Andrew Hendifar, MD, medical director of the Cedars-Sinai Cancer Clinical Trials Office and professor of Medicine, is available to discuss late-breaking, embargoed results of a trial of a new therapy for advanced pancreatic cancer, as well as Phase II results from a trial of a combination therapy that targets specific genetic mutations in pancreatic cancer cells.

Additional Cedars-Sinai Experts

Leslie Ballas, MD, professor of Radiation Oncology, will participate in a panel discussion and can discuss evidence related to use of biomarkers or circulating tumor DNA in treatment decisions for patients with muscle-invasive bladder cancer.

Fahima Dossa, MD, PhD, a surgical oncologist, will present research on which patients with high-risk localized soft tissue sarcoma are most likely to benefit from chemotherapy.

Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle, will present a post hoc analysis of the EMBARK trial in advanced prostate cancer, detailing testosterone recovery following treatment suspension. Freedland can also discuss research from his lab on use of olaparib, an enzyme blocker, in metastatic castration-resistant prostate cancer, and statin use in prostate cancer patients receiving hormone treatment after prostate-removal surgery.

Lawrence Liu, MD, a hematology oncologist, will present research on recent advances in CAR T-cell therapies for patients with relapsed multiple myeloma. The work involves mezigdomide, part of a new drug class in myeloma, following infusion with idecabtagene vicleucel, a genetically modified CAR T therapy derived from the patient’s own cells.

Arsen Osipov, MD, associate professor of Medicine and medical director of Pancreatic Cancer, can discuss research from his lab on the comprehensive molecular profiles associated with variants of the KRAS gene and patient survival in pancreatic cancer. KRAS mutations are found in more than 90% of pancreatic cancer cases.

Karen Reckamp, MD, professor of Medicine and director of the Division of Medical Oncology, can discuss the treatment landscape for non-small cell and small cell lung cancer. She can explain research from her lab on a machine learning approach for predicting immune-related pneumonitis, a noninfectious lung inflammation that can occur following treatment with immune checkpoint inhibitors. She can also speak about new data from Lung MAP, a clinical trial designed to efficiently test treatments for advanced non-small cell lung cancers. And she will make a presentation on support of academic nonclinical efforts for cancer investigator faculty at the Association of American Cancer Institutes.

Kamya Sankar, MD, assistant professor of Medicine and co-director of the Thoracic Disease Research Group, will present an analysis of factors associated with early cachexia—also known as cancer wasting disease—in metastatic non-small cell lung cancer. She can also speak about treatment of both non-small cell and small cell lung cancer.

From The Angeles Clinic and Research Institute

Mark Faries, MD, surgical oncologist and professor of Surgery, can discuss a five-year update from the KEYNOTE-942 study in resected melanoma and a new study of lymph node resection versus therapeutic dissection in advanced melanoma, as well as recurrence in advanced melanoma across time.

Erwin Grussie, MD, a hematology oncologist, can discuss results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study testing targeted therapies in patients with solid tumors.

Omid Hamid, MD, professor of Medicine and chief of Translational Research and Immuno-Oncology, will present results from a study of a medication that blocks the action of cortisol in patients with advanced solid tumors, as well as a study of causes of limited immunotherapy response in melanoma. He can also discuss new results from three trials of therapies in advanced melanoma.

Inderjit Mehmi, MD, a hematology oncologist, can discuss the association of prior immunotherapy treatment with limited response to subsequent immunotherapy in melanoma.

Media Contact

To schedule an interview, contact Christina Elston at christina.elston@cshs.org or 626-298-0702.

The study, which was published in the New England Journal of Medicine and presented at the European Society for Medical Oncology Congress in October, reported that the combination of enzalutamide and leuprolide—currently approved for use in metastatic disease—was effective for improving overall survival in patients whose prostate cancer had returned after primary surgery or radiation therapy.

Prostate cancer is the second-leading cause of cancer death among men, behind lung cancer, and more than 300,000 cases are expected to be diagnosed in the United States this year alone, according to the American Cancer Society.

