Publications by authors named "Robert S Svatek"

Unlabelled: Despite its immunogenic nature, bladder cancer (BCa) responds sub-optimally to FDA-approved immunotherapy.

Background/objectives: We have previously shown that natural killer (NK) cells are major contributors to overall patient survival in BCa. In our efforts to identify clinically approved agents that enhance NK cell activation, we identified eribulin, a microtubule destabilizer primarily used in breast cancer.

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Background: Whether extended lymphadenectomy is associated with improved disease-free and overall survival, as compared with standard lymphadenectomy, among patients with localized muscle-invasive bladder cancer undergoing radical cystectomy is unclear.

Methods: We randomly assigned, in a 1:1 ratio, patients with localized muscle-invasive bladder cancer of clinical stage T2 (confined to muscle) to T4a (invading adjacent organs) with two or fewer positive nodes (N0, N1, or N2) to undergo bilateral standard lymphadenectomy (dissection of lymph nodes on both sides of the pelvis) or extended lymphadenectomy involving removal of common iliac, presciatic, and presacral nodes. Randomization was performed during surgery and stratified according to the receipt and type of neoadjuvant chemotherapy, tumor stage (T2 vs.

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Article Synopsis
  • The study aimed to evaluate a genomic classifier (GC) to identify a subgroup of bladder cancer patients with a favorable prognosis based on long non-coding RNA (lncRNA) profiles following radical cystectomy (RC).
  • Researchers analyzed tumor samples from 226 patients and classified them into subtypes, with a focus on overall survival and cancer-specific mortality as key outcomes.
  • Results indicated that patients with the luminal favorable subtype had significantly better survival rates and lower risks of cancer progression compared to others, supporting the GC's effectiveness in assessing tumor aggressiveness.
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Background: Aside from the canonical role of PDL1 as a tumour surface-expressed immune checkpoint molecule, tumour-intrinsic PDL1 signals regulate non-canonical immunopathological pathways mediating treatment resistance whose significance, mechanisms, and therapeutic targeting remain incompletely understood. Recent reports implicate tumour-intrinsic PDL1 signals in the DNA damage response (DDR), including promoting homologous recombination DNA damage repair and mRNA stability of DDR proteins, but many mechanistic details remain undefined.

Methods: We genetically depleted PDL1 from transplantable mouse and human cancer cell lines to understand consequences of tumour-intrinsic PDL1 signals in the DNA damage response.

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Bladder cancer (BCa) is a prevalent urogenital malignancy, characterized by a myriad of genetic and environmental risk factors that drive its progression. Approximately 75% of bladder tumors are non-muscle-invasive at diagnosis. For such cases, bladder preservation is often feasible with intravesical chemotherapy or immunotherapy.

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Article Synopsis
  • There has been an increase in agents for treating bacillus Calmette-Guérin-unresponsive (BCG-U) non-muscle-invasive bladder cancer (NMIBC), and there is a pressing need for patient and therapy selection guidelines due to a lack of randomized trials.
  • A global expert committee developed recommendations through literature reviews and a voting process, refining these guidelines during a live meeting in August 2023, achieving over 75% agreement on the final recommendations.
  • No single optimal treatment exists for BCG-U patients; personalized treatment based on individual preferences, tumor characteristics, and available agent data is essential, with specific options recommended for carcinoma in situ and papillary-only tumors, and clinical trial participation encouraged.
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Background: Despite recent drug development for non-muscle invasive bladder cancer (NMIBC), few therapies have been approved by the US Food and Drug Administration (FDA), and there remains an unmet clinical need. Bacillus Calmette-Guerin (BCG) supply issues underscore the importance of developing safe and effective drugs for NMIBC.

Objective: On November 18-19, 2021, the FDA held a public virtual workshop to discuss NMIBC research needs and potential trial designs for future development of effective therapies.

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Checkpoint inhibitors offer promise in treating muscle-invasive and metastatic bladder cancer, but the optimal timing of their administration-neoadjuvant or adjuvant-remains unclear. To determine the efficacy of combining checkpoint inhibition with standard cisplatin-based chemotherapy, we conducted a phase II trial of neoadjuvant anti-PD-1 (αPD-1) and anti-CTLA-4 (αCTLA-4), in combination with cisplatin-gemcitabine, for patients with muscle-invasive bladder cancer prior to radical cystectomy. In addition, a novel murine model of spontaneous metastatic bladder cancer was used to compare the efficacy of neoadjuvant versus adjuvant anti-PD-L1 (αPD-L1) treatment.

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There are multiple ongoing and planned clinical trials that are evaluating novel therapies to treat patients with BCG-unresponsive high grade nonmuscle invasive bladder cancer (NMIBC). Importantly, there is considerable variation in surveillance strategies between these clinical trials, specifically with regards to the use of advanced imaging, enhanced cystoscopy, and mandatory biopsies, which could impact landmark efficacy assessments of investigational agents. To present guideline recommendations for the standardization of cystoscopic evaluation, surveillance, and efficacy assessments for patients with BCG-unresponsive NMIBC participating in clinical trials.

