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The objective of the current research was to explore the potential prognostic value of readily available clinical and pathologic variables in bladder cancer. The novel association found between cholesterol levels and prognosis may provide the rationale for exploring novel treatments. Patients included had histologically confirmed urothelial bladder cancer and were treated with at least 3 cycles of cisplatin-based neoadjuvant chemotherapy before radical cystectomy with lymphadenectomy. A total of 245 patients at low, intermediate and high risk, presenting with 0-1, 2 or 3-4 risk factors, including positive lymph nodes, Hb 12.8, NLR ≥2.7 and cholesterol levels ≥199, were included. Five-year cancer-specific survival rate was 0.67, 0.78 and 0.94 at high, intermediate and low risk, respectively. Total cholesterol levels at the time of cystectomy may represent a commonly assessable prognostic factor and may be incorporated in a clinically meaningful risk-group classification model.Lay abstract This present study assessed a large group of patients with urothelial bladder cancer treated with chemotherapy followed by radical cystectomy, to capture the predictive power of commonly collected clinical, pathological and biochemical factors. The design of the study highlighted that higher cholesterol levels at the time of cystectomy were associated with shorter cancer-specific survival. This finding suggests that high blood-cholesterol levels truly have a negative influence on surviving cancer. In conclusion, total cholesterol levels at the time of cystectomy may represent a commonly assessable prognostic factor and could be incorporated into a clinically meaningful and valuable risk-group classification model.

Cancer currently represents a leading cause of morbidity and mortality, and it can be held responsible for about one in six deaths worldwide [...]

The benefit of neoadjuvant systemic therapy (NAST) is not yet supported by randomized controlled trials in upper tract urothelial carcinoma (UTUC), but the evidence is increasing. This narrative systematic review was conducted to evaluate the available evidence on the role of NAST in patients undergoing radical nephroureterectomy (RNU) for UTUC.We searched for all relevant articles or conference abstracts published and indexed in PubMed, Embase, and Scopus on July 19, 2021. The study was reported according to the PRISMA criteria and designed within the PICOS framework. We included studies comparing patients with non-metastatic UTUC who received neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) with patients who underwent definitive surgery alone or surgery plus adjuvant systemic therapy. Prospective uncontrolled studies were also included.We identified 27 reports (NAC, N.=24 and NAI, N.=3) published between 2010 and 2021. Twenty of the 24 studies on NAC were retrospective comparative analyses, whereas the remaining four were prospective single-arm studies. One of the three NAI studies exclusively enrolled patients with UTUC. NAC was associated with improved survival and better pathological response relative to surgery alone, but there was no clear advantage when compared to surgery plus adjuvant chemotherapy. Overall, the drug-induced toxicity and risk of disease progression were acceptable but the inherent bias across study designs, inadequate reporting and heterogeneous definition of primary outcomes render it difficult to synthesize results, compare centers, and inform practice.The current level of evidence supporting NAST for UTUC is relatively low and the inability to predict responsiveness and thereby pinpoint the optimal candidates remains a major challenge. There is a need to compare NAST to adjuvant therapies using clearly defined primary endpoints as minimum reporting standards developed by a multidisciplinary team.

The aim of the present study is to assess saliva as a reliable specimen for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by real-time reverse transcription-PCR (RT-PCR), especially in community mass screening programs. The performance analysis considered 1,221 total samples [nasopharyngeal (NP) swabs and corresponding saliva], tested by means of a reference diagnostic real-time RT-PCR assay. Conflicting results were further investigated with a second, more sensitive, reference assay. Analysis of agreement showed a good concordance (95.82%), with a k coefficient value of.74 (p < 0.001); moreover, a follow-up analysis revealed the presence of viral gene targets in saliva samples at the time point the corresponding NP swabs turned negative. Data obtained prove the reliability of this alternative biofluid for SARS-CoV-2 detection in real-time RT-PCR. Considering the role of saliva in the coronavirus disease 2019 (COVID-19) transmission and pathogenesis, and the advantages in the use of salivary diagnostics, the present validation supports the use of saliva as an optimal choice in large-scale population screening and monitoring of the SARS-CoV-2 virus.

Contains fulltext : 248285.pdf (Publisher’s version ) (Closed access) Bladder cancer is the most common malignancy of the urinary tract. Cystoscopy represents the gold standard in the diagnosis of suspicious bladder lesions. However, the procedure is invasive and burdened by pain, discomfort and infective complications. Cytology, which represents an alternative diagnostic possibility is limited by poor sensitivity. Considering the limitations of both procedures, and the necessity to perform multiple evaluations in patients who are in follow-up for bladder cancer, an improved non-invasive methodology is required in the clinical management of this disease. Liquid biopsy, e.g. the detection of clinical biomarkers in urine, represent a promising novel and non-invasive approach that could overcome those limitations and be integrated into the current clinical practice. The aim of this review is to summarize the state of the art of this approach and the latest novelties regarding detection, prognosis and surveillance of bladder cancer.

As of November 17, 2021, SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2), the causative agent of COVID-19 (COronaVIrus Disease 19), has infected ~250 million people worldwide, causing around five million deaths. Titers of anti-SARS-CoV-2 neutralizing antibodies were relatively stable for at least 9 months in a population-based study conducted in Wuhan, China, both in symptomatic and in asymptomatic individuals. In the mass screening campaign conducted in the town of Ariano Irpino (Avellino, Italy) in May, 2020, 5.7% (95% CI: 5.3-6-1) of the 13,444 asymptomatic citizens screened were positive for anti-nucleocapsid antibodies against SARS-CoV-2. Among these, 422 citizens were re-tested for anti SARS-CoV-2 antibodies in January, 2021 and/or in April, 2021 and enrolled in this longitudinal observational study. Median (interquartile range) age of the study cohort was 46 years (29–59), with 47 (11.1%) participants of minor age, while 217 (51.4%) participants were females. There was no evidence of re-infection in any of the subjects included. Presence of anti-nuclear antibodies antibodies (Elecysis, Roche) was reported in 95.7 and 93.7% of evaluable participants in January and April, 2021. Multiple logistic regression analysis used to explore associations between age, sex and seroprevalence showed that adults vs. minors had significantly lower odds of having anti-S1 antibodies (Biorad) both in January, 2021 and in April, 2021. Our findings showed that antibodies remained detectable at least 11.5 months after infection in >90% of never symptomatic cases. Further investigation is required to establish duration of immunity against SARS-CoV-2.

