The meeting also brings personal recognition for UCLA leadership in the field. Dr. Daniel Low, professor and vice chair of medical physics research and innovation in the department of radiation oncology, is receiving the 2026 ASTRO Gold Medal, the organization’s highest honor, in recognition of his outstanding contributions to radiation oncology through research and professional service. He will be recognized during the Awards Ceremony on September 29. Dr. Luca Valle, associate professor of radiation oncology at the David Geffen School of Medicine at UCLA, has been selected for the 2026 ASTRO-PCF Young Investigator Award from ASTRO and the Prostate Cancer Foundation, and Dr. Jie Deng, assistant professor-in-residence of radiation oncology, has received an American Cancer Society Clinician Scientist Development Grant co-sponsored by ASTRO and designated in honor of Felix Feng, MD, an expert in translational genomics and preclinical therapeutics for prostate cancer.

Dr. Michael Steinberg, professor and chair of radiation oncology at the David Geffen School of Medicine at UCLA and director of Clinical Affairs at the Jonsson Comprehensive Cancer Center, framed the presentations as evidence of rapid evolution across the discipline. Radiation oncology, he noted, continues to evolve quickly, and the research being presented reflects the breadth of innovation in the department, from more personalized approaches to treatment to new ways of combining radiation with other therapies. In his view, the studies demonstrate how advances in technology, biology, and clinical research are shaping the way cancer treatment and care are approached. That combination of physics, genomics, and clinical trial design is a recurring theme throughout the UCLA program at this year’s meeting.

Among the most consequential findings is a study validating a genetic test that identifies men with prostate cancer who are at higher risk of long-term urinary side effects after stereotactic body radiation therapy, a technique that delivers very high doses of radiation in a small number of treatments. The test, called PROSTOX, examines inherited genetic differences that may influence how a patient responds to radiation. Led by Dr. Amar Kishan, executive vice chair of radiation oncology, and Dr. Joanne Weidhaas, professor of radiation oncology and vice chair of molecular and cellular oncology, the work addresses one of the central dilemmas in modern prostate cancer care: SBRT is convenient and increasingly popular, but a subset of patients experience lasting genitourinary toxicity that can substantially affect quality of life.

The clinical implications of the PROSTOX validation are striking. In a prospective clinical trial, using the test to guide treatment reduced the risk of moderate to severe urinary side effects, in part by steering patients flagged as high risk toward a longer course of conventional radiation instead of SBRT. To quantify how strongly the genetic signal predicts toxicity, the researchers analyzed pooled data from four clinical trials involving 457 men. Patients classified as high risk by PROSTOX were approximately 36 times more likely to develop late urinary side effects than those classified as low risk, an effect size that is unusual in the field of radiation toxicity prediction and suggests the test captures a genuinely informative biological mechanism rather than a marginal statistical association. Kishan will present the research, Abstract 311, on Tuesday, September 29, and the findings point toward a routine role for germline genetic testing in counseling men before they choose a radiation regimen.

Weidhaas will also present separate findings, Abstract 1238, showing that inherited genetic differences may help identify patients with head and neck cancer who are more likely to experience serious side effects from radiation and chemotherapy, or to have shorter overall survival. The study analyzed genetic and clinical data from 171 patients treated with radiation and cisplatin in a large clinical trial. Models that combined genetic markers with clinical factors outperformed clinical information alone in predicting both short-term and long-term treatment side effects. The models also stratified survival: patients identified as higher risk of dying within four years had a median survival of 2.25 years, compared with 4.46 years among those predicted to be at lower risk. If validated more broadly, such testing could allow oncologists to intensify monitoring or modify treatment for vulnerable patients before severe toxicity or disease progression occurs, rather than reacting after the fact.

A third UCLA presentation extends precision radiation into a challenging transplant setting. Dr. Trudy Wu, assistant professor of radiation oncology, conducted a retrospective analysis spanning 14 years of clinical data suggesting that MRI-guided stereotactic body radiation therapy can provide strong and lasting local control for patients with unresectable cholangiocarcinoma, a cancer of the bile ducts, while they await liver transplantation. Because transplant waiting periods can be lengthy, controlling the tumor during that interval is a critical clinical problem, and radiation may offer an important bridge while patients receive systemic therapy and await a donor organ. The study reviewed 38 patients who received MRI-guided SBRT followed by chemotherapy or chemoimmunotherapy at UCLA while being evaluated for transplantation. The use of MRI guidance is technically significant, because it allows clinicians to visualize the tumor and adjacent organs in real time during treatment delivery, enabling ablative doses to be concentrated on the tumor while sparing the remaining functional liver tissue.

The outcomes in the bile duct cancer cohort were notable for both survival and tolerability. Eleven patients ultimately underwent liver transplantation and had significantly longer overall survival than those who did not, with a median survival of about 150 weeks compared with 94 weeks. Among the patients who underwent transplantation, more than one-third had no remaining cancer detected in the liver at the time of surgery, a finding that suggests the radiation may have eradicated viable tumor in a substantial fraction of cases. The treatment was also generally well tolerated, with most patients reporting no radiation-related side effects. Wu will present the research, Abstract 1159, on Tuesday, September 29, and the results highlight the potential of precise, MRI-guided radiation as a well-tolerated strategy to control an otherwise unresectable tumor and help patients maintain control of their disease while pursuing transplantation.

