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- EAU Guidelines on Prostate Cancer. Part II: Treatment of Advanced, Relapsing, and Castration-Resistant Prostate Cancer. [JOURNAL ARTICLE]
- Eur Urol 2013 Nov 12.
To present a summary of the 2013 version of the European Association of Urology (EAU) guidelines on the treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC).The working panel performed a literature review of the new data (2011-2013). The guidelines were updated, and levels of evidence and/or grades of recommendation were added to the text based on a systematic review of the literature that included a search of online databases and bibliographic reviews.Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). LHRH antagonists decrease testosterone without any testosterone surge, and they may be associated with an oncologic benefit compared with LHRH analogues. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation results in noninferior oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir and after radiation therapy (RT). Therapy for PSA relapse after RP includes salvage RT (SRT) at PSA levels <0.5 ng/ml and SRP or cryosurgical ablation of the prostate in radiation failures. Endorectal magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (PET/CT) are of limited importance if the PSA is <1.0 ng/ml; bone scans and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include analysis of PSA and testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Treatment of CRPC includes sipuleucel-T, abiraterone acetate plus prednisone (AA/P), or chemotherapy with docetaxel at 75mg/m(2) every 3 wk. Cabazitaxel, AA/P, enzalutamide, and radium-223 are available for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications.The knowledge in the field of advanced, metastatic, and castration-resistant PCa is rapidly changing. These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice. A full version is available at the EAU office or at www.uroweb.org.We present a summary of the 2013 version of the European Association of Urology guidelines on treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC). Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). LHRH antagonists decrease testosterone without any testosterone surge, and they might be associated with an oncologic benefit compared with LHRH analogues. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation results in noninferior oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir and after radiation therapy. Therapy for PSA relapse after RP includes salvage radiation therapy at PSA levels <0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures. Multiparametric magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (PET/CT) are of limited importance if the PSA is <1.0 ng/ml; bone scans, and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include analysis of PSA and testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Treatment of castration-resistant CRPC includes sipuleucel-T, abiraterone acetate plus prednisone (AA/P), or chemotherapy with docetaxel 75mg/m(2) every 3 wk. Cabazitaxel, AA/P, enzalutamide, and radium-223 are available for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications. The guidelines reported should be adhered to in daily routine to improve the quality of care in PCa patients. As we have shown recently, guideline compliance is only in the area of 30-40%.
- Salvage therapy of small volume prostate cancer nodal failures: A review of the literature. [JOURNAL ARTICLE]
- Crit Rev Oncol Hematol 2013 Nov 21.
New imaging modalities may be useful to identify prostate cancer patients with small volume, limited nodal relapse ("oligo-recurrent") potentially amenable to local treatments (radiotherapy, surgery) with the aim of long-term control of the disease, even in a condition traditionally considered prognostically unfavorable. This report reviews the new diagnostic tools and the main published data about the role of surgery and radiation therapy in this particular subgroup of patients.
- Association of early PSA failure time with increased distant metastasis and decreased survival in prostate brachytherapy patients. [JOURNAL ARTICLE]
- Radiother Oncol 2013 Nov 30.
We investigated whether earlier PSA failure following prostate brachytherapy is associated with increased rates of distant metastases (DM), prostate cancer-specific mortality (PCSM), and overall mortality.We retrospectively analyzed 2818 patients who underwent brachytherapy±external beam radiation therapy (EBRT)±androgen deprivation therapy (ADT). With median follow-up of 5.52years, 264 patients experienced PSA failure at a median time of 3.25years. Patients were stratified to early vs. late PSA failures at cutoffs of 1.5years, 3years, or 5years, and tested in univariate/multivariate analyses for freedom from DM, cause-specific survival (CSS), and overall survival (OS).Among patients with PSA failures, 69 (26%) patients experienced DM, 47 (18%) PCSM, and 56 (21%) deaths from other causes. Patients with rapid PSA failures demonstrated increased rates of DM, PCSM, and overall mortality, despite higher total BED and longer ADT. In multivariate analysis with a PSA failure interval <3years, the hazard ratio (HR) for DM was 3.92 (95% CI: 2.34-6.55; p=0.000); HR for PCSM was 2.79 (95% CI: 1.45-5.38; p=0.002); and HR for overall mortality was 2.28 (95% CI: 1.50-3.48; p=0.000).Early PSA failure following radiation is a poor prognostic factor, as it is associated with increased DM, PCSM, and overall mortality.
- Primary signet ring cell carcinoma of the prostate. [JOURNAL ARTICLE]
- Can Urol Assoc J 2013 11; 7(11-12):E768-E771.
