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178 Abstracts

  • Introduction & Objectives

    Deregulation of FGF-2 expression is a frequent event in prostate cancer. It has previously been suggested that FGF-2 is secreted by stroma cell as paracrine growth factor at early stage of tumour development whereas later stages are characterized by a primarily autocrine secretion that renders tumour cells independent from microenvironmental signaling cues.

    Material & Methods

    We used a tissue microarray consisting of 571 tumour cores from 165 prostate cancer patients to show that this notion needs to be revisited. An immunohistochemical  protocol was used to assess FGF-2 expression in tumour and stroma cells. Tumour cells and stroma cells were examined and scored separately.

    Results

    FGF-2 was strongly expressed in tumour cells in %32.1 (53/165) patients and in stroma cells in %16.4 (27/165) patients. We surprisingly found that stromal FGF-2 expression was significantly correlated with poor BCR-free survival (p <0.05) while tumour-associated FGF-2 expression did not predict survival. In addition, higher stromal FGF-2 expression was closely related with Gleason grade (p ≤ 0.005) and clinical stage (p < 0.005). FGF-2 expression levels were found to be related with metastasis in both tumour cells (p<0.05) and stroma cells (p < 0.01).

    Conclusions

    Our results show that microenvironmental effects play a critical role in tumour progression and disease outcomes, moreover these results may be suggested that FGF-2 expression in stroma cells can be used as an independent prognostic factor for prostate cancer.

  • Introduction & Objectives

    After cystectomy, >40% of patients (pts) with muscle-invasive UBC (MIUBC) will develop a recurrence. Despite neoadjuvant chemotherapy is recommended, a minor survival benefit compared to cystectomy alone is deemed. SGC combination is an open-label, single-group, phase 2 trial (NCT01222676).

    Material & Methods

    Patients with T2-T4a N0 UBC received 4 cycles of cisplatin 70 mg/m2 day 1, and gemcitabine 1000 mg/m2 day 1 and 8, q3 weeks. Sorafenib 400 mg q12h was administered daily from day 1 until radical cystectomy. Intention-to-treat analysis was applied. In a Simon’s 2-stage design, 45 pts will be accrued and the rate of pathologic complete responses (pT0) is the primary endpoint. Residual carcinoma in situ was considered as pT0. The treatment will be considered active with ≥14 pT0, assuming H0: £0.20 and H1: ³0.40 (Type I and type II error of 5% and 10%). Molecular characterization of responders is planned through Next Generation Sequencing (NGS). DNA was isolated from FFPE of TURB samples using the GeneRead DNA FFPE kit™ (Qiagen). Ion AmpliSeq™ Comprehensive Cancer Panel (Life Technologies) was utilized, targeting the coding sequences of 406 genes, the Ion AmpliSeq Library Kit2.0™ and the Ion Torrent Personal Genome Machine™ platform (Life Technologies).

    Results

    37 pts were enrolled from 04/11 to 03/15. Median age was 61yrs (IQR: 54-66). 24 (64.9%) had T2, 12 (32.4%) T3, and one a T4. 9 (24%) pts had hydronephrosis. 22 (59.4%) pts had a macroscopical disease before SGC (including bioptic TURB in 9 pts). 34 completed the treatment and are evaluable for the primary endpoint. 17/23 RECIST-evaluable pts had a partial response.
    16 pts (47.1%, 95%CI: 29.8-64.9) had a pT0 (baseline T2 in 13 and T3b in 3) and 20 pts had a pT 9 (26.5%) and 6 (17.6%) pts had G3-4 hematologic and extrahematologic toxicity. After a median follow up of 22.3 months, 5 pts relapsed and 7 pts died (2 for second-cancers). 2-y PFS and OS were 79.4% (95%CI: 54.5-91.6) and 84.6% (95%CI: 63.4-94.1). NGS analyses of 2 cases with exceptional response (T3b who achieved pT0) are available: mutations in chromatin-remodelling genes and transcriptional regulation (SMARCA4 in one case and MLL, EP400, TET2 in the other) as well as in genes involved in NF-kB activation (MALT1, IKBE) were found in both. All mutations were missense substitutions except for the nonsense observed in MLL gene.

    Conclusions

    Pending the completion of accrual, the primary endpoint was met. SGC combination is tolerable and endowed of antitumour activity in MIUBC. NGS might provide insights into the relevant biology of responders, and mature results will be presented.

  • Introduction & Objectives

    The cut-off level of prostate-specific antigen (PSA) at 4.0 ng/ml has been the most important and widely used value in the screening, detection and monitoring of prostate cancer. The aim of this study is to assess the diagnostic significance of prostate-specific antigen (PSA), density (PSAD) accuracy, and PSAD adjusted by transition zone volume (PSATZD) in men with PSA levels between 2.0 and 4.0 ng/ml.

