Upper tract urothelial (UTUC) is an uncommon malignancy. Defining the impact of adjuvant chemotherapy on long term outcomes in UTUC patients is a critical clinical question. Recently, Birtle et al. reported in The Lancet the results of a landmark Phase III, open-label, randomized controlled
POUT trial to evaluate the use of adjuvant platinum-based chemotherapy after radical nephroureterectomy in UTUC patients
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Published March 26, 2020
The role of adjuvant therapy in muscle-invasive urothelial carcinoma is unclear, despite the high risk of metastatic recurrence. Adjuvant cisplatin-based chemotherapy is challenging to administer, and some patients are ineligible for or decline neoadjuvant cisplatin-based chemotherapy. Therefore, ongoing trials are designed to evaluate the efficacy of adjuvant immunotherapy.
Published February 7, 2022
Our knowledge of the role of the gut microbiome has evolved in recent years. However, less is known about the urinary microbiome. Changes in urinary microbiota have been reported in cases of urinary incontinence, pelvic pain, and bladder cancers. However, studies have produced mixed findings on whether bladder cancer is associated with an increase or decrease in the diversity of urinary microbiota. Recently, Hrbáček et al. aimed to investigate urinary microbiota changes in males with bladder cancer.
Published January 30, 2023
Risk factors associated with bladder cancer, such as smoking, age, and BMI, can alter metabolic profiles and can be evaluated in patients through metabolomic analysis. Recently, Jacyna et al. collected urine from ten patients (eight men and two women) with non-muscle-invasive bladder cancer at three different time points: before trans-urethral resection of bladder tumor (TURBT), the day after TURBT, and at a follow-up visit two weeks later. These samples were analyzed using high-performance liquid chromatography time-of-flight mass spectrometry (HPLC-TOF/MS) and gas chromatography with triple quadrupole mass spectrometry (GCQqQ/MS).
Published April 5, 2022
The immune checkpoint inhibitor (ICI) pembrolizumab is approved for the treatment of solid tumors with a high tumor mutational burden (TMB-high ≥ 10 variants/Mb). However, measurements of TMB as a biomarker for ICI response are mainly based on studies in European populations. A recent study by Nassar et al. investigated the interplay between genetic ancestry, TMB, and tumor-only versus tumor-normal paired sequencing of solid tumors.
Published October 13, 2022
Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm in muscle-invasive bladder cancer (MIBC). However, not all patients have consistent responses to these agents, and predictive biomarkers are still needed. Antibiotic (AB) use can potentially decrease the efficacy of ICIs in advanced stage MIBC by altering the microbiome and the antitumor immune response. This detrimental effect of AB use was not evaluated in the neoadjuvant setting.
Published December 16, 2021
The standard treatment for metastatic urothelial carcinoma (mUC) is platinum-based chemotherapy followed by immunotherapy. Recently, two antibody-drug conjugates (ADCs), enfortumab vedotin (EV) and sacituzumab govitecan (SG) have been approved for mUC. Due to a potential synergistic effect between the modes of action of the two drugs and non-overlapping toxicities, McGregor et al. designed a phase I clinical trial (Double Antibody Drug Conjugate, DAD) to test the safety and dosing of EV and SG for treatment-resistant mUC.
Published April 3, 2024
Carcinogenic agents may act by inducing genetic mutations that contribute to bladder cancer development. The most commonly mutated genes in non-muscle invasive bladder cancer (NMIBC) are FGFR3 and PIK3CA, occurring in 65% and 25% of tumors, respectively. The most common mutations in muscle-invasive bladder cancer (MIBC) are in tumor suppressor genes. Rao et al. hypothesized that recurrent mutations in these genes could be caused by environmental risk factors such as smoking and sought to determine the link between these two variables.
Published January 16, 2024
FGFR3 mutations are common in urothelial carcinoma. The APOBEC mutational process is the dominant mutational mechanism in bladder cancer. The relationship between the overexpression of FGFR3 S249C mutation and APOBEC mutagenesis is not well understood. A new study published by Shi et al. in European Urology examined the link between the APOBEC mutational load and different FGFR3 recurrent mutations in bladder cancer.
Published August 16, 2019
AT-rich interactive domain-containing protein 1A Arid1a, also known as Baf250a, is the largest subunit of the SWI/SNF or BAF chromatin remodeling ATPase complex. Somatic mutations in ARID1A are common in patients with urothelial bladder carcinomas. Recently, Guo et al. set out to elucidate the function of Arid1ain bladder urothelial cells.
Published April 26, 2022
The introduction of immune checkpoint inhibitors (ICIs) has improved the outcomes for a subset of metastatic urothelial carcinoma (mUCC) patients. There is a need for a predictive tool to identify those who will benefit from these treatments. A recent study published by Goswami et al. in Science Translational Medicine assessed the use of biomarkers as a predictive tool for response to ICIs in music patients.
Published September 1, 2020
Arsenic exposure is associated with a higher risk of developing urothelial carcinoma (UC). Previous studies mostly focused on UC of the bladder. A deeper understanding of how this environmental exposure affects clinical outcomes in upper tract urothelial carcinoma (UTUC) is needed.
Published June 29, 2020
Treatment for high-risk non-muscle invasive bladder cancer (NMIBC) typically includes intravesical administration of bacillus Calmette-Guérin (BCG) as a form of immunotherapy. BCG is thought to activate both innate and adaptive immune responses with anti-tumor effects.