“Many patients when they’re diagnosed with prostate cancer will choose to undergo surgery or radiation with the hope that that cures the cancer. Unfortunately, in about a third of those patients the cancer will come back,” Freedland told Healthline.

An effective treatment option offers new hope for these patients, who can experience a recurrence of their cancer.

Freedland told WebMD that these results mean a 70-year-old man whose prostate cancer returns could live up to another 15 years, thanks to the combination treatment.

"For many of these patients, I think we are turning [prostate cancer] into a chronic disease, which is really exciting,” Freedland said. He expressed optimism about advances in prostate cancer care and treatment.

“We’re really revolutionizing the management of prostate cancer convincingly over and over,” Freedland told Healthline.

Read the complete stories from WebMD and Healthline.

The combination therapy, which adds a drug called enzalutamide to commonly prescribed hormone therapy, reduced deaths in patients with recurrent prostate cancer after surgery or radiation for whom other treatments are no longer an option. The trial results were published in The New England Journal of Medicine (NEJM) with simultaneous presentation during the European Society for Medical Oncology Congress (ESMO) Oct. 19 in Berlin.

“After initial treatment, some patients see their prostate cancer come back in an aggressive way and are at risk for their disease to spread quickly,” said Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer and co-principal investigator of the study. “Hormone therapy, which is what we’ve been offering patients for 30 years, has not improved survival and neither has anything else. That makes these findings a real game changer.”

The trial included more than 1,000 patients from 244 sites in 17 countries. All the patients were diagnosed with what is known as high-risk biochemically recurrent prostate cancer. Following the patients’ surgery or radiation therapy, the levels of prostate specific antigen, or PSA, in their blood had risen rapidly. PSA is a protein used to detect prostate cancer, and a rapid rise in PSA levels after treatment indicates a patient’s cancer is likely to return and spread—often to the bones or spine.

“We know these patients are at high risk of developing metastatic disease and dying of their cancer unless we offer a meaningful treatment option,” said Freedland, professor of Urology and the Warschaw, Robertson, Law Families Chair in Prostate Cancer.

Patients were randomly selected to receive standard hormone therapy alone, enzalutamide alone, or a combination of the two. After eight years, the risk of death was 40.3% lower in the combination group than in the other two groups, Freedland said.

“This clinical trial, one of many that Cedars-Sinai Cancer has offered to its patients, is an example of the translational work being done by our physician-scientists,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “The result will be improved treatment and better outcomes for patients everywhere.”

Freedland noted that, based on previous results published by the team, enzalutamide is approved by the Food and Drug Administration and listed in National Comprehensive Cancer Network treatment guidelines. These latest results, he said, are likely to strengthen the network’s recommendation and solidify this drug combination as the standard of care for patients with high-risk biochemically recurrent prostate cancer.

“These important findings identify a treatment that prolongs survival in men with aggressive prostate cancer,” said Hyung Kim, MD, a urologic oncologist and chair of the Department of Urology at Cedars-Sinai.  “The latest analysis complements previous studies that found enzalutamide significantly improved survival in other prostate cancer settings, and will change how we take care of our patients.”

Additional authors include Neal D. Shore, M.D.; Murilo de Almeida Luz, M.D.; Ugo De Giorgi, M.D., Ph.D.; Martin Gleave, M.D.; Geoffrey T. Gotto, M.D., M.P.H.; Christopher M. Pieczonka, M.D.; Gabriel P. Haas, M.D.; Choung-Soo Kim, M.D.; Miguel Ramirez-Backhaus, M.D.; Antti Rannikko, M.D., Ph.D.; Matko Kalac, M.D., Ph.D.; Swetha Sridharan, M.B.B.S.; Matt Rosales, Ph.D.; Yiyun Tang, Ph.D.; Ronald F. Tutrone Jr, M.D.; Balaji Venugopal, M.B.B.S., M.D.; Arnauld Villers, M.D., Ph.D.; Henry H. Woo, M.B.B.S., D.Med.Sc.; and Fong Wang, M.D., Ph.D.