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Introduction: The management of non-metastatic clinically advanced lymph nodal (cN2/N3) bladder cancer (Stage IIIB) could involve radical cystectomy, chemoradiation, or systemic therapy alone. However, a definitive comparison between these approaches is lacking. This study aims to compare the outcomes of patients undergoing radical cystectomy with pelvic lymph node dissection (RC-PLND), chemoradiation therapy (CRT) or systemic therapy (including immunotherapy) (ST) only in patients with stage IIIB bladder cancer.

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Bladder tumors have a high mutational burden and tend to be responsive to immune therapies; however, response rates remain modest. To date, immunotherapy in bladder cancer has largely focused on enhancing T-cell immune responses in the bladder tumor microenvironment. It is anticipated that other immune cells, including innate lymphoid cells (ILC), which play an important role in bladder oncogenesis and tumor suppression, could be targeted to improve response to existing therapies.

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Purpose: To assess the impact of rural and remote residence on the receipt of guidelines-recommended treatment, quality of treatment and overall survival (OS) in patients with non-metastatic muscle-invasive bladder cancer (MIBC).

Materials And Methods: Patients with MIBC were identified using National Cancer Database. Patients were classified into three residential areas.

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Context: Several recent phase 2 and 3 trials have evaluated the efficacy and toxicity of checkpoint inhibitor (CPI) therapy for urothelial carcinoma (UC) in the metastatic, localized muscle-invasive UC (MIUC), upper tract UC, and non-muscle-invasive bladder cancer (NMIBC) disease state.

Objective: To assess the outcomes and toxicity of CPIs across the treatment landscape of UC and contextualize their application to current real-world treatment.

Evidence Acquisition: We queried PubMed, Web of Science, and EMBASE databases and conference abstracts to identify prospective trials examining CPIs in UC.

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To examine the role of endophytic tumor volume (TV) assessment (endophycity) on perioperative partial nephrectomy (PN) outcomes. Retrospective review of 212 consecutive laparoscopic and open partial nephrectomies from single institution using preoperative imaging and 1-year follow-up. Demographics, comorbidities, RENAL nephrometry scores, and all peri- and postoperative outcomes were recorded.

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Objective: The reconstruction of inferior vena cava (IVC) during radical nephrectomy and venous tumor thrombectomy (RN-VTT) is mostly performed with primary repair or with a patch/graft. We sought to systematically evaluate the outcomes of IVC patency over short- to intermediate-term follow-up for patients undergoing primary repair of IVC and to assess the association with survival.

Methods: A retrospective review of patients undergoing RN-VTT between January 2013 and August 2018 was conducted.

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Article Synopsis
  • This study evaluated different high-risk factors for prostate cancer to see how well they predict patient outcomes after surgery.
  • Researchers analyzed data from over 61,000 patients to compare groups based on specific risk criteria (PSA levels, cancer stage, and Gleason grades).
  • The findings suggest that high PSA levels or specific cancer stages have better survival rates compared to more aggressive Gleason Grade diseases, indicating that breaking down high-risk categories could improve patient care.
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Background: Bladder tumor-infiltrating CD56 NK cells are more tumor cytotoxic than their CD56 counterparts. Identification of NK cell subsets is labor-intensive and has limited utility in the clinical setting. Here, we sought to identify a surrogate marker of bladder CD56 NK cells and to test its prognostic significance.

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Introduction: Androgen suppression therapy has been associated with a lower incidence of bladder cancer (BCa) or improved overall/cancer-specific survival. Results are ofent conflicting; therefore, we aim to assess the impact of use of finasteride on overall survival (OS) for BCa using multi-institutional database.

Methods: The South Texas Veterans Healthcare System from 5 medical centers was queried for patients with BCa with or without use of finasteride after diagnosis of BCa.

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Background: Intravenous immune checkpoint inhibition is an effective anticancer strategy for bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) but may be associated with greater systemic toxicity compared with localized therapies.

Objective: We assessed the safety and antitumor activity of intravesical pembrolizumab combined with BCG.

Design, Setting, And Participants: A 3 + 3 phase 1 trial of pembrolizumab + BCG was conducted in patients with BCG-unresponsive NMIBC (NCT02808143).

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Objectives: To assess the utilisation trends of robot-assisted radical cystectomy (RARC), rates of performing continent urinary diversions (CUDs), and impact of diffusion of RARC on CUD rates.

Methods: We investigated the National Cancer Database for patients with muscle-invasive bladder cancer (MIBC) who underwent RC between 2004 and 2015. Patients were stratified by surgical technique into open (ORC) and RARC groups, and by type of urinary diversion into continent (CUD) and ileal conduit (ICUD) groups.

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Purpose: Open radical nephrectomy with inferior vena cava thrombectomy (O-CT) is standard management for renal cell carcinoma with inferior vena cava thrombus. First reported a decade ago, robotic-assisted radical nephrectomy with inferior vena cava thrombectomy (R-CT) is a minimally invasive option for this disease. W aimed to perform a systematic review to assess the safety and feasibility of R-CT in terms of perioperative outcomes and compare the outcomes between R-CT and O-CT.

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