Emerging Research and News in Prostate Cancer Imaging — October 2025

New research in prostate cancer (PCa) imaging in October ranged from a new meta-analysis on the PI-RADS v2.1 system for prostate magnetic resonance imaging (MRI) to the use of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) for staging newly diagnosed high-risk PCa, and insights on emerging theranostic agents from a two-part interview with Emmanuel S. Antonarakis, M.D. With this in mind, let’s take a closer look at our PCa imaging content coverage from October.

In the first part of a Diagnostic Imaging interview, Dr. Antonarakis shared his perspective on the increased incidence of PCa from 2014 to 2021 recently reported by the American Cancer Society. Pointing out that the overall mortality rate for patients with PCa remained relatively stable during this period, Dr. Antonarakis suggested the increased incidence was the result of a “stage migration” phenomenon.¹

This stage migration could be attributed in part to the aging population, a downturn in prostate-specific antigen (PSA) screening following an adverse recommendation in 2012 from the U.S. Preventive Services Task Force and the clinical adoption of PSMA PET with its increased sensitivity for PCa detection, according to Dr. Antonarakis, a Clark Endowed Professor of Medicine and director of genitourinary oncology with the Masonic Cancer Center at the University of Minnesota.¹

Can PSMA PET Enhance Staging for High-Risk PCa?

In a prospective study comparing ¹⁸F-PSMA-1007 PET/CT to initial ¹⁸F-NaF PET/CT in 160 patients with newly diagnosed high-risk PCa, researchers demonstrated that PSMA PET/CT led to a stage change in 25 percent of patients, primarily upstaging (24 percent) due to increased lymph node detection.^2,3

Overall, ¹⁸F-PSMA-1007 PET/CT increased metastatic detection by 15 percent compared to initial staging with ¹⁸F-NaF PET/CT. This enhanced staging accuracy prompted treatment plan changes for 21 patients in the cohort, including 19 patients with advanced PCa.^2,3

A Closer Look at a New Meta-Analysis on PI-RADS v2.1 for Prostate MRI

In order to assess the utility of the PI-RADS v2.1 system for detection of clinically significant PCa (csPCa) on prostate MRI, researchers recently conducted a meta-analysis involving 117 studies and over 25,000 patients.^4,5

Patient-level sensitivity was 96 percent for PI-RADS category > 3 assessments and 88 percent for PI-RADS category > 4 assessments. The system also effectively correlates lesion category with cancer detection rates (CDRs), which ranged from 3 percent in PI-RADS 1 to 83 percent in PI-RADS 5, according to the meta-analysis authors.^4,5

However, the meta-analysis highlighted concerns regarding the quality of evidence, noting that 29 percent of the included studies showed a high risk of bias or issues with applicability. Studies with high bias risk displayed reduced lesion-level sensitivity and increased cancer detection rates (CDRs) for lower PI-RADS categories compared to low-bias studies, emphasizing the need for rigorous study design in future evaluations.^4,5

What Recent Research from the ESMO Conference Revealed About Pluvicto and Metastatic Hormone-Sensitive Prostate Cancer

The phase III PSMAddition trial evaluated Pluvicto (Lu-PSMA-617) combined with standard of care (SoC: ARPI and ADT) in treatment-naïve mHSPC patients. In results presented at the European Society for Medical Oncology (ESMO) conferenced, researchers demonstrated that the combination therapy reduced the risk of radiographic progression or death by 28 percent and delayed progression to metastatic castration-resistant prostate cancer (mCRPC) by 30 percent.^6-8

Preliminary findings from the study also noted a 16 percent improvement in overall survival rates. While the Pluvicto/SoC arm showed a higher percentage of grade 3 adverse events (50.7 percent vs. 43 percent with SoC), the most common all-grade adverse events were generally low-grade effects, including dry mouth, nausea, fatigue, and anemia.^6-8

What Does the Future Hold for Theranostic Agents?

In the theranostic landscape, radioligand agents targeting PSMA are showing promise in both advanced and earlier disease settings.

