[¹⁷⁷Lu]Lu-PSMA-617 in Metastatic Hormone-Sensitive Prostate Cancer: Evidence from PSMAddition and Considerations for Treatment Sequencing.
- 1Associazione O.R.A. ETS-Oncology Research Assistance, 84134 Salerno, Italy.
- 2School of Medicine, UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy.
Abstract
Introducing [¹⁷⁷Lu]Lu-PSMA-617 into metastatic hormone-sensitive prostate cancer (mHSPC) raises questions about patient selection and treatment sequencing. This non-systematic narrative review examines PSMAddition alongside evidence on alternative treatments, prostate-specific membrane antigen (PSMA) imaging, safety, and subsequent therapy. In the peer-reviewed analysis, with a data cutoff of 13 January 2025, adding radioligand therapy to androgen-deprivation therapy and an investigator-selected androgen receptor pathway inhibitor improved radiographic progression-free survival (hazard ratio 0.72; 95% confidence interval 0.58-0.90). Overall survival was immature and did not meet the prespecified interim significance threshold (hazard ratio 0.84; 95% confidence interval 0.63-1.13). A subsequent non-peer-reviewed sponsor update supported the radiographic findings, although the updated analysis was not controlled for type I error and overall survival remained immature. Radioligand intensification increased grade ≥3 adverse events (51% versus 43%). Prespecified composite quality-of-life and pain endpoints showed no statistically significant differences, although their interpretation is limited by the inclusion of progression or death. Control-arm crossover after progression was optional. Direct mHSPC evidence is distinguished from contextual castration-resistant evidence. Neither a preferred hormonal partner nor superiority over docetaxel-containing triplet therapy has been established. A non-prescriptive five-domain framework integrates target expression, disease characteristics, patient fitness, subsequent treatment options, and delivery capacity to support multidisciplinary assessment.
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BibTeX
@article{buonerba2026¹⁷⁷lulupsma617,
title = {{[¹⁷⁷Lu]Lu-PSMA-617 in Metastatic Hormone-Sensitive Prostate Cancer: Evidence from PSMAddition and Considerations for Treatment Sequencing.}},
author = {Carlo Buonerba and Giuseppe Di Lorenzo},
journal = {Current oncology (Toronto, Ont.)},
year = {2026},
month = oct,
doi = {10.3390/curroncol33100624},
url = {https://europepmc.org/article/MED/42930191},
note = {CC BY},
}
RIS
TY - JOUR
TI - [¹⁷⁷Lu]Lu-PSMA-617 in Metastatic Hormone-Sensitive Prostate Cancer: Evidence from PSMAddition and Considerations for Treatment Sequencing.
AU - Carlo Buonerba
AU - Giuseppe Di Lorenzo
PY - 2026
DA - 2026/10/16
JO - Current oncology (Toronto, Ont.)
DO - 10.3390/curroncol33100624
UR - https://europepmc.org/article/MED/42930191
AB - Introducing [¹⁷⁷Lu]Lu-PSMA-617 into metastatic hormone-sensitive prostate cancer (mHSPC) raises questions about patient selection and treatment sequencing. This non-systematic narrative review examines PSMAddition alongside evidence on alternative treatments, prostate-specific membrane antigen (PSMA) imaging, safety, and subsequent therapy. In the peer-reviewed analysis, with a data cutoff of 13 January 2025, adding radioligand therapy to androgen-deprivation therapy and an investigator-selected androgen receptor pathway inhibitor improved radiographic progression-free survival (hazard ratio 0.72; 95% confidence interval 0.58-0.90). Overall survival was immature and did not meet the prespecified interim significance threshold (hazard ratio 0.84; 95% confidence interval 0.63-1.13). A subsequent non-peer-reviewed sponsor update supported the radiographic findings, although the updated analysis was not controlled for type I error and overall survival remained immature. Radioligand intensification increased grade ≥3 adverse events (51% versus 43%). Prespecified composite quality-of-life and pain endpoints showed no statistically significant differences, although their interpretation is limited by the inclusion of progression or death. Control-arm crossover after progression was optional. Direct mHSPC evidence is distinguished from contextual castration-resistant evidence. Neither a preferred hormonal partner nor superiority over docetaxel-containing triplet therapy has been established. A non-prescriptive five-domain framework integrates target expression, disease characteristics, patient fitness, subsequent treatment options, and delivery capacity to support multidisciplinary assessment.
SN - 1198-0052
SN - 1718-7729
ER -