Prostate Cancer Management

Introduction to PSMA-Targeted Therapies

The National Comprehensive Cancer Network recommends 177Lu-PSMA-617 therapy for patients with confirmed PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) without dominant PSMA-negative lesions, showing significant survival benefits (median OS of 15.3 vs 11.3 months) 1, 2

Patients should have at least one PSMA-positive lesion with no dominant PSMA-negative metastatic lesions to be considered for PSMA-targeted therapies like 177Lu-PSMA-617 1
PSMA-negative lesions are defined as metastatic disease lacking 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 1
Homogeneous PSMA expression, indicated by uniform uptake of PSMA-targeted radiotracers across all lesions on PET imaging, is essential for effective PSMA-targeted therapies like 177Lu-PSMA-617 3, 4

The FDA has approved Ga-68 PSMA-11 for use with Lu-177-PSMA-617, but F-18 piflufolastat PSMA and F-18 flotufolastat PSMA can also be used due to equivalency of these imaging agents 1
False-negatives and false-positives can occur with PSMA PET imaging, highlighting the need for careful assessment and interpretation of imaging results 3
Technical factors such as imaging protocols and timing can affect the assessment of PSMA expression homogeneity, and should be carefully considered when evaluating patients for PSMA-targeted therapies 3

Prior treatments, especially androgen pathway inhibitors, may affect PSMA expression patterns, and should be taken into account when evaluating patients for PSMA-targeted therapies 2
Treatment history, particularly with androgen receptor pathway inhibitors, may alter PSMA expression patterns, and should be carefully considered when selecting patients for treatment 2
For patients with heterogeneous PSMA expression, consider alternative therapies such as conventional systemic therapies (chemotherapy, androgen receptor pathway inhibitors) or targeted therapies based on molecular profiling (e.g., PARP inhibitors for BRCA mutations) 1