Introduction: Cancer aggravates COVID-19 prognosis. Nosocomial transmission of SARS-CoV-2 is particularly frequent in cancer patients, who need to attend hospitals regularly. Since March 2020, all cancer patients having access to the Oncology Unit at the “Andrea Tortora” Hospital (Pagani, Salerno – referred to as “the Hospital”) as inpatients or outpatients receiving intravenous therapy have been screened for SARS-CoV-2 using RT-PCR nasal swab. The ongoing COICA (COVID-19 infection in cancer patients) study is an ambispective, multicenter, observational study designed to assess the prognosis of SARS-CoV-2 infection in cancer patients. The aim of the study presented here was to explore potential differences in COVID-19-related outcomes among screening-detected versus nonscreening-detected SARS-CoV-2-infected patients. Methods: The COICA study enrolled cancer patients who had received any anticancer systemic therapy within 3 months since the day they tested positive for SARS-CoV-2 on RT-PCR. The target accrual is 128 patients, and the study was approved by the competent Ethics Committee. Only the subgroup of patients enrolled at the Hospital was considered in this unplanned interim analysis. Logistic regression analysis was used to evaluate the association of screening-based versus nonscreening-based diagnosis. Results: Since March 15, 2020, until August 15, 2021, a total of 931 outpatients and 230 inpatients were repeatedly screened for SARS-CoV-2 using RT-PCR nasal swab at the Hospital. Among these, 71 asymptomatic patients were positive on routine screening and 5 patients were positive for SARS-CoV-2 outside the institutional screening. Seven patients died because of COVID-19. At univariate analysis, nonscreening- versus screening-detected SARS-CoV-2 infection was associated with significantly higher odds of O2 therapy (OR = 16.2; 95% CI = 2.2–117.1; p = 0.006), hospital admission (OR = 31.5; 95% CI = 3.1–317.8; p = 0.003), admission to ICU (OR = 23.0; 95% CI = 2.4–223.8; p = 0.007), and death (OR = 8.8; 95% CI = 1.2–65.5; p = 0.034). Conclusion: Routine screening with RT-PCR may represent a feasible and effective strategy in reducing viral circulation and possibly COVID-19 mortality in patients with active cancer having repeated access to hospital facilities.

Prostate and bladder cancer represent the two most frequently diagnosed genito-urinary malignancies. Diet has been implicated in both prostate and bladder cancer. Given their prolonged latency and high prevalence rates, both prostate and bladder cancer represent attractive candidates for dietary preventive measures, including the use of nutritional supplements. Flavonols, a class of flavonoids, are commonly found in fruit and vegetables and are known for their protective effect against diabetes and cardiovascular diseases. Furthermore, a higher dietary intake of flavonols was associated with a lower risk of both bladder and prostate cancer in epidemiological studies. In this systematic review, we gathered all available evidence supporting the anti-cancer potential of selected flavonols (kaempferol, fisetin and myricetin) against bladder and prostate cancer. A total of 21, 15 and 7 pre-clinical articles on bladder or prostate cancer reporting on kaempferol, fisetin and myricetin, respectively, were found, while more limited evidence was available from animal models and epidemiological studies or clinical trials. In conclusion, the available evidence supports the potential use of these flavonols in prostate and bladder cancer, with a low expected toxicity, thus providing the rationale for clinical trials that explore dosing, settings for clinical use as well as their use in combination with other pharmacological and non-pharmacological interventions.

Background This multi-institutional retrospective real life study was conducted in 22 Italian Oncology Centers and evaluated the role of Axitinib in second line treatment in not selected mRCC patients. Methods 148 mRCC patients were evaluated. According to Heng score 15.5%, 60.1% and 24.4% of patients were at poor risk, intermediate and favorable risk, respectively. Results PFS, OS, DCR and ORR were 7.14 months, 15.5 months, 70.6% and 16.6%, respectively. The duration of prior sunitinib treatment correlated with a longer significant mPFS, 8.8 vs 6.3 months, respectively. Axitinib therapy was safe, without grade 4 adverse events. The most frequent toxicities of all grades were: fatigue (50%), hypertension (26%), and hypothyroidism (18%). G3 blood pressure elevation significantly correlated with longer mPFS and mOS compared to G1-G2 or no toxicity. Dose titration (DT) to 7 mg and 10 mg bid was feasible in 24% with no statistically significant differences in mPFS and mOS. The sunitinib-axitinib sequence was safe and effective, the mOS was 41.15 months. At multivariate analysis, gender, DCR to axitinib and to previous sunitinib correlated significantly with PFS; whereas DCR to axitinib, nephrectomy and Heng score independently affected overall survival. Conclusions Axitinib was effective and safe in a not selected real life mRCC population. Trial registration INT – Napoli – 11/16 oss. Registered 20 April 2016. http://www.istitutotumori.na.it

Prostate cancer (PC) is a major health issue in developed countries, with, on the one hand, men suffering from sequelae related to unnecessary treatment of non-lethal PC, and, on the other hand, still dying because of advanced PC that progresses to castration-resistant disease. Systemic treatment is the mainstay of therapy of castration-resistant PC (CRPC). To date, a multitude of systemic agents have been tested and many of these have failed to provide a clinically meaningful benefit in CRPC, while others have been approved by the US Food and Drug Administration and/or the European Medicines Agency, including antiandrogen hormonal drugs (abiraterone, enzalutamide, apalutamide), chemotherapy (docetaxel and cabazitaxel), immunotherapy (Sipuleucel-T), and radiopharmaceutical (Radium-223) agents. In this review, systemic treatments regarded as most likely to have an impact in clinical practice are presented and discussed. In addition to the pivotal clinical studies, selected retrospective and non-randomized clinical trials are also discussed if deemed to have an impact on clinical practice or future research. A comprehensive appraisal of the expanding landscape of systemic therapies for advanced PC is provided from an expert perspective, with a focus on novel classification and diagnostic tools that have been paving the way for the development of precision medicine in PC.

Background Although statin use has been associated with favorable effects in various solid malignancies, no conclusive evidence is available at present. Statins are safe and inexpensive, and may synergize with novel antiandrogen agents abiraterone via pharmacokinetic interactions and decrease substrate availability for de novo androgen biosynthesis. Objective To determine whether statin use affects survival in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. Design, setting, and participants Medical records of patients with documented mCRPC between September 2011 and August 2016 were reviewed at multiple participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. A total of 187 patients receiving abiraterone for mCRPC between September 2011 and August 2016 were eligible for inclusion in this retrospective study. Outcome measurements and statistical analysis Patients were assessed for overall survival (OS), statin use at the time of treatment initiation, prostate-specific antigen (PSA) variations, and other variables of interest. Univariable and multivariable analysis was used to explore the association of variables of interest with OS and PSA declines. Results and limitations Statin use was a significant prognostic factor for longer OS in univariable (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.37–0.72; p p 50% decline at 12 wk: 72.1% in statin users vs 38.5% in non-users; p Conclusions Our study suggests a prognostic impact of statin use in patients receiving abiraterone for mCRPC. The mechanism of this interaction warrants elucidation, but may include enhancement of the antitumor activity of abiraterone as well as cardioprotective effects. Patient summary We assessed the effects of statin use in patients with advanced prostate cancer receiving abiraterone. Patients treated with a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further studies assessing the use of abiraterone plus statins are warranted.