Funding: The study was sponsored by Pfizer Inc. and Astellas Pharma Inc., the co‑developers of enzalutamide.

Disclosures: Stephen J. Freedland reports being a consultant to Astellas Pharma Inc., AstraZeneca, Bayer, Eli Lilly, Johnson & Johnson Innovative Medicine (formerly Janssen), Merck, Novartis, Pfizer Inc., Sanofi, Sumitomo Pharma America, Inc. (formerly Myovant Sciences, Inc.), and Tolmar.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The prostate, a small gland that helps make semen, also produces a protein called prostate-specific antigen, or PSA. Blood levels of PSA tend to be elevated in people who have prostate cancer, and the PSA test, which measures those levels, is a common prostate cancer screening tool.

“Many transgender women take estrogen as part of their gender-affirming care,” said Stephen Freedland, MD, the Warschaw, Robertson, Law Families Chair in Prostate Cancer at Cedars-Sinai and senior author of the study. “This drastically lowers PSA levels, which could mean the threshold we are using as ‘normal’ is too high to detect early-stage cancer in these patients. We undertook this study to determine typical PSA values for this population so that we can screen them more appropriately.”

According to current guidelines, PSA levels above 4.0 nanograms per milliliter of blood (ng/mL) suggest cancer could be present, and that additional investigation, such as a prostate biopsy, is needed.

"In the study, we used Veterans Health Administration records to identify 210 transgender women without known prostate cancer who were taking estrogen,” said Farnoosh Nik-Ahd, MD, a urology resident at the University of California, San Francisco, and first author of the study. “We found that the median PSA value, the midpoint in the range of participants, was 0.02 ng/mL, which is fiftyfold lower than PSA values reported in similar-aged cisgender men.”

This suggests that if they are taking estrogen, transgender women who develop prostate cancer wouldn’t see their PSA rise to levels that trigger additional screening until their cancer was at a later stage, making it more difficult to treat. Nik-Ahd said that patients and clinicians should be aware of this and interpret results with caution.

“Cedars-Sinai Cancer serves one of the most diverse patient populations in the country,” said Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer and the PHASE ONE Foundation Distinguished Chair. “This work is part of our mission to conduct research that helps us understand the unique needs of our patients, then translate our findings into practices that improve patient outcomes.”

Additional research is needed to pinpoint a specific PSA level that indicates a transgender woman taking estrogen is at high risk for developing prostate cancer. And Freedland, who is also a professor of Urology at Cedars-Sinai and staff physician at the Durham VA Medical Center in North Carolina, said this study is not a call for transgender women to be screened.

“We know that PSA screening reduces the risk that cisgender men ages 55 to 69 will die of prostate cancer, but we don’t know that it does the same thing for transgender women taking estrogen,” Freedland said. “However, because some of these women are being screened, we want to raise awareness that their typical PSA levels are different.”

Along with increased awareness, Freedland hopes to eventually see updated PSA screening guidelines. In the meantime, he advises transgender women who are taking estrogen to consult with their healthcare providers.

“Don't forget that you have a prostate and that prostates can become cancerous,” Freedland said. “The best way we know to find those cancers early and reduce the risk of death is a PSA test. And if you choose to do that, keep in mind that the test values are not calibrated for you. Bring your results—and possibly this study—to your urologist so that your results will be interpreted by someone who understands what to do with that information.”

Funding: Research reported in this publication was supported by NIA grant number R38AG07017, the 2023 Urology Care Foundation Residency Research Award Program, and the Robert J. Krane, MD, Urology Research Fund.

Additional authors include: Amanda M. De Hoedt, MS; Christi Butler, MD; Jennifer T. Anger, MD; Peter R. Carroll, MD, MPH; and Matthew R. Cooperberg, MD, MPH.

Read more on the Cedars-Sinai Blog: More Options to Treat Prostate Cancer

In 2020, 41% of U.S. adults between 20 and 44 were experiencing obesity—having excessive body fat that can cause serious health problems—a significant increase from 2009, when 33% of adults experienced obesity. Scientific research suggests that obesity may increase the incidence rate of certain cancers, such as breast, colorectal and prostate cancer, in young adults—people who are too young for routine cancer screenings. 

