Consecutive TGR N1 and TGR N2 were available in 24 patients. There was a high correlation between TGR N1 and TGR N2 (r=0.7), suggesting that first evaluation of tumor kinetics adequately reflects subsequent response to nivolumab. However, 4/24 patients (17%) had an initial increase in TGR N1 with subsequent decrease in TGR N2, defining potentially the pseudo-progressors. Conversely, 6/24 patients (25%) had an initial decrease in TGR N1 before a rebound in TGR N2 suggesting a prompt acquired resistance to nivolumab. Conclusions: We report the first TGR assessment of mRCC patients under nivolumab. Overall, 59 % of patients had a decrease in TGR under nivolumab compared to pre nivolumab. TGR in patients with mRCC might provide early information about tumor response to nivolumab. Analysis extended to the entire study population and correlation with PFS and OS will be reported.
Clinical activity of PD1/PDL1 inhibitors in metastatic non-clear cell renal cell carcinoma (nccRCC).
Authors: Moreira Raphael Brandao , McKay Rana R. , Xie Wanling , Heng Daniel Yick Chin , de Velasco Guillermo , Castellano Daniel E. , Fay Andre Poisl , Schutz Fabio Augusto Barros , Wells Connor , Hsu JoAnn , Pal Sumanta K. , Lee Jae-Lyun , Motzer Robert J. , Feldman Darren R. , Choueiri Toni K.
Published: March 2017

482

Background: PD1/PDL1 inhibitors have shown significant activity in the treatment of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC), but their activity in nccRCC is poorly characterized. Methods: We conducted a retrospective multicenter study of pts with metastatic nccRCC treated with PD1/PDL1 inhibitors. Baseline clinical parameters, overall response rate (ORR) by RECIST, time-to-treatment failure (TTF), and overall survival (OS) were summarized. Results: We identified 40 pts across 8 academic institutions. Fourteen (35%) had papillary histology, 10 (25%) chromophobe, 3 (8%) translocation, and 7 (18%) unclassified. Six (16%) had ccRCC with a sarcomatoid component > 30%. 20% had International Metastatic RCC Database Consortium (IMDC) favorable-risk disease, 60% intermediate, and 20% poor-risk. Ten (25%) were treatment-naïve and the majority received PD1/PDL1 monotherapy (n=30, 75%), while the remaining received a combination of PD1/PDL1 with anti-VEGF(R) or anti-CTLA4 therapy. ORR for the total cohort was 18% and 10% for PD1/PDL1 monotherapy pts (Table). With a median follow-up of 5.6 months, the overall median TTF was 4.7 months (2.9-15.9) and six-month OS was 81% (60-91%). Conclusions: PD1/PDL1 blockade resulted in some activity in pts with various nccRCC histologies. In the absence of available clinical trials, this data may support the use of PD1/PDL1 blocking agents in pts with nccRCC. [Table: see text]
Tumor genomic analysis for 128 renal cell carcinoma (RCC) patients receiving first-line everolimus: Correlation between outcome and mutations status in MTOR, TSC1, and TSC2.
Authors: Voss Martin Henner , Chen David , Marker Mahtab , Xu Jianing , Patel Parul , Han Xia , Hsieh James , Motzer Robert J.
Published: March 2017

484

Background: MTOR inhibitors are standard agents in the management of advanced RCC. Case series have suggested somatic mutations in MTOR, TSC1, and TSC2 may sensitize tumors to everolimus (EVE) [Voss et al., CCR 2014; Kwiatkowski et al., CCR 2016]. We sought to test this hypothesis through next generation sequencing (NGS) of tumors from a large cohort of patients (pts) treated with everolimus (EVE) on the randomized RECORD3 trial of first-line EVE vs. sunitinib. Methods: Somatic mutations were investigated using a custom exon-targeted NGS platform with deep sequence coverage. This analysis focused on mutations in TSC1, TSC2, PTEN, PIK3CA, and MTOR. Association between genotypes and progression free survival (PFS) was assessed by Cox PH models and log-rank tests. Mutations in other pathways and non-genetic covariates were investigated. Functional investigation of individual mutations in MTOR, TSC1, and TSC2 were undertaken. Results: 238 pts received 1st line EVE with median PFS of 7.85 mo (95% CI 5.6-8.2). Tumor sampleswere analyzed for 128 pts. Median depth of coverage was ~540X. There was no correlation between PFS and mutation status of mTOR, TSC1, or TSC2 (15 pts [12%]; HR 0.99 [95% CI 0.47-2.07]; p=0.4697); the objective response rate (ORR) in this group was 0%. Individual PFS for all 15 pts clustered outside the 95% CI for the population of 128 everolimus-treated pts (8 pts PFS<2.8mo; 7pts PFS>8.3mo). 3 of 8 pts with PFS<2.8mo had >1 mutation in MTOR, TSC1, or TSC2, while none among the 7 pts with PFS >8.3mo. When including pts with mutations in PTEN, PIK3Ca, MTOR, or TSC1 (30pts [23%]), we found no association between mutation status and PFS (HR 1.02 [95% CI 0.61-1.71]; p=0.3025). Functional investigations suggest varying biologic effects of individual mutations. Conclusions: "One-dimensional" mutation status for core components of the MTOR signaling pathway did not correlate with PFS in this dataset. Grouping based on more detailed characterization incorporating copy number status and functional annotation may provide better insights and should be considered for future biomarker development. Clinical trial information: NCT00903175.
Fourth-line targeted therapy in metastatic renal cell carcinoma (mRCC): Results from the International mRCC Database Consortium (IMDC).
Authors: Stukalin Igor , Wells Connor , Fraccon Anna Paola , Pasini Felice , Porta Camillo , Moreira Raphael Brandao , Srinivas Sandy , Bowman I. Alex , Brugarolas James , Lee Jae-Lyun , Donskov Frede , Beuselinck Benoit , Bamias Aristotelis , Rini Brian I. , Sim Hao-Wen , Agarwal Neeraj , Rha Sun Young , Kanesvaran Ravindran , Choueiri Toni K. , Heng Daniel Yick Chin
Published: March 2017

