Salvage Radioligand Therapy with Repeated Cycles of 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer with Diffuse Bone Marrow Involvement

Abstract

Advanced stage metastatic prostate cancer with extensive bone marrow involvement is associated with a high risk of therapy-induced myelotoxicity and unfavorable outcomes. The role of salvage radioligand therapy (RLT) with 177Lu-PSMA-617 in this subset of patients remains to be further elucidated. Forty-five patients with progressive metastatic castration-resistant prostate cancer (mCRPC) and diffuse bone marrow involvement were treated with repeated cycles of RLT after having exhausted standard treatment options. A mean treatment activity of 7.4 ± 1.4 GBq 177Lu-PSMA-617 was administered in a median of four treatment cycles (IQR 2-6) and the mean cumulative activity was 32.6 ± 20.1 GBq. After two RLT cycles, ≥50% PSA decline was observed in 25/45 (56%) patients and imaging-based partial remission (PR) was observed in 18/45 (40%) patients. Median imaging-based progression-free survival (PFS) was 6.4 mo (95% CI, 3.0–9.8) and the median overall survival (OS) was 10.2 months (95% CI, 7.2–12.8). The biochemical response translated into a significantly prolonged PFS (12.9 vs. 2.8 mo, p < 0.001) and OS (13.5 vs. 6.7 mo, p < 0.001). Patients with PR on interim imaging after two cycles had a longer median OS compared to patients with stable or progressive disease (15.5 vs. 7.1 mo, p < 0.001). Previous taxane-based chemotherapy (HR 3.21, 95%CI 1.18–8.70, p = 0.02) and baseline LDH levels (HR 1.001, 95%CI 1.000–1.001, p = 0.04) were inversely associated with OS on a Cox-regression analysis. Grade ≥ 3 hematological decline was observed after 22/201 (11%) cycles with anemia, leukopenia and thrombocytopenia in 15/45 (33%), 6/45 (13%) and 8/45 (18%) patients, respectively. Cumulative treatment activity and absorbed whole-body dose were not correlated with new onset grade ≥ 3 hematotoxicity (p = 0.91, p = 0.69). No event of grade ≥ 3 chronic kidney disease was observed during RLT or the follow-up. Last line RLT with 177Lu-PSMA-617 in mCRPC patients with diffuse bone marrow involvement may thus contribute to prolonged disease control at an acceptable safety profile.

Safety and Efficacy of 177Lutetium-PSMA-617 Radioligand Therapy Shortly after Failing 223Radium-Dichloride

“…The significance of initial PSA response (≥50% after 4 weeks) to 177 Lu-PSMA-617 as a positive predictor of outcome remains controversial. A few studies in heterogeneous patient cohorts showed a longer OS in patients with early PSA response [13,21,25], whereas other studies reported no significantly longer survival in early responders [23,26]. In a study by Leibowitz et al on 24 elderly patients at >75 years of age, 14 of whom previously treated with 223 Ra, a PSA decline of ≥ 50% was associated with a significantly longer OS (10.9 vs. 3.1 months, p = 0.0006) [13].…”

The global status of research in prostate cancer bone metastasis: A bibliometric and visualized analysis

“…For example, 177Lu-PSMA-617 can accurately deliver radiation to PSMA-positive PCa cells without damaging surrounding healthy tissues. As a result, RLT effectively prolongs the OS of advanced CRPC and bone metastasis, significantly delaying the progression of disease symptoms (28)(29)(30).…”

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen

“…A constant challenge to treating prostate cancer is acquired resistance to hormone therapy and treatment with docetaxel [ 6 ]. Many patients with advanced cancer become unresponsive to ADTs, referred to as having metastatic castration-resistant prostate cancer (mCRPC) which has shown positive treatment response with lutetium-177 ( 177 Lu)-prostate-specific membrane antigen (PSMA)-617 [ 6 ]. It is a radioligand therapy that uses a β-emitting radioisotope lutetium-177 which is added to the ligand PSMA-617.…”

“…An increase or decrease in prostate-specific antigen (PSA) levels from a baseline value is used to determine treatment success or failure [ 4 ]. Several studies included in this review reported notable decreases in PSA levels [ 6 , 8 , 9 , 10 ]. Further, studies that examined the efficacy and safety of 177 Lu-PSMA-617 proved it to be promising [ 6 , 10 , 11 ].…”

“…Several studies included in this review reported notable decreases in PSA levels [ 6 , 8 , 9 , 10 ]. Further, studies that examined the efficacy and safety of 177 Lu-PSMA-617 proved it to be promising [ 6 , 10 , 11 ]. Although 177 Lu-PSMA-617 has shown notable results in the treatment of mCRPC, there is no consensus on its dose schedule.…”