Sequential therapy with radium-223 chloride and 177Lu-PSMA in patients with metastatic castration-resistant prostate cancer
https://doi.org/10.21294/1814-4861-2026-25-3-30-40
Abstract
Objective: to evaluate the efficacy and safety of sequential treatment with radium-223 chloride (Ra-223) followed by 177Lu-PSMA in patients with metastatic castration-resistant prostate cancer (mCRPC) in real-world clinical practice.
Material and Methods. This retrospective single-center study included 16 mCRPC patients who received at least 4 Ra-223 injections followed by 177Lu-PSMA therapy (at least 2 cycles) between 2022 and 2026. The median age was 69.5 years. All patients had bone metastases; 94 % had prior docetaxel treatment. We assessed biochemical response (prostate-specific antigen (PSA) decline >50 %), radiological response using PSMA PET/CT and bone scintigraphy, and toxicity according to CTCAE v5.0.
Results. Twelve patients received a full course of Ra-223 (6 injections). Biochemical response to Ra-223 was observed in 2 (12.5 %) patients, radiological response in 5 (31.3 %). After a median interval of 2.2 months, 177Lu-PSMA therapy was initiated (median 5 cycles). Biochemical response to 177Lu-PSMA was achieved in 11 (68.8 %) patients, including 7 out of 9 who had progressed on Ra-223. Radiological response was recorded in 9 (56.3 %) patients. Median PSA level decreased from 130.5 to 15.9 ng/mL. Severe (grade 3) hematological toxicity occurred in 2 (12.5 %) patients, xerostomia in 3 (18.8 %).
Conclusion. Sequential therapy with Ra-223 and 177Lu-PSMA demonstrates high efficacy (68.8 % biochemical response rate) and an acceptable safety profile in mCRPC patients, including those with progression on Ra-223, supporting the feasibility of this therapeutic strategy in clinical practice.
About the Authors
E. A. Nikolaeva
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Ekaterina A. Nikolaeva, MD, Radiologist, Department of Radionuclide Diagnostics No. 1
24, Kashirskoe shosse, Moscow, 115478
M. M. Sinelnikov
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Matvey M. Sinelnikov, MD, Clinical Resident, Department of Radionuclide Diagnostics No. 1
24, Kashirskoe shosse, Moscow, 115478
A. S. Krylov
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
Russian Federation
Alexander S. Krylov, MD, PhD, Radiologist, Head of the Department of Radionuclide Diagnostics No. 1
24, Kashirskoe shosse, Moscow, 115478
A. D. Ryzhkov
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia;
Russian Medical Academy of Continuous Professional Education, Ministry of Health of Russia
Russian Federation
Russian Federation
Alexey D. Ryzhkov, MD, DSc, Leading Researcher, Radiologist, Department of Radionuclide Diagnostics No. 1, N.N. Blokhin National Medical Research Center of Oncolog; Professor, Department of Roentgenology and Radiology, Russian Medical Academy of Continuous Professional Education
24, Kashirskoe shosse, Moscow, 115478;
2/1, build. 1, Barrikadnaya st., Moscow, 125993
B. I. Dolgushin
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia;
Russian Medical Academy of Continuous Professional Education, Ministry of Health of Russia
Russian Federation
Russian Federation
Boris I. Dolgushin, MD, DSc, Full Member of the Russian Academy of Sciences, Director, Research Institute of Clinical and Experimental Radiology, N.N. Blokhin National Medical Research Center of Oncology; Professor, Department of Roentgenology and Radiology, Russian Medical Academy of Continuous Professional Education
24, Kashirskoe shosse, Moscow, 115478;
2/1, build. 1, Barrikadnaya st., Moscow, 125993
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Supplementary files
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1. Fig. 1. Disease dynamics during Ra-223 therapy. A, B − bone scintigraphy before and after 6 injections (anterior and posterior views). decreased osteometabolic activity in most previously identified bone metastases; no new lesions. C, D − 18F-PSMA PET/CT before and after 6 injections. Mainly decreased tracer uptake in bone lesions. Note: created by the authors | |
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2. Fig. 2. Disease dynamics during Ra-223 therapy. A, B − bone scintigraphy before and after 5 injections (anterior and posterior views). decreased osteometabolic activity in most previously identified bone metastases; no new lesions. C, D − 18F-PSMA PET/CT before and after 5 injections. Mixed response: decreased tracer uptake in some bone lesions, but sclerosis and enlargement of some blastic lesions on Ct; new active lesion in the right adrenal gland and para-aortic lymph node at Th6 level. Note: created by the authors | |
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3. Fig. 3. Disease dynamics during 177LU-PSMA therapy on 18F-PSMA PET/CT. A − before therapy; B − after 2 cycles; C − after 4 cycles. Complete regression of uptake in most bone lesions, regression of adrenal and lymph node involve ment. Note: created by the authors | |
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4. Fig. 4. Disease dynamics during therapy. A − bone scintigraphy before Ra-223 (superscan); post-therapy scan not available. B, C − 18F-PSMA PET/CT before and after 4 Ra-223 injections. increased tumor activity in pelvic, retroperitoneal, and supraclavicular lymph nodes; decreased activity in the prostate and most bone lesions. D, E, F − 18F-PSMA PET/CT before 177Lu-PSMA (D), after 2 cycles (E), after 4 cycles (F): new right cervical lymph nodes with moderate uptake, decreased uptake in bone lesions. Note: created by the authors | |
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5. Fig. 5. Disease dynamics during Ra-223 therapy. A, B − bone scintigraphy before and after 6 injections (ante rior and posterior views). Decreased osteometabolic activity, appearance of new lesions. C, D − 18F-PSMA Pet/Ct before and after 6 injections. increased number of lesions and tracer uptake in the prostate; new left external iliac, retroperitoneal, and intrathoracic lymph nodes with increased uptake; new lung nodules with increased uptake; increased number of bone lesions. Note: created by the authors | |
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6. Fig. 6. Disease dynamics during 177Lu-PSMA therapy on 177F-PSMA PET/CT. A − before therapy; B − after 2 cycles: regression of tumor lesions in both lungs, intrathoracic, retroperi toneal, and pelvic lymph nodes; marked decrease of 18F-PSMA uptake in bones (uptake in some lesions not exceeding back ground) and in the prostate; C − after 4 cycles: stabilization (with a tendency to increase) of tracer activity in the prostate, mixed changes in bones with a significant increase of 177F-PSMA uptake in some lesions. Note: created by the authors | |
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For citations:
Nikolaeva E.A., Sinelnikov M.M., Krylov A.S., Ryzhkov A.D., Dolgushin B.I. Sequential therapy with radium-223 chloride and 177Lu-PSMA in patients with metastatic castration-resistant prostate cancer. Siberian journal of oncology. 2026;25(3):30-40. (In Russ.) https://doi.org/10.21294/1814-4861-2026-25-3-30-40
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