Publications by authors named "Seth Lerner"
Background And Objective: Non-muscle-invasive bladder cancer (NMIBC) patients treated with additional bacillus Calmette-Guérin (BCG) may become unresponsive to BCG. Recently, sequential intravesical gemcitabine and docetaxel (gem/doce) are being used for NMIBC. This study aims to compare oncologic outcomes between sequential intravesical gem/doce versus additional BCG in patients with BCG-unresponsive NMIBC.
View Article and Find Full Text PDFBackground: 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.
Article Synopsis
- A study explored the relationship between body mass index (BMI) and overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC), finding that higher BMI may lead to better survival outcomes.
- Out of 1,279 patients analyzed from the SWOG-1216 trial, survival rates increased with higher BMI categories, with the median OS being longest in the obese group at 6.8 years.
- The analysis suggests that these findings, indicating a lower risk of death among patients with higher BMI, need further validation in additional clinical trials.
Article Synopsis
- * Researchers analyzed tumor samples from 179 patients and found 23% had harmful DDR gene alterations, which were linked to better pathologic responses after treatment.
- * The findings suggest that these DDR alterations could serve as potential biomarkers for predicting treatment response in bladder cancer patients receiving neoadjuvant chemotherapy.
Background: Trimodality therapy (TMT) is a viable option for muscle-invasive localized bladder cancer, providing an alternative to radical cystectomy in properly selected patients. The approval of novel therapeutics in different stages of bladder cancer treatment has sparked interest in exploring concurrent systemic therapies with radiation in clinical trials to enhance long-term outcomes. Achieving uniformity in trial eligibility criteria and endpoint definitions is imperative in describing clinical significance, comparing trials, and changing standard of care guidelines.
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- In men with metastatic hormone-sensitive prostate cancer (mHSPC), new treatments help many live longer, but how well each person does can be really different.
- Researchers are looking at a blood test that counts tiny cancer cells (CTCs) to see if it can help predict a patient’s survival.
- They studied 503 men to see if the number of CTCs in their blood was linked to how long they lived and how well their treatment worked.
JCO Mesenchymal-epithelial transition (MET) signaling pathway plays a role in the pathogenesis of selected patients with papillary renal cell carcinoma (PRCC). In the phase II PAPMET trial (ClinicalTrials.gov identifier: NCT02761057), cabozantinib significantly prolonged progression-free survival and improved objective response rate compared with sunitinib in patients with advanced PRCC.
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- - Bladder cancer mortality rates are higher in African American (AA) patients compared to European American (EA) patients, but the reasons for this disparity are not fully understood.
- - Research using RNA-Seq, proteomics, and metabolomics shows that AA bladder cancer has increased mitochondrial oxidative phosphorylation (OXPHOS) driven by complex I activation, leading to metabolic changes that promote disease progression.
- - Targeting components of complex I and the enzyme GLS1 could be a potential therapeutic strategy, as knocking down these factors reduced tumor growth and mitochondrial activity in AA bladder cancer cells.
Article Synopsis
- - The study aimed to compare the cancer risks of bladder-sparing therapy (BST) versus radical cystectomy (RC) in patients with BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC).
- - Data from 578 patients showed no significant differences in survival outcomes between the two treatment options, but the BST group had higher rates of high-grade recurrences and progressions to muscle-invasive bladder cancer (MIBC) over time.
- - The findings suggest that while BST and upfront RC provide similar survival rates in the intermediate term, patients receiving BST face increasing recurrence and progression risks, particularly with additional treatment attempts.
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.
Importance: Clinical trial data on adjuvant therapy in patients with non-clear cell renal cell carcinoma (RCC) are scant.
Objective: To evaluate the effect of adjuvant everolimus after nephrectomy on recurrence-free survival (RFS) and overall survival (OS) in patients with localized papillary and chromophobe RCC.
Design, Setting, And Participants: This prespecified subgroup analysis of a phase 3 randomized clinical trial, EVEREST, included patients enrolled between April 1, 2011, and September 15, 2016.
Objective: To evaluate the clinical significance of subtyping (type 1 vs 2) of papillary renal cell carcinoma (PRCC) in patients treated with targeted therapy, as well as the concordance, sensitivity and positive predictive value (PPV) of local review pathology review.