498

Background: Fourthline targeted therapy efficacy in mRCC is not well characterized and is not reimbursed in many jurisdictions worldwide. Methods: The IMDC consists of consecutive patient series from 35 international cancer centers. It was queried for mRCC patients who received fourth line targeted therapy. Kaplan Meier estimates were used for time to treatment failure (TTF) and overall survival (OS). Results: 594 out of 7498 (8%) mRCC patients initially treated with first line targeted therapy eventually received fourth line therapy from a class of approved agents. Baseline characteristics are displayed in Table 1. The most common fourth line therapies were everolimus 17%, sorafenib 15%, axitinib 13%, pazopanib 13%, sunitinib 13%, nivolumab 7%. IMDC prognostic group distributions (Heng et al JCO 2009) and their associated survivals (both determined from fourth line therapy initiation) were 5% favorable risk (OS 23.1 (14.7-not reached)), 66% intermediate risk (OS 13.8 (11.4-17.5)), and 29% poor risk (OS 7.8 (4.93-12.2)) (OS p<0.0001). Overall response rate for fourth-line therapy was 12.5% and 41.5% had stable disease in those patients that were evaluable (n=407). Median TTF on fourth line therapy was 4.40 months (95% CI 3.98-5.06) and median OS from fourth line therapy initiation was 12.8 months (95% CI 11.4-14.4). Conclusions: Fourth line targeted therapy has demonstrated activity, is uncommon, and should be offered to clinically eligible patients. Further studies are required to determine appropriate sequencing. IMDC criteria appear to stratify favorable/intermediate/poor risk patients well in the fourth line setting. [Table: see text]
Litmus test or destination systemic therapy? Trends in referral for surgery after initial systemic therapy in metastatic kidney cancer.
Authors: Macleod Liam Connor , Dash Atreya , Schade George , Tykodi Scott S. , Gore John L.
Published: March 2017

502

Background: With nine new targeted and immunotherapeutic agents for metastatic kidney cancer (mRCC) since 2005, there is no randomized data supporting sequencing cytoreductive nephrectomy (CN) and newer systemic therapies (ST). Increased disease control with ST engenders concern that CN may shorten life or delay therapy. Thus, in all the best prognostic candidates, initial ST as a “litmus” test may be advocated prior to CN. We evaluated use of CN after initial ST, hypothesizing receipt of deferred CN to be associated with increased survival time, markers of increased performance status, less rapid disease, and socioeconomic status. Methods: The National Cancer Database was screened for adult patients with biopsy-proven mRCC treated with initial systemic therapy between 2006-2013. Covariates included demographic, oncologic, hospital-level, and geographic variables. Unadjusted and multivariable logistic regression was performed, identifying factors associated with CN after initial ST. Results: Of 14,651 patients treated with initial ST for mRCC, 709 (4.8%, median OS 19 months, IQR 9-35) underwent delayed CN compared with 13,942 (95.2%, median OS 5 months, IQR 2-13) treated with ST alone. On multivariable analysis, survival ≥3 months was highly associated with receipt of CN (OR 10.6, 95% CI 5.5, 20.5). However, of 9,796 surviving ≥3 months, only 689 (7%) underwent CN. Factors associated with lower odds of CN included older age, greater comorbidity, higher clinical stage (T and N), and unfavorable metastatic sites (i.e., brain, bone, liver) with all p<0.001. Educational attainment was associated with receipt of CN, but hospital characteristics and travel burden were not. Conclusions: Effectiveness of CN in the modern mRCC era is uncertain. Initial ST is typically for those with poor prognosis. Yet, after an initial litmus test, re-evaluation of risk rarely leads to CN. Socioeconomic factors may affect CN decision-making, a potential disparity that merits further investigation.
Categorization of gene expression subtypes in clear cell renal cell carcinoma with sarcomatoid features.
Authors: Joshi Shreyas , Peri Suraj , Ross Eric A. , Uzzo Robert G. , Kutikov Alexander , Geynisman Daniel M.
Published: March 2017

