First experience with whole-body magnetic resonance imaging using MET-RADS-P criteria for interim efficacy evaluation of 225Ac-PSMA radioligand therapy in metastatic castration-resistant prostate cancer

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Abstract

BACKGROUND: Radioligand therapy with actinium-225–prostate-specific membrane antigen (225Ac-PSMA) is a novel and promising treatment modality for metastatic castration-resistant prostate cancer. Whole-body magnetic resonance imaging (WB-MRI) is a noninvasive, non-ionizing imaging technique that provides comprehensive information on skeletal and extraskeletal metastatic lesions, structured using the MET-RADS-P (METastasis Reporting and Data System for Prostate Cancer) and enabling detailed assessment of treatment response. However, the use of this system has not been widely adopted, and its diagnostic accuracy requires clinical validation.

AIM: This study aimed to evaluate the interim efficacy of 225Ac-PSMA radioligand therapy using WB-MRI based on MET-RADS-P criteria in patients with metastatic castration-resistant prostate cancer, assess method reproducibility (intra-observer agreement), and compare imaging findings with changes in prostate-specific antigen (PSA) levels.

METHODS: WB-MRI was performed twice in patients with metastatic castration-resistant prostate cancer: before administration of 225Ac-PSMA-617 with activity 6–12 MBq and 1–2 months after a single cycle of radioligand therapy, with parallel measurement of PSA levels. Prospective response assessment was conducted using MET-RADS-P criteria for WB-MRI and PCWG criteria for PSA level trends. Reproducibility of MET-RADS-P criteria was evaluated through repeated reading of WB-MRI studies by the same radiologist with a 6-month interval.

RESULTS: After one cycle of radioligand therapy, MET-RADS-P progression was identified in 4 of 20 patients with metastatic castration-resistant prostate cancer (20%) who completed the study. In three of these patients, progression was detected at an earlier time point than indicated by PSA level trends. More than half of the patients demonstrated discordant responses, including three with progression. Differences in PSA level trends were observed between concordant positive responses and various patterns of discordant response according to MET-RADS-P criteria. In cases of concordant response, the MET-RADS-P integrated assessment showed good correlation with biochemical response. MET-RADS-P criteria demonstrated excellent reproducibility for the primary response category pattern and for integrated response assessment. Reproducibility for the secondary response category pattern was substantial.

CONCLUSION: The use of MET-RADS-P criteria to WB-MRI in patients with metastatic castration-resistant prostate cancer enabled earlier detection of progression in skeletal and extraskeletal lesions compared with PSA level trends and demonstrated good intra-observer agreement. Further investigation of the prognostic value of MET-RADS-P criteria in the context of 225Ac-PSMA radioligand therapy is warranted.

About the authors

Tatiana P. Berezovskaia

A.F. Tsyb Medical Radiology Centre, National Medical Research Radiological Center

Author for correspondence.
Email: berez@mrrc.obninsk.ru
ORCID iD: 0000-0002-3549-4499
SPIN-code: 5837-3465

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Obninsk

Vladislav O. Ripp

A.F. Tsyb Medical Radiology Centre, National Medical Research Radiological Center

Email: rippnba@gmail.com
ORCID iD: 0000-0001-8970-4212
SPIN-code: 3350-7131
Russian Federation, Obninsk

Tatiana Yu. Kochetova

A.F. Tsyb Medical Radiology Centre, National Medical Research Radiological Center

Email: tat_mail@inbox.ru
ORCID iD: 0000-0002-7809-1059
SPIN-code: 7542-9537
Russian Federation, Obninsk

Valeriy V. Krylov

A.F. Tsyb Medical Radiology Centre, National Medical Research Radiological Center

Email: krylov.mrrc@mail.ru
ORCID iD: 0000-0001-6655-5592
SPIN-code: 2555-1790

MD, Dr. Sci. (Medicine)