The term "hemp" refers to Cannabis sativa cultivars grown for industrial purposes that are characterized by lower levels of tetrahydrocannabinol (THC), the active principle responsible for Cannabis psychotropic effects. Hemp is an extraordinary crop, with enormous social and economic value, since it can be used to produce food, textiles, clothing, biodegradable plastics, paper, paint, biofuel, and animal feed, as well as lighting oil. Various parts of the hemp plant represent a valuable source of food and ingredients for nutritional supplements. While hemp inflorescence is rich in nonpsychoactive, yet biologically active cannabinoids, such as cannabidiol (CBD), which exerts potent anxiolytic, spasmolytic, as well as anticonvulsant effects, hempseed has a pleasant nutty taste and represents a valuable source of essential amino acids and fatty acids, minerals, vitamins, and fibers. In addition, hempseed oil is a source of healthy polyunsaturated fatty acids, and hemp sprouts are rich in antioxidants. This review article aims to provide a comprehensive outlook from a multidisciplinary perspective on the scientific evidence supporting hemp beneficial properties when consumed as food or supplement. Marketing of hemp-derived products is subjected to diversified and complex regulations worldwide for several reasons, including the fact that CBD is also the active principal of pharmaceutical agents and that regulatory bodies in some cases ban Cannabis inflorescence regardless of its THC content. Some key regulatory aspects of such a complex scenario are also analyzed and discussed in this review article.

Molecular heterogeneity and availability of different therapeutic strategies are relevant clinical features of prostate cancer. On this basis, there is an urgent need to identify prognostic and predictive biomarkers for an individualized therapeutic approach. In this context, researchers focused their attention on biomarkers able to discriminate potential life-threatening from organ-confined disease identify high-grade tumors. Such biomarker could provide aid in clinical decision making, helping in order to choose the treatment which ensures the best results in terms of patient survival and quality of life. To address this need, many new laboratory tests have been proposed, witha clear tendency to use panels of combined biomarkers. In this review we evaluate current data on the application in clinical practice for of the most promising laboratory tests: Phi, 4Kscore and Stockholm 3 as circulating biomarkers, and Mi-prostate score, Exo DX Prostate and Select MD-X as urinary biomarkers, Confirm MDx, Oncotype Dx, Prolaris and Decipher as tissue biomarkers. In particular, the ability of these tests in the identification of clinically significant PCa and their potential use for precision medicine have been explored in this review.

Introduction: The association between obesity and clinically significant prostate cancer (PCa) is still a matter of debate. In this study, we evaluated the effect of body mass index (BMI) on the prediction of pathological unfavorable disease (UD), positive surgical margins (PSMs), and biochemical recurrence (BCR) in patients with clinically localized (≤cT2c) International Society of Urological Pathology (ISUP) grade group 1 PCa at biopsy. Methods: 427 patients with ISUP grade group 1 PCa who have undergone radical prostatectomy and BMI evaluation were included. The outcome of interest was the presence of UD (defined as ISUP grade group ≥3 and pT ≥3a), PSM, and BCR. Results: Statistically significant differences resulted in comparing BMI with prostate-specific antigen (PSA) and serum testosterone levels (both p < 0.0001). Patients with UD and PSM had higher BMI values (p < 0.0001 and p = 0.006, respectively). BCR-free survival was significantly decreased in patients with higher BMI values (p < 0.0001). BMI was an independent risk factor for BCR and PSM. Receiver-operating characteristic analysis testing PSA accuracy in different BMI groups, showed that PSA had a reduced predictive value (area under the curve [AUC] = 0.535; 95% confidence interval [CI] = 0.422–0.646), in obese men compared to overweight (AUC = 0.664; 95% CI = 0.598–0.725) and normal weight patients (AUC = 0.721; 95% CI = 0.660–0.777). Conclusion: Our findings show that increased BMI is a significant predictor of UD and PSM at RP in patients with preoperative low-to intermediate-risk diseases, suggesting that BMI evaluation may be useful in a clinical setting to identify patients with favorable preoperative disease characteristics harboring high-risk PCa.

Introduction We aimed to test the hypothesis that the immune-modulatory effect of statins may improve survival outcomes in patients with non-muscle invasive bladder cancer (NMIBC). We focused on a cohort of patients diagnosed with high risk NMIBC, that were treated with intravesical BCG immunotherapy. Patients and methods We included patients at first diagnosis of T1 high grade NMIBC after transurethral resection of bladder (TURB). All procedures were performed at 18 different tertiary institutions between January 2002 and December 2012. Univariable and multivariable models were used to test differences in terms of residual tumour, disease recurrence, disease progression and overall mortality (OM) rates. Results Overall, 1510 patients with T1 high grade NMIBC at TURB were included in our analyses. Of these, 402 (26.6%) were statin users. At multivariable analysis, statin use was associated with a higher rates of high grade BC at re-TURB (OR: 1.37, 95%CI: 1.04-1.78; p=0.022), while at follow-up it was not independently associated with OM (HR: 0.71, 95%CI: 0.50-1.03; p=0.068) and disease progression rates (HR: 0.97, 95%CI: 0.79-1.19; p=0.753). Conversely, statin use has been shown to be independently associated with a lower risk of recurrence (HR:0.80, 95%CI: 0.67-0.95; p=0.009). The median recurrence-free survival was 47 (95%CI 40-49) months for those classified as non-statin users vs. 53 (95%CI 48-68) months in those classified as statin users. Conclusions Statin daily intake do not compromise oncological outcomes in high risk NMIBC patients treated with BCG. Moreover, statin may have a beneficial effect on recurrence rates in this cohort of patients.

