Metabolomic Approaches for Detection and Identification of Biomarkers and Altered Pathways in Bladder Cancer

Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a “signature pathway” associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice

Molecular Imaging Diagnosis of Renal Cancer Using 99mTc-Sestamibi SPECT/CT and Girentuximab PET-CT-Current Evidence and Future Development of Novel Techniques

: Novel molecular imaging opportunities to preoperatively diagnose renal cell carcinoma is under development and will add more value in limiting the postoperative renal function loss and morbidity. We aimed to comprehensively review the research on single photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography computed tomography (PET-CT) molecular imaging and to enhance the urologists' and radiologists' knowledge of the current research pattern. We identified an increase in prospective and also retrospective studies that researched to distinguish between benign and malignant lesions and between different clear cell renal cell carcinoma subtypes, with small numbers of patients studied, nonetheless with excellent results on specificity, sensitivity and accuracy, especially for 99mTc-sestamibi SPECT/CT that delivers quick results compared to a long acquisition time for girentuximab PET-CT, which instead gives better image quality. Nuclear medicine has helped clinicians in evaluating primary and secondary lesions, and has lately returned with new and exciting insights with novel radiotracers to reinforce its diagnostic potential in renal carcinoma. To further limit the renal function loss and post-surgery morbidity, future research is mandatory to validate the results and to clinically implement the diagnostic techniques in the context of precision medicine

Emerging Hallmarks of Metabolic Reprogramming in Prostate Cancer

Prostate cancer (PCa) is the most common male malignancy and the fifth leading cause of cancer death in men worldwide. Prostate cancer cells are characterized by a hybrid glycolytic/oxidative phosphorylation phenotype determined by androgen receptor signaling. An increased lipogenesis and cholesterogenesis have been described in PCa cells. Many studies have shown that enzymes involved in these pathways are overexpressed in PCa. Glutamine becomes an essential amino acid for PCa cells, and its metabolism is thought to become an attractive therapeutic target. A crosstalk between cancer and stromal cells occurs in the tumor microenvironment because of the release of different cytokines and growth factors and due to changes in the extracellular matrix. A deeper insight into the metabolic changes may be obtained by a multi-omic approach integrating genomics, transcriptomics, metabolomics, lipidomics, and radiomics data

Cellular and Molecular Players in the Tumor Microenvironment of Renal Cell Carcinoma

Globally, clear-cell renal cell carcinoma (ccRCC) represents the most prevalent type of kidney cancer. Surgery plays a key role in the treatment of this cancer, although one third of patients are diagnosed with metastatic ccRCC and about 25% of patients will develop a recurrence after nephrectomy with curative intent. Molecular-target-based agents, such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), are recommended for advanced cancers. In addition to cancer cells, the tumor microenvironment (TME) includes non-malignant cell types embedded in an altered extracellular matrix (ECM). The evidence confirms that interactions among cancer cells and TME elements exist and are thought to play crucial roles in the development of cancer, making them promising therapeutic targets. In the TME, an unfavorable pH, waste product accumulation, and competition for nutrients between cancer and immune cells may be regarded as further possible mechanisms of immune escape. To enhance immunotherapies and reduce resistance, it is crucial first to understand how the immune cells work and interact with cancer and other cancer-associated cells in such a complex tumor microenvironment

Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical Practice

Renal cell carcinoma (RCC) is the seventh most common cancer in men and the ninth most common cancer in women worldwide. There is plenty of evidence about the role of the immune system in surveillance against tumors. Thanks to a better understanding of immunosurveillance mechanisms, immunotherapy has been introduced as a promising cancer treatment in recent years. Renal cell carcinoma (RCC) has long been thought chemoresistant but highly immunogenic. Considering that up to 30% of the patients present metastatic disease at diagnosis, and around 20–30% of patients undergoing surgery will suffer recurrence, we need to identify novel therapeutic targets. The introduction of immune checkpoint inhibitors (ICIs) in the clinical management of RCC has revolutionized the therapeutic approach against this tumor. Several clinical trials have shown that therapy with ICIs in combination or ICIs and the tyrosine kinase inhibitor has a very good response rate. In this review article we summarize the mechanisms of immunity modulation and immune checkpoints in RCC and discuss the potential therapeutic strategies in renal cancer treatment