519

Background: Presence of sarcomatoid features in Renal Cell Carcinoma (sRCC) tumors signals aggressive clinical behavior and poor prognosis compared to Clear Cell Renal Cell Carcinoma (ccRCC). However, the underlying gene expression patterns of sRCC are poorly understood. We sought to categorize ccRCC and sRCC gene expression subtypes and compare survival outcomes, as well as evaluate whether sRCC gene expression patterns are similar to non-renal sarcomas. Methods: We identified 511 ccRCC cases, of which 36 had a sarcomatoid component from The Cancer Genome Atlas. Enrichment analysis was used to measure associations between gene expression signatures for soft tissue sarcomas and expression profiles of sRCC and ccRCC cases measured by RNA-Seq. The resulting scores were used to identify distinct patient groups using K-means clustering. Overall survival (OS) was evaluated by Kaplan-Meier, log rank, and Cox regression methods. Results: Our analysis identified 4 distinct clusters that differ in enrichment for soft-tissue sarcoma gene expression profiles. The clusters showed significantly different OS distributions (p-value<0.001 log rank). Most sRCC cases (69%) segregated into a single cluster with the worst prognosis. Among ccRCC cases, 57% of patients with higher levels of sarcoma signature enrichment were associated with a shorter OS, which is independent of tumor stage. 5-year/median OS survival estimates for ccRCC cases in the 4 clusters, by increasing levels of sarcoma profile enrichment, were 83%/NR, 75%/NR, 67%/90.9 mo, and 49%/56.7 mo. We also validated existence of these clusters in another sRCC cohort (Sircar 2015). Conclusions: We identified strong associations between sarcoma expression signatures and gene expression profiles of sRCC. We also found that 57% of morphologically non-sRCC cases demonstrate enrichment for sarcoma expression signatures, and these patients have worse OS than their non-sarcoma enriched ccRCC counterparts. The presence of sarcoma expression signatures has not been previously evaluated in RCC. These signatures portend poor survival and may be clinically actionable, as they describe unique subtypes of RCC that may not correspond to histologic characterization.
Beyond classical risk adjustment: Socioeconomic status and hospital performance in urologic oncology.
Authors: Odisho Anobel Y. , Gore John L. , Etzioni Ruth Douglas
Published: March 2017

526

Background: Safety-net hospitals care for more patients of lower socioeconomic status (SES) than non-safety-net hospitals and may be disproportionately punished under readmission risk adjustment models that do not incorporate (SES). We developed a readmission risk adjustment framework incorporating SES to assess impact of SES on safety-net hospital rankings for patients undergoing major surgery for urologic malignancies. Methods: Quasi-experimental design using California Office of Statewide Health Planning and Development data from 2007-2011. Subjects included all patients undergoing radical cystectomy for bladder cancer (n = 3,771), partial nephrectomy (n = 5,556), and radical nephrectomy (n = 13,136) for kidney cancer. Unadjusted hospital rankings and predicted rankings under a base model, which simulated the Medicare Hospital Readmissions Reduction Program model, were compared with predicted rankings under models incorporating socioeconomic status. Socioeconomic status was derived from a multifactorial neighborhood score at the ZIP code level calculated from US Census data. The main outcome measures were hospital rankings based on 30-day all-cause readmission rate and differences between model predicted rankings. Results: For all procedures, the addition of socioeconomic status, geographic, and hospital factors changed the overall hospital rankings significantly compared with the base model (p < 0.01), with the exception of socioeconomic status in radical cystectomy (p = 0.07) and socioeconomic status and rural factors in partial nephrectomy (p = 0.12). For radical nephrectomy and partial nephrectomy, the addition of socioeconomic status and hospital factors significantly improved the mean ranking of safety-net hospitals and improved the ratio of observed relative to expected rankings (p < 0.01). For radical cystectomy there was no significant change in rankings with the addition of socioeconomic status, rural status, or hospital factors. Conclusions: Adding socioeconomic status to existing Medicare readmission risk adjustment models leads to significant changes in hospital rankings, with a differential impact on safety-net hospitals.
Clinical outcomes and late toxicity of hypofractionated intensity-modulated radiotherapy for high-risk prostate cancer.
Authors: Wang Michael , Pearcey Robert , Pervez Nadeem , Yee Don , Mihai Alina , Patel Samir , Amanie John , Parliament Matthew , Murtha Albert , Ghosh Sunita , Mackenzie Marc , Field Colin , Usmani Nawaid
Published: March 2017

56

Background: Since prostate cancer has intrinsic high radiation-fraction sensitivity, hypofractionated radiotherapy (HFRT) could offer treatment advantages. However, dose-escalated HFRT may increase risks of late genitourinary (GU) and gastrointestinal (GI) toxicity. Intensity-modulated radiotherapy (IMRT) can potentially deliver dose-escalated HFRT without increasing late toxicities. This study’s acute toxicity data was previously published. We now present five-year efficacy results and late toxicity data for prostate cancer patients treated with HFRT using IMRT. Methods: From 2005-2012, our Phase II prospective study enrolled one hundred patients with either high risk disease (one or more of: Stage ≥ T3, Gleason ≥ 8, or PSA ≥ 20 ng/mL) or high tier intermediate risk disease (Gleason 7 and PSA ≥ 15 ng/mL). All patients received HFRT using IMRT in 25 daily fractions. Sixty patients received 68 Gy to the prostate and proximal seminal vesicles, with simultaneous integrated boost (SIB) of 45 Gy to pelvic lymph nodes and distal seminal vesicles. Forty patients received 68 Gy to the prostate, and a SIB of 50 Gy to pelvic lymph nodes and seminal vesicles. Adjuvant hormonal therapy was given for two to three years. Biochemical failure was determined by the Phoenix definition. Late toxicity scores were recorded every 6 months after completing RT. Results: Median age of patients was 67 years. 33% had Stage ≥ T3, 52% had Gleason ≥ 8, and 44% had PSA ≥ 20 ng/mL. After a median follow-up of 5.4 years, median PSA at last follow-up was 0.10 ng/mL. Five-year biochemical control rate (BCR) was 91.8%, five-year progression-free survival (PFS) was 92.8%, and five-year overall survival (OS) was 88.7%. Five-year cumulative incidence of Grade ≥ 3 GU and GI toxicity were 13.0% and 16.7% respectively. At the five-year efficacy endpoint, ongoing Grade ≥ 3 GU and GI toxicity were 1.9% and 0% respectively. Conclusions: Dose-escalated HFRT using IMRT results in favourable five-year BCR, PFS, and OS for patients with localized high-risk prostate cancer, and is well-tolerated with acceptable late GU and GI toxicity. These findings support ongoing Phase III trials that are assessing the clinical use of IMRT-based HFRT. Clinical trial information: NCT00126802.
Does higher number of lymph nodes (LNs) excised during radical prostatectomy (RP) improve biochemical relapse-free survival (bRFS) in patients with pT2-3a/pN0 prostate cancer?
Authors: Seyedin Steven Neema , Mitchell Darrion L , Russo James Kyle , Mott Sarah L , Parkhurst Jessica , Smith Mark C , Buatti John Michael , Watkins John Morgan
Published: March 2017

