Publications by authors named "Rana Mckay"
Urachal cancer, a rare malignancy, generally presents in the clinical setting with advanced stages of disease. Systemic treatment with chemotherapy is generally utilized in this setting. However, there remains a paucity of data on the effectiveness of immune checkpoint inhibitors or targeted therapies for urachal cancer.
View Article and Find Full Text PDFBackground: FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.
Patients And Methods: We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI.
Background And Objective: Our aim was to determine the clinical characteristics, temporal trends, and survival outcomes for sarcomatoid-dedifferentiated renal cell carcinoma (sRCC), as sRCC has historically had poor prognosis and a contemporary cohort has not been well characterized in a population-based study.
Methods: Data for 302 630 RCC cases from 2010 to 2019 were extracted from the National Cancer Data Base, of which 4.1% (12 329) were sRCC.
Article Synopsis
- This study focused on the diverse types of FOXA1 genetic alterations found in prostate cancer and their implications for clinical management.
- Researchers classified FOXA1 mutations into four distinct classes, each with specific characteristics and prognostic significance based on survival outcomes.
- Results indicated that certain FOXA1 alterations, particularly class 1A, were linked to improved survival rates, while other classes, especially class 2 and amplified versions, were associated with poorer outcomes and higher risks in treatment response.
Background And Objective: Patients receiving immune checkpoint blockade (ICB) therapy may experience periods of prolonged disease control without a need for systemic therapy. Treatment-free survival (TFS) is an important measure for this period, but no data are available for patients with metastatic renal cell carcinoma (mRCC) starting first-line agents. Our aim was to analyze TFS outcomes for patients with mRCC starting first-line therapy.
View Article and Find Full Text PDFLenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib in treatment of advanced renal cell carcinoma (aRCC) in the phase 3 CLEAR study. We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib plus pembrolizumab versus sunitinib, at the final overall survival analysis time point of CLEAR (cutoff: July 31, 2022). Treatment-naïve adults with aRCC were randomized to: lenvatinib (20 mg PO QD in 21-day cycles) plus pembrolizumab (n = 355; 200 mg IV Q3W); lenvatinib plus everolimus (not reported here); or sunitinib (n = 357; 50 mg PO QD; 4 weeks on/2 weeks off).
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- The study assesses real-world outcomes and failure patterns in patients with muscle-invasive bladder cancer (MIBC) who underwent trimodality therapy (TMT) between 2000 and 2018, utilizing data from the Veterans Affairs database.
- Results indicate that out of 347 patients treated with TMT, 44% had no recurrence, while 37% experienced metastatic recurrence (MR) and 34% had local recurrence (LR), highlighting significant rates of recurrence within the patient population.
- The findings suggest that TMT is generally effective in treating MIBC, but the high recurrence rates, particularly with lymph node positive disease and pre-treatment hydronephrosis, stress the importance of ongoing patient monitoring and the exploration of better treatment strategies
Article Synopsis
- The importance of germline genetic testing (GGT) for prostate cancer patients has grown, as it helps tailor treatment plans and manage the disease more effectively.
- GGT is now considered a standard practice not just for prostate cancer, but also for other cancers like breast and ovarian, emphasizing the need for all patients to have equitable access to this testing.
- Offering comprehensive GGT allows for better decision-making between patients and doctors, aids in detecting potential future cancers, and facilitates testing for family members who may be at risk.
Chemotherapies remain standard therapy for cancers but have limited efficacy and cause significant side effects, highlighting the need for targeted approaches. In the progression of cancer, tumors increase matrix metalloproteinase (MMP) activity. Leveraging and therapeutically redirecting tumor MMPs through activatable cell-penetrating peptide (ACPP) technology offers new approaches for tumor-selective drug delivery and for studying how drug payloads engage the tumor immune microenvironment.
View Article and Find Full Text PDFBackground And Objective: Lenvatinib is a multitargeted tyrosine kinase inhibitor (TKI) used in the upfront and refractory settings for metastatic renal cell carcinoma (mRCC). However, there are limited data on the efficacy of subsequent TKI therapies after lenvatinib. We investigated the activity of TKI therapies after lenvatinib in patients with mRCC.
View Article and Find Full Text PDFCurrent US clinical practice guidelines for advanced prostate cancer management contain recommendations based on high-level evidence from randomized controlled trials; however, these guidelines do not address the nuanced clinical questions that are unanswered by prospective trials but nonetheless encountered in day-to-day practice. To address these practical questions, the 2024 US Prostate Cancer Conference (USPCC 2024) was created to generate US-focused expert clinical decision-making guidance for circumstances in which level 1 evidence is lacking. At the second annual USPCC meeting (USPCC 2024), a multidisciplinary panel of experts convened to discuss ongoing clinical challenges related to 5 topic areas: biochemical recurrence; metastatic, castration-sensitive prostate cancer; poly [ADP-ribose] polymerase inhibitors; prostate-specific membrane antigen radioligand therapy; and metastatic, castration-resistant prostate cancer.
View Article and Find Full Text PDFAnalysis of 27,810 patients with advanced cancers treated with anti-PD-1/L1 therapies shows that immune gene signatures or immune cell infiltration is not universally associated with mutation burden or long-term survivors after immunotherapies across cancer entities. Thus, immunological stratification of tumors has limited bearing on the immunogenicity of tumors or immunotherapy outcomes.
