mPCa Patients Research Articles

Method for semi-automated microscopy of filtration-enriched circulating tumor cells.

BackgroundCirculating tumor cell (CTC)-filtration methods capture high numbers of CTCs in non-small-cell lung cancer (NSCLC) and metastatic prostate cancer (mPCa) patients, and hold promise as a non-invasive technique for treatment selection and disease monitoring. However filters have drawbacks that make the automation of microscopy challenging. We report the semi-automated microscopy method we developed to analyze filtration-enriched CTCs from NSCLC and mPCa patients.MethodsSpiked cell lines in normal blood and CTCs were enriched by ISET (isolation by size of epithelial tumor cells). Fluorescent staining was carried out using epithelial (pan-cytokeratins, EpCAM), mesenchymal (vimentin, N-cadherin), leukocyte (CD45) markers and DAPI. Cytomorphological staining was carried out with Mayer-Hemalun or Diff-Quik. ALK-, ROS1-, ERG-rearrangement were detected by filter-adapted-FISH (FA-FISH). Microscopy was carried out using an Ariol scanner.ResultsTwo combined assays were developed. The first assay sequentially combined four-color fluorescent staining, scanning, automated selection of CD45− cells, cytomorphological staining, then scanning and analysis of CD45− cell phenotypical and cytomorphological characteristics. CD45− cell selection was based on DAPI and CD45 intensity, and a nuclear area >55 μm2. The second assay sequentially combined fluorescent staining, automated selection of CD45− cells, FISH scanning on CD45− cells, then analysis of CD45− cell FISH signals. Specific scanning parameters were developed to deal with the uneven surface of filters and CTC characteristics. Thirty z-stacks spaced 0.6 μm apart were defined as the optimal setting, scanning 82 %, 91 %, and 95 % of CTCs in ALK-, ROS1-, and ERG-rearranged patients respectively. A multi-exposure protocol consisting of three separate exposure times for green and red fluorochromes was optimized to analyze the intensity, size and thickness of FISH signals.ConclusionsThe semi-automated microscopy method reported here increases the feasibility and reliability of filtration-enriched CTC assays and can help progress towards their validation and translation to the clinic.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2461-4) contains supplementary material, which is available to authorized users.

Clinical and radiological characteristics of metastatic prostate cancer (mPCa) patients (pts) with liver metastases (LM) and association with overall survival (OS).

5043Background: The diagnosis (Dx) of LM in PCa pts carries a poor prognosis and its incidence is increasing. We conducted a retrospective analysis to identify clinical and radiological factors ass...

The Irish Programme for Stratified Prostate Cancer Therapy (iPROSPECT).

335 Background: iPROSPECT is a prospective longitudinal translational study, funded through the Irish Cancer Society in partnership with Movember that is examining blood and tissue markers that might correlate with treatment response and survival and aid future stratification of metastatic prostate cancer (mPCa) patients with regard to optimal personalised treatment regimens. Methods: Patients with metastatic prostate cancer who are beginning or changing treatment are eligible for inclusion. Nine hospital sites supported by four research laboratories are open to recruitment. Cohort 1 (n = 15) includes patients with newly diagnosed mPCa who are beginning treatment with androgen deprivation therapy (ADT). Cohort 2 (n = 45) includes patients with CRPC who are beginning or changing treatment. All enrolled patients have blood drawn for plasma, serum and CTC analysis at baseline and thereafter every 4 months. All eligible patients with metastatic bone disease are offered an optional substudy of bone marrow biopsy performed prior to starting treatment. Any patient with visceral or nodal disease is offered a targeted CT guided biopsy. All patients are offered the PCa Research Consortium questionnaire, FACT-P and the Brief Pain inventory short form. Results: Between March and August 2015, 15 patients within cohort 1 (100%) have been enrolled and 22 patients in cohort 2 (48.8%). In cohort 1, the median age of patients was 66, median PSA at entry was 9.2 with an average Gleason score of 8. In cohort 2, the median age of patients was 68, median PSA at entry was 236.4 with an average Gleason score of 8. Eight patients underwent bone marrow biopsy, and 2 patients underwent CT guided biopsies. All patients had archival FFPE tissue collected. Questionnaires were collected from all eligible patients. Conclusions: The recruitment rate to date has indicated successful implementation of this study. Results will identify how clinical and biological patterns change over time and relate to each individual’s treatment response and progression of disease. [Table: see text]