Published November 15, 2022
Immunotherapy-based combinations have had a dramatic improvement in outcomes for patients with metastatic renal cell carcinoma, with some patients having deep and durable responses. Developing biomarkers to predict which patients are most likely to respond to immunotherapy may help limit the number of patients who require upfront and long-term exposure to VEGF-TKIs. Additionally, the identification of biomarkers may help further our understanding of the tumor microenvironment (TME), enabling new mechanisms and combinations to improve outcomes for patients.
Published November 22, 2021
Talazoparib is a PARP inhibitor used to treat patients with genetic alterations in BRCA1/2 or other genes. PARP inhibitors may exhibit synergy in conjunction with immune checkpoint inhibitors. The JAVELIN PARP Medley trial was initiated to define the safety and efficacy of combination treatment with avelumab and talazoparib in a specific subset of patients.
Published January 11, 2023
Platinum-resistant urothelial carcinoma is a lethal disease. After a long period of therapeutic stagnation, the last two years have witnessed an explosion in the development of new second-line therapies.
Published August 10, 2017
Treatment options available for intermediate or high-risk non-muscle invasive bladder cancer include intravesical Bacillus Calmette-Guerin (BCG) and radical cystectomy.
Published February 5, 2020
Understanding differences in bladder cancer outcomes between men and women can help physicians tailor optimal treatment and follow-up strategies.
Published November 11, 2019
Non-muscle invasive bladder cancer (NMIBC) has one of the highest local recurrence rates of any malignancy. The current standards of care for NMIBC surveillance are white light cystoscopy and urine cytology. However, novel surveillance tests are needed to improve the detection of recurrent NMIBC. A recent study by Cochetti et al. examined the performance of Bladder EpiCheck (BE), a urine test that assesses 15 methylation biomarkers and photodynamic diagnosis (PDD)-guided cystoscopy for surveillance of high-risk NMIBC.
Published January 5, 2022
Patients with clinically node-positive (cN+) bladder cancer have a worse prognosis than patients without node involvement. Nevertheless, most treatments are more established in patients with node-negative bladder cancer. This includes favorable bladder-sparing protocols that consist of transurethral resection of bladder tumor (TURBT) followed by radical dose radiotherapy with a concurrent radiosensitizing agent. A recent study by Swinton et al. characterized clinical outcomes among patients with cN+ bladder cancer across different treatment modalities.
Published September 20, 2023
Up to a third of patients with muscle-invasive bladder cancer (MIBC) present with clinically lymph node-positive disease (cN+), associated with poor prognosis. Eligible patients can be treated with cisplatin-based induction chemotherapy (IC) followed by radical cystectomy if they exhibit a clinical response. Although cisplatin-ineligible patients comprise up to 50% of patients, little is known about optimal treatment modalities for this patient subgroup. von Deimling et al. conducted a retrospective study to compare the efficacy of gemcitabine/carboplatin IC versus cisplatin-based combination IC in patients with cN+ bladder cancer.
Published May 3, 2023
Carcinoma in situ (CIS) is a distinct pathological entity. The significance of histological variants associated with CIS is not well-understood.
Published September 9, 2019
Catheter-associated urinary tract infections (CAUTIs) are a major cause of harm in hospitalized children. While CAUTI prevention insertion and maintenance bundles have been developed, implemented, and validated in adult populations, their applicability to pediatric populations has been unclear because validation studies in children have been limited to small populations with a short duration of follow up. Our report in Pediatrics describes the CAUTI prevention efforts of the Children’s Hospitals’ Solution for Patient Safety (SPS), a pediatric safety engagement network consisting of over 135 children’s hospitals.1,2
Published October 20, 2020
Clear-cell renal cell carcinoma (ccRCC) represents 75% of renal carcinomas, yet its molecular, cellular, and immune features remain poorly understood. To characterize ccRCC tumors and elucidate factors that contribute to poor response to immune checkpoint inhibitor treatment, Davidson et al. established a high-resolution ccRCC cell atlas using single-cell RNA sequencing.
Published August 8, 2023
Radiation therapy is commonly used for the definitive and palliative treatment of pelvic malignancies. Secondary pelvic cancers have been reported after radiation therapy, including radiation-associated muscle-invasive bladder cancer (RA-MIBC). The treatment of these cancers poses a challenge due to their inherent resistance and the risk of surgical and re-irradiation options.
Published July 7, 2021
Approximately 25% of bladder cancer patients harbor a deletion in MTAP, a gene involved in purine synthesis. Importantly, MTAP deletion has been associated with enhanced sensitivity to the anti-metabolite pemetrexed (in patients and in vitro). On the other hand, MTAP-deleted tumors exhibit low responsiveness to immune checkpoint inhibitors. De Souza et al. recently investigated patients' clinical, pathologic, and genomic characteristics with MTAP-deleted metastatic urothelial carcinoma.
Published March 29, 2023
Sarcomatoid urothelial bladder cancer (SARC) comprises less than 1% of all bladder cancers and is characterized by early metastasis and poor prognosis. SARC is commonly identified alongside conventional urothelial carcinoma (UC), which has led to the hypothesis that they share a common clonal origin. In line with this, molecular studies have identified shared genomic features. Garioni et al. developed patient-derived organoids (PDOs) of SARC, characterized tumor features, and identified potential treatments.
Published January 30, 2024
Patients with advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitors have exhibited low objective response rates (ORR) of 20-30%. ORR can reach around 40% among patients with FGFR2/3 alterations who receive FGFR inhibitors. Two antibody-drug conjugates (ADCs), sacituzumab govitecan (SG) and enfortumab vedotin (EV) were recently approved for refractory aUC.
Published March 15, 2024