View Article and Find Full Text PDFAndrogen receptor stimulation by testosterone and dihydrotestosterone is crucial for prostate cancer progression. Despite the initial effectiveness of androgen deprivation therapy (ADT), castration-resistant prostate cancer eventually develops in most men. A common germline missense-encoding polymorphism in HSD3B1 increases extra-gonadal androgen biosynthesis from adrenal precursors owing to increased availability of the encoded enzyme 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) - hence, it is called the adrenal-permissive enzyme.
View Article and Find Full Text PDFPurpose: The Brazilian Public Health System (BPHS) serves approximately 71,730 patients with prostate cancer (PC) every year for which androgen deprivation therapy (ADT) is the primary treatment for patients with advanced hormone-sensitive prostate cancer (aHSPC). Androgen receptor pathway inhibitors (ARPIs) are not accessible through the BPHS. Using the BPHS as a model, this study assesses the long-term economic effect of surgical versus medical castration in aHSPC treatment to strategize cost reduction and the incorporation of ARPI in developing countries.
View Article and Find Full Text PDFStriving for Equity: Examining Health Disparities in Urologic Oncology.
Cancers (Basel)
October 2024
Article Synopsis
- - Health disparities in urologic cancers like prostate, bladder, kidney, and testicular significantly affect outcomes based on race, socioeconomic status, and location.
- - A review of literature and cancer databases shows that minorities and those in underserved areas receive less timely and appropriate care, resulting in worse health outcomes.
- - The study calls for targeted interventions, including policy changes and increased funding, to improve access to high-quality cancer care and achieve health equity.
Muscle-invasive bladder cancer represents a potentially curable disease, yet often disease recurs and is ultimately fatal. Outcomes for patients with localized urothelial carcinoma are heterogeneous with some patients cured with surgery alone, deriving no benefit from perioperative systemic therapy, while others are left with residual disease and may benefit from additional therapy. Neoadjuvant chemotherapy increases cure rates but comes with significant toxicity.
View Article and Find Full Text PDFImmunotherapy has changed the treatment paradigm for many types of cancer, but immune checkpoint inhibitors (ICIs) have not shown benefit in prostate cancer (PCa). Chronic inflammation contributes to the immunosuppressive prostate tumor microenvironment (TME) and is associated with poor response to ICIs. The primary source of inflammatory cytokine production is the inflammasome.
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- - The study analyzed genomic and transcriptomic data from 138 germ cell tumors to find out why some tumors resist treatment with cisplatin, a common chemotherapy drug.
- - They focused on specific genetic mutations (like KRAS, TP53, and KIT) and patterns in gene copies that might contribute to this resistance, observing that certain mutations were more common in primary tumors compared to metastatic ones.
- - The research found that tumors with platinum-resistant alterations had lower transcriptomic scores linked to sensitivity to cisplatin, indicating a possible connection between these genetic changes and treatment resistance.
Purpose: The availability of targeted therapies for advanced prostate cancer led to the expansion of national guidelines recommending germline genetic testing. The aim of this study was to describe recent trends in germline test ordering patterns for patients with prostate cancer.
Materials And Methods: A retrospective cohort analysis of patients with prostate cancer who underwent germline testing through a single commercial laboratory (Invitae Corporation) between 2015-2020 was performed.
Article Synopsis
- Dramatic advances in biological discoveries since the 1990s have changed how metastatic renal cell carcinoma (RCC) is treated, focusing on gene alterations like VHL that promote tumor growth.
- Antiangiogenic strategies targeting the VHL/HIF/VEGF pathway have shown improved survival rates, while the introduction of immune checkpoint inhibitors has shifted treatment paradigms to include combination therapies.
- Despite progress, the projected 14,390 RCC deaths in 2024 highlight the ongoing need for research and development of optimized treatment options for patients.
Article Synopsis
- Innovations in advanced prostate cancer have improved outcomes, but there's still a lack of high-level evidence in clinical management, prompting the 2024 Advanced Prostate Cancer Consensus Conference to survey experts for insights.
- A panel of 120 international experts developed and voted on 183 consensus questions through a web-based survey prior to the conference, defining consensus as ≥75% agreement.
- The voting results highlight areas of agreement and disagreement that can guide clinical decisions and future research, with a focus on individualizing treatment based on patient characteristics and encouraging participation in clinical trials.
Purpose: The aim of this project was to characterize the incidence of men's health disorders, specifically focusing on the incidence of erectile dysfunction (ED) and testosterone deficiency (TD) in a large, nationwide study of testicular cancer (TC) survivors treated in a centralized health care system.
Materials And Methods: We conducted a retrospective cohort study of US veterans diagnosed with TC from 1990 to 2021. These veterans were compared with an age-matched and race-matched control group of US veterans without a diagnosis of TC.
Article Synopsis
- The acid phosphatase 1 gene is linked to prostate cancer, showing higher expression in metastatic cases compared to primary tumors, suggesting it could be a therapeutic target.
- Researchers utilized advanced sequencing techniques on over 5,000 samples to analyze gene expression and mutations, finding significant differences in tumor characteristics and signaling pathways between high and low expression groups.
- While overall survival rates did not show statistically significant differences between high and low expression levels, there was a trend indicating worse survival for those with higher expression in prostate cancer samples.
Article Synopsis
- Advanced prostate cancer treatment is evolving with the use of bipolar androgen therapy (BAT), which raises testosterone levels to combat metastatic castration-resistant prostate cancer (mCRPC) by taking advantage of androgen receptor (AR) signaling mechanisms.
- Case studies showcase the effectiveness of BAT, with patients experiencing PSA declines and improved quality of life, although some ultimately faced disease progression despite initial successes.
- The findings highlight the potential of BAT as a viable treatment strategy for mCRPC, emphasizing the need for more research to better understand which patients will respond best to this therapy.