Rechallenge With 177Lu-PSMA Radioligand Therapy in Metastatic Castration-resistant and Hormone-sensitive Prostate Cancer - Lessons From a Multicase Experience

Sep 22, 2026

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We report four patients with metastatic hormone-sensitive or castration-resistant prostate cancer treated with 177Lu-PSMA-617 radioligand therapy, including rechallenge after progression. Initial treatment produced marked PSA declines, pain relief, and radiographic responses. At biochemical or clinical progression, additional 177Lu-PSMA cycles restored PSA reductions, maintained symptomatic benefit, and showed favorable tolerability. No grade III–IV hematologic or renal toxicities were observed. These cases support dynamic use of 177Lu-PSMA across disease stages and indicate that prior exposure does not preclude subsequent retreatment.

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INTERESTING IMAGE Rechallenge With 177 Lu-PSMA Radioligand Therapy in Metastatic Castration-resistant and Hormone-sensitive Prostate Cancer Lessons From a Multicase Experience Faeze Rabani, MD, Nikoo Rezaei, MD, Amin Tanha Saber, MD, Emran Askari, MD, Atena Aghaee, MD, and Kamran Aryana, MD Abstract: We report 4 patients with metastatic hormone-sensitive (mHSPC) or castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA-617 radioligand therapy (RLT), including rechallenge after disease progression. Initial RLT induced significant PSA declines, pain relief, and radiographic responses. Upon biochemical or clinical progression, rechallenge with additional 177Lu-PSMA cycles achieved renewed PSA reductions, sustained symptomatic improvement, and favorable safety, with no grade III–IV hematologic or renal toxicities. These cases illustrate the dynamic application of 177Lu-PSMA across disease stages and suggest that prior exposure does not preclude subsequent retreatment, supporting the feasibility and efficacy of RLT rechallenge in both mCRPC and mHSPC settings. Key Words: theragnostic, prostate-specific membrane antigen, hormone-naïve, androgen deprivation therapy, biochemical response (Clin Nucl Med 2026;51:e901–e904) Received for publication January 6, 2026; accepted March 22, 2026. From the Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Conflicts of interest and sources of funding: none declared. Correspondence to: Kamran Aryana, MD, Nuclear Medicine Research Center, Mashhad University of Medical Science, Ghaem Hospitalbeginning of Ahmadabad Avenue, Mashhad 91766-99199, Iran. [E-mail: AryanaK@mums.ac.ir](E-mail: AryanaK@mums.ac.ir). Copyright © 2026 Wolters Kluwer Health, LLC. All rights reserved. DOI: 10. 1097/RLU.0000000000006490 REFERENCES 1. Gafita A, Rauscher I, Retz M, et al. Early experience of rechallenge 177Lu-PSMA radioligand therapy after an initial good response in patients with advanced prostate cancer. JNucl Med. 2019;60:644–648 . 2. Fallah J, Agrawal S, Gittleman H, et al. FDA approval summary: lutetium Lu 177 vipivotide tetraxetan for patients with metastatic castration-resistant prostate cancer. Clin Cancer Res. 2023;29:1651–1657 . 3. Bastian MB, Sieben M, Burgard C, et al. Outcome and renal safety of PSMA-targeted radioligand therapy in mCRPC patients with preexisting impaired renal function. Clin Nucl Med. 2025;50:165–171 . 4. Yadav MP, Ballal S, Bal C, et al. Efficacy and safety of 177Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer patients. Clin Nucl Med. 2020;45:19–31 . 5. Rahbar K, Bode A, Weckesser M, et al. Radioligand therapy with 177Lu-PSMA-617 as a novel therapeutic option inpatients with metastatic castration resistant prostate cancer. Clin Nucl Med. 2016;41:522–528 . 6. Roll W, Bode A, Weckesser M, et al. Excellent response to 177Lu-PSMA-617 radioligand therapy in a patient with advanced metastatic castration resistant prostate cancer evaluated by 68Ga-PSMA PET/CT. Clin Nucl Med. 2017;42: 152–153. 7. Kim YJ, Kim Y. Therapeutic responses and survival effects of 177Lu-PSMA-617 radioligand therapy in metastatic castrateresistant prostate cancer. Clin Nucl Med. 2018;43:728–734 . 8. Zhang J, Kulkarni HR, Singh A, et al. Complete regression of lung metastases in a patient with metastatic castration-resistant prostate cancer using 177Lu-PSMA radioligand therapy. Clin Nucl Med. 2020;45:e48–e50 . 9. Aggarwal P, Gunasekaran V, Sood A, et al. Re-rechallenge 177Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer. Clin Nucl Med. 2025;50: 231–233. 10. Banda A, Privé BM, Allach Y, et al. PSMA-RLT in patients with metastatic hormone-sensitive prostate cancer: a retrospective study. Cancers (Basel) . 2022;15:297 . 11. Dhiantravan N, Emmett L, Joshua AM, et al. UpFrontPSMA: a randomized phase 2 study of sequential 177Lu-PSMA-617 and docetaxel vs docetax

FAQs

What treatment approach is described in the paper?

The paper reports metastatic prostate cancer patients treated with 177Lu-PSMA-617 radioligand therapy, including rechallenge after disease progression.

What outcomes were observed after the initial 177Lu-PSMA therapy?

Initial therapy led to significant PSA declines, pain relief, and radiographic responses.

How did patients respond to 177Lu-PSMA rechallenge after progression, and what safety signals were reported?

After biochemical or clinical progression, additional 177Lu-PSMA cycles achieved renewed PSA reductions and sustained symptom improvement, with favorable safety and no grade III–IV hematologic or renal toxicities.

Sep 22, 2026

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