Introduction. Metastatic castration-resistant prostate cancer (mCRPC) is a deadly disease. Enzalutamide is an oral second-generation anti-androgen that is active in mCRPC. Circulating tumor cells (CTC) count correlates with overall survival (OS) in mCRPC, whereas detection of the androgen-receptor splice variant 7 (AR-V7) in CTC predicts poor response to oral second-generation anti-androgens. Also, loss of PTEN (phosphatase and tensin homolog) in CTC is a biomarker of poor prognosis in mCRPC. Patients and methods. In this translational study, we employed flow cytometry to assess total, PTEN–, and AR-V7+ CTC count per 7.5 mL of whole blood in a prospective cohort of patients with mCRPC receiving enzalutamide. Results. CTCs were assessed in a total of 45 men with mCRPC at baseline and at 12 weeks. Overall, CTC, PTEN– CTC, and AR-V7+ CTC detection rate was high, at baseline, with 84.4%, 71.1%, and 51.1% of samples showing at least 1 cell/7.5-mL blood, respectively, and after 3 months, with 93.3%, 64.4%, and 77.7% of samples showing at least 1 cell/7.5-mL blood, respectively. Median radiographic progression-free survival (rPFS) and OS were 6 (95% confidence interval [CI], 5.6-9) and 14.3 (95% CI, 12.8-20.3) months, respectively. Median (interquartile range) total CTC count at baseline was 5 (3; 8), whereas median (interquartile range) PTEN– CTC count was 2 (0; 4) and median (interquartile range) AR-V7+ CTC count was 1 (0; 3). At baseline, ≥ 5 versus < 5 total CTC count was associated with worse rPFS (hazard ratio [HR], 2.35; 95% CI, 1.14-4.84; P=.021) and OS (HR, 3.08; 95% CI, 1.45-6.54; P =.003), whereas ≥ 2 versus < 2 PTEN– CTC count was associated with worse rPFS (HR, 3.96; 95% CI, 1.8-8.72; P=.001) and OS (HR, 2.36; 95% CI, 1.12-5; P=.025). Finally, ≥ 1 versus < 1 AR-V7+ CTC count was also associated with worse rPFS (HR, 5.05; 95% CI, 2.4-10.64; P

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10−5) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.

Although both docetaxel and androgen-receptor-axis-targeted (ARAT) agents have yielded survival improvements in combination with androgen deprivation therapy (ADT) compared to ADT alone in metastatic castration-sensitive prostate cancer (mCSPC) patients, the optimal therapeutic choice remains to be established. We analyzed estimates of the hazard ratios for death (OS-HRs) in patients treated in the first-line setting enrolled in the GETUG-AFU15, CHAARTED, STAMPEDE, LATITUDE, ENZAMET, and TITAN trials. Overall, men with mCSPC receiving ADT with vs. without either an ARAT agent or docetaxel as first-line systemic therapy showed a pooled OS-HR of 0.69 (95 % CI: 0.61−0.78), with significant heterogeneity (p = 0.045, I2 = 52.5 %). Network meta-analysis showed an OS-HR in patients receiving an ARAT agent vs. docetaxel of 0.78 (95 %CI: 0.67−0.91). In conclusion, the evidence analysed indicates that an ARAT agent may provide improved OS outcomes compared to docetaxel. Prospective randomized trials are warranted.

To identify host genetic determinants involved in humoral immunity and associated with the risk of developing severe COVID-19, we analyzed 500 SARS-CoV-2 positive subjects from Southern Italy. We examined the coding sequences of 10 common variable immunodeficiency-associated genes obtained by the whole-exome sequencing of 121 hospitalized patients. These 10 genes showed significant enrichment in predicted pathogenic point mutations in severe patients compared with the non-severe ones. Moreover, in the TNFRSF13C gene, the minor allele of the p.His159Tyr variant, which is known to increase NF-kB activation and B-cell production, was significantly more frequent in the 38 severe cases compared to both the 83 non-severe patients and the 375 asymptomatic subjects further genotyped. This finding identified a potential genetic risk factor of severe COVID-19 that not only may serve to unravel the mechanisms underlying the disease severity but, also, may contribute to build the rationale for individualized management based on B-cell therapy.

BACKGROUND: Basophils, eosinophils and monocytes may be involved in BCG-induced immune responses and be associated with outcomes of bladder cancer patients receiving intravesical BCG. Our objective was to explore the association of baseline counts of basophils, eosinophils and monocytes with outcomes of patients with high-grade T1 bladder cancer receiving a standard course of intravesical BCG. METHODS: We retrospectively reviewed medical records of patients with primary T1 HG/G3 bladder cancer. After re-TURBT, patients were treated with a 6-week course of intravesical BCG induction followed by intravesical BCG every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months from initiation of therapy The analysis of potential risk factors for recurrence, muscle invasion and cancer-specific and overall survival was performed using univariable Cox regression models. Those factors that presented, at univariate analysis, an association with the event at a liberal p

Background The evaluation of environmental exposure risk requires a global analysis of pollution phenomena, including biological effects and potentially correlated clinical outcomes in susceptible populations. Although human biomonitoring plays a fundamental role in assessing the degree of contamination, it is not effective alone in identifying a direct link between exposure, biomolecular effects and outcomes on target organisms. While toxicogenomics and epidemiology are mainly focused on the investigation of molecular reactions and clinical outcomes, the monitoring of environmental matrices works independently to characterize the territorial distribution of toxic compounds, without proving any correlated health risk for residents. Objectives We propose a new biomonitoring model based on a whole systemic analytical evaluation of environmental context. The paradigm of the method consists of identifying the sources of pollution, the migration pathways of those pollutants and their effects on target organisms. By means of this innovative, holistic epidemiological approach, we included healthy human subjects in a cohort to identify potential risks of exposure and predict possible correlated clinical outcomes. 4205 residents of the Campania region were enrolled in the “SPES” biomonitoring study, which especially focused on the areas dubbed “Land of Fires” in the recent decades. Discussion The analysis of environmental exposure risk suffers the lack of data integration from various science fields, and this comes down to a limited point of view and a limited knowledge of phenomena. In implementing our model, we first constructed an analytical picture of the Real-world situation. We next conducted a comparative risk assessment, in order to identify possible correlations between pollution and health within a holistic view. Conclusion This type of research activities aims to support the implementation of public health interventions and to become a reference model in the evaluation of the risk of exposure to environmental pollutants.

Colorectal cancer (CRC) represents one of the most commonly diagnosed cancers worldwide. It is the second leading cause of cancer death in Western Countries. In the last decade, the survival of patients with metastatic CRC has improved dramatically. Due to the advent of new drugs (irinotecan and oxaliplatin) and target therapies (i.e. bevacizumab, cetuximab, panitumab, aflibercept and regorafenib), the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently. Molecular studies have recently widened the opportunity for testing new possible markers, but actually, only few markers can be recommended for practical use in clinic. In the next future, the hope is to have a complete panel of clinical biomarkers to use in every setting of CRC disease, and at the same time: 1) to receive information about prognostic significance by their expression and 2) to be oriented in the choice of the adequate treatment. Moreover, molecular analyses have shown that the natural history of all CRCs is not the same. Individual patients with same stage tumors may have different long-term prognosis and response to therapy. In addition, some prognostic variables are likely to be more important than others. Here we review the role of serum and tissue markers according to the recently published English literature. This paper is an extension of the article "Biological and clinical markers in colorectal cancer: state of art" by Cappellani A published in Jan 2010.