61

Background: In published series of extended pelvic LN dissection (LND), an association between higher number of LNs resected and both higher rate of occult LN disease discovery and long-term bRFS (for pN0) was observed. Despite this, practice patterns of LND extent (and associated number of LNs examined) vary, with the majority being limited to local nodal sampling. It remains unclear whether the LN yield correlates with bRFS in this context. The present investigation examines whether the number of LNs examined at RP is associated with bRFS. Methods: Patients with clinically localized prostate cancer, initial PSA < 30, and pT2-3a/N0 disease at RP were retrospectively identified for inclusion. Those who received pre-RP or adjuvant radiotherapy or hormone therapy were excluded. Kaplan-Meier method was employed for survival probability estimation. Cox regression models were used to assess bRFS differences. Results: From 2002 to 2010, 672 patients were eligible for this analysis. The median age was 61 yrs (range, 43-76). Most patients had cT1c (83%), Gleason Score (GS) 4-6 (63%), and were low risk by D’Amico classification (56%), with median PSA of 5.6 ng/dL (0.9-28.0). At RP, 213 (32%) patients had positive margins (M+). At a median follow-up of 82 months, 140 patients (21%) experienced PSA failure with estimated bRFS of 81%/76% at 5/8 years. Univariate analysis identified GS ³ 7 (biopsy or RP), intermediate/high risk, M+, higher percentage of biopsy cores involved, and performance of LND as adversely associated with bRFS (all p < 0.01). Of 446 patients (66%) who had LN sampling , 396 had a specific number of LNs reported (median 5; range 1-24, with single outlier case [33] excluded for statistical analysis). A higher number of LNs excised was not associated with bRFS for the entire cohort (HR = 0.99, p = 0.60), or for any biopsy GS subgroup (GS4-6 HR = 0.92, GS7 HR = 1.00, GS8-10 HR = 0.11). Conclusions: In the context of limited LND, this study did not demonstrate an association between LN yield and bRFS in patients with clinically localized pT2-3a/pN0 prostate cancer managed with RP alone, either in the entire population or with stratification by GS.
Permanent seed brachytherapy for low risk prostate cancer, long term outcome, and urinary toxicity.
Authors: Raziee Hamid , Berlin Alejandro , Chung Peter W. M. , Helou Joelle Antoine , Jiang Haiyan , Crook Juanita M. , Catton Charles N
Published: March 2017

66

Background: Low dose rate seed brachytherapy is an established treatment modality for low risk prostate cancer (CaP). Herein, we report long term biochemical control and urinary toxicity from a single institution. Methods: Data from a prospectively-collected institutional database was used, completed with retrospective chart reviews. All patients with low-risk CaP (NCCN criteria) who underwent ultrasound-guided permanent iodine-125 brachytherapy from March 1999 to December 2005 were included. Urinary function was evaluated by the International Prostate Symptom Score (IPSS). PSA relapse was defined by Phoenix Criteria (nadir + 2 ng/ml). Time to IPSS return-to-baseline score ±3 was recorded. Results: 582 patients with a median age of 64 years were included. Median initial PSA was 5.5 ng/ml (0.3-10). 66% and 34% were T1 and T2a, respectively. Gleason score was 6 (96%) and < 6 (4%). Prescription dose was 145Gy, with a median V100 coverage of 94% (IQR [interquartile range] 89-97%) and median D90 of 157Gy (IQR 144-171 Gy). With a median follow up of 131 months (IQR 94-149 months), 27 patients showed biochemical failure (4.6%), and PSA bounce was detected in 38 cases (7%). Biochemical progression-free rates were 97% (96-98%), 96% (94-97%), and 94% (91-96%) at 5, 10, and 15 years, respectively. Median PSA level at 5, 10 and 15 years was 0.06, 0.05 and 0.018 ng/ml, respectively. PSA relapses were observed out to 148 months. At 1, 5, 10 and 15 years, 5.5%, 16.5%, 39.5% and 89.2% of patients were lost to PSA follow up. Median baseline IPSS score was 5. In 515 (88.5%) patients IPSS returned to baseline, with a median time to return-to-baseline of 9 months. The proportion of return-to-baseline at 1, 2, 5, and 10 years was 62%, 75%, 88%, and 90%, respectively. 22 (4%) patients required post-implant urinary catheter. After 3, 6 and 12 months, 9 (1.5%), 6 (1%) and 4 (0.7%) patients continued to be catheterized. Conclusions: Within the limits of retrospective analysis, permanent seed brachytherapy for low risk prostate cancer is an effective treatment modality with low urinary toxicity. Treatment resulted in excellent long-term biochemical control although late relapses were observed.
The importance of surgical margins for biochemical recurrence in high-risk prostate cancer patients.
Authors: Srougi Victor , Sanchez-Salas Rafael , Secin Fernando P. , Nunes-Silva Igor , Baghdadi Mohammed , Barreras Silvia Garcia , Rembeyo Gregory , Rozet Francois , Galiano Marc , Barret Eric , Cathelineau Xavier
Published: March 2017

