You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Bladder cancer – the neglected tumor: a descriptive analysis of publications referenced in MEDLINE and data from the register clinicaltrials.gov
Abstract 1:
Background Uro-oncological neoplasms have both a high incidence and mortality rate and are therefore a major public health problem . The aim of this study was to evaluate research activity in uro-oncology over the last decade . Methods We search ed MEDLINE and Clinical Trials.gov systematic ally for studies on prostatic , urinary bladder , kidney , and testicular neoplasms . The increase in newly published reports per year was analyzed using linear regression . The results are presented with 95 % confidence intervals , and a p value < 0.05 was considered statistically significant . Results The number of new publications per year increased significantly for prostatic , kidney and urinary bladder neoplasms ( all < 0.0001 ) . We identified 1,885 r and omized  controlled trials ( RCTs ) ; also for RCTs , the number of newly published reports increased significantly for prostatic ( p = 0.001 ) and kidney cancer ( p = 0.005 ) , but not for bladder ( p = 0.09 ) or testicular ( p = 0.44 ) neoplasms . We identified 3,114 registered uro-oncological studies in Clinical Trials.gov . However , 85 % of these studies are focusing on prostatic ( 45 % ) and kidney neoplasms ( 40 % ) , whereas only 11 % were registered for bladder cancers . Conclusions While the number of publications on uro-oncologic research rises yearly for prostatic and kidney neoplasms , urothelial carcinomas of the bladder seem to be neglected despite their important clinical role . Clinical research on neoplasms of the urothelial bladder must be explicitly addressed and supported


Title 2:
Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer.
Abstract 2:
PURPOSE Pre clinical data suggest a contribution of the immune system to chemotherapy response . In this study , we investigated the prespecified hypothesis that the presence of a lymphocytic infiltrate in cancer tissue predicts the response to neoadjuvant chemotherapy . METHODS We investigated intratumoral and stromal lymphocytes in a total of 1,058 pretherapeutic breast cancer core biopsies from two neoadjuvant anthracycline/taxane-based studies ( GeparDuo , n = 218 , training cohort ; and GeparTrio , n = 840 , validation cohort ) . Molecular parameters of lymphocyte recruitment and activation were evaluated by kinetic polymerase chain reaction in 134 formalin-fixed , paraffin-embedded tumor sample s. Results In a multivariate regression analysis including all known predictive clinicopathologic factors , the percentage of intratumoral lymphocytes was a significant independent parameter for pathologic complete response ( pCR ) in both cohorts ( training cohort : P = .012 ; validation cohort : P = .001 ) . Lymphocyte-predominant breast cancer responded , with pCR rates of 42 % ( training cohort ) and 40 % ( validation cohort ) . In contrast , those tumors without any infiltrating lymphocytes had pCR rates of 3 % ( training cohort ) and 7 % ( validation cohort ) . The expression of inflammatory marker genes and proteins was linked to the histopathologic infiltrate , and logistic regression showed a significant association of the T-cell-related markers CD3D and CXCL9 with pCR . CONCLUSION The presence of tumor-associated lymphocytes in breast cancer is a new independent predictor of response to anthracycline/taxane neoadjuvant chemotherapy and provides useful information for oncologists to identify a subgroup of patients with a high benefit from this type of chemotherapy


Title 3:
Application of Multi-SNP Approaches Bayesian LASSO and AUC-RF to Detect Main Effects of Inflammatory-Gene Variants Associated with Bladder Cancer Risk
Abstract 3:
The relationship between inflammation and cancer is well established in several tumor types , including bladder cancer . We performed an association study between 886 inflammatory-gene variants and bladder cancer risk in 1,047 cases and 988 controls from the Spanish Bladder Cancer (SBC)/EPICURO Study . A preliminary exploration with the widely used univariate logistic regression approach did not identify any significant SNP after correcting for multiple testing . We further applied two more comprehensive methods to capture the complexity of bladder cancer genetic susceptibility : Bayesian Threshold LASSO ( BTL ) , a regularized regression method , and AUC-R and om Forest , a machine-learning algorithm . Both approaches explore the joint effect of markers . BTL analysis identified a signature of 37 SNPs in 34 genes showing an association with bladder cancer . AUC-RF detected an optimal predictive subset of 56 SNPs . 13 SNPs were identified by both methods in the total population . Using re sources from the Texas Bladder Cancer study we were able to replicate 30 % of the SNPs assessed . The associations between inflammatory SNPs and bladder cancer were reexamined among non-smokers to eliminate the effect of tobacco , one of the strongest and most prevalent environmental risk factor for this tumor . A 9 SNP-signature was detected by BTL . Here we report , for the first time , a set of SNP in inflammatory genes jointly associated with bladder cancer risk . These results highlight the importance of the complex structure of genetic susceptibility associated with cancer risk


Title 4:
The value of tumor-associated tissue inflammatory reaction in primary superficial bladder cancer
Abstract 4:
Summary The data of 92 patients who entered the prospect i ve study between 1980 and 1982 were evaluable . The prevalence of tumor-associated tissue inflammatory reaction according to the tumorparameters stage , grade , multiplicity , tumor-weight and concomittant urothelial changes in primary superficial transitional cell cancer was estimated . Using high power field on the microscope tumor-associated cells were classified as lymphocytes , plasma cells , mast cells and eosinophils by morphological criteria . Recurrence rate , tumor progression and survival rate were evaluated for the group with tumor-associated cell infiltration and compared with the data of the group without any tumor-associated inflammatory reaction . According to recurrence rate , progression rate and survival rate there was a tendency to better prognosis for tumors with associated inflammatory reaction but this could not be proven by statistical analyses


Title 5:
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
Abstract 5:
BACKGROUND Programmed death 1 ( PD-1 ) protein , a T-cell coinhibitory receptor , and one of its lig and s , PD-L1 , play a pivotal role in the ability of tumor cells to evade the host 's immune system . Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in pre clinical models . METHODS In this multicenter phase 1 trial , we administered intravenous anti-PD-L1 antibody ( at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight ) to patients with selected advanced cancers .  Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression . RESULTS As of February 24 , 2012 , a total of 207 patients --75 with non-small-cell lung cancer , 55 with melanoma , 18 with colorectal cancer , 17 with renal-cell cancer , 17 with ovarian cancer , 14 with pancreatic cancer , 7 with gastric cancer , and 4 with breast cancer -- had received anti-PD-L1 antibody . The median duration of therapy was 12 weeks ( range , 2 to 111 ) . Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9 % of patients . Among patients with a response that could be evaluated , an objective response ( a complete or partial response ) was observed in 9 of 52 patients with melanoma , 2 of 17 with renal-cell cancer , 5 of 49 with non-small-cell lung cancer , and 1 of 17 with ovarian cancer . Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up . CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression ( objective response rate of 6 to 17 % ) and prolonged stabilization of disease ( rates of 12 to 41 % at 24 weeks ) in patients with advanced cancers , including non-small-cell lung cancer , melanoma , and renal-cell cancer . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00729664 . )
Inflammatory cells , costimulatory molecules in tumour cells , and serum cytokines showed prognostic significance , mainly in univariable analyses .
High C-reactive protein values were consistently reported as an independent prognostic factor for mortality in invasive UBC .
There is a dearth of studies on InfBMs in UBC compared with other tumour types .
Evidence suggests that InfBMs may have an impact on the management of patients with UBC .
PATIENT SUMMARY In this review , we analysed studies evaluating the impact of inflammatory response on bladder cancer progression .