A 61-year-old Korean man was referred to our institution because of high prostate-specific antigen (PSA) (8.1ng/mL) and frequency, nocturia that had lasted for the previous 4 months. The first transrectal ultrasonography (TRUS)-guided prostate biopsy result was benign prostatic hyperplasia. About 3 years later, the patients revisited our institute for elevated PSA (14.7 ng/mL) and back pain. The patient underwent a second TRUS-guided prostate biopsy. Histological examination and immunohistochemical staining showed a signet ring cell carcinoma (SRCC). Also there were multiple bony metastasis. Androgen deprivation therapy (ADT) was started. Nine months later, the patient was diagnosed with hormone refractory prostate cancer and the ADT was changed into docetaxel chemotherapy. The patient died after 2 cycles of chemotherapy. We report this case of a SRCC of the prostate and review the literature.
- Exercise effects on adipokines and the IGF axis in men with prostate cancer treated with androgen deprivation: A randomized study. [JOURNAL ARTICLE]
- Can Urol Assoc J 2013 11; 7(11-12):E692-E698.
Androgen deprivation therapy (ADT) has significant deleterious effects on body composition that may be accompanied by unfavourable changes in adipokine levels. While exercise has been shown to improve a number of side effects associated with ADT for prostate cancer, no studies have assessed the effect of exercise on adiponectin and leptin levels, which have been shown to alter the mitogenic environment.Twenty-six men with prostate cancer treated with ADT were randomized to home-based aerobic exercise training or resistance exercise training for 24 weeks. Adiponectin, leptin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3) were analyzed by ELISA (enzyme-linked immunosorbent assay), in addition to physical activity volume, peak aerobic capacity, and anthropometric measurements, at baseline, 3 months and 6 months.Resistance exercise significantly reduced IGF-1 after 3 months (p = 0.019); however, this change was not maintained at 6 months. At 6 months, IGFBP-3 was significantly increased compared to baseline for the resistance training group (p = 0.044). In an exploratory analysis of all exercisers, favourable changes in body composition and aerobic fitness were correlated with favourable levels of leptin, and favourable leptin:adiponectin and IGF-1:IGFBP-3 ratios at 3 and 6 months.Home-based exercise is correlated with positive changes in adipokine levels and the IGF-axis that may be related to healthy changes in physical fitness and body composition. While the improvements of adipokine markers appear to be more apparent with resistance training compared to aerobic exercise, these findings must be considered cautiously and require replication from larger randomized controlled trials to clarify the role of exercise on adipokines and IGF-axis proteins for men with prostate cancer.
- Anomalously increased oxygen reduction reaction activity with accelerated durability test cycles for platinum on thiolated carbon nanotubes. [Journal Article]
- Chem Commun (Camb) 2014 Jan 18; 50(5):596-8.
We report an anomalous phenomenon in Pt supported on thiolated multi-walled carbon nanotubes (Pt-S-MWNT): oxygen reduction reaction (ORR) activity increases with accelerated durability test (ADT) cycles. Sub-nanometer-sized Pt clusters on S-MWNT were gradually agglomerated to an optimal size with ADT cycles, and finally showed increased ORR activity after the ADT.
- The Cancer of the Prostate Risk Assessment (CAPRA) score predicts biochemical recurrence in intermediate risk prostate cancer treated with external beam radiotherapy (EBRT) dose escalation or low-dose rate (LDR) brachytherapy. [JOURNAL ARTICLE]
- BJU Int 2013 Nov 26.
To study the prognostic value of the University of California, San Francisco Cancer of the Prostate Risk Assessment (CAPRA) score to predict biochemical failure (bF) after various doses of external beam radiotherapy (EBRT) and/or permanent seed prostate brachytherapy (PB).We retrospectively analyzed 345 patients with a PSA 10 - 20 ng/ml and/or Gleason 7 including 244 EBRT patients (70.2 - 80 Gy) and 101 patients treated with PB. Minimum follow up was 3 years. No patient received primary androgen deprivation therapy (ADT). Biochemical failure (bF) was defined according to Phoenix definition. Cox regression analysis was used to estimate the differences between CAPRA groups.Overall bF was 13% (45/345). The CAPRA score as a continuous variable was statistically significant in multivariate analysis for predicting bF (HR: 1.37, 95%CI 1.10-1.72, p=0.006). There was a trend for lower bF rate in patients treated with brachytherapy when compared to those treated by EBRT ≤74 Gy (HR: 0.234, 95%CI 0.05-1.03, p=0.055) in multivariate analysis. In the subgroup of patients with a CAPRA of 3 - 5, CAPRA remained predictive of bF as a continuous variable (HR: 1.51, 95%CI 1.01-2.27, 0.047) in multivariate analysis.The CAPRA score is useful to predict biochemical recurrence in patients treated for intermediate-risk prostate cancer with EBRT or PB. It could help in treatment decisions and can be completed by incorporating Cell Cycle Progression scores.
