Treatment for Recurrent Metastatic Castration-Resistant Prostate Cancer with PSMA Expression

Introduction to Treatment Options

The European Society for Medical Oncology (ESMO) assigns 177Lu-PSMA-617 a high score (4m on Form 2a) for clinical benefit in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy 1

The National Comprehensive Cancer Network (NCCN) recommends docetaxel-based chemotherapy as a first-line option after AR pathway inhibitor failure, demonstrating improved overall survival with a median OS of 16.3 months (OS gain: 2.9 months; HR: 0.79) 1
The NCCN suggests 177Lu-PSMA-617 as a preferred second-line option for patients with PSMA-positive disease, providing significant survival benefit (HR: 0.62) 1
Cabazitaxel + prednisone is an effective second-line option after docetaxel failure, with a median OS of 12.7 months (OS gain: 2.4 months; HR: 0.70) 1
Abiraterone + prednisone can be used as a second-line option if not previously used, providing an OS gain of 4.6 months (HR: 0.74) after docetaxel failure 4
Enzalutamide can be used as a second-line option if not previously used, providing an OS gain of 4.8 months (HR: 0.53-0.75) after docetaxel therapy 1

Molecular testing, including MSI/MMR and HRR gene mutations, is crucial for identifying patients who may benefit from targeted therapies, as recommended by the NCCN 2
Continuation of ADT with an LHRH agonist or antagonist is essential to maintain castrate serum testosterone levels (<50 ng/dL) throughout all treatment phases, as suggested by the NCCN 2

Regular PSA monitoring is necessary to assess treatment response, as recommended by the NCCN 2
Imaging studies should be used to evaluate disease progression, with the NCCN suggesting regular monitoring 2
Treatment-specific adverse effects should be monitored, including Grade 3 adverse events with 177Lu-PSMA-617, which occurred in 52.7% of patients 1
The NCCN recommends monitoring for neutropenia, fatigue, and anemia with docetaxel 2
Cabazitaxel requires monitoring for neutropenia and gastrointestinal effects, as suggested by the ESMO 1

The NCCN advises against discontinuing ADT, as maintaining castrate testosterone levels is essential even when adding other therapies 2, 4
The NCCN recommends against repeating failed therapy, except in specific cases such as docetaxel rechallenge after progression on novel hormone therapy 5
The NCCN emphasizes the importance of molecular testing for MSI/MMR and HRR gene mutations to identify patients who may benefit from targeted therapies 2