Prostate Cancer: Systemic Therapy by Disease State

Prostate Cancer: Systemic Therapy by Disease State: overview

This algorithm sequences systemic therapy for prostate cancer by disease state. In metastatic hormone-sensitive prostate cancer (mHSPC), the chart offers doublet therapy with ADT plus an androgen receptor pathway inhibitor (ARPI), supported by TITAN and ARCHES, or triplet therapy with ADT plus docetaxel plus darolutamide (ARASENS) or ADT plus abiraterone plus docetaxel (PEACE-1). The site's PEACE-1 summary describes the abiraterone triplet as the most intensified standard for fit patients with de novo high-volume disease. For nonmetastatic castration-resistant disease (nmCRPC, M0), the options are apalutamide (SPARTAN), enzalutamide (PROSPER) or darolutamide (ARAMIS), each of which prolonged metastasis-free and overall survival versus placebo.

In metastatic castration-resistant prostate cancer (mCRPC), choices include abiraterone or enzalutamide if not used earlier, docetaxel then cabazitaxel (CARD), 177Lu-PSMA-617 (VISION), a PARP inhibitor for HRR mutations (PROfound), radium-223 for bone-only disease (ALSYMPCA) and pembrolizumab for MSI-high or dMMR tumors (KEYNOTE-158). CARD supports cabazitaxel over a sequential ARPI switch after docetaxel and abiraterone or enzalutamide.

Trials behind this algorithm

Titan Trial Chi KN et al, NEJM, 2019, PMID: 31150574
ARASENS trial, Docetaxel+ADT +/- Darolutamide Smith MR et al, NEJM, 2022; PMID: 35179323
PEACE-1 Fizazi K et al, Lancet, 2022; PMID: 35405085
SPARTAN Smith MR et al, NEJM, 2018; PMID: 29420164
PROSPER Hussain M et al, NEJM, 2018; PMID: 29949494
ARAMIS Fizazi K et al, NEJM, 2020; PMID: 32905676
Affirm Trial Scher HI et al, NEJM, 2012, PMID 22894553
CARD de Wit R et al, NEJM, 2019; PMID: 31566937
Vision Trial Sartor O et al, NEJM, 2021, PMID: 34161051
PROfound de Bono J et al, NEJM, 2020; PMID: 32343890
ALSYMPCA Parker C et al, NEJM, 2013; PMID: 23863050
KEYNOTE-158 Marabelle A et al, Lancet Oncol, 2020; PMID: 32919526

Background reading: Prostate cancer board review notes.

Prostate Cancer: Systemic Therapy by Disease State: the algorithm in words

Starting point: Prostate cancer systemic therapy by disease state. Full background: Prostate cancer notes.

mHSPC (first-line): Doublet: ADT + ARPI (TITAN / ARCHES); Triplet: ADT + docetaxel + darolutamide (ARASENS); Triplet: ADT + abiraterone + docetaxel (PEACE-1).
nmCRPC (M0) (first-line): ARPI: Apalutamide (SPARTAN); ARPI: Enzalutamide (PROSPER); ARPI: Darolutamide (ARAMIS).
mCRPC (second-line): ARPI: Abiraterone / enzalutamide (if not used earlier); Taxane: Docetaxel → cabazitaxel (CARD); PSMA: 177Lu-PSMA-617 (VISION); HRR mut: PARP inhibitor (PROfound); Bone-only: Radium-223 (ALSYMPCA); MSI-H: Pembrolizumab (dMMR / MSI-high).