Researchers at UCLA Jonsson Comprehensive Cancer Center led a large international study providing what is believed to be the first evidence (albeit indirect) that a recently approved imaging technique improves risk-stratification and long-term prognostic capabilities for patients with high-risk prostate cancer whose conventional imaging showed only localized disease.
“Our findings also suggest that previously undetected, non-localized disease may be the primary driver of outcomes in this high-risk population,” said Dr. Amar Kishan, chief of the Genitourinary Oncology Service for the Department of Radiation Oncology at the David Geffen School of Medicine at UCLA and the UCLA Jonsson Comprehensive Cancer Center. He is the senior author of an article in the Dec. 13 issue of JAMA Network Open.
Although early experience with PSMA PET/CT indicates it can detect low-volume, non-localized prostate cancer that is not seen with conventional imaging, direct, prospective evidence of its prognostic value is still several years away because clinical use of the technique has been available in the United States less than a year, said Kishan, associate professor and vice chair of clinical and translational research in the Department of Radiation Oncology at UCLA. But a tool created for this study may serve as a proxy for the new technology’s long-term prognostic and clinical significance.
In a recently published study, UCLA researchers had developed a PSMA PET/CT-specific “nomogram,” a tool that takes a variety of variables into account to predict the probability of finding non-localized disease using PSMA PET/CT in patients who appeared to have no regional lymph node involvement or distant metastasis based on conventional imaging at the time of diagnosis.
In this new study, the researchers—representing 15 centers in the U.S., Canada, Norway, Germany, and Spain—looked at the prognostic significance of the PSMA nomogram on long-term, clinically meaningful outcomes, then compared its prognostic capabilities with those of other, existing risk-stratification tools.
“The PSMA nomogram was designed to predict the positivity of PSMA PET/CT at initial diagnosis, without regard to eventual clinical outcomes, but interestingly, this PSMA PET/CT-based tool provided better risk discrimination than existing tools that were designed specifically to predict clinical outcomes. This may speak to the significance of using PSMA PET/CT findings as a marker of overall disease course, and our results contribute to a growing body of data supporting the clinical use of this technique in the initial evaluation and management of high-risk patients,” said Dr. Michael Xiang, assistant clinical professor in the Department of Radiation Oncology at the David Geffen School of Medicine at UCLA. Xiang is the corresponding author and a co-first author of the paper, with Dr. Ting Martin Ma, resident physician in the Department of Radiation Oncology.
Among highlights and details:
- The study evaluated the prognostic significance of the PSMA nomogram (and, by proxy, PSMA PET/CT itself) on long-term, clinically meaningful endpoints, including distant metastasis, prostate cancer-specific mortality, and overall survival.
- The primary study included a cohort of 5,275 patients with high-risk or very high-risk prostate cancer, based on National Comprehensive Cancer Network criteria. The patients were treated at 15 centers between 1995 and 2018 using radiation or surgery.
- In statistical analyses, the PSMA nomogram was significantly prognostic of all clinical endpoints, regardless of treatment type.
- Findings were validated externally using two large registry-based cohorts: the Surveillance, Epidemiology, and End Results (SEER) Program database (23,989 patients), and the National Cancer Database (88,909 patients). Nomogram risk was significantly prognostic in age-related regression analyses.
Several of the JAMA Network Open article authors, including Kishan and Drs. Johannes Czernin, Jeremie Calais, Robert Reiter, Matthew Rettig, and Nicholas Nickols, are UCLA faculty and members of the UCLA Jonsson Comprehensive Cancer Center who helped lead the clinical trials for the use of PSMA PET imaging in the United States. Calais, co-senior principal investigator on this study, was senior author of a Sept. 16 article in JAMA Oncology on the diagnostic accuracy of PSMA PET technology for pelvic node metastasis detection. That study, a collaboration between UCLA and the University of California, San Francisco, led to U.S. Food and Drug Administration approval of the technology for this purpose.
“PSMA PET is now part of the National Comprehensive Cancer Network guidelines as a replacement of other front-line imaging tools. With insurance coverage, this game-changer technology will ultimately become part of the routine staging of prostate cancer patients,” said Calais, assistant professor and director of the Clinical Research Program of the Ahmanson Translational Theranostics Division of the Department of Molecular and Medical Pharmacology at UCLA. He is also a member of the UCLA Jonsson Comprehensive Cancer Center and the UCLA Institute of Urologic Oncology.
