Exploring the role of respiratory microbiome in lung cancer: A systematic review.

Giving the potential contribute in cancer initiation and progression, lung microbiota represents a promising topic in cancer research, although still unexplored. We performed a systematic literature search to identify clinical studies evaluating lung microbiota composition, its correlation with lung cancer patients' clinico-pathological features and prognosis. Of the identified 370 studies, 21 were eligible and included. Although studies were heterogeneous, lung cancer resulted to be enriched in peculiar microbial communities, with differences in composition and diversity according to clinico-pathological parameters. Few studies explored how lung microbiota influences cancer outcome. In light of these findings and borrowing the suggestions coming from gut microbiota, we speculate that respiratory microbiome may influence pathogenesis, progression and outcome of lung cancer. Taking advantage of the experience of chronical lung diseases, prospective studies should be designed to evaluate lung microbiota changes throughout any phase of lung cancer course, particularly with the advent of immunotherapy as pivotal treatment.

Correction to: Angiogenesis Genotyping and Clinical Outcomes in Patients with Advanced Hepatocellular Carcinoma Receiving Sorafenib: The ALICE­2 Study.

The listing of the author names and affiliations, which previously read.

Author Correction: A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Angiogenesis Genotyping and Clinical Outcomes in Patients with Advanced Hepatocellular Carcinoma Receiving Sorafenib: The ALICE-2 Study.

BACKGROUND: Sorafenib represents one of the therapeutic strongholds for advanced hepatocellular carcinoma (HCC), but unfortunately, predictive factors are lacking. We previously reported that the VEGF single nucleotide polymorphisms (SNPs) rs2010963 and rs4604006 might correlate with clinical outcomes in sorafenib-treated HCC patients. OBJECTIVE: The objective of the ALICE-2 study is to define a prognostic angiogenesis profile to better identify HCC patients who are more likely to benefit from sorafenib treatment. PATIENTS AND METHODS: From 2008 to 2015, all consecutive HCC patients receiving sorafenib according to the Italian label were tested for specific HIF-1α, VEGF, and VEGFR SNPs. Results from angiogenesis genotyping were then correlated with clinical outcome parameters. RESULTS: Globally, a total of 210 patients were enrolled. At multivariate analysis rs12434438 of HIF1α, rs2010963 of VEGF-A, and rs4604006 of VEGF-C were confirmed as independent predictive factors. At the combined analysis of significant SNPs, the presence of two favourable alleles of rs2010963 and rs4604006 of VEGF compared to only one or to none favourable alleles, was able to identify three separate patients populations with different time-to-progression (TTP) (10.8 vs. 5.6 vs. 3.7 months, respectively; p < 0.0001) and overall survival (OS) (19.0 vs. 13.5 vs. 7.5 months, respectively; p < 0.0001). Furthermore, the presence of the GG genotype of rs12434438 (HIF-1α) seemed able to select a population with a particularly poor outcome, independently from the clinical effect of the two VEGF SNPs (TTP: 2.6 months, HR: 0.54, p = 0.0374; OS: 6.6 months, p = 0.0061, HR: 0.43). CONCLUSIONS: Our findings show that polymorphism analysis of HIF-1α, VEGF, and VEGFR genes may represent a prognostic panel to better identify HCC patients who are more likely to benefit from sorafenib treatment.

Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter.

Upper tract urothelial carcinoma (UTUC) accounts for 5% of urothelial carcinomas (UCs), the estimated annual incidence being 1-2 cases per 100,000 inhabitants. Similarly to bladder UC, divergent differentiations and histologic variants confer an adverse risk factor in comparison with pure UTUC. Molecular and genomic characterization studies on UTUC have shown changes occurring at differing frequencies from bladder cancer, with unique molecular and clinical subtypes, potentially with different responses to treatment. Systemic chemotherapy is the standard approach for patients with inoperable locally advanced or metastatic UCs. Although initial response rates are high, the median survival with combination chemotherapy is about 15 months. In first-line chemotherapy several cisplatin-based regimens have been proposed. For patients with advanced UC who progress to first-line treatment, the only product licensed in Europe is vinflunine, a third-generation, semisynthetic, vinca alkaloid. Better response rates (15-60%), with higher toxicity rates and no overall survival (OS) benefit, are generally achieved in multidrug combinations, which often include taxanes and gemcitabine. The US FDA has recently approved five agents targeting the programmed death-1 and programmed death ligand-1 pathway as a second-line therapy in patients with locally advanced or metastatic UC with disease progression during or following platinum-containing chemotherapy. Potential therapeutic targets are present in 69% of tumours analyzed. Specific molecular alterations include those involved in the RTK/Ras/PI(3)K, cell-cycle regulation and chromatin-remodeling pathways, many of them have either targeted therapies approved or under investigation. Angiogenic agents, anti-epidermal growth factor receptor therapy, phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) pathway inhibitors and immunotherapeutic drugs are being successfully investigated.