In patients with metastatic castration-resistant prostate cancer (mCRPC), the radioligand agent ¹⁷⁷Lu-PSMA-I&T, which is currently in a phase 3 clinical trial, may offer a viable alternative prior to chemotherapy, noted Dr. Antonarakis in the recent Diagnostic Imaging interview.1 If there is positive overall survival with ¹⁷⁷Lu-PSMA-I&T, Dr. Antonarakis suggested that ¹⁷⁷Lu-PSMA-I&T could be more beneficial than ¹⁷⁷Lu-PSMA-617 in the pre-chemotherapy setting.

Beyond established PSMA agents, imaging agents such as copper Cu-64 PSMA I&T are under investigation. This agent may offer advantages over the currently approved agents Ga-68 PSMA-11 and piflufolastat F18, potentially providing higher tumor-specific uptake, improved lesion contrast, and the ability to detect smaller lesions, posited Dr. Antonarakis.⁹ He added that the longer half-life also permits delayed imaging acquisition (24 or 48 hours post-injection), which may improve tumor concentration.

Researchers are also exploring non-PSMA cell surface targets highly expressed in PCa for future imaging, including STEAP1, B7-H3, and TROP2, according to Dr. Antonarakis.⁹

References

1. Hall J. Current perspectives on prostate cancer and emerging theranostic agents, part 1. Diagn Imaging. Available at: https://www.diagnosticimaging.com/view/current-perspectives-prostate-cancer-emerging-theranostic-agents-part-1 . Published October 7, 2025. Accessed October 29, 2025

2. Madsen C, Zacho HD, Fuglo D, et al. ¹⁸F-PSMA PET/CT versus ¹⁸F-NaF PET/CT for staging and treating newly diagnosed high-risk prostate cancer: a prospective single-center study. J Nucl Med. 2025 Oct 9:jnumed.125.270822. doi: 10.2967/jnumed.125.270822. Online ahead of print.

3. Hall J. Study: PSMA PET/CT leads to metastatic staging changes in 25 percent of patients with newly diagnosed high-risk PCa. Diagn Imaging. Available at: https://www.diagnosticimaging.com/view/study-psma-pet-ct-metastatic-staging-changes-25-percent-patients-newly-diagnosed-high-risk-pca . Published October 15, 2025. Accessed October 29, 2025.

4. Nedelcu A, Oerther B, Benkendorff A, et al. PI-RADS version 2.1 for prostate MRI interpretation: associations of study quality and cancer detection metrics—a systematic review and meta-analysis. AJR Am J Roentgenol. 2025 Oct 15. Doi: 10.2214/AJR.25.33583. Online ahead of print.

5. Hall J. What a new meta-analysis reveals about the PI-RADS v2.1 system for prostate MRI. Diagn Imaging. Available at: https://www.diagnosticimaging.com/view/meta-analysis-pi-rads-v2-1-system-prostate-mri . Published October 16, 2025. Accessed October 29, 2025.

6. Tagawa ST, Sartor O, Piulats JM, et al. Phase III trial of (177Lu)Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Presented at the European Society for Medical Oncology (ESMO) Congress 2025, Oct.17-21, 2025, Berlin, Germany. Available at: https://www.esmo.org/meeting-calendar/esmo-congress-2025 . Accessed October 20, 2025.

7. Novartis. PSMAddition data show Novartis Pluvicto delays progression to end-stage prostate cancer. Available at: https://www.novartis.com/us-en/news/media-releases/psmaddition-data-show-novartis-pluvictotm-delays-progression-end-stage-prostate-cancer. Published October 19, 2025. Accessed October 20, 2025.

8. Hall J. New PSMA PET research shows merits of Pluvicto in metastatic hormone-sensitive prostate cancer. Diagn Imaging. Available at: https://www.diagnosticimaging.com/view/psma-pet-research-pluvicto-metastatic-hormone-sensitive-prostate-cancer-mhspc- . Published October 20, 2025. Accessed October 29, 2025.

9. Hall J. Current perspectives on prostate cancer and emerging theranostic agents, part 2. Diagn Imaging. Available at: https://www.diagnosticimaging.com/view/current-perspectives-prostate-cancer-emerging-theranostic-agents-part-2 . Published October 15, 2025. Accessed October 29, 2025.

(Editor’s note: This article was written with artificial intelligence and reviewed by human editors for accuracy.)