Radiogenomics in Renal Cancer Management-Current Evidence and Future Prospects

Renal cancer management is challenging from diagnosis to treatment and follow-up. In cases of small renal masses and cystic lesions the differential diagnosis of benign or malignant tissues has potential pitfalls when imaging or even renal biopsy is applied. The recent artificial intelligence, imaging techniques, and genomics advancements have the ability to help clinicians set the stratification risk, treatment selection, follow-up strategy, and prognosis of the disease. The combination of radiomics features and genomics data has achieved good results but is currently limited by the retrospective design and the small number of patients included in clinical trials. The road ahead for radiogenomics is open to new, well-designed prospective studies, with large cohorts of patients required to validate previously obtained results and enter clinical practice

The Efficacy of Flogofilm® in the Treatment of Chronic Bacterial Prostatitis as an Adjuvant to Antibiotic Therapy: A Randomized Prospective Trial

Introduction: Bacterial prostatitis (BP) is a common prostatic infection characterized by a bimodal distribution in young and older men, with a prevalence between 5-10% among all cases of prostatitis and a high impact on quality of life. Although the management of bacterial prostatitis involves the use of appropriate spectrum antibiotics, which represent the first choice of treatment, a multimodal approach encompassing antibiotics and nutraceutical products in order to improve the efficacy of chosen antimicrobial regimen is often required. Objective: To evaluate the efficacy of Flogofilm® in association with fluoroquinolones in patients with chronic bacterial prostatitis (CBP). Methods: Patients diagnosed with prostatitis (positivity to Meares-Stamey Test and symptoms duration > 3 months) at the University of Naples "Federico II", Italy, from July 2021 to December 2021, were included in this study. All patients underwent bacterial cultures and trans-rectal ultrasounds. Patients were randomized into two groups (A and B) receiving antibiotic alone or an association of antibiotics plus Flogofilm® tablets containing Flogomicina® for one month, respectively. The NIH-CPSI and IPSS questionnaires were administered at baseline, four weeks, twelve and twenty-four weeks. Results: A total of 96 (Group A = 47, Group B = 49) patients concluded the study protocol. The mean age was comparable, with a mean age of 34.62 ± 9.04 years for Group A and 35.29 ± 10.32 years for Group B (p = 0.755), and IPSS at the baseline was 8.28 ± 6.33 and 9.88 ± 6.89 (p = 0.256), respectively, while NIH-CPSI at baseline was 21.70 ± 4.38 and 21.67 ± 6.06 (p = 0.959), respectively. At 1, 3 and 6 months, the IPSS score was 6.45 ± 4.8 versus 4.31 ± 4.35 (p = 0.020), 5.32 ± 4.63 versus 3.20 ± 3.05 (p = 0.042) and 4.91 ± 4.47 versus 2.63 ± 3.28 (p = 0.005) for Groups A and B, respectively. Similarly, the NIH-CPSI total score at 1, 3 and 6 months was 16.15 ± 3.31 versus 13.10 ± 5.03 (p < 0.0001), 13.47 ± 3.07 versus 9.65 ± 4.23 (p < 0.0001) and 9.83 ± 2.53 versus 5.51 ± 2.84 (p < 0.0001), respectively. Conclusions: Flogofilm®, associated with fluoroquinolones, demonstrate a significant improvement in pain, urinary symptoms and quality of life in patients affected by chronic bacterial prostatitis in both IPSS and NIH-CPSI scores compared with fluoroquinolones alone

The Impact of Meat Intake on Bladder Cancer Incidence: Is It Really a Relevant Risk?

