Lutetium-177 PSMA Radioligand Therapy for Abiraterone-Resistant Prostate Cancer

Evidence for Disease Control

The National Comprehensive Cancer Network recommends Lutetium-177 PSMA-617 as a treatment option for patients with abiraterone-resistant metastatic castration-resistant prostate cancer, resulting in improved progression-free survival from 3.4 months to 8.7 months (HR 0.40, 99.2% CI 0.29-0.57, P<0.001) 1
The American Urological Association provides a Strong Recommendation (Evidence Level Grade B) for offering Lu-177-PSMA-617 to progressive mCRPC patients with prior docetaxel and androgen pathway inhibitor exposure who have positive PSMA PET imaging, leading to extended overall survival from 11.3 months to 15.3 months (HR 0.62, 95% CI 0.52-0.74, P<0.001) 1, 2

The National Comprehensive Cancer Network suggests that patients with metastatic castration-resistant prostate cancer should have prior treatment with at least one androgen receptor pathway inhibitor (abiraterone or enzalutamide) and prior treatment with at least one taxane-based chemotherapy (docetaxel) before receiving Lu-177-PSMA-617 1
The Journal of Clinical Oncology recommends obtaining PSMA PET imaging using Ga-68 PSMA-11, F-18 piflufolastat, or F-18 flotufolastat to confirm at least one PSMA-positive metastatic lesion 3

The National Comprehensive Cancer Network designates Lu-177-PSMA-617 as a Category 1 treatment option, with a standard regimen of 7.4 GBq (200 mCi) intravenously every 6 weeks, for 4-6 cycles total 1
The American Urological Association recommends mandatory concurrent therapy with bone-protecting agents (denosumab or zoledronic acid) to reduce fracture risk, based on PEACE III trial data showing fracture rates of 2.8% with bone protection versus 45.9% without 4

The National Comprehensive Cancer Network provides a Category 1 Recommendation for Lu-177-PSMA-617 as a treatment option for patients meeting the eligibility criteria, with a high level of evidence 1
The American Urological Association and the American Society of Clinical Oncology support the use of Lu-177-PSMA-617 for patients with progressive mCRPC and positive PSMA PET imaging, with a Strong Recommendation (Evidence Level Grade B) 2, 3

Lutetium-177 PSMA-617 therapy is strongly recommended for patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel and androgen pathway inhibitor treatment and have PSMA-positive disease confirmed by imaging, as recommended by the American Urological Association 5
Lutetium-177 PSMA-617 therapy is indicated for patients with progressive mCRPC after prior treatment with at least one androgen receptor pathway inhibitor and taxane-based chemotherapy, according to the European Association of Urology 5
Patients with bone-predominant metastatic disease may benefit from Lutetium-177 PSMA-617 therapy, as suggested by the European Society for Medical Oncology 6
The American Society of Clinical Oncology recommends Lutetium-177 PSMA-617 therapy for patients with limited response to previous standard therapies 5

The TheraP trial showed superior PSA response rates with Lutetium-177 PSMA-617 (66%) compared to cabazitaxel (37%) in patients previously treated with docetaxel, as reported by the National Comprehensive Cancer Network 7

Standard treatment consists of 4-6 cycles of Lutetium-177 PSMA-617 at 6-week intervals, as recommended by the European Association of Urology 8
Pre-treatment assessment should include complete blood count, renal and hepatic function tests, and performance status evaluation, according to the American College of Radiology 8

Combination approaches, such as combining Lutetium-177 PSMA-617 with bone-targeted agents, should be used with caution, as advised by the European Society for Medical Oncology 6
The American Society of Clinical Oncology recommends starting bone-targeted agents before Lutetium-177 PSMA therapy to reduce fracture risk 6

Regular monitoring during treatment should include PSA levels before each cycle, complete blood count, renal and hepatic function, and clinical assessment for symptoms and adverse events, as recommended by the National Comprehensive Cancer Network 8

The European Society for Medical Oncology (ESMO) guidelines recommend continuing abiraterone during Lutetium-177 PSMA-617 therapy, with a high benefit score (ESMO-MCBS v1.1 score: 4), in men with cancer expressing PSMA on PET-PSMA and without PSMA non-expressing lesions who have received a novel androgen receptor axis inhibitor and docetaxel 9
The American Urological Association (AUA) and Society of Urologic Oncology (SUO) guidelines provide a Strong Recommendation (Evidence Level: Grade B) for Lu-177-PSMA-617 in patients with progressive mCRPC having previously received docetaxel and androgen pathway inhibitor, without any instruction to discontinue the androgen pathway inhibitor 10

The National Comprehensive Cancer Network (NCCN) recommends maintaining abiraterone with prednisone at standard dosing of 1,000 mg daily (or 500 mg with low-fat breakfast) plus prednisone 5 mg twice daily during Lu-177 PSMA-617 treatment 11, 12
Administer Lu-177 PSMA-617 at 7.4 GBq (200 mCi) every 6 weeks for 4-6 cycles, as recommended by the Journal of Urology 10

The VISION trial demonstrated overall survival improvement (15.3 vs 11.3 months, HR 0.62, 95% CI 0.52-0.74, P<0.001) and progression-free survival improvement (8.7 vs 3.4 months, HR 0.40, 99.2% CI 0.29-0.57, P<0.001) with continued abiraterone during Lu-177 PSMA-617 therapy 9, 10

Monitor liver function, potassium, phosphate, and blood pressure monthly during abiraterone therapy, as recommended by the NCCN 11, 12
Perform PSMA PET imaging at baseline and after completion of Lu-177 therapy or at PSA progression, as recommended by the Journal of Urology 10