Predictors of Response to Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with ¹⁷⁷Lu-PSMA-617

Abstract

Radioligand therapy (RLT) with 177 Lu-PSMA-617 (PSMA is prostatespecific membrane antigen) is a novel targeted therapy for metastatic prostate cancer. In this study, we evaluated the effect of different pretherapeutic parameters on the therapeutic response measured by prostate-specific antigen (PSA) 2 mo after RLT. Methods: RLT was performed in 40 hormone-refractory patients with distant metastases and progressive disease (mean age, 71.4 y). 68 Ga-PSMA-11 PET/CT was performed in all patients 1-2 wk before RLT. All patients were treated with a mean of 6 GBq. The SUV max of tumor lesions was determined using region-of-interest analysis. Complete blood counts, renal and liver function assessments, previous therapies, pain medication, and SUVs were included in the analysis. PSA was assessed 2 mo after RLT. Results: In the univariate analysis, younger age, higher levels of g-glutamyl transferase, lower pretherapeutic hemoglobin, a higher Gleason score, a higher number of platelets, higher C-reactive protein, regular need for pain medication, and higher lactate dehydrogenase had a negative impact on the therapeutic response; however, the multivariate analysis revealed that the most significant independent factors were the number of platelets and regular need for pain medication. The response was independent of the amount of PSMA uptake as well as previous therapies and other measured factors. Conclusion: A PSA decline of more than 50% was observed significantly more in patients without a regular need for analgesics.

Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

“…Cutoffs of PSMA intensity on 68 Ga‐PSMA below which 177 Lu PSMA therapy may not be effective have not yet been established. A recent study of 40 patients identified platelet level and the need for pain relief as the most significant predictor of poor response to 177 LU‐PSMA, likely reflective of the burden of metastatic bone disease 26. This same study did not find that intensity of PSMA activity on 68 Ga‐PSMA staging PET/CT was predictive of response, but this is likely because intense PSMA activity on 68 Ga‐PSMA imaging was one of the inclusion criteria for receiving 177 Lu PSMA therapy initially 26.…”

“…A recent study of 40 patients identified platelet level and the need for pain relief as the most significant predictor of poor response to 177 LU‐PSMA, likely reflective of the burden of metastatic bone disease 26. This same study did not find that intensity of PSMA activity on 68 Ga‐PSMA staging PET/CT was predictive of response, but this is likely because intense PSMA activity on 68 Ga‐PSMA imaging was one of the inclusion criteria for receiving 177 Lu PSMA therapy initially 26. Other studies have commented that bone metastases appear to respond less well than visceral or lymph nodal disease to treatment with Lu PSMA 3…”

Theranostics in nuclear medicine practice

“…Nuclear targeted therapies play an essential role, especially in patients with advanced neuroendocrine tumors, such as gastroenteropancreatic (GEP) tumors, bronchopulmonary neuroendocrine tumors, pheochromocytoma, and neuroblastoma 10,11,20,22–27. Furthermore, there are positive results with radioligand therapies in metastatic PC and metastatic melanoma 8,13,19,28,29…”

“…In fact, nearly 70% of patients have benefited from this therapy 13,28,85–90. Dosimetry studies have shown that the most critical organs are the kidneys, with a maximum kidney radiation dose of 0.88 Gy/GBq for [ 177 Lu]Lu-PSMA-617 and 0.93 Gy/GBq for [ 177 Lu]Lu-PSMA-I&T 91,92.…”

From NETTER to PETTER: PSMA-Targeted Radioligand Therapy

“…Initial clinical experience was followed by multiple relatively small single-institution studies reporting on initial clinical experience with 177 Lu-PSMA RLT (3)(4)(5)(6)(7)(8). However, these studies included a wide range of patients with varying initial and subsequent treatments, different disease stages, and variable study endpoints.…”