Publications by authors named "Rana R McKay"
Background: Real-world outcomes, especially patterns of failure, are limited for patients with muscle-invasive bladder cancer (MIBC) treated with trimodality therapy (TMT). We aim to evaluate patterns of failure after TMT for MIBC in a typical heterogeneous population.
Methods: In the national Veterans Affairs database, patients with urothelial histology, MIBC (T2-4a/N0-3/M0) who underwent definitive intent TMT between 2000-2018.
Indications for and implications of germline genetic testing (GGT) in patients with prostate cancer have expanded over the past decade, particularly related to precision therapies and management. GGT has become the standard of care for many cancers such as breast, ovarian, colorectal, pancreatic, and metastatic prostate cancer, and it is imperative that patients be offered timely and equitable access to testing as it can inform patient-physician shared decision making for management of the current cancer as well as anticipatory guidance for disease progression. Additionally, GGT guides screening for and prevention of secondary malignancies for the patient and cascade testing for at-risk family members.
View Article and Find Full Text PDFChemotherapies 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.
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Striving 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.
Purpose: The acid phosphatase 1 () gene encodes low-molecular-weight protein tyrosine phosphatase, which is overexpressed in prostate cancer (PC) and a potential therapeutic target. We analyzed expression in primary/metastatic PC and its association with molecular profiles and clinical outcomes.
Methods: NextGen sequencing of DNA (592-gene/whole-exome sequencing)/RNA(whole-transcriptome sequencing) was performed for 5,028 specimens.
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.
Article Synopsis
- A study compared the combination treatment of tivozanib and nivolumab against tivozanib alone for patients with advanced renal cell carcinoma who progressed after one or two prior therapies, focusing on the post-immune checkpoint inhibitor (ICI) setting.
- The TiNivo-2 trial included 343 patients from 190 sites across multiple continents, with the primary goal of evaluating progression-free survival (PFS) as the main outcome.
- Results showed that the median PFS was 5.7 months for the combination therapy and 7.4 months for tivozanib monotherapy, indicating no significant advantage for the combination treatment based on the hazard ratio.
Association of Tumor Mutational Burden and Microsatellite Instability With Response and Outcomes in Patients With Urothelial Carcinoma Treated With Immune Checkpoint Inhibitor.
Clin Genitourin Cancer
December 2024
Article Synopsis
- - The study investigated the relationship between Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) status in patients with urothelial carcinoma (UC) receiving immune checkpoint inhibitors (ICI), focusing on overall survival (OS).
- - Results showed that patients with a higher TMB (≥10 mut/Mb) generally experienced longer median OS compared to those with lower TMB, although these differences weren't always statistically significant.
- - Notably, patients treated with maintenance avelumab had a significantly better OS when TMB was high (61 months vs. 17 months for low TMB), indicating potential benefits of ICI based on TMB and MSI status, warranting further investigation.
Article Synopsis
- This study compares outcomes of radical nephrectomy (RN) versus partial nephrectomy (PN) for treating sarcomatoid renal cell carcinoma (sRCC) using a large national database from 2004 to 2019.
- The analysis found that patients receiving PN had better overall survival rates, particularly in early-stage tumors (cT1 and cT3), although factors like age and tumor characteristics influenced the likelihood of receiving PN.
- The results suggest that PN can be a viable option for certain patients without compromising outcomes, but disparities in care exist based on income and insurance status, affecting survival rates.
Article Synopsis
- The study assessed the effectiveness of poly(ADP-ribose)polymerase inhibitors (PARPi) and platinum chemotherapy in men with prostate cancer (PC) and specific genetic mutations related to DNA repair.
- It utilized data from the PROMISE consortium to compare outcomes between three groups based on their mutation profiles: one with direct BRCA complex interactions and two without.
- Results showed that patients with BRCA mutations had significantly better responses to PARPi, including higher PSA response rates and longer progression-free survival, compared to those without direct BRCA interactions.
Article Synopsis
- * Methods: Researchers analyzed data from 94 patients treated at 29 institutions, assessing various factors like type of therapy, timing of recurrence, and patient risk categories, while also monitoring treatment-related side effects.
- * Key Findings: The study revealed an 18-month PFS rate of 45% and overall survival (OS) rate of 85%, with common treatment-related side effects including skin toxicity and fatigue; it did have limitations due to patient selection.
Breast and ovarian cancers harboring homologous recombination deficiency (HRD) are sensitive to PARP inhibitors and platinum chemotherapy. Conventionally, detecting HRD involves screening for defects in , , and other relevant genes. Recent analyses have shown that HRD cancers exhibit characteristic mutational patterns due to the activities of HRD-associated mutational signatures.
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