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Karen M. Winkfield, MD, PhD; Narjust Florez, MD, FASCO; Gilberto de Lima Lopes Junior, MD, MBA, FASCO; Coral Olazagasti, MD; Vonetta M. Williams, MD, PhD

 Fighting Disparities and Saving Lives: An Exploration of Challenges and Solutions in Cancer Care

Jeneth Aquino, DNP, FNP-BC; Beth Sandy, MSN, CRNP, FAPO; Allison M. Walker, ACNP, MSN, MSW, BS

Differentiating Adverse Events for Antibody-Drug Conjugates Across Solid Tumor Management

Benjamin P. Levy, MD; John O. Mascarenhas, MD; Tiffany A. Traina, MD, FASCO; Cathy Eng, MD, FACP, FASCO; John P. Leonard, MD

 42nd Annual CFS: Chemotherapy Foundation Symposium®: Innovative Cancer Therapy for Tomorrow

Adam Weiner, MD, a urologic oncology fellow at the University of California, Los Angeles, discusses his journey toward becoming an oncologist, highlighting his passion for personalized medicine in prostate cancer. He starts by discussing what drew him to the field and explains some of the key experiences he has gained thus far.

Weiner emphasizes the importance of understanding one's passions and motivations. For himself, the latest developments in personalized medicine for prostate cancer, including the use of prostate-specific membrane antigen (PSMA) PET imaging, targeted therapies, and biomarkers like prostate-specific antigen (PSA), are of particular interest.

“My research and clinical focus is on prostate cancer. It is a complex cancer…so you have to help navigate patients and their family members through that initial diagnosis and what can be a very complex evaluation period. Then, you have to help patients figure out what treatment makes the most sense for them by balancing their health priorities and the potential [adverse] effects of treatment,” explains Weiner. “It is a complex process that I find incredibly rewarding.”

Weiner delves deeper into the ongoing research surrounding PSMA positivity and its influence on treatment decisions for patients with prostate cancer. He emphasizes the need for further investigation, particularly in newly diagnosed patients, to fully understand how PSMA expression helps experts decide on what treatments are best.

He also highlights the promise of emerging methods for assessing PSA expression, including correlating PET scan results with RNA and protein levels in tumor tissue. This ongoing research holds the potential to further refine the use of PSMA in personalized medicine.

While there are a number of exciting advancements in prostate cancer treatment, including ongoing clinical trials that combine PSMA with other treatment modalities and the potential of PSMA radioligand therapy as a neoadjuvant treatment prior to surgery, Weiner also underscores the significant unmet needs in precision oncology. Specifically, he shares that there is a need to address the overtreatment and undertreatment of patients, where he highlights the role ongoing research plays in creating individualized care.

This conversation provides valuable insights into the complexities of prostate cancer and the potential of PSMA to revolutionize personalized medicine in this field. Weiner’s passion for research and his commitment to patient care offer a promising outlook for the future of prostate cancer treatment.

Weiner concludes by emphasizing the importance of collaboration within the prostate cancer research community and encourages others to actively engage with the community, share ideas, and contribute to the development of innovative treatment approaches.

“Regardless of any fellows, clinical, or research interests, find that community and become a part of it. Give back to it, and learn what interesting trials or research studies are going on. Expose your research ideas to that community, so that it can be evaluated, criticized, developed, and turned into something that is going to be the most likely to be helpful to your patients.”

Adam Weiner, MD, discusses his journey toward becoming an oncologist with a focus in urology in this episode of Emerging Experts.

Transforming Prostate Cancer Care Through Personalized Medicine

In season 5, episode 1 of Targeted Talks, Badrinath Konety, MD, president of the Allina Health Cancer Institute and the chief academic officer for Allina Health, delves into the critical topic of prostate cancer screening, particularly for men within a community setting, and discusses some of the recent advancements in the prostate cancer space.

Prostate cancer remains one of the most common cancers among men, leaving many navigating a complex array of decisions regarding screening, treatment, and new advancements. Here, Konety unpacks the latest recommendations, acknowledging the evolving role of the prostate-specific antigen (PSA) test. However, he also acknowledges recognizes its limitations, noting how the use of additional tests may improve accuracy and reduce unnecessary procedures, as well as leveraging MRI.

