Optimizing the treatment pathway in post-docetaxel mCRPC: PSMA-RLT vs cabazitaxel
In brief
PSMA radioligand therapy causes fewer severe side effects than cabazitaxel
A review found severe side effects in 33% of patients receiving lutetium-177 PSMA therapy versus 53% with cabazitaxel; the randomized TheraP trial also found higher PSA response rates, but no overall survival difference. Observational studies reported longer survival with PSMA therapy, though those findings are not randomized evidence. Patient selection, access and treatment sequencing remain important open questions.
- Journal
- Cancer treatment reviews (Q1)
- Published
- 21 September 2026
- Study design
- Narrative review / expert opinion
- Evidence level
- Level 5, Expert Opinion (CEBM 5)
- Authors
- Francesco Mattana, Erica Palesandro, Valentino Dragonetti, Giuseppe Curigliano, Marcello Tucci, Francesco Ceci
- PMID
- 42800445
- DOI
- 10.1016/j.ctrv.2026.103216
Why clinicians should know about it
- Picked for Urology (paper of the day, 2 October 2026): Optimizing treatment pathway post‑docetaxel mCRPC: PSMA‑RLT vs cabazitaxel
Abstract
BACKGROUND: The management of metastatic castration-resistant prostate cancer (mCRPC) after progression on androgen receptor pathway inhibitors (ARPI) and docetaxel presents a critical therapeutic choice between cabazitaxel and [177Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT). This review provides a comprehensive analysis of efficacy, toxicity, biomarkers, and treatment sequencing to guide clinical decision-making. METHODS: A critical review of the scientific literature was conducted, integrating data from randomized clinical trials, real-world evidence (RWE) studies, and preliminary data presented at major scientific conferences. FINDINGS: The head-to-head phase II TheraP trial demonstrated superior PSA response rates (66% vs 37%) and progression-free survival for [177Lu]Lu-PSMA-617 over cabazitaxel, without significant difference in overall survival (OS). In contrast, large RWE studies, including the ARON-3 study, consistently show a significant OS advantage for [177Lu]Lu-PSMA-617 (median OS 20.2 vs 14.8 months). [177Lu]Lu-PSMA-617 is associated with a more favorable safety profile, with a lower incidence of grade 3-4 adverse events (33% vs 53%) and superior patient-reported quality of life compared to cabazitaxel. PSMA-PET imaging serves as a key predictive biomarker, with a high SUVmean (≥10) identifying patients with the highest probability of response to PSMA-RLT. While both treatment sequences are clinically valid, a biological rationale may favor a PSMA-RLT -first approach. However, also cost-effectiveness analyses and local barriers play a role in the selection of the treatment pathway. CONCLUSION: Available data suggest [177Lu]Lu-PSMA-617 as the preferred therapeutic option for the majority of patients with PSMA-positive mCRPC who progressed to ARPI and docetaxel. PSMA-RLT is preferred for most PSMA positive patients, with eligibility assessed individually rather than by rigid thresholds. Cabazitaxel remains a crucial treatment for patients with low PSMA expression, those ineligible for PSMA-RLT, or as an effective sequential therapy. Modern management of mCRPC demands a personalized, multidisciplinary approach to optimally balance survival gain with quality of life.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.