75

Background: High-risk prostate cancer (PCa) is associated with greater risk of biochemical recurrence and cancer specific lethality. A multi-modal treatment is required for this group of patients, comprising surgery as part of it. However, the role of surgery as monotherapy is still under investigation. The purpose of this study is to analyze the influence of surgical margins on biochemical recurrence (BCR) among patients with high-risk prostate cancer (PCa) treated with robot assisted radical prostatectomy (RARP) since the start of our robotic program. Methods: We retrospectively analyzed our prospectively collected database of 5695 minimally invasive prostatectomies performed between 2000 and 2015. Clinical, pathological and oncological outcomes were evaluated in patients fulfilling Damico´s high risk characteristics. Primary endpoint was BCR, defined as post-operative PSA ≥ 0,2. Patients with neoadjuvant or adjuvant therapy were excluded. BCR was estimated with Kaplan-Meier curves. Cox proportional hazards regression was used to estimate variables associated with BCR. Results: We identified 199 high-risk PCa patients treated with RARP during the study period. Gleason score ≥ 8, PSA ≥ 20 and clinical stage ≥ T2c were present in 44%, 35% and 11% of the patients, respectively. The rate of positive surgical margins was 25%. With a median follow-up of 23 months (interquartile 12 – 34 months), 31% of the patients had BCR. Five-year BCR-free survival was 34,5%. Gleason score ≥ 8, PSA ≥ 20 and positive surgical margins were not predictors of BCR. A positive correlation of pathological stage ≥ T3 and BCR was found with (HR = 2.9; 95% CI = 1.2-6.9). Conclusions: The 5-years BCR-free survival was poor despite a low rate of positive surgical margins, when compared to historical series. We found that pathological stage ≥ T3 has a significant correlation with the BCR and that negative surgical margins do not assure good prognosis for high-risk patients.
Localized prostate cancer and salvage treatment: EBRT first + salvage HIFU or HIFU first + salvage EBRT? A single-institution matched pair analysis over a 20-year period.
Authors: Pasticier Gilles , Lee Ji-Wann , Crouzet Sebastien , Soria J , Medollima Christelle , Mege-Lechevallier Florence , Chapelon Jean-Yves , Rouviere Olivier , Gelet Albert
Published: March 2017

77

Background: In the field of curative treatment for localized prostate cancer, HIFU (High Intensity Focused ultrasound) is one of salvage option after EBRT(external beam radiation therapy) failure and EBRT is the standard salvage option for local relapse after HIFU.Our aim was to compare and evaluate the oncologic outcomes between HIFU first + salvage EBRT versus EBRT first +salvage HIFU. Methods: Using a matched pair analysis, 342 Patients (171 in each group) treated between 1994 and 2014 in the same institution were prospectively followed and matched to a 1:1 basis. Outcome measurements: Overall Survival Rate(OSR), cancer specific(CSSR) and metastasis free (MFSR) survival rates were the primary endpoints. Secondary endpoints were survival rate free of hormone therapy (HTFR) and the rate of side effects Clavien score ≥ 3. Results: Mean follow-up were 114 and 124 months for HIFU+ S-EBRT and EBRT + S-HIFU respectively. At 7 years from the primary treatment , the MFSR were significantly better after HIFU first +S- EBRT than after EBRT first+S- HIFU: 96% vs 91%% (p:0.011). The OSR and the CSSR were not significantly different in the two arms (97% and 99% after HIFU+S- EBRT versus 96% and 98% after EBRT+S- HIFU). The HTFR at 7 years was significantly different (p <0.001) after HIFU+ S-EBRT than after EBRT+ S-HIFU 90% versus 69%. In multivariable Cox regression, the initial Gleason sum ≥ 8 and the treatment strategy were predictors of MFSR (risk ratio 3.2 for treatment modality). The rate of side effect Clavien score≥ 3 was significantly higher (p:0.01) in the EBRT+ S-HIFU arm than in the HIFU+ S-EBRT arm. The rate of urinary toxicity (severe incontinence and bladder outlet obstruction) were worse in the EBRT+ S-HIFU arm than in HIFU+S-EBRT arm: 9.4% and 15.2% vs 1.2% and 7.6% (p:0.01 and 0.078). Conclusions: In this single-institution Matched Pair comparison, the MFSR and HTFR were significantly better in the HIFU+S-EBRT arm than in the EBRT+S-HIFU arm. The rate of urinairy toxicity and Clavien≥3 side-effects were Higher in the EBRT + S-HIFU arm than in the HIFU + S-EBRT arm.
Is there a relationship between testosterone levels at the end of short-term androgen deprivation therapy and outcomes in intermediate risk prostate cancer? Prospective data from a phase III trial.
Authors: Nabid Abdenour , Garant Marie-Pierre , Vigneault Eric , Souhami Luis , Lemaire Celine , Brassard Marc-Andre , Bahoric Boris , Archambault Robert , Vincent Francois , Nguyen-Huynh Thu-Van , Bettahar Redouane , Wilke Derek R
Published: March 2017

