Publications by authors named "Tanya B Dorff"
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.
Current 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.
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- 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
- 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.
PROTACing the androgen receptor and other emerging therapeutics in prostate cancer.
Expert Rev Anticancer Ther
September 2024
Introduction: The androgen receptor (AR) is a critical driver of prostate cancer progression, and the advent of androgen receptor pathway inhibitors (ARPIs) has transformed the treatment landscape of metastatic prostate cancer. However, resistance to ARPIs eventually develops via mutations in AR, AR overexpression, and alternative AR signaling which have required novel approaches to target effectively.
Areas Covered: The mechanism of action and early clinical results of proteolysis targeting chimera (PROTAC) agents targeting AR are reviewed.
Clinical implications of Wnt pathway genetic alterations in men with advanced prostate cancer.
Prostate Cancer Prostatic Dis
July 2024
Article Synopsis
- Aberrant Wnt signaling is linked to advanced prostate cancer, but its genetic impact on patients is still uncertain.
- A study analyzed data from the PROMISE database, finding that 12.9% of patients had Wnt alterations which were associated with significantly higher rates of liver and lung metastases compared to those without these alterations.
- Despite the increased prevalence of other genetic mutations in Wnt-altered patients, there were no significant differences in overall survival or treatment outcomes between groups.
Despite recent therapeutic advances, metastatic castration-resistant prostate cancer (mCRPC) remains lethal. Chimeric antigen receptor (CAR) T cell therapies have demonstrated durable remissions in hematological malignancies. We report results from a phase 1, first-in-human study of prostate stem cell antigen (PSCA)-directed CAR T cells in men with mCRPC.
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- The study looked at how often men with advanced prostate cancer get tested with a special method called next-generation sequencing (NGS) to find helpful information about their disease.
- They analyzed data from 1,597 patients and found that only 9% had more than one NGS test, often discovering new useful information on the second test.
- The results suggest that doing these tests more than once could help doctors make better treatment choices for men with advanced prostate cancer.
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.
Immuno-oncology (IO) has made monumental gains in the past decade in the genitourinary space. In this review, we highlight advances with IO in renal cell carcinoma where it now has become standard-of-care frontline therapy in the metastatic setting but also discuss challenges with the initial approach. In urothelial carcinoma, we discuss the growing use of IO including exciting recent updates with IO-based regimens that may soon become the new standard of care.
View Article and Find Full Text PDFUnlabelled: Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.
View Article and Find Full Text PDFCystectomy is a standard treatment for muscle-invasive bladder cancer (MIBC), but it is life-altering. We initiated a phase 2 study in which patients with MIBC received four cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging. Patients achieving a clinical complete response (cCR) could proceed without cystectomy.
View Article and Find Full Text PDFImportance: Black men have higher incidence and mortality from prostate cancer. Whether precision oncology disparities affect Black men with metastatic castration-resistant prostate cancer (mCRPC) is unknown.
Objective: To compare precision medicine data and outcomes between Black and White men with mCRPC.
Objectives: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative.
Methods: vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported.
The lack of success in prostate cancer from immune checkpoint inhibitors, which is likely multifactorial, has led to the development and investigation of a number of other novel immunotherapeutic techniques, including antibody-drug conjugates, T-cell redirected bispecific therapies, cancer vaccines and chimeric antigen receptor T-cell therapies. Prostate-specific membrane antigen (PSMA) is a tumour-associated antigen (TAA) that is highly expressed in metastatic prostate cancer and has been validated as an effective target for radionuclide treatment. But while PSMA has thus far been the 'front runner' target for these novel immunotherapeutic techniques, it may not be the ideal target for immunotherapy and there are other potential targetable TAAs that will require further exploration.
View Article and Find Full Text PDFBackground: Metastasis-directed therapy is widely utilized for oligometastatic prostate cancer patients, but standard imaging does not always identify metastases definitively and, even with PSMA PET, there may be equivocal findings. Not all clinicians have access to detailed imaging review, particularly outside of academic cancer centers, and PET scan access is also limited. We sought to understand how imaging interpretation impacted recruitment to a clinical trial for oligometastatic prostate cancer.
View Article and Find Full Text PDFChemotherapy and radiotherapy are first-line treatments in the management of advanced solid tumors. Whereas these treatments are directed at eliminating cancer cells, they cause significant adverse effects that can be detrimental to a patient's quality of life and even life-threatening. Diet is a modifiable risk factor that has been shown to affect cancer risk, recurrence, and treatment toxicity, but little information is known how diet interacts with cancer treatment modalities.
View Article and Find Full Text PDFSince the approval of the COVID-19 vaccines, their safety and efficacy has been widely demonstrated in patients with cancer. However, there remain patients with reservations regarding vaccination. We aimed to assess genitourinary cancer patients' perceptions of the vaccines as well as barriers and influencers of decision-making through the completion of a questionnaire.
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- The tumor microenvironment (TME) negatively impacts T cell function and hinders effective immunotherapy for solid tumors, especially those infiltrated with M2 macrophages, which are linked to tumor growth and poor immunotherapy response.
- A novel in vitro co-culture system was developed to study the interactions between tumor cells, CAR T cells, and different macrophage types (M1 and M2) to assess T cell activity and molecular responses.
- Results showed that M2 macrophages inhibit CAR T cell activity by increasing PD-L1 expression, whereas M1 macrophages do not have this negative effect; targeting PD-L1 during CAR T therapy enhances T cell function and anti-tumor effects by converting M2 macrophages to a more favorable
Background: Patients with metastatic castration-resistant prostate cancer have few treatment options after novel hormonal therapy (eg, abiraterone or enzalutamide). We aimed to evaluate cabozantinib, a tyrosine kinase inhibitor with immunomodulatory properties, in combination with the PD-L1 inhibitor atezolizumab in metastatic castration-resistant prostate cancer.
Methods: COSMIC-021 is an ongoing, multicentre, open-label, phase 1b study with a dose-escalation stage followed by tumour-specific expansion stages.