Mismatch repair deficiency may affect clinical outcome through immune response activation in metastatic gastric cancer patients receiving first-line chemotherapy.

INTRODUCTION: The microsatellite-instable gastric cancer subtype, because of its supposed high antigenic potential, is a promising candidate for immunotherapy. We analyzed if the presence of a defective mismatch repair (MMR) system is associated with other markers of immune response and their relationship with outcome in advanced gastric cancer patients. METHODS: We analyzed the relationship between clinical outcome and MMR status, the presence of tumor-infiltrating lymphocytes (TIL), lymphocytosis, and neutrophil-to-lymphocyte ratio (NLR) in metastatic gastric cancer patients treated with a chemotherapy doublet in the first-line setting. Other stratification factors were sex, age, Eastern Cooperative Oncology Group performance status, adjuvant/neoadjuvant chemotherapy, metastatic sites, and histotype. RESULTS: One hundred three patients were eligible for analysis. Defective MMR was found in 15 patients (14 %), TILs were found in 18 patients (17 %), lymphocytosis was found in 24 patients (23 %), and high NLR was found in 75 patients (72 %). Significant correlations were found between defective MMR and TIL positivity (p = 0.0004), between defective MMR and lymphocytosis (p = 0.0062), between defective MMR and low NLR (p = 0.000069), and between TIL positivity and lymphocytosis (p = 0.000147). All factors had a statistically significant impact on overall survival, although on multivariate analysis only defective MMR (p = 0.0001) and TIL positivity (p = 0.0192) maintained their independent prognostic role. Similar results were observed for progression-free survival, with defective MMR (p = 0.0001) and TIL positivity (p = 0.0195) maintaining their prognostic role on multivariate analysis. CONCLUSIONS: Our analysis confirms the favorable prognosis of metastatic gastric cancer patients with a defective MMR system and suggests that expression of TILs might also be linked to better outcome. Because of the correlation between defective MMR status and measures of immune system activity, this group of patients would be the best candidates for novel immunotherapy-based therapies.

The Role of Aspirin as Antitumoral Agent for Heavily Pretreated Patients With Metastatic Colorectal Cancer Receiving Capecitabine Monotherapy.

BACKGROUND: The potential clinical impact of aspirin use beyond its canonical indications is a novel matter of scientific debate. In patients with metastatic colorectal cancer failing all available options, regorafenib and TAS 102 represent the only chance of treatment. Although effective, these therapeutic options bring along a not-negligible burden in terms of economic costs and toxicity. In this setting, the indication to use aspirin in combination with chemotherapy would potentially represent a medical revolution under the economic and toxicity profile. PATIENTS AND METHODS: We assessed the role of aspirin in patients with metastatic colorectal cancer who failed all previous treatments and were receiving capecitabine as a salvage option before the introduction of regorafenib and TAS-102. RESULTS: Sixty-six patients were eligible. Twenty patients (30%) were on incidental treatment with aspirin for cardiovascular diseases. Twelve (60%) partial responses were seen in patients on treatment with aspirin, compared with 3 (6%) partial responses in the remaining patients (P = .00007). Sixteen patients on aspirin (80%) obtained disease control versus 14 (30%) patients who were not on aspirin (P = .000377). The median progression-free survival for patients receiving treatment with aspirin was 6.5 months versus 3.3 months for patients who were not on aspirin (hazard ratio, 0.48; 95% confidence interval, 0.30-0.79; P = .0042). A significantly improved overall survival was also evident in aspirin users (median overall survival, 14.7 vs. 8.7 months, respectively; hazard ratio, 0.43; 95% confidence interval, 0.26-0.72; P = .0023). CONCLUSION: Aspirin may improve the clinical outcome of heavily pre-treated patients with metastatic colorectal cancer receiving chemotherapy. Further studies are necessary before application in the clinical practice.

