New anti-angiogenic targeted therapy in advanced renal cell carcinoma (RCC): Current status and future prospects

Objectives: To address the rationale for anti-angiogenic targeted therapies in advanced RCC. Methods: We reviewed the international recent literature, using Pubmed search. Results: RCC is genetically linked to factors regulating angiogenesis, in particular vascular endothelial growth factor (VEGF). Sunitinib is a multitarget receptor tyrosine-kinase (TK) inhibitor, acting on VEGF receptor (VEGFR) and platelet-derived growth factor receptors (PDGFR). Sorafenib is an oral multikinase inhibitor (VEGFR and PDGFR) showing also inhibitors effect on the Raf system. Phase I trials showed no life threatening toxicities relates to these agents. Phase II and phase III trials showed that these antiangiogenic agents are effective in the treatment of advanced RCC, mainly in cytokine refractory metastatic RCC. Survival benefits exist in particular when advanced RCC patients undergo cytoreductive nephrectomies before the initiation of the systemic therapy. To better use this kind of targeted therapy in advanced RCC, different points must be developed: the identification of clinical characteristic of RCC able to predict outcomes and responses to therapy; differences among different compounds; advantages of combination or sequential therapies. Conlusions: Targeted therapy with Sunitinib and Sorafenib has been approved to FDA and is revolutioning how we clinically approach advanced RCC. © 2008 Bentham Science Publishers Ltd

Use of 3D T2-Weighted MR Sequences for the Assessment of Neurovascular Bundle Changes after Nerve-Sparing Radical Retropubic Prostatectomy (RRP): A Potential Diagnostic Tool for Optimal Management of Erectile Dysfunction after RRP

Erectile dysfunction (ED) is one of the complications after radical retropubic prostatectomy (RRP), and recovery of erectile function is quantitatively related to the preservation of the neurovascular bundles (NVBs). The aim of our study was to assess, in patients submitted to a nerve-sparing RRP, the capability of a dedicated 3D isotropic magnetic resonance imaging (MRI) T2-weighted sequence in the depiction of postsurgical changes of NVB formation. Fifty-three consecutive patients underwent a bilateral nerve-sparing RRP. Two postoperative magnetic resonance (MR) examinations and International Index of Erectile Function Five-Item (IIEF-5) questionnaire were carried out at 6 and 12 months. Morphological imaging of the postprostatectomy fossa was performed by first acquiring turbo spin echo T2-weighted sequences in the axial and coronal planes and then with 3D T2-weighted isotropic sequence on axial plane. Image findings were scored using a relative 5-point classification (0 = normal; I = mild; II = mild to moderate; III = moderate; IV = severe alterations) and correlated with postoperative IIEF-5 score questionnaire. The degree of association between the alteration score values obtained by postoperative MR morphologic evaluation for MR sequence and IIEF-5 score. Image interpretation was performed by two radiologists, that scoring MR alterations by the use of axial and multiplanar reconstruction 3D T2 isotropic sequence. The radiologists placed 43.30% of patients in class 0 (23/53 normal or quite normal), 32.00% in class I (17/53 mild), 11.40% in class II (6/53 mild to moderate), 7.50% in class III (4/53 moderate), and 5.70% in class IV (3/53 severe). In all cases, the correlation and regression analyses between the 3D T2 isotropic sequence and IIEF-5 score, resulted in higher coefficient values (rho = 0.45; P = 0.0010). The MRI protocol and NVB change classification score proposed in this study would represent an additional tool in the postoperative phase of those patients with ED. Sciarra A, Panebianco V, Salciccia S, Alfarone A, Gentilucci A, Lisi D, Passariello R, and Gentile V. Use of 3D T2-weighted MR sequences for the assessment of neurovascular bundle changes after nerve-sparing radical retropubic prostatectomy (RRP): A potential diagnostic tool for optimal management of erectile dysfunction after RRP. J Sex Med 2009;6:1430-1437

Predictors for response to intermittent androgen deprivation (IAD) in prostate cancer cases with biochemical progression after surgery

Objective: To define characteristics of the first cycle of intermittent androgen deprivation (IAD) that would predict for outcomes in a long term follow-up. Material and methods: In 1996 we started a prospective study of IAD for the treatment of biochemical progression (BP) after radical prostatectomy (RP) for prostate cancer (PC). The end-points of the trial were time to clinical progression (CP) and time to castration resistance PC (CRPC). Eighty-four cases were included in the study. In all cases, after an initial induction period, an acceptable nadir to switch from on-to-off-phase of IAD was considered to be a serum PSA 0.4 ng/ml and for those with an off-phase interval 48 weeks, respectively. Conclusions: Cases with BP after RP selected to IAD that show at the first cycle a PSA nadir <= 0.1 ng/ml and a off-phase interval 48 weeks may identify candidates who will experience better response to IAD treatments and delayed CP or CRPC development. (C) 2013 Elsevier Inc. All rights reserved

Prostate cancer unit for an optimal management of prostate cancer unit. ["Prostate cancer unit" per un management ottimale dei pazienti con tumore prostatico]