The prostate cancer program at UCLA also includes a study, Abstract 1217, comparing treatment approaches for men whose prostate cancer has returned in a small number of locations, with the goal of delaying progression while avoiding or limiting hormone therapy, which can cause significant quality-of-life burdens. Dr. Esther Yu, a radiation oncology resident at UCLA Health, will present findings comparing patients who received metastasis-directed SBRT alone with those who received SBRT combined with either a targeted radioligand therapy called 177Lu-PSMA or a combination of hormone-blocking drugs. Radioligand therapy represents a distinct therapeutic paradigm: a radioactive molecule is linked to a compound that binds a specific target on cancer cells, in this case the prostate-specific membrane antigen, delivering radiation directly to tumor deposits while limiting exposure to healthy tissue.

The results of the comparison favor combination treatment, with important nuances. Both combination approaches significantly delayed cancer progression compared with SBRT alone, with a median time to progression of 19.4 months for SBRT plus radioligand therapy and 21.7 months for SBRT plus hormone therapy, compared with 6 months for SBRT alone. The two combination strategies produced similar efficacy, but the toxicity profiles differed: grade 3 or higher side effects occurred in 10 percent of patients receiving SBRT plus radioligand therapy, compared with 21 percent of those receiving the hormone therapy combination, although the difference was not statistically significant. The research, led by Kishan and Dr. Nicholas Nickols, assistant professor of radiation oncology, will be presented by Yu on Tuesday, September 30. Taken together with the PROSTOX findings and the head and neck genetic signatures study, the UCLA presentations at ASTRO 2026 argue that the next phase of radiation oncology will be defined not only by better machines and sharper imaging, but by genomic tests that match each patient to the regimen most likely to control the cancer while sparing them the side effects they are least able to tolerate.

Subject of Research: Personalized radiation therapy and radioligand approaches for prostate, bile duct, and head and neck cancers presented at ASTRO 2026

Article Title: ASTRO: Targeted radioactive therapy for prostate cancer, new SBRT approaches, personalized radiation and more

Article References: ASTRO: Targeted radioactive therapy for prostate cancer, new SBRT approaches, personalized radiation and more. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: radiation oncology, ASTRO 2026, prostate cancer, SBRT, PROSTOX genetic test, radioligand therapy, 177Lu-PSMA, cholangiocarcinoma, liver transplantation, head and neck cancer, genetic biomarkers, UCLA Health

Radioligand therapy with 177Lu-PSMA-617 has transformed the treatment landscape for metastatic castration-resistant prostate cancer, a lethal stage of the disease in which roughly half of patients survive less than five years after their metastatic diagnosis. The therapy exploits prostate-specific membrane antigen, a protein abundantly displayed on the surface of prostate cancer cells and further upregulated as tumors become castration resistant. A ligand called PSMA-617 delivers the beta-emitting radioisotope lutetium-177 directly to tumor cells, irradiating metastases throughout the body while sparing much of the surrounding healthy tissue. Following the landmark phase III VISION trial, the approach gained approval from the United States Food and Drug Administration in March 2022 for PSMA-positive patients who had already received an androgen receptor pathway inhibitor and taxane chemotherapy.

Yet the therapy has an uncomfortable secret: only about half of eligible patients derive meaningful clinical benefit. Except for PSMA PET imaging criteria used to confirm that tumors carry the target molecule, clinicians currently lack validated biomarkers to identify who will respond and who will progress despite treatment. This gap matters both scientifically and economically. A recent cost-effectiveness analysis based on the VISION trial concluded that adding 177Lu-PSMA to standard care may only be cost-effective under specific clinical and economic assumptions, underscoring the urgency of better patient selection.

To address this problem, investigators at IRCCS Istituto Romagnolo per lo Studio dei Tumori in Meldola, Italy, enrolled 145 patients between April 2017 and October 2022 in a prospective observational biological study nested within a single-arm phase II trial of 177Lu-PSMA-617. Of these, 142 patients received at least one dose and were fully evaluable. Within seven days of the first infusion, the researchers collected baseline blood samples and measured a panel of routinely available laboratory markers, including hemoglobin, alkaline phosphatase, prostate-specific antigen, chromogranin A, neuron-specific enolase, and CEA, along with inflammatory ratios derived from the complete blood count. All patients received treatment in four cycles administered every eight to twelve weeks, using either a lower activity of 3.7 to 4.4 gigabecquerels or a higher activity of 5.5 gigabecquerels per cycle.