Objectives: The aim of this multicenter study was to investigate the prognostic role of type 2 diabetes mellitus (T2DM) comorbidity in a large multi-institutional cohort of patients with primary T1HG/G3 non–muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB). Materials and methods: A total of 1,172 patients with primary T1 HG/G3 who had NMIBC on re-TURB and who received adjuvant intravesical bacillus Calmette-Guérin therapy with maintenance were included. Endpoints were recurrence-free survival and progression-free survival. Results: A total of 231 (19.7%) of patients had T2DM prior to TURB. Five-year recurrence-free survival estimates were 12.5% in patients with T2DM compared to 36% in patients without T2DM, P < 0.0001. Five-year PFS estimates were 60.5% in patients with T2DM compared to 70.2% in patients without T2DM, P = 0.003. T2DM was independently associated with disease recurrence (hazard ratio = 1.41; 95% confidence interval = 1.20–1.66, P < 0.001) and progression (hazard ratio = 1.27; 95% confidence interval = 0.99–1.63, P < 0.001), after adjusting for other known predictive factors such as tumor size, multifocality, T1G3 on re-TURB, body mass index, lymphovascular invasion, and neutrophil-to-lymphocytes ratio. Conclusions: Given the potential implications for management, prospective validation of this finding along with translational studies designed to investigate the underlying biology of such an association are warranted.

Introduction: An altered metabolic regulation is involved in the development and progression of different cancer types. As well as this, many genes associated with tumors are shown to have an important role in control of the metabolism. The incidence of prostate cancer (PCa) is increased in men with metabolic disorders. In particular, obesity is an established risk factor for PCa. An increased body mass index correlates with aggressive disease, and a higher risk of biochemical recurrence and prostate cancer-specific mortality. Increased lipogenesis is also one of the most significant events in PCa metabolism reprogramming. Areas covered: In this article, we provide an updated review of the current understanding of the PCa metabolome and evaluate the possibility of unveiling novel therapeutic targets. Expert opinion: Obesity is an established risk factor for PCa, and an increased BMI correlates with aggressive disease, and a higher risk of biochemical recurrence and prostate cancer-specific mortality. PCa metabolome is characterized by the accumulation of metabolic intermediates and an increased expression of genes in the tricarboxylic acid cycle, the induction of de novo lipogenesis and cholesterogenesis. PCa cells can induce different alterations in their microenvironment by modulating the crosstalk between cancer and stromal cells.

Cancer-related fatigue (CRF) is a complex condition that is reported in > 50% of cancer patients. In men with castration-resistant prostate cancer (CRPC), CRF was reported in 12–21% of patients. Approved systemic therapy against CRPC is commonly administered in combination with androgen-deprivation treatment (ADT) and, in some cases, with daily, low-dose corticosteroids. Importantly, the use of low-dose corticosteroids is associated with multiple negative effects, including reduced muscle mass. On these grounds, we hypothesized that the chronic use of corticosteroids may increase the incidence of fatigue in patients with prostate cancer. We reviewed all randomized trials published during the last 15 years conducted in patients with prostate cancer receiving systemic treatment and we performed a sub-group analysis to gather insights regarding the potential differences in the incidence of fatigue in patients receiving vs. not receiving daily corticosteroids as part of their systemic anti-neoplastic regimen. Overall, 22,734 men enrolled in prospective randomized phase II and III trials were evaluable for fatigue. Estimated pooled incidence of grade 1–2 fatigue was 30.89% (95% CI = 25.34–36.74), while estimated pooled incidence of grade 3–4 fatigue was reported in 3.90% (95% CI = 2.91–5.02). Sub-group analysis showed that grade 3–4 fatigue was approximately double in patients who received daily corticosteroids as part of their anti-neoplastic treatment (5.58; 95% CI = 4.33–6.98) vs. those who did not (2.67%; 95% CI = 1.53–4.11). Our findings highlight the need for ad hoc-designed prospective clinical trials to investigate whether the benefits associated with low-dose, daily corticosteroids outweigh the risks associated with corticosteroid-related adverse events such as fatigue.

Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer.

Background: Glioblastoma multiforme (GBM) is a rare and deadly disease, with a reported average incidence rate of 3.19 cases per 100,000 inhabitants. Fotemustine, a third-generation nitrosourea with an alanine phosphor carrier that facilitates cellular penetration, has been extensively investigated in the setting of recurrent/progressive disease after initial treatment. Fotemustine is usually administered following a schedule consisting of 3 doses every week, followed by maintenance doses administered every 3 weeks. Methods: In this phase I/II trial, we aimed to assess whether the use of a biweekly regimen allowed administration of higher dose than the standard 100 mg/m2 dose approved per label indication in a population of patients with recurrent GBM. In this phase I/II trial, fotemustine was administered intravenously over 1 hour every 2 weeks at either 120 or 140 mg/m2 doses for up to 1 year, until disease progression, unacceptable toxicity, or patient's request to withdraw from the study. The phase I part of the trial was conducted following the classic 3+3 study design. The phase II part of the trial was a single-arm study. The primary efficacy endpoint was the percentage of patients who had not progressed after 24 weeks (PFS-24). Results: Thirty-seven patients were enrolled in this phase I/II trial from August 2006 to November 2011. Treatment was well tolerated in the overall population. Main severe toxicity was grades 3 and 4 thrombocytopenia, which occurred in 4 of 6 patients treated at the 140 mg/m2 dose level and in 3 of 31 patients treated at 120 mg/m2. Median PFS and overall survival were 12.1 (1–40.2) weeks and 19.7 (1–102) weeks, respectively. Conclusion: We conclude that fotemustine can be safely administered at 120 mg/m2 biweekly. The efficacy of such modified schedule and doses should be compared to the biweekly schedule at 80 mg2 and the standard weekly schedule at 80 to 100 mg/m2.

The oligometastatic state of prostate cancer (PC) is of clinical importance because of its implications for surgery, radiotherapy, and systemic therapy. Improving the definition of oligometastatic PC will offer an opportunity to discover whether disease burden is a clinically meaningful variable or if oligometastasis is a distinctive state of PC with a largely unexplored biological background.