Prostate cancer (PC) is established as one of the most important medical problems affecting the male population. PC is the most common solid neoplasm (214 cases per 1000 men) and the second most common cause of cancer death in men. Its management involves several complex issues for both clinicians and patients. An early diagnosis is necessary to implement well-balanced therapeutic options, and the correct evaluation can reduce the risk of overtreatment with its consequential adverse effects. Breast and Prostate cancers, respectively, are the most common cancers in women and in men, and different similarities have been underlined. The paradigm of the patient consulting a multidisciplinary medical team has been an established standard approach in treating breast cancer. Such multidisciplinary approach can offer the same optional care for men with PC as it does for women with breast cancer. A multidisciplinary team (MDT) comprises healthcare professionals from different disciplines whose goal of providing optimal patient care is achieved through coordination and communication with one another. A Prostate Cancer Unit is a place where men can be cared for by specialists in PC, working together within a multi-professional team. The MTD approach guarantees a higher probability for the PC patient to receive adequate information on the disease and on all possible therapeutic strategies, balancing advantages and related side effects. The future of PC patients relies on a successful multidisciplinary collaboration between experienced physicians, which can lead to important advantages in all the phases and aspects of PC management

Early Recovery of Urinary Continence After Radical Prostatectomy Using Early Pelvic Floor Electrical Stimulation and Biofeedback Associated Treatment

Purpose: We analyzed the benefit of the early combined use of functional pelvic floor electrical stimulation and biofeedback in terms of time to recovery and rate of continence after radical prostatectomy. Materials and Methods: A total of 60 consecutive patients who underwent radical prostatectomy were included in the study. Patients were prospectively randomized to a treatment group (group 1) vs a control group (group 2). In group 1 a program of pelvic floor electrical stimulation plus biofeedback began 7 days after catheter removal, twice a week for 6 weeks. Each of the 12 treatment sessions was composed of biofeedback (15 minutes) followed by pelvic floor electrical stimulation (20 minutes). The evaluation of continence was performed at time 0, at 2 and 4 weeks, and at 2, 3, 4, 5 and 6 months during followup. Evaluations were performed using the 24-hour pad test and the incontinence section of the International Continence Society questionnaire. Results: The mean leakage weight became significantly lower (p < 0.05) in group 1 than in group 2 starting at 4 weeks until 6 months of followup. A significant difference (p < 0.05) between groups 1 and 2 in terms of percentage of continent patients was achieved from 4 weeks (63.3% group 1 and 30.0% group 2) to 6 months (96.7% group 1 and 66.7% group 2). Conclusions: Early, noninvasive physical treatment with biofeedback and pelvic floor electrical stimulation has a significant positive impact on the early recovery of urinary continence after radical prostatectomy

Distribution of High Chromogranin A Serum Levels in Patients with Nonmetastatic and Metastatic Prostate Adenocarcinoma

Objectives: We analyzed the incidence of elevated serum levels of chromogranin A (CgA) (as marker of neuroendocrine activity) in nonmetastatic and metastatic prostate cancer populations. Material and Methods: 264 consecutive men with nonmetastatic prostate adenocarcinoma considered for radical prostatectomy (group 1) and 89 consecutive men with metastatic prostate adenocarcinoma (group 2) represented our population. In all 353 cases a blood sample for the determination of serum total PSA and CgA levels was obtained (RIA). Two different cut-off for elevated serum CgA levels were used: > 60 and > 90 ng/ml. Results: In group 1, 35.0% of cases presented CgA levels > 60 ng/ml and 6.4% > 90 ng/ml. In group 2, 100% of cases presented CgA levels > 60 ng/ml and 69.7% > 90 ng/ml. The OR for CgA level > 60 and > 90 ng/ml significantly increased from nonmetastatic to metastatic cases (p = 0.0001). In group 1 the percentage of cases with CgA > 60 ng/ml was 29.6% in Gleason score 90 ng/ml was 51.8% in Gleason score <= 7 (3 + 4) and 77.4% in Gleason score <= 7 (4 + 3) (p = 0.0028). Conclusions: We describe a significant incidence of elevated serum levels of CgA either in nonmetastatic (using 60 ng/ml as cut-off) or in metastatic (using 90 ng/ml as cut-off) prostate adenocarcinoma cases. Copyright (C) 2009 S. Karger AG, Base

Update on screening in prostate cancer based on recent clinical trials

Introduction and Aim: Prostate cancer (Pc) is a major public health problem, affecting 679,000 men and causing 221,000 deaths every year. Over the past decade, there has been a marked decline in Pc mortality corresponding to the introduction of prostate specific antigen (PSA) test as a screening tool (1986). Despite this clear result, the screening recommendations of various organizations differ. Recently, a large number of studies have highlighted the benefits and risks of PSA based screening. The aim of this article is to review the current screening guidelines and summarise the benefits and harms of PSA testing, analysing two large long awaited randomized multicenter clinical trials of PSA screening reported this year. Methods for the Review: We reviewed the recent literature using PUBMED research, using as words for research: Prostate-Specific Antigen, mass screening, Prostatic neoplasm mortality, follow-up studies, overdiagnosis and overtreatment. In particular, we analysed two clinical trials reported on "The New England Journal of Medicine" this year: the European Randomized Study of Screening for Prostate Cancer (ERSPC) by Scroeder et al. and the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial by Andriole et al. Results and Conclusions: The goal of a screening is to detect a cancer at an early stage, when it is still curable. In Pc case there are different treatments with curative intent, that are associated with significant morbidity. Some man have an aggressive form for which screening might be helpful but many have a slow growing cancer that would never progress and their detection could cause anxiety and bring unnecessary medical treatment. With this review we tried to understand where we should stop the management: Overdiagnosis or Overtreatment? © 2011 Bentham Science Publishers Ltd