Bladder cancer (BC) represents the second most common genitourinary malignancy. The major risk factors for BC include age, gender, smoking, occupational exposure, and infections. The BC etiology and pathogenesis have not been fully defined yet. Since catabolites are excreted through the urinary tract, the diet may play a pivotal role in bladder carcinogenesis. Meat, conventionally classified as "red", "white" or "processed", represents a significant risk factor for chronic diseases like cardiovascular disease, obesity, type 2 diabetes, and cancer. In particular, red and processed meat consumption seems to increase the risk of BC onset. The most accepted mechanism proposed for explaining the correlation between meat intake and BC involves the generation of carcinogens, such as heterocyclic amines and polycyclic aromatic hydrocarbons by high-temperature cooking. This evidence claims the consumption limitation of meat. We reviewed the current literature on potential biological mechanisms underlying the impact of meat (red, white, and processed) intake on the increased risk of BC development and progression. Toward this purpose, we performed an online search on PubMed using the term "bladder cancer" in combination with "meat", "red meat", "white meat" or "processed meat". Although some studies did not report any association between BC and meat intake, several reports highlighted a positive correlation between red or processed meat intake, especially salami, pastrami, corned beef and bacon, and BC risk. We speculate that a reduction or rather a weighting of the consumption of red and processed meat can reduce the risk of developing BC. Obviously, this remark claims future indications regarding food education (type of meat to be preferred, quantity of red meat to be eaten and how to cook it) to reduce the risk of developing BC. Further well-designed prospective studies are needed to corroborate these findings

Predictive clinico-pathological factors to identify BCG, unresponsive patients, after re-resection for T1 high grade non-muscle invasive bladder cancer

Introduction: Seventy-five percent of bladder cancers are non-muscle invasive. The treatment strategy includes the transurethral resection of bladder tumor (TURB) followed by intravesical immunotherapy with the bacillus of Calmette-Guerin (BCG) or chemotherapy, depending on the grade of bladder tumor. Despite a proper BCG intravesical instillations schedule, up to 40% of patients present a failure within 2 years. The aim of this retrospective study was to investigate the predictive factors in the response to BCG in patients with a high-grade non-muscle invasive bladder cancer diagnosis. Materials and methods: Patients with non-muscle invasive bladder cancer from 13 hospitals and academic institutions were identified and treated, from January 1, 2002, until December 31, 2012, with TURB and a subsequent re-TURB for restaging before receiving BCG. Follow-up was performed with urine cytology and cystoscopy every 3 months for 1 year and, successively every 6 months. Univariate and multivariate Cox regression models addressed the response to BCG therapy. Kaplan-Meier overall survival (OS) and cancer-specific survival (CSS) estimates were determined for BCG responsive vs. BCG unresponsive patients. Results: A total of 1,228 patients with non-muscle invasive bladder cancer were enrolled. Of 257 (20.9%) patients were BCG unresponsive. Independent predictive factors for response to BCG were: multifocality (HR: 1.4; 95% CI 1.05-1.86; P = 0.019), lymphovascular invasion (HR: 1.75; 95% CI 1.22-2.49; P = 0.002) and high-grade on re-TURB (HR: 1.39; 95% CI 1.02-1.91; P = 0.037). Overall survival was significantly reduced in BCG-unresponsive patients compared to BCG-responsive patients at 5 years (82.9% vs. 92.4%, P < 0.0001) and at 10 years (44.2% vs. 74.4%, P < 0.0001). Similarly, cancer-specific survival was reduced in BCG-unresponsive patients at 5 years (90.6% vs. 97.3%, P < 0.0001) and at 10 years (72.3% vs. 87.2%, P < 0.0001). Conclusion: Multifocality, lymphovascular invasion, and high-grade on re-TURB were independent predictors for response to BCG treatment. BCG-unresponsive patients reported worse oncological outcomes