Episode 22: PSMA-based radioligand therapy: a new treatment modality for patients with metastatic castration-resistant prostate cancer

In this new episode of ‘What’s New Doc’ in Prostate cancer, Prof Bertrand Tombal from the Cliniques Universitaires Saint-Luc in Brussels and Prof Steven Joniau from the University Hospitals Leuven discuss the use of PSMA-based radioligand therapy in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).

The basis for this discussion was formed by the results of the phase III VISION and PSMAfore trials, evaluating ¹⁷⁷Lu-PSMA-617 in previously treated mCRPC patients.^1,2 In the VISION study ¹⁷⁷Lu-PSMA-617 significantly prolonged the radiographic progression-free and overall survival compared to standard of care in PSMA-positive mCRPC patients who previously received at least one androgen-receptor-pathway inhibitor (ARPI) and one or two taxane regimens.¹ In PSMAfore, a significant benefit in radiographic progression-free survival was reported with ¹⁷⁷Lu-PSMA-617 vs. an ARPI change in PSMA-positive, taxane-naïve mCRPC patients with disease progression after one second-generation ARPI.²

Notwithstanding the fact that these studies did not always use an optimal treatment strategy in the comparator arm, these results are convincing enough for Prof Tombal and Prof Joniau to expect that PSMA-based radioligand therapy will become an integral part of the prostate cancer treatment algorithm. In the short term, PSMA-based radioligand therapy will likely become a standard of care for PSMA-positive, BRCA-wildtype mCRPC patients with disease progression on an ARPI (and a taxane). The latter is further supported by the results of a phase II study reported by Hofman et al., indicating a lower incidence of adverse events and a superior PSA response with ¹⁷⁷Lu-PSMA-617 than with cabazitaxel in mCRPC patients for whom cabazitaxel was considered the next appropriate standard treatment.³ In addition to this, several studies are currently underway evaluating the potential of this treatment modality in earlier disease stages.