78

Background: The purpose of this analysis was to assess whether the testosterone level measured at the end of short term androgen deprivation therapy (STADT) and prostate radiotherapy (RT) has an impact on treatment outcomes in patients with intermediate risk prostate cancer (IRPC) treated on a randomized trial (PCS III ClinicalTrials.gov #NCT00223145). Methods: From December 2000 to September 2010, 400 patients with IRPC received 6 months of STADT (bicalutamide 50mg die and goserelin 10.8mg x 2) and RT. Castrate level of testosterone was defined as <1.7 nmol/L: lower level <0.7 and upper level 0.7-1.7. In 347/400 patients, testosterone levels were available at the end of STADT and were divided into 3 groups based on measured testosterone levels: <0.7, 0.7 to 1.7 and >1.7 nmol/L. Patient’s characteristics were compared with ANOVA and Fisher’s exact test. Biochemical failure, prostate cancer recurrence and death were compared with Cox regression. Results: Patient’s characteristics were well balanced between the 3 groups with no statistical difference for age, performance status, PSA at start, Gleason score and stage. At the end of STADT 55.3% (192/347) presented testosterone levels <0.7 and 38.9% (135/347) levels between 0.7 and 1.7 for a total of 94.2% (327/ 347) reaching castrate levels ≤1.7 nmol/L. In 5.8% of patients (20/347) a castrate testosterone level was not achieved. With a median follow-up of 8.1 years, outcomes are shown in the table. Conclusions: In IRPC patients treated with STADT and RT, the majority of patients (94.2%) achieve a castrate level of testosterone (<1.7 nmol/L). Although we could not show a difference in outcomes between castrate and non-castrate patients, these data have to be viewed with caution given the small number of non-castrate patients studied. Source of Funding: AstraZeneca Pharmaceuticals Grant. Clinical trial information: NCT00223145. [Table: see text]
Does a community cancer center one-day prostate cancer multidisciplinary clinic result in a change in treatment recommendation?
Authors: Cushman Taylor Reid , Mashni Joseph W , Kumar Rachit
Published: March 2017

82

Background: Multi-disciplinary clinics (MDCs) offer patients the opportunity to meet with multiple providers to discuss treatment options for recently diagnosed prostate cancer. Multiple academic centers have published their experience with these clinics. However, this approach has been sparsely reported in the community setting. Herein, we assess if an MDC results in more appropriate treatment recommendations for patients based on NCCN risk category compared to incoming (non-MDC) treatment recommendations. Methods: A retrospective chart review of patients evaluated in the institutional prostate cancer MDC clinic were reviewed over a 22 month period (January 2015 through October 2016). A single urologist and radiation oncologist served as clinic consultants for all patients. Patients were asked to report the recommendation for treatment prior to evaluation in the MDC clinic, and the patient selection for treatment after evaluation in the MDC clinic. Changes in treatment recommendation were recorded based on NCCN risk category (low [LR], intermediate [IR], and high [HR] risk groups). Results: Eighty patients were evaluated in the MDC. Of the 80 patients, 64 (80%) chose to continue care with the providers in the prostate MDC. Evaluable records (i.e. initial treatment recommendations) were available for 46 of the 64 patients (72%). Median age of the evaluable patients was 67 years (range 43-83). By risk category, 15 (33%) were LR, 21 (46%) were IR, and 10 (22%) were HR. Eleven patients in the LR group (73%) had altered treatment recommendations, 82% of whom were changed from any treatment (surgery or radiation) to active surveillance. Ten patients in the IR group (48%) and four patients in the HR group (40%) had altered treatment recommendations, mostly from surgery to radiation +/- ADT (50% in the IR, and 75% in the HR group). For all patients seen in the MDC, eight (10%) enrolled on a clinical trial (prostate stereotactic radiation). Conclusions: Implementation of a community-based, one-day prostate MDC resulted in significant changes in treatment recommendations, particularly in increasing active surveillance for LR patients and reducing surgical intervention in IR and HR patients.
Focal cryo-hemiablation to treat unilateral localized prostate cancer: A prospective midterm oncologic and functional outcomes.
Authors: Baghdadi Mohammed , Barret Eric , Sivaraman Arjun , Sanchez-Salas Rafael , Nunes-Silva Igor , Srougi Victor , Ahallal Youness , Rembeyo Gregory , Barreras Silvia Garcia , Rozet François , Galiano Marc , Cathelineau Xavier
Published: March 2017