Freedland told Verywell Health that multiple factors may lead to some cancers, such as prostate cancer, which progresses unnoticed until it’s harder to treat.

“As we get more and more obese as a country, we’re probably missing some prostate cancers, but it’s causing more prostate cancer deaths,” said Freedland, the Warschaw, Robertson, Law Families Chair in Prostate Cancer at Cedars-Sinai Cancer.

Freedland told Verywell Health that it can be challenging for investigators to fully understand how obesity affects cancer risk in young people and how it may affect them as they age. 

“I don’t want to say weight loss is not beneficial—I absolutely think it is,” Freedland told Verywell Health. “We just don’t have the clear evidence. There are a lot of questions to answer.”

Click here to read the complete article in Verywell Health.

“If these treatments are approved by the Food and Drug Administration, our results will be practice changing,” said Stephen Freedland, MD, associate director for Training and Education and the Warschaw, Robertson, Law Families Chair in Prostate Cancer at Cedars-Sinai, and lead author of the study. “In the study, both of these new options improved metastasis-free survival while preserving quality of life.”

Cancer of the prostate, a walnut-sized gland that helps make semen, will be diagnosed in 288,300 men in the U.S. in 2023, according to American Cancer Society estimates. For some, treatment may never be needed because they have a slow-growing form of the disease, but those with more aggressive prostate cancer are often first treated with surgery or radiation therapy.

“Unfortunately, in about a third of those patients, the cancer recurs within 10 years,” Freedland said.

Patients with aggressive recurrence are treated with androgen deprivation therapy (ADT), also known as hormone therapy, which reduces the patient’s production of the male sex hormone testosterone. Testosterone helps prostate cancer cells grow and spread, and the hormone therapy effectively reduces the growth-stimulating effects. But Freedland said ADT has two downsides: It doesn’t completely eliminate testosterone, and it can cause many side effects.

“When you go on ADT, the testosterone level in the blood is reduced, but not completely eliminated,” Freedland said. “And the concern is that the testosterone that remains may still be enough to stimulate tumor growth. Also, patients don’t love the idea of being on hormones.”

In this study of 1,068 prostate cancer patients from 244 sites in 17 countries, Freedland and fellow investigators tested two experimental interventions—one to address each of these issues.

In the randomized clinical trial, one-third of the patients received ADT plus a medication called enzalutamide, which blocks the effects of testosterone. Enzalutamide keeps any testosterone remaining in the blood from stimulating the growth of cancer cells.

Another third of the patients received enzalutamide alone. This option relied on the medication to block the effects of testosterone even though testosterone levels in the patients’ blood were not reduced.

“We wanted to see whether enzalutamide on its own was so effective that we didn’t need the ADT,” Freedland said.

The final group of patients received ADT alone, which is the current standard treatment.

Investigators found that the combination of ADT plus enzalutamide reduced the risk of metastasis or death by 58% over ADT alone. They found that enzalutamide alone reduced the risk of metastasis or death by 37% over ADT alone. Both treatments maintained quality of life relative to the ADT alone.

“While the combination therapy offers greater risk reduction, some men might prefer enzalutamide alone. It does a good job of preventing cancer spread or death, with different side effects that may be more acceptable for some men,” Freedland said.

The next step is for the makers of enzalutamide to apply for FDA approval, so the experimental therapy can come into wide use, Freedland said.

“Optimizing therapy for patients with aggressive recurrence after their prostate cancer is initially treated has been an unmet need,” said Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer and the PHASE ONE Distinguished Chair. “The results of this trial point the way to two options which the study showed were more effective than current standard of care, giving these patients and their providers the opportunity to choose a potentially improved course of therapy that best meets their needs.”

Funding: The study was sponsored by Pfizer and Astellas Pharma, the co-developers of enzalutamide.

Read more on the Cedars-Sinai Blog: Radiation Therapy as Effective as Surgery for Prostate Cancer