MP73-15 PROSTATE-SPECIFIC ANTIGEN HALF-LIFE IDENTIFIED AT THE FIRST FOLLOW UP TIME IS AN EARLY PROGNOSTIC FACTOR OF NEWLY DIAGNOSED METASTATIC PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced I1 Apr 2015MP73-15 PROSTATE-SPECIFIC ANTIGEN HALF-LIFE IDENTIFIED AT THE FIRST FOLLOW UP TIME IS AN EARLY PROGNOSTIC FACTOR OF NEWLY DIAGNOSED METASTATIC PROSTATE CANCER Ki Hong Kim, Kyung Seok Han, and Sung Joon Hong Ki Hong KimKi Hong Kim More articles by this author , Kyung Seok HanKyung Seok Han More articles by this author , and Sung Joon HongSung Joon Hong More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2691AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Several prostate-specific antigen (PSA) kinetics parameters such as nadir PSA or time to nadir PSA are used commonly as predictive prognostic factors for metastatic prostate cancer (mPCa) patients who have undergone androgen deprivation therapy (ADT). However, they had the limitation in that they were recorded at the same time as when the PSA declined in response to ADT to its lowest point, which is a time point that cannot be predicted in advance. Therefore, earlier and more clinically available prognostic factors are needed. We examined the PSA half-life (PSAHL) estimated at the first follow-up visit as a prognostic factor of newly diagnosed mPCa. METHODS We performed a retrospective review of 398 newly diagnosed mPCa patients who had undergone ADT. After categorizing the included patients to a long and short PSAHL groups based on a cut-off value identified by Contal and O'Quigely's method, Cox regression analyses were performed to identify independent prognostic factors of newly diagnosed mPCa. The Kaplan-Meier method was used for detecting differences in survival between the two groups. RESULTS Long PSAHL group (HR: 2.383; p<0.001), nadir PSA (HR: 1.004; p<0.001), time to nadir PSA (HR: 0.856; p<0.001), and Gleason score (HR: 2.025; p=0.008) were found to be independent predictors. By the Kaplan-Meier method, the median PCSM-free survival of the short PSAHL group was 73.7 (95% CI, 54.8-92.6) and of the long PSAHL group was 52.5 months (95% CI, 33.4-71.6). This difference between the two groups was found to be statistically significant (p=0.014, log rank test). CONCLUSIONS PSAHL estimated at the first follow-up visit is an independent prognostic factor for newly diagnosed mPCa. If the prospective validation test is performed on a large scale, it may demonstrate that PSAHL is an early surrogate prognostic factor of newly diagnosed mPCa. Table. Predictors of prostate cancer specific mortality (PSAHL as categorical variable) Variable HR 95% CI P Bone pain relative to absence presence 1.468 0.732-2.942 0.279 Gleason score relative to 6-7 8-10 2.025 1.207-3.400 0.008 Clinical T stage relative to <4 ≥4 1.468 0.732-2.942 0.279 Clinical N stage relative to 0 1 1.379 0.954-1.994 0.087 Nadir PSA 1.004 1.002-1.005 <0.001 TTN 0.856 0.823-0.890 <0.001 PSAHL relative to short PSAHL group Long PSAHL group 2.383 2.383 <0.001 ADT, androgen deprivation therapy; IQR, interquartile range; PSA, prostate specific antigen; PS, performance status; TTN, time to nadir PSA; PSAHL, prostate specific antigen half-life © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e935-e936 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ki Hong Kim More articles by this author Kyung Seok Han More articles by this author Sung Joon Hong More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Identifying Optimal Candidates for Local Treatment of the Primary Tumor Among Patients Diagnosed with Metastatic Prostate Cancer: A SEER-based Study

A recent study observed a survival benefit in men diagnosed with metastatic prostate cancer (mPCa) and managed with local treatment of the primary tumor (LT; either radical prostatectomy plus pelvic lymph node dissection or radiation therapy). We tested the hypothesis that only specific mPCa patients would benefit from LT and that the potential benefit would vary based on primary tumor characteristics. A total of 8197 mPCa patients at diagnosis (M1a, M1b, and M1c) were identified using the Surveillance Epidemiology and End Results database (2004–2011) and were divided according to treatment type: LT versus nonlocal treatment of the primary tumor (NLT; either androgen deprivation therapy or observation). Multivariable Cox regression analysis was used to predict cancer-specific mortality (CSM) in patients that received NLT. To assess whether the benefit of LT was different by baseline risk, we tested an interaction with CSM risk and LT. At multivariable analysis, all predictors were significantly associated with CSM, and the interaction test was statistically significant (p<0.0001). Local treatment of the primary tumor, compared with NLT, conferred a higher CSM-free survival rate in patients with a predicted CSM risk <40%. The number needed to treat according to the predicted CSM risk at 3 yr after diagnosis remained substantially constant from 10% to 30%, whereas it exponentially increased for predicted CSM risk >40%. These results should serve as a foundation for future prospective trials. Patient summaryAmong metastatic prostate cancer patients, the potential benefit of local treatment to the primary tumor depends greatly on tumor characteristics, and patient selection is essential to avoid either over- or undertreatment.

9310 The cytotoxic activity of the phage E protein suppress the growth of murine B16 melanomas in vitro and in vivo

A recent study observed a survival benefit in men diagnosed with metastatic prostate cancer (mPCa) and managed with local treatment of the primary tumor (LT; either radical prostatectomy plus pelvic lymph node dissection or radiation therapy). We tested the hypothesis that only specific mPCa patients would benefit from LT and that the potential benefit would vary based on primary tumor characteristics. A total of 8197 mPCa patients at diagnosis (M1a, M1b, and M1c) were identified using the Surveillance Epidemiology and End Results database (2004–2011) and were divided according to treatment type: LT versus nonlocal treatment of the primary tumor (NLT; either androgen deprivation therapy or observation). Multivariable Cox regression analysis was used to predict cancer-specific mortality (CSM) in patients that received NLT. To assess whether the benefit of LT was different by baseline risk, we tested an interaction with CSM risk and LT. At multivariable analysis, all predictors were significantly associated with CSM, and the interaction test was statistically significant (p < 0.0001). Local treatment of the primary tumor, compared with NLT, conferred a higher CSM-free survival rate in patients with a predicted CSM risk <40%. The number needed to treat according to the predicted CSM risk at 3 yr after diagnosis remained substantially constant from 10% to 30%, whereas it exponentially increased for predicted CSM risk >40%. These results should serve as a foundation for future prospective trials.Among metastatic prostate cancer patients, the potential benefit of local treatment to the primary tumor depends greatly on tumor characteristics, and patient selection is essential to avoid either over- or undertreatment.