“PSA still seems to be the bedrock of prostate cancer screening. It's not a great marker, but it is perhaps the best cancer specific marker out there in terms of blood tests,” Konety explains. “MRI is definitely a great adjunct to follow patients who have an elevated PSA and a negative biopsy to better stage the cancer. It's becoming a valuable tool, 1 to guide where to biopsy, but also [to] guide the decision making around whether to biopsy.”

Konety also provides a valuable overview of the treatment landscape, outlining the range of options available for prostate cancer patients. He emphasizes the importance of tailoring treatment based on individual factors, and provides valuable insights into the considerations made when choosing between treatment approaches.

“Now that we're understanding the multidimensionality of cancer and how it can express itself, we're able to better tailor the treatments,” Konety explains.

In addition, the episode explores the impact of minimally invasive and robotic-assisted surgical techniques on both treatment efficacy and accessibility within community settings. Konety discusses the advantages these advancements offer, including potentially improved outcomes, highlighting the possibility for wider access to cutting-edge therapies.

Konety's expertise shines throughout the conversation, offering listeners a comprehensive understanding of the current state of prostate cancer care.

In season 5, episode 1 of Targeted Talks, Badrinath Konety, MD, delves into the critical topic of prostate cancer screening and discusses some of the recent advancements in the prostate cancer space.

A Deep Dive Into the Evolving Landscape of Prostate Cancer

In season 4, episode 14 of Targeted Talks, Alicia Morgans, MD, MPH, medical director of the Survivorship Program, physician at Dana-Farber Cancer Institute, and associate professor of Medicine, Harvard Medical School, discusses comparative real-world data from the DEAR study of darolutamide (Nubeqa), enzalutamide (Xtandi), and apalutamide (Erleada) for the treatment of United States-based patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).

DEAR was the first study to evaluate the real-world utilization of the second-generation androgen receptor (AR) inhibitors in patients with nmCRPC. According to results presented at the American Society of Clinical Oncology Annual Meeting in June 2023, fewer patients with nmCRPC who received darolutamide experienced discontinued initial AR inhibitor treatment or progressed to metastasis (DIS/MET) versus patients treated with enzalutamide and apalutamide. Further, time to DIS/MET was longer for patients treated with darolutamide.

At a median follow-up of 18.4 months in the darolutamide arm, 19.7 in the enzalutamide arm, and 21.4 months in the apalutamide arm, the percentage of patients with DIS/MET events was 35.9%, compared with 52.1%, and 50.9%, respectively.

“There were also lower rates in terms of reasons for discontinuation of progression to mCRPC for patients who were treated with darolutamide when compared with those patients treated with enzalutamide and apalutamide. This is a numeric comparison, and there was not a statistical test performed to actually formally compare these though,” says Morgans.

The overall takeaway from this real-world research is that darolutamide is a very specific AR inhibitor and has low potential for crossing the blood-brain barrier.

“When we looked, additionally, at this progression to mCRPC we saw that the proportion of patients with progression to mCRPC was lower among patients treated with darolutamide than among patients treated with apalutamide or enzalutamide. And this was assessed in a formal statistical comparison in both unadjusted and adjusted analyses,” explains Morgans.

George DJ, Khan N, Constantinovici N, et al. Real-world use of darolutamide, enzalutamide, and apalutamide for non-metastatic castration-resistant prostate cancer (DEAR). 

. 2023;41(suppl 6). doi: 10.1200/JCO.2023.41.6_suppl.332

A review of real-world data from the DEAR study of darolutamide, enzalutamide and apalutamide for the treatment of nonmetastatic castration-resistant prostate cancer is given by Alicia Morgans, MD, MPH.

First Real-World Data on Second-Generation AR Inhibitor Use in nmCRPC

In season 4, episode 3 of Targeted Talks, Pedro Barata, MD, MSc, director, Clinical Genitourinary Medical Oncology Research Program, UH Seidman Cancer Center, and associate professor of Medicine, Section of Hematology and Medical Oncology at Case Western University, discusses the present and future of metastatic prostate cancer precision medicine.

Barata explains that molecular profiling provides helpful information for treatment decision and to assess how patients will respond to targeted therapy. For example, Barata says that 2%-3% of prostate cancers have microsatellite instability or high tumor mutational burden, and these tumors are known to be responsive to immune checkpoint inhibitors. In other cases, homologous recombination deficient tumors are known to respond to PARP inhibitors. There are many other biomarkers, Barata notes, including PSMA.

