Management of Metastatic Prostate Cancer

Treatment Sequencing in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

The American Urological Association and Society of Urologic Oncology guidelines provide a strong recommendation (Evidence Level: Grade B) for continuing effective docetaxel therapy until disease progression occurs in patients with metastatic prostate cancer 1, 2
The National Comprehensive Cancer Network recommends that patients continue receiving docetaxel for up to 10 cycles if there is no disease progression and no prohibitive toxicities 3
The American Urological Association and Society of Urologic Oncology guidelines provide a strong recommendation (Evidence Level: Grade B) for Lu-177 PSMA-617 only after disease progression on docetaxel 1
The National Comprehensive Cancer Network guidelines recommend Lu-177 PSMA-617 as a category 1 option only for patients who have been previously treated with androgen receptor-directed therapy and taxane-based chemotherapy 4

The phase 3 VISION study demonstrated that Lu-177 PSMA-617 improved both progression-free survival (8.7 vs 3.4 months) and overall survival (15.3 vs 11.3 months) compared to standard of care alone in patients who had previously failed docetaxel 1, 2
Before considering Lu-177 PSMA-617, patients must undergo PSMA PET imaging to confirm PSMA-positive disease 1, 4
Lu-177 PSMA-617 is specifically indicated for PSMA-positive M1 CRPC that has progressed after androgen receptor pathway inhibition and taxane-based chemotherapy 4

For patients on docetaxel without PSA progression or new symptoms, imaging should be performed at least annually to monitor for radiographic progression 1, 2
Approximately 24.5% of mCRPC patients may have radiographic progression without PSA progression, highlighting the importance of routine imaging 1

Patients must have at least one PSMA-positive metastatic lesion and no dominant PSMA-negative metastatic lesions on Ga-68 PSMA-11 PET/CT imaging 4
PSMA-negative lesions are defined as metastatic disease that lacks PSMA uptake including bone with soft tissue components ≥1.0 cm, lymph nodes ≥2.5 cm in short axis, and solid organ metastases ≥1.0 cm in size 4

The TheraP trial showed higher PSA response rates with Lu-177 PSMA-617 compared to cabazitaxel in patients previously treated with docetaxel (66% vs 37%) 5, 6

Switching from an effective therapy prematurely can compromise disease control and patient outcomes 1, 2
Not performing regular imaging during treatment may miss radiographic progression in patients without PSA progression 1
Using Lu-177 PSMA-617 before docetaxel failure is not supported by current guidelines and may limit future treatment options 1, 4