CLEVELAND--Prostate cancer is the leading cause of cancer in men worldwide, and radiotherapy is one of the common forms of treatment. In a first-of-its kind meta-analysis, published today in The Lancet Oncology, researchers from University Hospitals (UH) and Case Western Reserve University show that there is consistent improvement in overall survival in men with intermediate- and high-risk prostate cancer with the addition of hormone therapy to radiotherapy treatments.
Throughout the past 40 years, randomized trials have been conducted on the impact of adding hormone therapy to prostate cancer treatments. While these trials individually show the benefit of hormone therapy, there are inconsistencies in timing and duration of treatment recommendations.
“Our research team set out to conduct a first-of-its-kind, comprehensive analysis by collecting individual patient data from each and every randomized trial conducted around the world, and performed a meta-analysis of the impact of various treatment intensification strategies using hormone therapy with radiation therapy for localized prostate cancer,” said senior author Daniel E. Spratt, MD, Vincent K. Smith Chair in Radiation Oncology at UH Seidman Cancer Center, Professor in the Department of Radiation Oncology at Case Western Reserve School of Medicine, and Member of the Developmental Therapeutics Program at Case Comprehensive Cancer Center. “Our goal is to better personalize therapy for prostate cancer patients, by providing the most precise and accurate estimates of the benefit of hormone therapy.”
In this analysis, the team made three key discoveries:
1) Men with intermediate- and high-risk prostate cancer have an increased survival rate from the addition of hormone therapy to radiotherapy. This was seen in both younger and older men, and in men treated with lower and higher doses of radiotherapy.
2) Survival rate in men with prostate cancer improves with the prolongation of adjuvant hormone therapy to radiotherapy. This benefit was seen in both younger and older men, in men treated with lower and higher doses of radiotherapy, and in men with both intermediate- and high-risk prostate cancer. Prior to this analysis, no trial was large enough to show a clear benefit in intermediate risk disease from extending the duration of adjuvant hormone therapy.
3) The prolongation of neoadjuvant hormone therapy before radiotherapy did not benefit men in any outcome measured. This is an important finding, because some countries routinely give extended durations of hormone therapy before radiotherapy. The team showed that this method isn’t advantageous over shorter durations.
“We now have estimates that show the benefit of adding and prolonging adjuvant hormone therapy for clinically relevant subsets of patients,” explained Dr. Spratt. “Our team showed that treating a group of approximately ten to 15 men with hormone therapy or extended adjuvant hormone therapy, for at least 18 months, prevented one man from developing metastatic disease ten years after treatment. This is dependent on patient and tumor specific factors, but gives us a more precise estimate to work with when it comes to recommending treatment options.”
The Meta-Analysis of Randomized Trials in Cancer of the Prostate (MARCAP) Consortium, is the first, comprehensive, international collaboration of randomized phase III clinical trial individual patient data. The ability to analyze data from every clinical trial group in the world, investigating the impact of hormone therapy with radiotherapy, demonstrates immense progress in the prostate oncology field.
“This work from the MARCAP consortium will bring confidence in recommending various treatment intensification strategies, and allow providers to have more accurate, shared-decision making conversations with patients about the benefits of using hormone therapy with radiotherapy for prostate cancer treatment,” emphasized Dr. Spratt.
In this MARCAP analysis, 12 randomized trials were included. The research team now has more than 20 trials, and that number is continuing to grow, from groups from around the world that have agreed to share data. In the next steps for this research, this repository will be used to investigate additional clinically relevant questions regarding optimal dosing of radiotherapy, fractionation, use of pelvic nodal radiotherapy, and extending studies into the recurrent and advanced disease states.
The Prostate Cancer Program at UH Seidman Cancer Center is one of the leading clinical and research programs nationally, and serves as one of the two international data repositories for the MARCAP consortium.
A special thanks to Dr. Jorge Garcia, Chief of Medical Oncology, UH Seidman Cancer Center; Dr. Nicholas Zaorsky, Vice Chair of Medical Education, UH Seidman Cancer Center Department of Radiation Oncology; Dr. Jonathan Shoag, UH Seidman Cancer Center, Department of Urology; Dr. Holly Hartman, Assistant Professor at Case Western Reserve University; and Dr. Yilun Sun, Director of Biostatistics at UH Seidman Cancer Center Department of Radiation Oncology, and Assistant Professor at Case Western Reserve University.
To see a full copy of the meta-analysis, and for more information about other research teams and funding involved in this work, please visit: The Lancet Oncology.
Kishan, A*, Sun Y*...Spratt, DE. “Androgen deprivation therapy use and duration with definitive radiotherapy for localised prostate cancer: an individual patient data meta-analysis.” The Lancet Oncology. DOI: 10.1016/S1470-2045(21)00705-1.
About University Hospitals / Cleveland, Ohio
Founded in 1866, University Hospitals serves the needs of patients through an integrated network of 23 hospitals (including 5 joint ventures), more than 50 health centers and outpatient facilities, and over 200 physician offices in 16 counties throughout northern Ohio. The system’s flagship quaternary care, academic medical center, University Hospitals Cleveland Medical Center, is affiliated with Case Western Reserve University School of Medicine, Oxford University and the Technion Israel Institute of Technology. The main campus also includes the UH Rainbow Babies & Children's Hospital, ranked among the top children’s hospitals in the nation; UH MacDonald Women's Hospital, Ohio's only hospital for women; and UH Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, with more than 3,000 active clinical trials and research studies underway. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including “America’s Best Hospitals” from U.S. News & World Report. UH is also home to 19 Clinical Care Delivery and Research Institutes. UH is one of the largest employers in Northeast Ohio with more than 30,000 employees. Follow UH on LinkedIn, Facebook and Twitter. For more information, visit UHhospitals.org.
About University Hospitals Seidman Cancer Center
UH Seidman Cancer Center is the only freestanding cancer hospital in Northeast Ohio, where all clinicians and staff are dedicated to the prevention, diagnosis and treatment of cancer while researching new and innovative treatment options through clinical trials. Nationally ranked cancer care is also available to patients through the 11-county region at 18 community-based locations. Our UH Seidman specialists make up 14 cancer-specific teams focused on determining integrated care plans tailored to patient’s needs. UH Seidman Cancer Center is part of the National Cancer Institute (NCI)-designated Case Comprehensive Cancer Center at Case Western Reserve University, one of 51 comprehensive cancer centers in the country. Patients have access to advanced treatment options, ranging from a pioneering stem cell transplant program founded more than 40 years ago and a wide range of immunotherapy to the first and only proton therapy center in northern Ohio for adults and children. Go to UHhospitals.org/Seidman for more information.
Case Western Reserve University is one of the country's leading private research institutions. Located in Cleveland, we offer a unique combination of forward-thinking educational opportunities in an inspiring cultural setting. Our leading-edge faculty engage in teaching and research in a collaborative, hands-on environment. Our nationally recognized programs include arts and sciences, dental medicine, engineering, law, management, medicine, nursing and social work. About 5,800 undergraduate and 6,300 graduate students comprise our student body. Visit case.edu to see how Case Western Reserve thinks beyond the possible.
The Lancet Oncology
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Androgen deprivation therapy use and duration with definitive radiotherapy for localised prostate cancer: an individual patient data meta-analysis
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