“We have other kind of biomarkers. I'm thinking of the expression of PSMA, and the use of a PSMA-based therapy such as lutetium PSMA. Or we can even have this kind of alteration genes, for example, TP53, RB1, p10, where you basically define molecularly, this aggressive variant, prostate cancer. For instance, there's data suggesting that for those patients, a combination of a chemotherapy regimen seems to be better than cabazitaxel [Jevtana] alone. With the emergence of molecular profiling, I think we are learning a lot more,” Barata says.

In terms of available treatment for these targets, Barata explains that immunotherapies have a disappointing response rate of around 10%. However, targeted therapies continue to show promise. The examples Barata give include PARP inhibitor therapy, PSMA-targeted therapy, and BiTE therapy.

The unanswered questions surrounding treatment of metastatic prostate cancer include how to sequence the available therapies, how to better predict response to therapy, and the future of immunotherapy. Additional challenges exist in the field, explains Barata.

“We can’t cure the vast majority of patients who present with metastatic prostate cancer. So, the goal then is to control the disease. So, once patients become castration-resistant, the number of treatments we use, unfortunately, are not able to provide as durable remissions,” he says.

Another issue in this space is racial disparity, which disproportional affect African American males, Barata explains. Although this group has been shown to response the same to systemic therapies as patients of other races, the is limited access to care and their diseases are caught in the later stages. Barata says there need to be collaboration in the field to address this issue.

Looking forward, studies focusing on things like PARP inhibition and treatment based on homologous recombination status have the potential to be practice-changing, according to Barata.

In season 4, episode 3 of Targeted Talks, Pedro Barata, MD, MSc, discusses the newest biomarkers for metastatic prostate cancer, how they inform oncologists' decisions, and challenges to overcome with targeted therapy. 

Hitting New Targets in Metastatic Prostate Cancer

In season 2, episode 9 of Targeted Talks, Sandy Srinivas, MD, medical oncologist, urologic specialist, genitourinary specialist, professor of Medicine of Urology Clinical Research Group leader, Urologic Program Stanford Healthcare and Nicholas J. Vogelzang, MD, chairman, Medical Oncology, Comprehensive Cancer Centers in Las Vegas, NV, discuss the optimal sequencing of therapies for a specific patient with metastatic castration-resistant prostate cancer (mCRPC).

The initial treatment for the 75-year-old patient of discussion was external beam radiation and androgen deprivation therapy for a period of 18 months. This strategy was selected based on the clinical work-up of the patient which showed a prostate-specific antigen level of 32.6 ng/mL, a Gleason score of 4 + 4 in the 4th grade group, as well as negative bone and abdominal pelvic CT scan.

Srinivas and Vogelzang provided their expert opinions on frontline therapy for the patients, along with advice on how to choose between chemotherapy and androgen receptor-targeted therapy, how to intervene if the patient progresses, and how to mitigate toxicities.

Several studies were mentioned to support each physician’s therapy choices for the patient. Most notably, the CARD trial (NCT02485691) of cabazitaxel versus AR-targeted therapy in patients with mCRPC previously treated with docetaxel or quickly failed of AR-targeted therapy.

In season 2, episode 9 of Targeted Talks, Sandy Srinivas, MD and Nicholas J. Vogelzang, MD, discuss he optimal sequencing of therapies for a specific patient with metastatic castration-resistant prostate cancer.

Sequencing Therapy for Metastatic Castration-Resistant Prostate Cancer

The FDA approved 177Lu PSMA-617 for prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer after androgen therapy.

FDA Expands Indication for Lutetium-177 PSMA-617 in PSMA-Positive mCRPC

A recent study suggests that using artificial intelligence to measure tumor size could reduce treatment failures by more than 70%.

New AI Tool Predicts Prostate Cancer Treatment Success 

TLX007-CDx is now an FDA-approved PSMA PET imaging agent in prostate cancer.

FDA OKs TLX007-CDx in Prostate Cancer Treatment

Analyzing AE Data to Guide Selection of Androgen Receptor Inhibitors in mHSPC

Scott Eggener, MD, gave a talk at the LUGPA annual meeting titled “Leveraging Cutting-Edge Technologies to Enhance Prostate Cancer Treatments.”