e537

Background: We report our mid-term oncologic and functional outcomes of focal cryo-hemiablation (FC-HA) for unilateral localized low-risk prostate cancer (PCa). Methods: Prospective single-arm interventional study analyzing mid-term data of PCa patients treated at our institution with FC-HA of diseased lobe. Inclusion criteria‎ were men with unilateral localized cancer, PSA < 15 ng/ml, clinical stage T1c-T2a, Gleason score ≤ 7 (3+4), maximum number of cancer-cores < 33%, maximum cancer involvement in a single core < 50%, no extra prostatic extension in mp-MRI, no previous PCa-related treatment and life expectancy ≥10 yr. PSA was measured every 3 mo during 1st yr post treatment, and biannually thereafter. mp-MRI and biopsy of both lobes were routinely done at 12 mo, while repeat biopsies were driven by PSA elevations. Continence, urinary and erectile functions were assessed using ICS, IPSS and IIEF-5 questionnaires, respectively. Treatment failure (primary outcome) was defined as residual cancer in treated lobe at follow up. Results: We studied 52 men with mean (SD) age of 65.8 (7.2) yrs and median (IQR) follow-up of 31 (21-44) mo. Baseline criteria were: median (IQR) of PSA of 6.8 (5.4–8.0) ng/ml, total number of cancer-cores of 2 (1-3) and percentage cancer-cores of 17% (8-25), and total cancer-core length of 7 (3-12) mm. Gleason score was 6 (3+3) in 33 (63.5%) and 7 (3+4) in 19 (36.5%) patients. Follow-up biopsies were done in 1st, 2nd and 3rd yrs for 52 (100%), 28 (53.8%) and 15 (28.8%) patients, respectively, revealing cancer-cores in 13/52 (25%) patients. 6 (11.5%), 5 (9.6%) and 2 (3.8%) patients showed cancer in ipsilateral lobe, contralateral lobe and bilaterally, respectively. Treatment failure was observed in the treated lobe in 8 (15.4%) patients. Median (IQR) PSA significantly (p < 0.0001) declined to nadir PSA of 2.9 (1.5-4.2) ng/ml (57.4% reduction) at 3 mo. None of patients demonstrated undetectable PSA. All patients maintained continence with insignificant worsening of IPSS (p <0.92) and IIEF-5 (p <0.07) and low toxicity. Conclusions: FC-HA appears to maintain acceptable oncologic control in mid-term follow-up with preserved genitourinary functions and low toxicity.
Prostate cancer stage at diagnosis: First data from a Middle-Eastern cohort.
Authors: Mukherji Deborah , Abed El Massih Sarah , Daher Marilyne , Chediak Alissar , Charafeddine Maya , Shahait Mohammed , Temraz Sally Naji , Geara Fady B. , El Hajj Albert , Nasr Rami , Wazzan Wassim , Bulbul Mohammad , Khauli Raja , Shamseddine Ali
Published: March 2017

e552

Background: Current data suggest that prostate cancer incidence is increasing in the Middle East and North Africa (MENA) region however remains significantly lower than the United States and Europe. No data are available regarding stage at diagnosis or treatment. SEER data from the US suggest that only 4% of patients present with metastatic disease. We hypothesized that rates of presentation with stage 4 disease are significantly higher in the MENA region. Methods: After IRB approval, a review of prostate cancer cases presenting to the leading tertiary referral center in Lebanon from January 2010 to July 2015 was undertaken. From September 2014 these data were collected prospectively. The American University of Beirut Medical Center sees approximately one third of all cancer cases in the country and is a major referral center for Syria and Iraq. Results: 582 cases were identified, median age at diagnosis was 68 (range 43-97); median PSA at diagnosis was 10.2ng/ml (range 2.3 – 3490), median Gleason score was 7. 480 patients had staging data available; 77.4% (449) presented with organ-confined disease, 22.6% (136) presented with stage 4 disease at diagnosis. 12% of this cohort were from Iraq, 57.6% presenting with stage 4 disease. Increasing age correlated with higher stage at presentation in this cohort. In patients presenting with PSA > 20, 62.3% were found to have stage 4 disease. Conclusions: This is the first report of prostate cancer stage at diagnosis from a large cohort of patients from the Middle East showing a median age at diagnosis of 68 and 22.6% presenting with stage 4 disease. These data highlight the importance of multi-disciplinary management and health-care system planning for the rising burden of prostate cancer affecting the MENA population.
Predictive factors and the important role of detectable prostatic specific antigen for the detection of clinical recurrence following robot-assisted radical prostatectomy.
Authors: Barreras Silvia Garcia , Rozet François , Nunes-Silva Igor , Srougi Victor , Baghdadi Mohammed , Sanchez-Salas Rafael , Barret Eric , Galiano Marc , Prapotnich Dominic , Cathelineau Xavier
Published: March 2017

