Theranostics in the management of prostate cancer: from concept to clinical practice.

Abstract

Introduction: Radiotheranostics, integrating diagnostic imaging with targeted radiotherapy using molecularly matched radioactive agents, has emerged as a transformative approach in the management of prostate cancer. Prostate-specific membrane antigen (PSMA) is the dominant clinically validated target, and PSMA-targeted radioligand therapy has rapidly reshaped the treatment landscape across disease states.

Areas covered: This is a comprehensive overview of the prostate cancer theranostics landscape, with a primary focus on PSMA. We synthesized evidence from landmark randomized trials, guideline documents, and emerging data on alpha-emitting agents, combination strategies, and next-generation constructs. Literature search encompassed pivotal phase II/III trials, guideline documents, and contemporary mechanistic studies. Patient selection, distinguishing clinical-trial eligibility, regulatory indications, and guideline recommendations, is critically appraised.

Expert opinion: PSMA-targeted radioligand therapy has fundamentally reshaped the treatment paradigm, with [¹⁷⁷Lu]Lu-PSMA-617 established in PSMA-positive metastatic castration-resistant prostate cancer and now expanding into earlier disease states, including metastatic hormone-sensitive prostate cancer. The future lies in biomarker refinement, rational combinations with poly(ADP-ribose) polymerase inhibitors, androgen receptor pathway inhibitors, and immunotherapy, and next-generation platforms including alpha-emitters and bispecific agents. Multidisciplinary integration and structured monitoring will be essential for optimizing outcomes as theranostics becomes a sequence-defining therapeutic platform.