Treatment of Metastatic Castration-Resistant Prostate Cancer: Review of Current Evidence and Synthesis of Expert Opinions on Radioligand Therapy

Darren Poon ^1,2* William S.K. Cheung ³ Peter K.F. Chiu ^4* Daniel H.S. Chung ⁵ John B.T. Kung ⁶ Daisy C.M. Lam ⁷ Angus K.C. Leung ⁸ Anthony Chi Fai Ng ⁴ Joe M O'Sullivan ⁹ Jeremy Teoh ⁴ Philip Y Wu ¹⁰ Sam K.K. Wu ³ Philip W.K. Kwong ¹¹

• ¹ Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK Pao Centre for Cancer, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR China
• ² Comprehensive Oncology Centre, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong, SAR China
• ³ Department of Nuclear Medicine & PET, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong, SAR China
• ⁴ S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR China
• ⁵ Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong, SAR China
• ⁶ Nuclear Medicine Unit, Department of Diagnostic and Interventional Radiology, Queen Elizabeth Hospital, Kowloon, Hong Kong, SAR China
• ⁷ Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR China
• ⁸ AMO Oncology Centre, Kowloon, Hong Kong, SAR China
• ⁹ The Patrick G Johnston Centre for Cancer Research, Faculty of Medicine, Health and Life Sciences, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom
• ¹⁰ Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, Hong Kong, SAR China
• ¹¹ Hong Kong Integrated Oncology Centre, Hong Kong, Hong Kong, SAR China

Background: Despite the boom in the development of cancer management in the last decade, most patients with metastatic prostate cancer (PCa) eventually progress to metastatic castration-resistant PCa (mCRPC) and often require multiple lines of treatment. The treatment landscape of mCRPC has evolved rapidly in recent years, introducing various types of systemic therapies, including taxane-based chemotherapy, androgen receptor pathway inhibitors, bone-targeted radionuclides (e.g. radium-223), immune checkpoint inhibitors, poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors, and radioligand therapies (RLTs, e.g. a prostate-specific membrane antigen [PSMA] ligand labelled with 177Lu). Methods: To help clinicians navigate the increasingly complex treatment landscape of mCRPC, this article reviews the evidence on different therapeutic regimens from pivotal trials. Additionally, it reports on the results of a questionnaire developed and distributed by the Hong Kong Society of Uro-Oncology (HKSUO) with the aim of collecting the perspectives of specialists experienced in treating advanced PCa in Hong Kong regarding the clinical application of RLT, primarily [177Lu]Lu-PSMA-617/analogues. Results: A total of 43 questionnaire respondents (including clinical oncologists, urologists, nuclear medicine specialists, and medical oncologists) voted on 27 consensus questions divided into eight sections. Consensus or strong consensus (≥ 75% or ≥ 90% acceptance for an answer option) was reached for 10 questions. Subsequently, a panel of 13 local and overseas experts coordinated by the HKSUO discussed the voting results and provided further insights into certain questions. Conclusion: The literature review, voting results of the questionnaire, and expert opinions are expected to facilitate better understanding of recent therapeutic advancements and the role of novel RLTs in the treatment of mCRPC among clinicians.