Lutetium-177-PSMA-617 radioligand therapy in patients with high volume metastatic prostate cancer prior to chemotherapy and new generation androgen deprivation therapy: Clinical Experience

Hell J Nucl Med. 2023 Sep-Dec;26(3):187-193. doi: 10.1967/s002449912603. Epub 2023 Dec 14.

Abstract

Objective: We aimed to evaluate the efficacy oflutetium-177-prostate-specific membrane antigen-617 (177Lu-PSMA-617) with the luteinizing hormone releasing hormone (LHRH) analogues in the first or in the second-line setting formetastatic castration sensitive patients and metastatic castration resistance after progression with LHRH analogues.

Subjects and methods: Sixteen consecutive patients with high volume metastatic prostate cancer undergone 177Lu-PSMA-617 therapy who were refused chemotherapy and were unable to use new generation anti-androgen drugs because of unavailibility of reimbursement, were included in this retrospective study. Prostate specific antigen (PSA) response (>50% decrease), disease control rate (DCR: complete or partial response), progression-free survival (PFS) and overall survival (OS) were calculated to evaluate according to the clinicopathological features of the patients. Treatment response evaluated by 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT).

Results: Mean age was 74,6 (SD±8,36). Among them, 7 (43,8%) patients has castration resistant disease, while the remaining has castration sensitive disease. Lutetium-177-PSMA-617 was administered to 10 (62,5%) patients as one of the first-line treatment and 6 patients received the treatment after progression on LHRH as a second-line treatment. Considering all patients, PSA response rate and DCR were 50% and 62% respectively. The median PFS and OS (with 95% CI) were 11,2 months (11-15) and 29 months (25,6-32,4), respectively in patients treated with 177Lu-PSMA-617 and LHRH analogues. Clinicopathological features and basal PSA level did not have effect on PSA response rates, DCR, OS and PFS. On the other hand, increment in PFS and OS (with 95% CI) was observed in castration resistant disease and in the second-line therapy; for castration resistant disease 16,5 months (12.3-19.7); 30 months (25.3-32.7), for the second-line therapy 14.5 months (12-20.5); 29 months (NR), respectively but statistically not significant. Serious toxicity was observed in a limited number of patients (18,7%), treatment-related death was not observed.

Conclusion: Favorable results can be achived with second-line 177Lu-PSMA-617 treatment in terms of OS and PFS, especially in castration-resistant disease, when chemotherapy and new generation ADT's cannot be used.

MeSH terms

  • Androgen Antagonists / therapeutic use
  • Androgens
  • Gonadotropin-Releasing Hormone
  • Humans
  • Male
  • Positron Emission Tomography Computed Tomography
  • Prostate-Specific Antigen*
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / radiotherapy
  • Retrospective Studies
  • Treatment Outcome

Substances

  • PSMA-617
  • Prostate-Specific Antigen
  • Lutetium-177
  • PSMA-11
  • Androgen Antagonists
  • Androgens
  • Gonadotropin-Releasing Hormone