The FDA approved the first PSMA PET/CT imaging drug, Gallium 68 PSMA-11, in December 2020, with initial approval going to UCLA and UCSF. A second drug, Pylarify, was approved in May 2021. The radioactive tracers are limited to use in certain patients: those with suspected prostate cancer metastasis who are potentially curable by surgery or radiation therapy, and those with suspected prostate cancer recurrence, based on elevated prostate-specific antigen (PSA) levels.
Administered by IV injection, the drugs bind to prostate-specific membrane antigen (PSMA), a protein that is usually found in high levels in prostate cancer cells. The tracers can be imaged by positron emission tomography (PET)/computed tomography (CT) to indicate the presence of cancer lesions.
Article: Performance of a Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography–Derived Risk-Stratification Tool for High-risk and Very High-risk Prostate Cancer; JAMA Network Open. 2021;4(12):e2138550. doi:10.1001/jamanetworkopen.2021.38550 (Reprinted) December 13, 2021
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Dr. Kishan’s work is supported by an ASTRO-PCF grant (the American Society for Radiation Oncology and the Prostate Cancer Foundation). Dr. Calais’ work is supported by the Prostate Cancer Foundation. The authors report no other sources of funding or potential conflicts of interest related to this article.
JAMA Network Open
Method of Research
Subject of Research
Performance of a Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography–Derived Risk-Stratification Tool for High-risk and Very High-risk Prostate Cancer
Article Publication Date
Dr Savjani reported receiving grants from Varian Medical Systems Research outside the submitted work. Dr Karnes reported delivering an advisory lecture for Telix/Lanteus outside the submitted work. Dr Tosoian reported be cofounder of and holding equity in LynxDx. Dr Trock reported receiving grants from Myriad Genetics and MDxHealth to their institution outside the submitted work. Dr Spratt reported receiving personal fees from Janssen Pharmaceuticals, AstraZeneca, Boston Scientific, and Varian outside the submitted work. Dr Song reported receiving grants from Candel Therapeutics, Bayer, Celgene, BioProtect, Allegheny Health Network, and the National Cancer Institute outside the submitted work. Dr Ross reported receiving personal fees from GenomeDx, Bayer, Astellas, Pfizer, Myovant, and Blue Earth outside the submitted work. Dr Boutros reported serving on the scientific advisory boards of Sage Bionetworks, BioSymetrics, Intersect Diagnostics outside the submitted work. Dr Nickols reported receiving grants from Lantheus during the conduct of the study; receiving grants from Janssen Pharmaceuticals and Bayer outside the submitted work; and receiving personal fees from Oncolinea outside the submitted work. Dr Rettig reported consulting for Amgen, Ambrx, and Roivant; serving as speaker for Bayer and Johnson & Johnson; receiving nonfinancial support from Merck and Novartis outside the submitted work; and having a patent pending for androgen receptor inhibitors. Dr Tward reported serving on the advisory board of Blue Earth Diagnostics during the conduct of the study and receiving grants from Bayer and Myriad Genetics outside the submitted work. Dr Steinberg reported receiving honoraria from Viewray outside the submitted work. Dr Tilki reported receiving personal fees from AAA/Novartis, Apogepha, AstraZeneca, Exact Sciences, Ipsen, Roche, Takeda, and mIR Scientific outside the submitted work. Dr Czernin reported being founder of Sofie Biosciences and Trethera Corporation outside the submitted work. Dr Calais reported receiving personal fees from Advanced Accelerator Applications, Blue Earth Diagnostics, Curium Pharma, GE Healthcare, EXINI, IBA RadioPharma, Janssen Pharmaceuticals, POINT biopharma, Lantheus, Radiomedix, and Telix Pharmaceuticals outside the submitted work. Dr Kishan reported receiving honoraria and consulting fees from Varian Medical Systems; receiving honoraria, consulting fees, and research support from ViewRay; receiving consulting fees from Intelligent Automation; and serving on the advisory board of Janssen Pharmaceuticals outside the submitted work. No other disclosures were reported.