Interferon (IFN) and PEG-IFN are the only drugs approved as adjuvant therapy in patients with melanoma at high-risk of recurrence after surgical resection. Several clinical trials of adjuvant IFN, using different doses and durations of therapy, have been conducted in these patients. Results generally suggest relapse-free survival and overall survival benefits; however, questions over the optimal dose and duration of treatment and concerns over toxicity have limited its use. IFN exerts its biological activity in melanoma via multiple mechanisms of action, most of which can be considered as indirect immunomodulatory effects. As such, IFN may also be of benefit in the neoadjuvant setting, where it may have a role in melanoma patients with locally advanced disease for whom immediate surgical excision is not possible. However, this has not been well studied. The use of IFN in patients with metastatic melanoma is controversial, with limited data and no convincing evidence of a survival benefit. However, IFN therapy combined with novel biological and immunotherapies offers the potential for a synergistic effect and improved clinical outcomes. Predictive and prognostic factors to better select melanoma patients for IFN treatment have been identified (e.g. disease stage, ulceration, various cytokines) and may also enhance its therapeutic efficacy, but their incorporation into the clinical decision-making process requires validation in prospective trials. In conclusion, the modest efficacy of IFN shown in clinical trials is largely a reflection of differences in response between patients. Despite advancements in the understanding of its biological mechanisms of action, the huge potential of IFN remains to be fully explored and utilized in patients with melanoma.

Penile cancer is a rare disease, with an incidence that is higher in less developed countries and is in the range of 1 - 10 per 100000 men worldwide. Early diagnosis is essential for cure, as 5 year cancer-specific survival is 90 - 100 % in patients with intraepithelial neoplasms and in those with low-grade superficial tumors without lymphovascular invasion, but it drops to 30% in men with multiple mobile or bilateral inguinal lymph nodes. The EGFR family plays a major role in penile cancer biology, with distinct receptors being involved in HPV-positive and -negative tumors. A number of anti-EGFR agents were used in penile cancer patients outside the context of a clinical trial, mainly as a salvage treatment after failure of first-line chemotherapy. A total of 28 patients received anti-EGFR monoclonal antibodies, with 50% of them showing a response to treatment, and a median PFS of ∼ 3 months. The rarity of the disease poses great challenge in terms of education and awareness of the general population, planning of preventive measures on a large scale, as well as conduction of prospective trials and approval of high-cost biological therapy.

In the METEOR study [3], cabozantinib appeared to be superior to everolimus in terms of objective response rate (21 vs 5%; p < 0.001) and PFS, with a statistically significant hazard ratio for progres sion or death of 0.58. A planned interim analysis showed that overall survival was longer with cabozantinib with respect to everolimus (hazard ratio for death: 0.67; 95% CI: 0.51–0.89; p = 0.005), although the p-value did not cross the prespecified boundary for statistical significance. Conversely, in the CheckMate 025 trial [4], the median overall survival associated with the use of nivolumab versus everolimus was 25.0 months (95% CI: 21.8–not estimable) versus 19.6 months (95% CI: 17.6–23.1), with a hazard ratio for death of 0.73 (98.5% CI: 0.57–0.93; p = 0.002), which did meet the prespecified criterion for superiority (p ≤ 0.0148). While the objective response rate was greater with nivolumab than with everolimus (25 vs 5%; p < 0.001), there was no difference in “Differently from everolimus and axitinib, both cabozantinib, a multityrosine kinasis inhibitor, and nivolumab, an anti-PD-1 agent, did yield an advantage in overall survival when compared with everolimus...”

Active surveillance (AS) is currently a widely accepted treatment option for men with clinically localized prostate cancer (PCa). Several reports have highlighted the association of low serum testosterone levels with high-grade, high-stage PCa. However, the impact of serum testosterone as a predictor of progression in men with low-risk PCa has been little assessed. In this study, we evaluated the association of circulating testosterone concentrations with a staging/grading reclassification in a cohort of low-risk PCa patients meeting the inclusion criteria for the AS protocol but opting for radical prostatectomy. Radical prostatectomy (RP) was performed in 338 patients, eligible for AS according to the following criteria: clinical stage T2a or less, PSApT2) and upgrading (GS=7; primary Gleason pattern 4) disease. Unfavorable disease was defined as the occurrence of pathological stage>pT2 and predominant Gleason score 4. Total testosterone was measured before surgery. Low serum testosterone levels (

The therapeutic improvements in renal cell carcinoma brought about by the transition from the 'cytokine era' to the 'targeted agents era', have not affected the peculiar prognostic heterogeneity of the disease, nor have they diminished the importance of risk group classification based on easily assessable and commonly available laboratory and clinical variables. In the landmark study conducted by Motzer et al. before biological agents were available, the median survival of patients in the good prognosis group was 20 months, while the patients in the poor-risk group had a median survival time of only 4 months. With the introduction of anti-VEGF agents, overall survival has approximately doubled in all risk classes. In a population-based analysis of 670 patients treated with anti-VEGF agents, either in the first-line setting or in the second-line setting after cytokines, stratification according to the Database Consortium model showed that patients in the favorable risk group had a median overall survival of 43.2 months, while patients in the poor-risk group had a median overall survival of 7.8 months.

Introduction: Currently, clinical factors related to the malignancy and patient-related factors such as performance status and comorbidities are employed to select agents to treat metastatic castration resistant prostate cancer (mCRPC).Areas covered: This paper covers emerging molecular panels that may be used in the clinic as prognostic or predictive biomarkers to treat mCRPC.Expert commentary: The expression of androgen receptor variant (AR-V)-7 in circulating tumor cells appears especially promising to select patients for taxane chemotherapy versus androgen inhibitors, abiraterone and enzalutamide. Additionally, the presence of DNA repair alterations such as BRCA alterations are rapidly emerging as a predictive biomarker to develop precision medicine using PARP inhibitors for these patients.

Obesity is associated with an increased risk of a number of serious medical conditions, including cancer. As far as prostate cancer is concerned, obesity is associated with an increased risk of high-grade tumors, which is possibly related to lower androgen levels. Diet may also affect prostate cancer risk since countries with a higher dietary fat intake also present higher prostate cancer mortality rates. Interestingly, prostate cancer is associated with a number of metabolic alterations that may provide valuable diagnostic and therapeutic targets. This review explores the available clinical as well as biological evidence supporting the relationship between obesity, diet, alteration in metabolic pathways and prostate cancer.

Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches. A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and “en bloc” removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy. The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery. Patients with advanced stage tumors of the bulbomembranous urethra should be managed with radical surgery including the corporas up to the ischiatic tuberosity attachment, and membranous urethra in continuity with the prostate and bladder. Neo-adjuvant treatment may be advisable with the aim of improving the poor prognosis, even if the efficacy is not certain while it can delay the radical treatment of the disease.