    Material & Methods

    Between 2000 and 2010, 138 men with PSA levels between 2 and 4.0 ng/ml underwent transrectal ultrasonography (TRUS) and 12-core prostate biopsy. Diagnostic accuracies for various cut-offs of PSAD and PSATZD were investigated according to subdivided PSA levels of 2.0 to 3.0 ng/ml and 3.1 to 4.0 ng/ml.

    Results

    The detection rate of prostate cancer was 23, 8% (32/134). The percentage of patients with extracapsular disease was 28.1% (10/32) and primary Gleason grade 4 or 5 was obtained in 8/ 32 cases (25%) patients. The transition zone volume and PSATZD in cancer cases were significantly different in comparison with those in non-cancer cases. The area under the receiver operating characteristic curve for PSATZD was significantly higher in comparison with that for PSAD in the same subdivided PSA ranges. The diagnostic efficiency for PSATZD was higher than that for PSAD. The diagnostic efficiency showed the highest value at the cut-off level for PSATZD of 0.23 and 0.28 in men with PSA levels of 2.0 to 3.0 ng/ml and 3.1 to 4.0 ng/ml, respectively.

    Conclusions

    The use of PSATZD cut-offs as a biopsy indication may reduce many unnecessary biopsies without missing most prostate cancer cases in the PSA range of 2.0 to 4.0 ng/ml.

  • Introduction & Objectives

    There is no standard treatment for nonmetastatic castration-resistant prostate cancer (nmCRPC) besides continuing androgen deprivation therapy (ADT). Preventing metastatic disease in nmCRPC is a major unmet need. Patients with nmCRPC who have shorter prostate-specific antigen (PSA) doubling time (PSADT) are at high risk for metastatic disease or death (Smith et al. J Clin Oncol. 2013;31:3800-3806). ODM-201, a novel second-generation oral androgen receptor inhibitor, has shown an excellent safety profile and promising anticancer activity in progressive CRPC (Fizazi et al. Lancet Oncol. 2014;15:975-985). The ARAMIS trial aims to evaluate the efficacy and safety of ODM-201 in high-risk nmCRPC.

    Material & Methods

    This international, randomized, double-blind, placebo-controlled phase 3 trial (NCT02200614) involves over 300 sites in more than 30 countries. 1500 patients on ADT will be randomized 2:1 to ODM‑201 600 mg or placebo twice daily. Patients will be stratified by PSADT and baseline use of a bone-targeting agent. Eligibility criteria include nmCRPC, PSADT ≤ 10 months, and screening PSA ≥ 2 ng/mL. Endpoints will be analysed using a stratified log-rank test, accounting for stratification. The trial has 90% power to detect a target hazard ratio of 0.75 based on a 2-sided log-rank test at an overall significance level of 0.05. Kaplan-Meier estimates will be produced for both treatment groups.

    Results

    The primary endpoint is metastasis-free survival based on central independent review of bone scan and CT/MRI every 16 weeks; progression of regional disease is not considered metastasis. Secondary endpoints are overall survival, time to first symptomatic skeletal event, initiation of first cytotoxic chemotherapy for prostate cancer, and pain progression. Additional endpoints are progression-free survival, time to first prostate cancer–related invasive procedure, initiation of subsequent antineoplastic therapy, PSA progression, change in ECOG status, and changes in health-related quality of life.

    Conclusions

    The ARAMIS trial is open and recruiting, with the first patient randomized in October 2014.

  • Introduction & Objectives

    To declare the indications of uretero-sigmoidostomy after radical cystectomy in modern urology.

    Material & Methods

    Between January 2004 and December 2013, 1080 radical cystectomies followed by uretro-sigmoidostomy were performed out of all urinary diversion procedures in our center. We retrospectively revised the indication of this operation in those patients. At the time of abstract submission, 501 (46.4%) patients are still alive. Evaluation included clinical and radiographic studies to determine the functional and oncological outcomes.

    Results

    The age range was 38-71 years. 820 patients (75.9%) were males and 260 (24.1%) were females. Early complications occurred in 179 patients (16.5 %). According to the modified Clavien system, It was Grade I in 55 patients, grade II in 43, grade IIIA in 22, IIIB in 19, grade IVa in 12, grade IVb in 9 and grade V in 19 patients. Late complications occurred in 389 (36%) patients. Daytime and nighttime continence were 88.8% and 86% respectively. Indications of uretero-sigmoidostomy were bladder neck tumors in markedly obese patients (BMI ≥ 40), previous multiple ileal resections, patients with multiple co-morbidities, intraoperative difficulties nessicitating rapid termination of the procedure, patients refusing the ileal conduit and those with physical or mental impairment who could not care with either the neobladder or the ileal conduit.

    Conclusions

    Inspite of being the least desired form of continent urinary diversion, uretero-sigmoidostomy still serves a larger number of patients in our country either due to advanced stage at presentation or in patients refusing the ileal conduit due to cultural and psychological purposes.

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