Lactate Dehydrogenase in Hepatocellular Carcinoma: Something Old, Something New.

Hepatocellular carcinoma (HCC) is the most common primary liver tumour (80-90%) and represents more than 5.7% of all cancers. Although in recent years the therapeutic options for these patients have increased, clinical results are yet unsatisfactory and the prognosis remains dismal. Clinical or molecular criteria allowing a more accurate selection of patients are in fact largely lacking. Lactic dehydrogenase (LDH) is a glycolytic key enzyme in the conversion of pyruvate to lactate under anaerobic conditions. In preclinical models, upregulation of LDH has been suggested to ensure both an efficient anaerobic/glycolytic metabolism and a reduced dependence on oxygen under hypoxic conditions in tumour cells. Data from several analyses on different tumour types seem to suggest that LDH levels may be a significant prognostic factor. The role of LDH in HCC has been investigated by different authors in heterogeneous populations of patients. It has been tested as a potential biomarker in retrospective, small, and nonfocused studies in patients undergoing surgery, transarterial chemoembolization (TACE), and systemic therapy. In the major part of these studies, high LDH serum levels seem to predict a poorer outcome. We have reviewed literature in this setting trying to resume basis for future studies validating the role of LDH in this disease.

Angiogenesis genotyping in the selection of first-line treatment with either sunitinib or pazopanib for advanced renal cell carcinoma.

INTRODUCTION: Recent data from the COMPARZ study seem to suggest a non-inferiority of pazopanib confronted with sunitinib in PFS and OS. We previously reported how VEGF and VEGFR polymorphisms might have a predictive role in patients treated with first-line sunitinib. Aim of our study was to investigate whether tumour angiogenesis genotyping could influence clinical outcome in RCC patients treated with either sunitinib or pazopanib, in order to help clinicians select the appropriate treatment for each patient. RESULTS: 19 patients were treated with pazopanib while 78 received sunitinib. VEGF A rs833061 resulted significant in PFS in sunitinib vs pazopanib patients (CC+CT>TT in sunitinib, TT>CC+CT in pazopanib; p<0,0001); VEGF A rs2010963 resulted significant in PFS in sunitinib vs pazopanib patients (GG+CG>CC in sunitinib, CC>GG+CG in pazopanib; p<0,0001); VEGF A rs699947 resulted significant in PFS in sunitinib vs pazopanib patients (AA+AC>CC in sunitinib, CC>AA+AC in pazopanib; p<0,0001). OS showed no statistically significant difference. CONCLUSIONS: in our analysis patients with opposite polymorphisms of rs833061, rs2010963, rs699947 of VEGF A seems to have a better PFS if treated with either sunitinib or pazopanib. Our data seem to suggest that biology could have a role choosing first line treatment for mRCC patients. METHODS: a retrospective analysis on 97 histologic samples of mRCC patients was conducted for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs).

The correlation between LDH serum levels and clinical outcome in advanced biliary tract cancer patients treated with first line chemotherapy.

LDH may represent an indirect marker of neo-angiogenesis and worse prognosis in many tumour types. We assessed the correlation between LDH and clinical outcome for biliary tract cancer (BTC) patients treated with first-line chemotherapy. Overall, 114 advanced BTC patients treated with first-line gemcitabine and cisplatin were included. Patients were divided into two groups (low vs. high LDH), according to pre-treatment LDH values. Patients were also classified according to pre- and post-treatment variation in LDH serum levels (increased vs. decreased). Median progression free survival (PFS) was 5.0 and 2.6 months respectively in patients with low and high pre-treatment LDH levels (p = 0.0042, HR = 0.56, 95% CI: 0.37-0.87). Median overall survival (OS) was 7.7 and 5.6 months (low vs. high LDH) (p = 0.324, HR = 0.81, 95% CI: 0.54-1.24). DCR was 71% vs. 43% (low vs. high LDH) (p = 0.002). In 38 patients with decreased LDH values after treatment, PFS and OS were respectively 6.2 and 12.1 months, whereas in 76 patients with post-treatment increased LDH levels, PFS and OS were respectively 3.0 and 5.1 months (PFS: p = 0.0009; HR = 0.49; 95% IC: 0.33-0.74; OS: p < 0.0001; HR = 0.42; 95% IC: 0.27-0.63). Our data seem to suggest that LDH serum level may predict clinical outcome in BTC patients receiving first-line chemotherapy.

Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients.

Regorafenib monotherapy is a potential option for metastatic colorectal cancer patients. However, the lack of predictive factors and the severe toxicities related to treatment have made its use in clinical practice challenging. Polymorphisms of VEGF and its receptor (VEGFR) genes might regulate angiogenesis and thus potentially influence outcome during anti-angiogenesis treatment such as regorafenib. Aim of our study was to evaluate the role of VEGF and VEGFR genotyping in determining clinical outcome for colorectal cancer patients receiving regorafenib. We retrospectively collected clinical data and samples (tumour or blood) of 138 metastatic colorectal cancer patients treated with regorafenib. We analysed the correlation of different VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs) with patients' progression-free survival (PFS) and overall survival (OS). Results from angiogenesis genotyping showed that only VEGF-A rs2010963 maintained an independent correlation with PFS and OS. Among clinical factors only ECOG PS was independently correlated with OS, whereas no correlation with PFS was evident. Grouping together those results allowed further patients stratification into 3 prognostic groups: favourable, intermediate and unfavourable. VEGF-A rs2010963 genotyping may represent an important tool for a more accurate selection of optimal candidates for regorafenib therapy.

Three drugs vs two drugs first-line chemotherapy regimen in advanced gastric cancer patients: a retrospective analysis.

The definition of the standard chemotherapy regimen for advanced gastric cancer is still a matter of debate. Aim of our analysis was to retrospectively assess whether an intensive, three-drugs, front line approach could be comparable to a sequential (two-drugs front line then second line) in terms of RR (response rate), PFS (progression free survival) and OS (overall survival) in advanced gastric cancer patients in the clinical practice. Patients with metastatic gastric cancer who have received a first-line combination chemotherapy with a two or three-drugs regimen were included in our analysis. We divided our patients into two groups, A and B, based on the first line chemotherapy administered (group A = three drugs; group B = two drugs). A total of 425 patients were eligible for our analysis. 216 patients (50.8 %) received three chemotherapeutic agents (group A) and 209 patients (49.2 %) received a two drugs regimen as first-line combination chemotherapy (group B). RR for group A and B was 44 and 29.6 %, respectively (p = 0.0005), median PFS was 7.3 months in group A and 4.5 months in group B (p = 0.0007). No significant difference was found in terms of OS. The addition of a third drug to a doublet chemotherapy regimen appeared more active in terms of response rate and PFS. However median OS resulted comparable. On this basis, the use of a sequential approach may represent a reasonable strategy for patients unwilling or unable to undergo a more intensive treatment without compromising OS.

The value of lactate dehydrogenase serum levels as a prognostic and predictive factor for advanced pancreatic cancer patients receiving sorafenib.

Although lactate dehydrogenase (LDH) serum levels, indirect markers of angiogenesis, are associated with a worse outcome in several tumours, their prognostic value is not defined in pancreatic cancer. Moreover, high levels are associated even with a lack of efficacy of tyrosine kinase inhibitors, contributing to explain negative results in clinical trials. We assessed the role of LDH in advanced pancreatic cancer receiving sorafenib. Seventy-one of 114 patients included in the randomised phase II trial MAPS (chemotherapy plus or not sorafenib) and with available serum LDH levels, were included in this analysis. Patients were categorized according to serum LDH levels (LDH ≤ vs.> upper normal rate). A significant difference was found in progression free survival (PFS) and in overall survival (OS) between patients with LDH values under or above the cut-off (PFS: 5.2 vs. 2.7 months, p = 0.0287; OS: 10.7 vs. 5.9 months, p = 0.0021). After stratification according to LDH serum levels and sorafenib treatment, patients with low LDH serum levels treated with sorafenib showed an advantage in PFS (p = 0.05) and OS (p = 0.0012). LDH appears to be a reliable parameter to assess the prognosis of advanced pancreatic cancer patients, and it may be a predictive parameter to select patients candidate to receive sorafenib.