Prior platinum-versus non-platinum-based chemotherapy did not affect survival after controlling for major prognostic factors in patients receiving salvage systemic chemotherapy for advanced urothelial carcinoma. Exposure to prior platinum therapy should not be required for the inclusion of patients in trials of salvage systemic therapy. Background: Trials of salvage therapy for advanced urothelial carcinoma have required prior platinum-based therapy. This practice requires scrutiny because non-platinum-based first-line therapy may be offered to cisplatin-ineligible patients. Patients and Methods: Data of patients receiving salvage systemic chemotherapy were collected. Data on prior first-line platinum exposure were required in addition to treatment-free interval, hemoglobin, Eastern Cooperative Oncology Group performance status, albumin, and liver metastasis status. Cox proportional hazard regression was used to evaluate their association with overall survival (OS) after accounting for salvage single-agent or combination chemotherapy. Results: Data were obtained from 455 patients previously exposed to platinum-based therapy and 37 not exposed to platinum. In the group exposed to prior platinum therapy, salvage therapy consisted of a single agent taxane (n = 184) or a taxane-containing combination chemotherapy (n = 271). In the group not exposed to prior platinum therapy, salvage therapy consisted of taxane or vinflunine (n = 20), 5-fluorouracil (n = 1), taxane-containing combination chemotherapy (n = 12), carboplatin-based combinations (n = 2), and cisplatin-based combinations (n = 2). The median OS for the prior platinum therapy group was 7.8 months (95% confidence interval, 7.0, 8.1), and for the group that had not received prior platinum therapy was 9.0 months (95% confidence interval, 6.0, 11.0; P = .50). In the multivariable analysis, prior platinum therapy versus no prior platinum exposure did not confer an independent impact on OS (hazard ratio, 1.10; 95% confidence interval, 0.75, 1.64; P = .62). Conclusion: Prior platinum-versus non-platinum-based chemotherapy did not have a prognostic impact on OS after accounting for major prognostic factors in patients receiving salvage systemic chemotherapy for advanced urothelial carcinoma. Lack of prior platinum therapy should not disqualify patients from inclusion onto trials of salvage therapy. (C) 2016 Elsevier Inc. All rights reserved.

Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel. Grade 3 to 4 (G3–4) neutropenia and febrile neutropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer (TROPIC) trial, but their incidence was lower in the Expanded Access Program (EAP). Although cumulative doses of docetaxel are associated with neuropathy, the effect of cumulative doses of cabazitaxel is unknown. In this retrospective review of prospectively collected data, the authors assessed “per cycle” incidence and predictors of toxicity in the Italian cohort of the EAP, with a focus on the effect of cumulative doses of cabazitaxel. The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP. The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis. “Per cycle” incidence of G 3 to 4 neutropenia was 8.7%, whereas febrile neutropenia was reported in 0.9% of cycles. All events of febrile neutropenia occurred during the first 3 cycles. Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased odds of having G3 to 4 neutropenia (OR = 0.90; 95% CI: 0.86–0.93; P 2 m2 presented increased odds of having G 3 to 4 neutropenia (OR = 0.93; 95% CI: 0.86–1; P = 0.07), but decreased odds of having G3 to 4 anemia. Among the toxicities assessed, the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered. Prior cumulative dose was associated with reduced G3 to 4 neutropenia and anemia. The apparent protective effect associated with higher doses of cabazitaxel is likely to be affected by early dose reduction and early toxicity-related treatment discontinuation. Because this analysis is limited by its retrospective design, prospective trials are required to assess the optimal duration of cabazitaxel treatment.

Guidelines on the treatment of metastatic squamous cell carcinoma of the penis are limited to a few prospective trials. Cisplatin-based regimens represent the standard of treatment with promising activity of taxanes. Recently, epidermal growth factor receptor overexpression has been shown in these patients. We treated an elderly man with a docetaxel-cetuximab combination after failure of the cisplatin regimen. We observed a necrosis of the inguinal lymph nodes and a reduction of (18)F-fluorodeoxyglucose uptake at PET/CT scan. Only mild mucositis and skin toxicity had been detected. Our case report, the first in the literature, shows that this combination is active and well tolerated in penile squamous cell carcinoma.

Background Previously published preliminary findings showed promising activity of paclitaxel in chemotherapy-pretreated metastatic penile cancer. Objective To evaluate the activity and safety of paclitaxel in pretreated metastatic penile cancer. Design, setting, and participants Twenty-five patients were enrolled in a single-arm phase 2 multicentre study and treated with 175mg/m 2 paclitaxel at 3-wk intervals until disease progression or irreversible toxicity. Measurements The objective response rate was the primary end point. Safety, progression-free survival (PFS), and overall survival (OS) were secondary end points. Results and limitations Partial responses were observed in 20% (5 of 25 patients). Grade 1–2 neutropenia, nausea, and oral mucositis were the most common side effects, noted in 13, 9, and 8 patients, respectively. Grade 3–4 neutropenia was reported in seven patients (28%). Median PFS was 11 wk (95% confidence interval [CI], 7–30); median OS was 23 wk (95% CI, 13–48). Median survival in responders was 32 wk (95% CI, 20–48). One limitation of our study was the limited accrual, which did not reach the target of 27 patients, due to the typical slow enrolment of a rare disease. Conclusions Final results of this study demonstrate that paclitaxel is moderately active and well tolerated. Further trials, which may also explore the combination of paclitaxel with other agents, are required to confirm our findings.

Thymic epithelial tumors (TETs) are rare tumors of the mediastinum, with an estimated incidence of about 3 cases per 100,000 inhabitants. Although anthracycline- and platinum-based chemotherapy is an active treatment for TETs, novel systemic therapeutic options are especially needed for metastatic disease, which is virtually incurable. On the basis of the radiographic response obtained with imatinib (Novartis Pharma, Basel, Switzerland) in a patient with thymic carcinoma harboring the V560del c-KIT mutation, a phase II trial was initiated at the Department of Molecular and Clinical Oncology and Endocrinology of University “Federico II of Naples” with the purpose to test imatinib in TETs. Imatinib was daily delivered at the dose of 400 mg to patients affected by TETs, who had progressed after at least one chemotherapy regimen. Positivity of c-KIT on immunohistochemistry was not mandatory for study entry. Radiographic responses were measured by CT scans performed every 3 months, according to the RECIST criteria. Toxicity was graded according to the Common Toxicity Criteria of the National Cancer Institute, version 3.0. Fifteen patients with advanced TETs were enrolled from March 2008 to May 2010. Three patients presented with thymic carcinomas. Two of these three patients presented c-kit expression on immunohistochemistry. No patient harbored a known c-kit activating mutation. Imatinib was very well tolerated, with no toxicity-related death. Diarrhea and migraine were the most frequent events, occurring both in 20% of patients, but were manageable and mild. No radiographic responses were recorded. Median progression-free survival was 3 months (interquartile range, 2.5–4). Median overall survival was not reached. The study was terminated before it reached its target accrual of 42 patients, because of the lack of responses and low accrual rate. This trial indicates the lack of effectiveness of imatinib in unselected patients with thymic epithelial tumors. Nevertheless, imatinib may represent a valuable option in selected patients with TETs, such as those harboring the V560del c-KIT mutation.

