PRRT in Prostate Cancer: Current Indications
177Lu-PSMA-617 is the only approved PSMA-targeted peptide receptor radionuclide therapy (PRRT) for prostate cancer, indicated specifically for adult patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have already received both androgen receptor pathway inhibition and taxane-based chemotherapy. 1
Specific Patient Selection Criteria
Treatment with 177Lu-PSMA-617 requires documented PSMA expression on PET imaging without PSMA non-expressing lesions. 1 This imaging prerequisite is essential because the therapy targets PSMA receptors on tumor cells, and heterogeneous or absent PSMA expression will result in treatment failure.
Position in Treatment Algorithm
PRRT with 177Lu-PSMA-617 is positioned as a third-line or later therapy for mCRPC, specifically after patients have progressed through: 1
- First requirement: Novel androgen receptor axis inhibitor (abiraterone or enzalutamide) 2, 1
- Second requirement: Taxane-based chemotherapy (docetaxel) 2, 1
The European Society for Medical Oncology assigns this indication a Level I, Grade A recommendation with an ESMO-MCBS score of 4, reflecting high-quality evidence. 1
Clinical Efficacy Data
The approval is based on demonstrated survival benefit showing: 1
- Median overall survival gain of 4.0 months (11.3 months vs 7.3 months)
- Hazard ratio of 0.62 (95% CI 0.52-0.74)
Alternative Third-Line Options
For patients in the same treatment setting (post-androgen receptor inhibitor and post-docetaxel), cabazitaxel remains an alternative option with Level I, Grade A evidence and ESMO-MCBS score of 3. 1 The choice between 177Lu-PSMA-617 and cabazitaxel should be guided by PSMA expression status on imaging, patient fitness for additional chemotherapy, and prior treatment toxicities.
Important Caveats
PRRT is NOT indicated for: 2, 3
- Hormone-naïve metastatic prostate cancer (use ADT ± docetaxel instead)
- First-line mCRPC (use abiraterone or enzalutamide)
- Chemotherapy-naïve mCRPC (use abiraterone, enzalutamide, or docetaxel)
- Bone-predominant symptomatic mCRPC without visceral metastases (consider radium-223 instead) 2
The 2015 ESMO guidelines do not mention PRRT because 177Lu-PSMA-617 was not yet approved at that time. 2 The treatment landscape has evolved significantly, with PSMA-targeted therapy now representing a major advance for heavily pretreated mCRPC patients with PSMA-expressing tumors. 1
Monitoring Requirements
While specific monitoring protocols for 177Lu-PSMA-617 are not detailed in the provided guidelines, renal function assessment is critical during PRRT as kidneys are the "critical organ" due to glomerular filtration and tubular reabsorption of radiolabeled peptides. 4 Patients require baseline and serial monitoring with precise GFR measurements using Tc-99m-DTPA or Cr-51-EDTA rather than serum creatinine alone, particularly in those with preexisting renal disease, hypertension, diabetes, or prior nephrotoxic chemotherapy. 4