At a median follow-up of 44 months, the cohort experienced a median progression-free survival of 7.0 months and a median overall survival of 16.8 months, outcomes broadly consistent with the pivotal VISION and TheraP trials. In univariable analyses, elevated platelet-to-lymphocyte ratio, alkaline phosphatase, PSA, and CEA each predicted shorter progression-free survival, while low hemoglobin and high neutrophil-to-lymphocyte ratio, along with the same markers, predicted shorter overall survival. But when the researchers integrated all clinical characteristics and serum biomarkers into multivariable Cox regression models, only a handful of factors retained independent significance: prior docetaxel exposure, low hemoglobin, high PSA, and, critically, elevated CEA. High CEA independently predicted both shorter progression-free survival, with a p-value of 0.026, and shorter overall survival, with a p-value of 0.003.

The statistical rigor of the analysis strengthens the claim. Multicollinearity checks using variance inflation factors confirmed that no variable simply duplicated another, with all values below two. When CEA was added to a model containing established prognostic factors, the overall model fit improved significantly according to a likelihood-ratio test, and Harrell’s concordance index rose from 0.732 to 0.742. Although PSA alone discriminated outcomes better than CEA alone, with C-indices of 0.652 versus 0.598, combining the two markers pushed the C-index to 0.694, demonstrating that CEA carries prognostic information that PSA does not capture. Exploratory correlation analyses reinforced this independence: baseline CEA showed essentially no relationship with PSA levels and only a weak association with chromogranin A, while it did not correlate with bone disease burden measured on PSMA PET scans.

The biological story behind elevated CEA may be as compelling as the statistics. CEA is an oncofetal glycoprotein long used as a tumor marker in colorectal and other cancers, and previous work has linked it to aggressive disease biology in prostate cancer. In particular, elevated serum CEA in castration-resistant prostate cancer has been associated with liver metastases, markedly shorter survival, and distinctive circulating tumor DNA alterations. It has also been tied to aggressive variant prostate cancer, a molecularly distinct and treatment-resistant phenotype. Although a single-arm design without a control group prevents the authors from claiming that CEA specifically predicts benefit from 177Lu-PSMA rather than simply flagging inherently aggressive disease, the finding raises the hypothesis that high CEA identifies a biologically distinct subgroup with intrinsic resistance to PSMA-targeted radioligand therapy. Notably, baseline FDG PET was not mandatory in this cohort, so the researchers could not test whether CEA-elevated patients harbored FDG-positive, PSMA-low lesions typical of aggressive variants.

Other markers behaved as expected. Lower hemoglobin, likely reflecting chronic inflammation and extensive bone marrow involvement rather than a direct effect on treatment response, remained independently associated with shorter overall survival. Alkaline phosphatase, a proxy for skeletal tumor burden, also independently predicted overall survival, consistent with three prior studies and a recent meta-analysis. Inflammatory ratios lost much of their significance after adjustment, although platelet-to-lymphocyte ratio retained an association with progression-free survival. An intriguing exploratory interaction suggested that the prognostic impact of CEA may differ according to the administered radiation activity, but the authors caution that this post hoc finding is hypothesis-generating only, since dose was not randomly assigned and lower activities were reserved for frailer patients.

The study’s limitations temper, but do not erase, its promise. The administered activities were lower than the currently approved Pluvicto regimen of 7.4 gigabecquerels every six weeks, potentially limiting generalizability, and no metastatic biopsies were available to histologically confirm neuroendocrine differentiation among patients with elevated chromogranin A or neuron-specific enolase, markers of limited specificity that can rise in many benign and malignant conditions. External validation in cohorts treated with the approved dosing schedule will be essential before CEA enters routine risk stratification. Still, the vision is clear: if validated, a marker already present on virtually every hospital laboratory requisition could, at essentially no added cost, help clinicians identify patients facing aggressive, inherently resistant disease, guide them toward alternative or combination strategies, and reserve this costly radioligand therapy for those most likely to benefit. In the precision oncology era, the humble CEA blood draw may prove an unexpectedly powerful ally.

Subject of Research: Baseline serum carcinoembryonic antigen as an independent prognostic biomarker for survival outcomes in metastatic castration-resistant prostate cancer patients treated with 177Lu-PSMA radioligand therapy

Article Title: Baseline serum carcinoembryonic antigen (CEA) is an independent prognostic biomarker for metastatic castration-resistant prostate cancer (mCRPC) patients receiving 177Lu-PSMA therapy

Article References: Giunta, E. F., Marini, I., Grassi, I., Nicolini, S., Foca, F., Celli, M., Caroli, P., Sarnelli, A., Brighi, N., Schepisi, G., Monti, M., De Giorgi, U., Lolli, C., & Sansovini, M. (2026). Baseline serum carcinoembryonic antigen (CEA) is an independent prognostic biomarker for metastatic castration-resistant prostate cancer (mCRPC) patients receiving 177Lu-PSMA therapy. European Journal of Nuclear Medicine and Molecular Imaging. https://doi.org/10.1007/s00259-026-08173-x

Image Credits: AI Generated

DOI: 10.1007/s00259-026-08173-x

Keywords: 177Lu-PSMA, prostate cancer, radioligand therapy, CEA, biomarker, metastatic castration-resistant prostate cancer, prognostic factors, PSMA, overall survival, progression-free survival, PSMA-617, serum tumor markers