Prognostic clinical factors in pretreated colorectal cancer patients receiving regorafenib: implications for clinical management.

BACKGROUND: We assessed the impact on survival of angiogenesis and inflammation-related factors, particularly LDH serum levels, platelet, neutrophil and lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR), in metastatic colorectal cancer patients receiving regorafenib monotherapy. METHODS: LDH serum levels, neutrophil, lymphocyte and platelet counts were collected at the start of regorafenib monotherapy. Cut-off values were calculated by ROC curve analysis. Survival analyses were performed by Kaplan-Meier method, and multivariate analysis by Cox method. RESULTS: A total of 208 patients were eligible for analysis. Among factors who were related with worse overall survival and who maintained their role at the multivariate analysis, high platelet count (Exp(b):1.4963, 95% CI:1.0130-2.2103, p = 0.0439) and high neutrophil/lymphocyte ratio (Exp(b):1.6963, 95% CI:1.0757-2.6751, p = 0.0237) were those who more deeply were related to worse overall survival. High lymphocyte count (Exp(b):0.4527, 95% CI:0.2801-0.7316, p = 0.0013) was correlated with improved overall survival. CONCLUSIONS: High neutrophil, high platelet, low lymphocyte count and/or high NLR may represent negative prognostic factors in patients receiving regorafenib monotherapy. It is advisable that these factors are taken into account in the design of subsequent trials in colorectal cancer patients receiving this drug.

Predictive factors for sunitinib treatment response in advanced renal cell carcinoma: are we really making steps forward?

Renal cell carcinoma is an aggressive neoplasm, frequently diagnosed incidentally in an advanced stage (local or metastatic). Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases, mainly directed against the angiogenic pathway. Sunitinib is largely used in first-line treatment, but response varies widely among patients. Thus, there is an urgent need to find predictive factors able to determine whether or not a patient would respond to treatment, thereby avoiding unnecessary toxicities. In this report we review the literature focusing on clinical, pathological, and molecular predictive factors currently being studied and more promising to enter clinical practice.

Prognostic Value for Incidental Antihypertensive Therapy With ß-Blockers in Metastatic Colorectal Cancer.

Previous studies suggested that the incidental use of ß-blockers might influence clinical outcome in solid tumors. We assessed the correlation between the incidental use of ß-blockers and clinical outcome in colorectal cancer patients treated with first-line chemotherapy alone or in combination with bevacizumab in metastatic colorectal cancer patients. We collected data from 235 metastatic colorectal cancer patients treated with first-line chemotherapy alone (128 patients) or with bevacizumab (107 patients). Patients were stratified for clinical factors such as ß-blockers use, age, sex, and site of metastases, previous adjuvant chemotherapy and ECOG performance status. In the chemotherapy alone group patients receiving ß-blockers showed an improved overall survival (median OS 41.3 vs 25.7 months, P = 0.03, HR: 2.26, 95% CI: 1.05-3.24). A significant relationship with improved response rate was also evident for B-blocker users (P = 0.044). On the contrary in the ß-blockers users group treated with chemotherapy in combination with bevacizumab we observed a trend toward a worse overall survival although nonstatistically significant (median OS 18.5 vs 23.6 months, HR: 0. 89, 95% CI: 0.38-2.03, P = 0.77). Our analysis confirmed a potential prognostic role for the use of ß-blockers in colorectal cancer patients treated with chemotherapy. Our findings also suggest a potential worse outcome for patients on ß-blockers receiving bevacizumab. Future prospective studies should include the incidental use of ß-blockers as stratification factor for clinical outcome.

Survival in patients with clear cell renal cell carcinoma is predicted by HIF-1α expression.