- Classification of aerodigestive tract invasion from thyroid cancer. [JOURNAL ARTICLE]
- Langenbecks Arch Surg 2013 Nov 24.
Widely invasive extrathyroidal thyroid cancer invading the aerodigestive tract (ADT) including larynx, trachea, hypopharynx, and/or esophagus occurs in 1-8 % of patients with thyroid cancer and is classified as T4a (current UICC/AJCC system). The T4a stage is associated with impaired tumor-free survival and increased disease-specific mortality. Concerning prognosis and outcome, further subdivisions of the T4a stage, however, have not been made so far.This study is based on a systematic review of the relevant literature in the PubMed database.Retrospective studies suggest a better outcome in patients with invasion of the trachea or the esophagus when compared to laryngeal invasion. Regarding surgical strategies, ADT invasion can be classified based on a three-dimensional assessment determining surgical resection options. Regardless of the invaded structure, tumor infiltration of the ADT can be subdivided into superficial, deep extraluminal, and intraluminal invasion. In contrast to superficial ADT invasion, allowing tangential incomplete wall resection (shaving/extramucosal esophagus resection), deeper wall and intraluminal invasions require complete wall resection (either window or sleeve). Based on the Dralle classification (types 1-6), particularly airway invasion, can be further classified according to the vertical and horizontal extents of tumor invasion.The Dralle classification can be considered as a reliable subdivision system evaluated regarding surgical options as well as oncological outcome. However, further studies determining the prognostic impact of this technically oriented classification system are required.
- Clinical outcomes after salvage radiotherapy without androgen deprivation therapy in patients with persistently detectable PSA after radical prostatectomy: results from a national multicentre study. [JOURNAL ARTICLE]
- World J Urol 2013 Nov 24.
To assess oncologic outcomes after salvage radiotherapy (SRT) without androgen deprivation therapy (ADT) in patients with persistently detectable PSA after radical prostatectomy (RT).Two hundred and one patients who failed to achieve an undetectable PSA received SRT without ADT. The primary endpoint was failure to SRT that was defined by clinical progression or use of second-line ADT. Clinicopathological parameters, 6-week PSA level, PSAV and pre-SRT PSA levels were assessed using time-dependent analyses.Median postoperative 6-week PSA and pre-SRT PSA levels were 0.25 and 0.48 ng/mL, respectively. Median time between surgery and SRT was 7 months. Failure to SRT was reported in 42.8 % of cases with the need for second-line ADT in 26.9 % of cases. Pre-SRT PSA was strongly correlated with postoperative 6-week PSA (p < 0.001) but not with PSAV. The risk of SRT failure was increased by threefold in case of Gleason score 8-10 (p = 0.036) or pT3b cancer (p = 0.006). Risk group classification based on these prognostic factors improved SRT failure prediction. Survival curves confirmed that 5-year ADT-free survival rates were significantly influenced by PSAV (p = 0.002) and pre-SRT PSA (p = 0.030).In patients with persistently detectable PSA after RP and selected for local salvage treatment, SRT offers good oncologic clinical outcomes. The most powerful pathologic predictive factors of SRT failure include a pT3b stage, a Gleason score 8 or more cancer and high PSAV and pre-SRT PSA levels. Patients having a high PSAV >0.04 ng/mL/mo would be potentially better candidates for a systemic therapy due to a high SRT failure rate.
- Modeling of bioheat equation for skin and a preliminary study on a noninvasive diagnostic method for skin burn wounds. [JOURNAL ARTICLE]
- Burns 2013 Nov 20.
Heat transfer in a unit three-dimensional skin tissue with an embedded vascular system of actual histology structure is computed in the present work. The tissue temperature and the blood temperatures in artery and vein vessels are solved with a multi-grid system. The mean temperature of the tissue over the cross-section of the unit skin area is evaluated. The resulting one-dimensional function is regarded as the temperature of healthy tissue (or injured skin but the blood perfusion is still normally working) for large area of skin in view of the symmetric and periodic structure of the paired artery-vein vessels in nature. A three-dimensional bioheat equation then is formulated by the superposition of the skin burn wound effect and the healthy skin temperature with and without thermal radiation exposure. When this bioheat equation is employed to simulate ADT process on burn wounds, the decaying factor of the skin surface temperature is found to be a sharply decreasing function of time in the self-cooling stage after a thermal radiation heating. Nevertheless, the boundary of non-healing (needing surgery) and healing regions in a large burn wound can be estimated by tracking the peak of the gradient of decaying factor within 30s after the thermal radiation is turned off. Experimental studies on the full ADT procedure are needed to justify the assumptions in the present computation.