Eggener Urges Pragmatic Approach to Prostate Cancer Innovations

Evaluating Key Challenges and Advancements in Prostate Cancer Care

Among the 4 major tumor locations—breast, lung, colon, and prostate—biological genotypes have yet to be established for prostate cancer, explains Alan H. Bryce, MD, chief clinical officer and professor of Medical Oncology and Developmental Therapeutics at City of Hope in Phoenix, Arizona, in this video. Clinical trial designs are being developed to better understand prostate cancer biology and establish a treatment paradigm.

Bryce notes that different genotypes of breast cancer are treated distinctly, leading to better efficacy and treatment optimization. However, achieving this level of precision remains an ongoing challenge in prostate cancer management. He highlights a recent breakthrough with capivasertib (Truqap) in combination therapy for 

-deficient metastatic hormone-sensitive prostate cancer, as announced in a recent press release.

Another major challenge that Bryce addresses is the advancement of non-castrating treatment approaches, which is a key concern for patients with prostate cancer. He questions whether effective treatment can be achieved without suppressing testosterone.

“With all of these things being evaluated, can we ask the question: ‘Can we do this without suppressing testosterone?’ I think that is something actively being worked on. On one hand, we have bipolar antigen therapy, which is promising, but it is still not non-castrating. So, we aim to push that advancement further.”

Bryce also discusses ongoing research in radioligand therapies (RLT), recognizing RLT as a platform for innovation and other potential for targeted therapies.

“There are other cell surface targets beyond prostate-specific membrane antigen that can be explored, and other isotopes besides lutetium that can be utilized” Bryce says.

He believes that in the future, there will be a 

 available for prostate cancer management, expanding treatment options and personalization for patients.

Truqap combination in PTEN-deficient metastatic hormone-sensitive prostate cancer demonstrated statistically significant and clinically meaningful improvement in radiographic progression-free survival in CAPItello-281 phase III trial.

 News release. AstraZeneca. November 25, 2024. Accessed March 21, 2025. https://tinyurl.com/5a6bje9m

Videos

Alan H. Bryce, MD, discusses ongoing research in radioligand therapies.

News

Expert Panel Reaches Consensus on Prostate Cancer Treatment Gaps

The 2024 US Prostate Cancer Conference (USPCC 2024) assembled in October to discuss areas of need to help guide treatment decisions in the clinic for prostate cancer management. In this video, Alan H. Bryce, MD, chief clinical officer and professor of Medical Oncology and Developmental Therapeutics at City of Hope in Phoenix, Arizona, provides an overview of these consensus recommendations.

Regarding the recommendation update, Bryce explains that “this is meant to be entirely practical. We were not there to debate esoteric research questions. We really were there to discuss the things that impact your clinic today, [speaking to the clinician].”

In the consensus recommendations, the expert panel identified 5 current areas of need in prostate cancer management. Each category outlines specific clinical scenarios and corresponding expert recommendations. These categories are as follows: biochemical recurrence, metastatic castration-sensitive prostate cancer, PARP inhibitors, prostate-specific membrane antigen radioligand therapy, and metastatic castration-resistant prostate cancer.

Bryce highlights that the goal of the USPCC 2024 conference was to identify those controversial questions and come together as experts to provide answers and clarity for these gray areas, following a strict Delphi process. The Delphi process is a widely recognized method for achieving expert consensus, involving multiple rounds of anonymous surveys where experts provide their input, followed by controlled feedback and discussion.

The conference is geared toward clinicians practicing in the US. Bryce explains that the “regulatory environment in the United States is entirely unique. No other country has access to all the drugs we have access to. Thus, no other community of physicians is facing the same types of questions that we face in the United States. This treatment guideline is specific for the American clinician in the American regulatory environment, with all the treatment options we have.”

Clinicians practicing in the US are encouraged to provide feedback on what topics they would like addressed in the upcoming USPCC 2025. Bryce explains that this enables the panel to address needs observed in the real world that level 1 evidence may not provide answers for.

Alan H. Bryce, MD, discusses areas of need to help guide treatment decisions in the clinic for prostate cancer management.

Prostate Cancer

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