AIM: To investigate hypoxia inducible factor-1α's (HIF-1α) immunohistochemical expression in clear cell renal cell carcinoma (ccRCC) treated with radical nephrectomy. PATIENTS AND METHODS: One hundred and forty-eight patients were considered from those who underwent radical nephrectomy between 1983 and 1993. Archived materials were retrieved from the Institute of Pathological Anatomy for immunostaining. The features considered on the histological specimens were tumor stage, grade, as well as cellular and vascular HIF-1α expression. All considered parameters were correlated with time to recurrence (TTR) and overall survival (OS). RESULTS: TTR was significantly longer in patients with low cellular HIF-1α expression; patients' survival was higher in those with low HIF-1α expression. Regarding vascular HIF-1α expression, the differences were not statistically significant when considering TTR and OS. On univariate analysis, age, clinical stage and HIF-1α cellular expression showed a significant association with OS. CONCLUSION: Cellular HIF-1α is an important indicator of prognosis in patients with ccRCC; high HIF-1α expression predicts poor survival.

Recent aspects of sunitinib therapy in patients with metastatic clear-cell renal cell carcinoma: a systematic review of the literature.

Sunitinib is an orally available inhibitor of multiple tyrosine-kinase receptors approved for the treatment of advanced clear-cell renal cell carcinoma (ccRCC), a disease which has habitually had a very poor patient survival rate. Although it has become the most widely used drug for this disease, it remains not completely clear the best treatment strategy with these agent. The aim of this review is to highlight the most recent and interesting aspects of the research on treatment of advanced ccRCC with sunitinib and eventually determine alternative treatment schedule to reduce the incidence of side effects; we also wanted to review recent biomarkers able to predict response to therapy and also to point out the mechanism of acquired resistance to this drug.

Tumor VEGF expression correlates with tumor stage and identifies prognostically different groups in patients with clear cell renal cell carcinoma.

OBJECTIVES: Vascular endothelial growth factor (VEGF) is a potent inducer of tumor angiogenesis and represents the key element in the pathogenesis of clear cell renal cell carcinoma (ccRCC). The aim of this study was to investigate the use of tumor VEGF expression as a parameter to identify tumor stage and prognostically different patient groups. METHODS AND MATERIALS: We retrospectively collected clinical data of 137 patients treated with partial or radical nephrectomy at our institutions for organ-confined, locally advanced, and metastatic ccRCCs between 1984 and 2013. Tumor cell VEGF immunohistochemical expression was compared with pathological and clinical features including age, sex, tumor stage, and Fuhrman grade. Comparison of VEGF expression levels between tumor stages was performed via Kruskal-Wallis nonparametric test. Survival analysis was conducted via Kaplan-Meier product-limit method, and Mantel-Haenszel log-rank test was employed to compare survival among groups. RESULTS: Median age at diagnosis was 61 years (range: 33-85 y). Tumor stage was pT1N0M0 in 67 patients (49%), pT2N0M0 in 5 (4%), and pT3N0M0 in 25 (18%), while 40 patients (29%) had metastatic tumors at diagnosis. Fuhrman nuclear grade was G1 in 22 patients (16%), G2 in 60 (44%), G3 in 33 (24%), G4 in 13 patients (9%), and unknown in 9 patients. Tumor VEGF was differentially expressed among different stages (P<0.001) and in low (G1-2) and high (G3-4) Fuhrman grade tumors (P<0.001). No significant differences were found when stratifying by sex (P = 0.06) or age (P = 0.29). Median overall survival (OS) from partial or radical nephrectomy was 161 months (range: 1-366). We observed a significantly longer OS in patients with low (<25%) vs. high (>25%) VEGF expression levels (median OS 206 vs. 65 mo, P<0.001). CONCLUSIONS: Our data show that tumor cell VEGF expression is significantly associated with tumor stage and Fuhrman grade and is able to predict patient outcome, suggesting a potential use of this parameter in identifying prognostically different patients with ccRCC.

Selected news from the 2014 Genitourinary Cancers Symposium: translating novel strategies into clinical practice.

2014 Genitourinary Cancers Symposium San Francisco, CA, USA, 30 January-1 February 2014 The American Society of Clinical Oncology symposium dedicated to genitourinary tumors represents an unmissable opportunity for the whole oncology community with a special interest in the diagnosis and treatment of genitorurinary tract malignancies, in particular kidney and prostate tumors. The 2014 Genitourinary Cancers Symposium focused attention on the need to find a personalized therapy for metastatic renal cell carcinoma and castration-resistant prostate cancer patients. The development of biomarkers for tumor response and/or resistance will represent a major step in this context and has been the focus of several researches at the symposium.