Methods: Patients with advanced refractory PRCC were randomised to receive sunitinib or cabozantinib, crizotinib or savolitinib, stratified by PRCC subtype (type 1, type 2, or not otherwise specified [NOS]/mixed) by local review. Central review was retrospectively conducted by three expert genitourinary pathologists who independently reviewed cases.
We previously reported that tumors harboring any one of four gene mutations (ATM, RB1, FANCC, or ERCC2) were likely to respond to neoadjuvant cisplatin-based chemotherapy (NAC), resulting in cancer-free surgical specimens at the time of cystectomy (pT0). Here, we report our validation of this finding. Using the CARIS 592 Gene Panel (Caris Life Sciences, Phoenix, AZ, USA), we analyzed 105 pre-NAC tumor specimens from a large multicenter trial (S1314) of either neoadjuvant gemcitabine and cisplatin (GC), or dose-dense methotrexate, vinblastine, Adriamycin, and cisplatin (DDMVAC).
View Article and Find Full Text PDFAdvancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer.
Bladder Cancer
September 2023
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.
Importance: The presence of bone pain is significantly associated with worse overall survival (OS) in patients with castration-resistant prostate cancer. However, there are few data regarding bone pain and survival outcomes in the context of metastatic, hormone-sensitive prostate cancer (MHSPC).
Objective: To compare survival outcomes among patients with MHSPC by presence or absence of baseline bone pain at diagnosis.
Article Synopsis
- The EVEREST trial investigated the effectiveness of adjuvant everolimus in patients with intermediate-high to very high risk of recurrence after kidney cancer surgery, showing a significant improvement in recurrence-free survival (RFS) but not in overall survival (OS).
- Of the 699 patients analyzed with very high-risk clear cell histology, those taking everolimus experienced a notable increase in RFS (HR 0.80) compared to placebo, although a high percentage (47%) of patients on everolimus discontinued treatment due to side effects.
- While everolimus improved RFS, the lack of statistically significant OS benefits suggests that further examination is needed to assess its long-term survival impact
Purpose: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up.
Materials And Methods: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50).
Article Synopsis
- The study investigates how changes in prostate-specific antigen (PSA) levels at 3 and 7 months of androgen deprivation therapy (ADT) relate to overall survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
- Results show that a complete response (CR) in PSA at both 3 and 7 months significantly correlates with improved overall survival compared to no response, with specific statistical measures supporting this association.
- The findings suggest that monitoring PSA levels can help identify patients at higher risk of death, aiding in treatment decisions and the design of future clinical trials.
Urothelial carcinoma (CIS) is an aggressive phenotype of non-muscle-invasive bladder cancer. Molecular features unique to CIS compared to high-grade papillary tumors are underexplored. RNA sequencing of CIS, papillary tumors, and normal urothelium showed lower immune marker expression in CIS compared to papillary tumors.
View Article and Find Full Text PDFSMARCB1 loss has long been observed in many solid tumors. However, there is a need to elucidate targetable pathways driving growth and metastasis in SMARCB1-deficient tumors. Here, we demonstrate that SMARCB1 deficiency, defined as genomic SMARCB1 copy number loss associated with reduced mRNA, drives disease progression in patients with bladder cancer by engaging STAT3.
View Article and Find Full Text PDFContext: Lymphadenectomy during surgery for genitourinary malignancies has varying benefits.
Objective: To review contemporary evidence on lymph node dissection in genitourinary cancers.
Evidence Acquisition: We performed a collaborative review to summarize current evidence supporting lymph node dissection in urothelial, prostate, kidney, penile, and testis cancers.
Purpose: The Coexpression Extrapolation (COXEN) gene expression model with chemotherapy-specific scores [for methotrexate, vinblastine, adriamycin, cisplatin (ddMVAC) and gemcitabine/cisplatin (GC)] was developed to identify responders to neoadjuvant chemotherapy (NAC). We investigated RNA-based molecular subtypes as additional predictive biomarkers for NAC response, progression-free survival (PFS), and overall survival (OS) in patients treated in S1314.
Experimental Design: A total of 237 patients were randomized between four cycles of ddMVAC (51%) and GC (49%).