Russian Federation, Obninsk

Sergei A. Ivanov

A.F. Tsyb Medical Radiology Centre, National Medical Research Radiological Center; Peoples' Friendship University of Russia

Email: ivanov.obninsk@mail.ru
ORCID iD: 0000-0001-7689-6032
SPIN-code: 4264-5167

MD, Dr. Sci. (Medicine), corresponding member of the Russian Academy of Sciences

Russian Federation, Obninsk; Moscow

Andrei D. Kaprin

Peoples' Friendship University of Russia; P.A. Herzen Moscow Research Institute of Oncology, National Medical Research Radiological Centre; National Medical Research Radiological Center

Email: mnioi@mail.ru
ORCID iD: 0000-0001-8784-8415
SPIN-code: 1759-8101

MD, Dr. Sci. (Medicine), Professor, academician of the Russian Academy of Sciences

Russian Federation, Moscow; Moscow; Obninsk

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2. Fig. 1. Study design. RLT — radioligand therapy; 225Ac-PSMA — 225Ac-prostate-specific membrane antigen; MRI — magnetic resonance imaging; PSA — prostate-specific antigen; RPP — radiopharmaceutical preparation; MET-RADS-P (METastasis Reporting and Data System for Prostate Cancer) — reporting and classification system for prostate cancer metastases; PSWG (Prostate Cancer Working Group) — international expert group that developed standardised criteria for assessing disease progression and response to therapy in metastatic and castration-resistant prostate cancer.

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3. Fig. 2. Representative magnetic resonance imaging response to radioligand therapy. A 64-year-old patient with metastatic castration-resistant prostate cancer with multiple bone lesions. Results of whole-body magnetic resonance imaging at the level of the target lesion in the right pelvic bone (red arrows) before treatment (a, b, c) and 2 months after one course of radioligand therapy (d, e, f). There are no changes in the lesion on STIR images (a, d) and diffusion-weighted images (b, e); diffusion coefficient maps (c, f) show an increase in signal intensity from 0.67 × 10−3 to 1.6 × 10−3 mm2/s, which corresponds to the most likely response to treatment (RAC 1). A decrease in prostate-specific antigen concentration from 468 to 51 ng/ml was noted.

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4. Fig. 3. Representative magnetic resonance imaging of progression. A 71-year-old patient with metastatic castration-resistant prostate cancer with multiple bone lesions. Results of whole-body magnetic resonance imaging before treatment (a, c, e) and 1 month after one course of radioligand therapy (b, d, f): T1-weighted images at the level of the proximal femur (a, b) and pelvic bones (c, d); reconstruction of diffusion-weighted images of the chest using the maximum intensity projection method. Red arrows indicate areas with an increase in the size and number of metastatic foci, with the appearance of confluent lesions. An increase in the concentration of prostate-specific antigen from 103 to 212 ng/ml was noted.

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5. Fig. 4. Results of a single course of radioligand therapy with 225Ac-PSMA for each patient based on prostate-specific antigen concentration dynamics (as a percentage of nadir) and integral response variant in accordance with MET-RADS-P. The arrows indicate patients who had no progression in terms of prostate-specific antigen concentration at the time of assessment, but who did show progression in subsequent follow-up examinations. PSA — prostate-specific antigen; MET-RADS-P (METastasis Reporting and Data System for Prostate Cancer) — a system for reporting and classifying metastases in prostate cancer.

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6. Fig. 5. Range of changes in prostate-specific antigen concentration (% to nadir) after one course of radioligand therapy for different integral responses to treatment according to the MET-RADS-P system. NBRP — non-concordant response without progression, dominant pattern indicated in brackets; NPR — non-concordant response with progression; PSA — prostate-specific antigen; MET-RADS-P (METastasis Reporting and Data System for Prostate Cancer) — a system for reporting and classifying metastases in prostate cancer; RAC (Response Assessment Criteria) — criteria for assessing response to treatment.

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