The US FDA recently approved sipuleucel-T (Provenge(®), Dendreon, Inc., WA, USA) on the grounds of the results reported by a Phase III trial, which are presented and discussed in detail in this article. This study was conducted in 512 metastatic castration-resistant prostate cancer patients randomized in a 2:1 ratio to receive either active therapy or placebo. Although no difference in time to progression was observed, a survival advantage was achieved, with a statistically meaningful 4.1-month improvement in median survival in the active arm with respect to the placebo arm (25.8 vs 21.7 months). In view of its favorable toxicity profile and manageable route of administration, sipuleucel-T is the ideal agent to be combined with other standard treatments, which include hormonal, cytotoxic and biological agents, and radiotherapy. Sipuleucel-T opens exciting new paradigms for prostate cancer and increases the possibility of survival prolongation for men with this deadly disease.

Thymomas are tumors with an indolent behavior and long clinical course, usually confined to the anterior mediastinum. Local recurrence is frequent while distant metastases are extremely rare. We report an unusual case of a B2 thymoma with a single renal metastasis The challenge in this case was the frozen section intraoperative diagnosis because of the clinical suspicion of malignant lymphoma. This report also highlights the role of surgical removal of solitary metastases.

153 ISSN 1479-6694 10.2217/FON.13.243 © 2014 Future Medicine Ltd Future Oncol. (2014) 10(2), 153–155 An unprecedented large number of agents capable of prolonging survival is presently available for patients with castrationresistant prostate cancer (CRPC) [1,2]. Survival expectancy of a patient with newly diagnosed CRPC has approximately doubled since the approval of docetaxel, although it still appears to be poor in selected populations [3,4], such as those with primary refractoriness to docetaxel [5]. US FDAand EMA-approved agents now include immunotherapy agent sipuleucel-T, CYP17A inhibitor abiraterone, antiandrogen receptor enzalutamide, cytotoxic agent cabazitaxel and radiopharmeceutical agent radium-223. These agents were approved in different settings. While sipuleucel-T was mainly tested in minimally symptomatic, chemotherapy-naive patients, abiraterone, enzalutamide and cabazitaxel were tested in patients pretreated with docetaxel. Radium-223 was approved in patients who were either ineligible to or refused or had already received docetaxel, and had symptomatic diffuse bone metastases. Although abiraterone proved to prolong progression-free survival in chemotherapy-naive patients, with a statistically significant improvement in overall survival that did not satisfy the statistical boundaries required by the study design, the potential detrimental effect on survival that postponing docetaxel in a population of metastatic CRPC might have was not adequately accounted for in this trial, and an opportunity to test sequential therapies was missed [6]. With multiple available effective agents, their optimal sequential use, their use in selected populations and the early assessment of efficacy in individual patients are three main issues. A few recently published case series showed only modest efficacy of cabazitaxel, abiraterone and enzalutamide when used as third-line agents, although prospective data are lacking. In 24 patients treated with cabazitaxel after docetaxel and abiraterone, a median of four cycles of cabazitaxel were delivered, with a median survival from initiation of cabazitaxel of 8.2 months (95% CI: 3.34–13.05) [7], and a median survival after docetaxel initiation of 32 months. In 35 patients treated with the sequence enzalutamide after docetaxel and abiraterone, a greater than 50% PSA decline was recorded in 45.7% of patients

Background Sunitinib and everolimus have been approved for first- and second-line treatment, respectively, in metastatic renal cell carcinoma (mRCC). The role of sorafenib, which is approved for second-line treatment after cytokines failure, is presently to be defined. Objective To determine whether third-line sorafenib after sequential use of sunitinib and mammalian target of rapamycin inhibitors (everolimus or temsirolimus) is feasible and effective. Design, setting, and participants One hundred fifty medical records of patients with mRCC treated with first-line sunitinib between January 2006 and January 2010 were reviewed at four participating centers. Data regarding patients treated with the sequence sunitinib–everolimus or temsirolimus–sorafenib were extracted. Central analysis of radiographic images was performed using RECIST criteria to determine progression-free survival (PFS) and overall response rate (oRR) to sorafenib treatment. Measurements PFS and oRR to sorafenib were the primary end points. Secondary outcomes were safety and overall survival (OS). Results and limitations Thirty-four patients were eligible for the study. A median PFS of 4 mo (range: 3–6 mo) and a median OS of 7 mo since sorafenib treatment (range: 6–10 mo) were reported. Of the patients, 23.5% showed response to sorafenib, with an overall disease control rate (complete responses plus partial responses plus stable disease) of 44%. Selection bias, data incompleteness, and absence of study design are inevitable limitations of the study, although central review can strengthen the quality of presented data. Conclusions Third-line sorafenib appears to be active and well tolerated in mRCC after first-line sunitinib and second-line everolimus or temsirolimus, with no patients interrupting sorafenib because of toxicity or lack of compliance. Prospective, placebo-controlled trials are completely lacking and are required in this setting.

Until very recently, docetaxel was the only approved agent in castration-resistant prostate cancer (CRPC) and other effective therapeutic options are urgently needed. In recent years, several new agents with promising activity and a favourable toxicity profile have been developed and clinically investigated in the fields of hormonal, cytotoxic, targeted and immune therapy. In particular, recent results from two large phase III trials of sipuleucel-T and cabazitaxel show that these two agents significantly prolong overall survival in CRPC. Indeed, sipuleucel-T has recently been approved by the US FDA for the treatment of CRPC. Many other pharmaceuticals, which are presented in this review, have been investigated recently or are being investigated in phase III trials and might prove to be effective in the future. Reviewed articles are discussed in light of the innovations in study design brought by the Prostate Cancer Clinical Trials Working Group (PCWG2), which updated the Prostate-Specific Antigen Working Group (PCWG1) guidelines, in order to allow better identification of potentially active drugs in clinical trials.

Aim: A higher Gleason score was associated with a lower tumor urotensin II receptor (UTII-R) expression in prostate cancer patients. Methods: A retrospective review of formalin-fixed paraffin-embedded tumor tissue derived from those who had prostatectomy and matching biopsy specimens was conducted at six Institutions. UTII-R expression was evaluated on biopsy by immunohistochemistry. Results: A total of 58 subjects undergoing radical prostatectomy were included. At multivariate analysis, low UTII-R expression was a significant predictor of Gleason upgrading, with an odds ratio of 10.3 (95% CI: 1.55–68.4), and of pathology upstaging, with an odds ratio of 11.1 (95% CI: 1.23–100.48). Conclusions: UTII-R expression on biopsy was associated with Gleason upgrading and pathology upstaging in prostate cancer patients.