Individual Abstract within a Delegate Designed Symposium Clinical Oncology Society of Australia Annual Scientific Meeting 2019

International experience with Lutetium and Actinium based radionuclide therapies in prostate cancer: current state of clinical practice and future directions (#49)

Aviral Singh 1 2
  1. Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka GmbH, Bad Berka, Germany
  2. GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands

Prostate-specific membrane antigen (PSMA) is expressed in poorly differentiated prostate cancers and can be identified by PSMA-ligand PET-imaging with subsequent PSMA-based radioligand therapy (PRLT) following the principle of Theranostics.  

Retrospective observational data report favorably on the efficacy and safety of PRLT with beta-emitting Lutetium-177 (177Lu). Results from a prospective phase-II clinical trial (LuPSMA) have confirmed high response rates, low toxicity, symptomatic pain relief, and improvement in the quality of life of patients with metastatic castration-resistant prostate cancer and treatment-refractory progressive disease. Compassionate use based observational studies and meta-analyses have reported the efficacy of 177Lu-PRLT with a biochemical response (PSA decline >50%) in more than half of the patients, and imaging derived partial response in about one-third of patients. Presence of visceral metastases and serum alkaline phosphatase ≥220 U/L associated with poor outcome.

Reports of safety analysis following 177Lu-PRLT demonstrated grade 3-4 hematotoxicity in less than 10% of patients. Other clinical symptoms observed include fatigue, xerostomia, nausea, and exacerbation of pain syndrome due to ‘flare phenomenon’.

Actinium-225 (225Ac)-based PSMA alpha radioligand therapy (PSMA-ART) utilizes the shorter tissue penetration range of the higher energy alpha particles. It is performed in patients with extensive lymph node, visceral or bone and bone marrow metastases, and sometimes as an escalation therapy in case of disease progression under 177Lu-PRLT.

TANDEM (177Lu/225Ac) PRLT is the approach of administering fractionated activities of both beta- and alpha-emitting radiation during the same cycle in order to maintain the therapeutic effect while attempting to avoid severe and treatment-limiting xerostomia, which could result as an adverse effect of ART with 225Ac.

Future developments are aimed at reducing side effects caused by radioligand therapy, combination therapies, dosimetry studies, application of novel radioligands and radioisotopes as well as novel imaging hardware and software, and most importantly, randomised controlled studies.

  1. Kulkarni HR, Singh A, Langbein T, Schuchardt C, Mueller D, Zhang J, Lehmann C, Baum RP. Theranostics of prostate cancer: from molecular imaging to precision molecular radiotherapy targeting the prostate specific membrane antigen. Br J Radiol. 2018 Nov;91(1091):20180308.
  2. Barber TW, Singh A, Kulkarni HR, Niepsch K, Billah B, Baum RP. Clinical Outcomes of (177)Lu-PSMA Radioligand Therapy in Earlier and Later Phases of Metastatic Castration-Resistant Prostate Cancer Grouped by Previous Taxane Chemotherapy. J Nucl Med. 2019 Jul;60(7):955-962.
  3. Edler von Eyben F, Singh A, Zhang J, Niepsch K, Meyrick D, Lenzo N, Kairemo K, Joensuu T, Virgolini I, Soydal C, Kulkarni HR, Baum RP. (177)Lu-PSMA radioligand therapy of predominant lymph node metastatic prostate cancer. Oncotarget. 2019 Mar 29;10(25):2451-2461.
  4. Sathekge M, Bruchertseifer F, Vorster M, Lawal I, Knoesen O, Mahapane J, Davis C, Reyneke F, Maes A, Kratochwil C, Lengana T, Giesel F, Van de Wiele C, Morgenstern A. Predictors of overall and disease free survival in metastatic castration-resistant prostate cancer patients receiving (225)Ac-PSMA-617 radioligand therapy. J Nucl Med. 2019 May 17.