e567

Background: To evaluate predictive factors associated with detectable prostate-specific antigen (PSA) and clinical recurrence (CR) after robot assisted radical prostatectomy (RARP). Methods: The study included 2500 patients who were treated with RARP between 2000 and 2016. Patients were divided into two groups according to PSA value at 6 weeks after surgery: undetectable PSA (PSA < 0.1 ng/dl) and PSA persistently elevated (PSA ≥ 0.1 ng/dl). Logistic regression analysis was used to evaluate association between covariates and: (1) detectable PSA, (2) CR (positive imaging during follow up) in persistently elevated PSA group. Kaplan-Meier analyses were used to assess CR and cancer-specific mortality (CSM) rates according to PSA persistence after surgery. Results: Overall, 229 patients (9.16%) experienced PSA persistence and from them, 38 (16.5%) had CR. Inside the group of detectable PSA ,146 men (63.75%) received adjuvant treatments and 44 (19.21%) salvage therapies. Gleason ≥ 7, ≥ pT3a, PSA > 10 ng/dl and positive margins were found as significant predictive factors of detectable PSA after surgery (all p < 0.001). Within patients with detectable PSA, stage ≥ pT3a (HR: 2.71; 95% CI, 1.10-6.67; p < 0.029) and to received adjuvant ADT (HR: 13.36; 95% CI, 5.18-34.48; p < 0.001) were associated with CR. CR-free survival in Gleason ≤ 6 at 3-year was 100% vs 60% for Gleason 7(4+3) and 20% for Gleason ≥ 8, (p 0.02). Men aged < 65 years had higher 3-year CR-free survival than older (35% vs 20%, p 0.05). 10-year CSM rates were higher for patients with CR (25% vs 0% no CR; p < 0.001), for men with Gleason ≥ 8 (10% at 10-y; p 0.003) and pathological stage ≥ pT3a (9% at 10-y; p 0.05). CSM rate for patients who received adjuvant ADT+ RT was 20%, 10% for men with ADT and 0% for patients without adjuvant treatment at 10-year (p 0,03). Conclusions: A detectable PSA is clearly affected by factors associated with high risk prostate cancer. Stage pT3 and adjuvant ADT have an important prognostic value in the prediction of CR. Patients with CR , Gleason ≥ 8, pathologic stage ≥ pT3 and those who are treated with adjuvant ADT+ RT must have a close monitoring due to the high rate of mortality.
Questionnaire to evaluate prostate cancer multidisciplinary committees in Spain.
Authors: Cassinello Javier , Henríquez López Iván , Gonzalez del Alba Aranzazu , González San Segundo Carmen , López Torrecilla José , Gallardo Díaz Enrique , Rodríguez Antolín Alfredo , Juárez Álvaro , Unda Miguel , Arranz Arija Jose Angel
Published: March 2017

e568

Background: Prostate Cancer (PC) management through Multidisciplinary Committees (MDC) has demonstrated some benefits that could be relevant in patient's outcomes. In Spain MDC are widely implemented although they are not homogeneous among hospitals. The aim of the study was to design a questionnaire to evaluate the functionality/effectiveness of PC MDC in Spain. Methods: The questionnaire was developed from a literature review (22 articles included) and validated by 9 opinion leaders (3 medical oncologists, 3 urologists and 3 radiation oncologists). Experts scored each questionnaire item regarding its ability to assess MDC functionality/effectiveness to obtain a final score of each hospital (from 0-minimum to 100-best functionality/effectiveness) used to classify them according to the cluster analysis (high/intermediate/low level of functionality/effectiveness). The questionnaire was distributed to different specialties by the Spanish Societies of Urological Cancer (URONCOR, GUO and SOGUG). Results: 218 physicians answered the questionnaire, 90 medical oncologists, 86 urologists and 42 radiation oncologists, from 109 hospitals with national representativeness. 91% of hospitals had a Urological MDC, 5% a PC MDC and 4% a General Tumour Committee. Core medical specialities (Urology, Medical Oncology, Radiation Oncology, Pathology, Radiology) were represented in > 80% of MDC. Only 9% MDC discussed the treatment of all patients with PC whereas in 60% of MDC less than 50% of the whole population of PC patients were evaluated. According to 95% of physicians, agreement in therapeutic strategies were reached in > 80% of cases discussed. A score was established that allowed the classification of MDC in each center according to its functionality into 3 clusters: 43% of centers fell in cluster 3 (high), 36% in cluster 2 (intermediate) and 21% in cluster 1 (low). Conclusions: Urological Cancer MDC is a widespread practice in Spain, which comprises a wide range of medical specialists that meet regularly to agree on therapeutic strategies for PC patients. Less than 50% of total PC patients are evaluated in Urological MDC. It is still necessary to improve some aspects allowing more hospitals to reach a higher level of functionality.
Impact of pharmacist-led monitoring of olaparib (O) for metastatic castrate resistant prostate cancer (mCRPC).
Authors: McNatty Andrea , Dow Elizabeth , Bryce Alan Haruo
Published: March 2017

e569

Background: O is a PARP inhibitor that has received breakthrough designation for use in mCRPC based on a study in which a subset of 16 patients with DNA repair defects had an 80% response rate. O is an oral tablet taken twice daily. Studies have demonstrated that compliance with oral agents is often poor, and the less frequent contact with medical staff increases the risk of toxicities when compared to IV therapies. This is compounded by a bias where oral medications are thought of as less toxic than IV medications. The toxicities of O include myelosuppression, nausea, vomiting, and fatigue. Our practice employs a pharmacist to conduct weekly phone calls for toxicity management, monitor patient adherence, and monitor for drug-drug interactions. We report our experience with patient adherence, toxicities, and response with O in mCRPC. Methods: A single institution, retrospective review was performed on 14 mCRPC patients treated with O from November 2015 - October 2016. Adherence and toxicity data were assessed and documented via phone calls conducted by a clinical pharmacist. The primary outcomes were number of missed doses, incidence of toxicities, and dose modifications. The secondary outcome was response rate, defined as a 50% reduction in PSA or radiographic response according to RECIST 1.1 for a duration of greater than 3 months. Results: Patients reported taking 99% of the prescribed doses. The toxicities observed most commonly were fatigue (64%), nausea (57%) and anemia (57%). As a result of toxicities, four patients required a dose reduction to 300 mg BID, three patients required a dose reduction to 200 mg BID and two patients were initiated on 200 mg BID and maintained on that dose until progression. Partial responses were seen in 6 of 14 patients. Conclusions: Our pharmacist led adherence program facilitated timely dose adjustments and high patient adherence. Response rates were comparable to published data.