Early PSA Change after [177Lu]PSMA-617 Radioligand Therapy as a Predicator of Biochemical Response and Overall Survival

Abstract

Purpose: Radioligand therapy with [177Lu]PSMA-617 (PSMA-RLT) is a promising therapeutic option for metastatic castration-resistant prostate cancer (mCPRP). This study assessed the prognostic value of early PSA measurements during PSMA-RLT. Methods: 27 patients with mCRPC scheduled for PSMA-RLT were prospectively enrolled for a serial short-interval PSA-assessment. Change in PSA (∆%PSA) during two treatment cycles was correlated with biochemical response (BR) and change in tumor volume on PET (TV) after 16 weeks (w16), as well as overall survival (OS). PCWG3 criteria and the recently recommended threshold of ∆%PSA ≤ −30% were assessed for their predictive value. Results: ∆%PSA first correlated with BR, TV and OS after 4 weeks (c1w4). At c1w4, ∆%PSA ≤ −30% was associated with the biochemical response at w16 (p = 0.003) and a longer median OS (p = 0.025), whereas the PCWG3-derived threshold of ∆%PSA ≤ −50% showed no such correlation. In contrast, ∆%PSA ≥ 25% at c1w4 was associated with biochemical progression at w16 (p = 0.003) and a shorter median OS (p < 0.001). Conclusion: PSA changes as early as four weeks after PSMA-RLT allow a significant prediction of later biochemical and PET-based imaging response, as well as OS. At this early time point, a more lenient threshold for a PSA decrease of at least 30% appears better-suited for the prediction of a positive biochemical response and longer OS. In contrast, the PCWG3-derived threshold for PSA increase (+25%) reliably anticipates biochemical progression and shorter OS.

Any decline in prostate‐specific antigen levels identifies survivors scheduled for prostate‐specific membrane antigen‐directed radioligand therapy

“…Those findings are consistent with a previous study reporting on 27 mCRPC patients receiving the latter agent. In this study, the PCWG3 recommended threshold of 50% PSA decline did not correlate with survival, while lower PSA deltas 4 weeks after treatment on‐set were linked to late biochemical response at week 17 and longer OS 12 . Including a substantially larger number of patients treated with the most commonly administered RLT agents, our study provides further evidence that early biochemical response is tightly linked to prolonged survival, irrespective of the magnitude of PSA decline and thus, even in patients not meeting the strict criteria of the PCWG3, RLT should be continued.…”

“…[1][2][3][4] Established criteria, such as the PCWG3, recommend analysis of PSA changes 12 weeks after initiating treatment. 5 Earlier assessments, however, have also been tested in the context of PSMA-RLT, 6,7,12 with significant correlations between OS and PSA decline as early as 4 weeks after therapy. 12…”

“…5 Earlier assessments, however, have also been tested in the context of PSMA-RLT, 6,7,12 with significant correlations between OS and PSA decline as early as 4 weeks after therapy. 12…”

“…Established criteria, such as the PCWG3, recommend analysis of PSA changes 12 weeks after initiating treatment 5 . Earlier assessments, however, have also been tested in the context of PSMA‐RLT, 6,7,12 with significant correlations between OS and PSA decline as early as 4 weeks after therapy 12 . We, therefore, analyzed changes in PSA levels as early as 8 weeks after the first cycle of RLT, thereby investigating a time frame that would still allow to alter treatment if necessary and if other treatment options are still available as PSMA‐RLT is often used as last line treatment.…”

[177Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer

“…In this context, first studies have already been performed to better predict the outcome of therapy with PSMA-617. Kind et al [ 45 ] for example recommend focusing on PSA changes at about four weeks after the start of therapy to better predict subsequent biochemical and PET-based response and OS. Further work is required to optimize clinical protocols related to the patient selection and therapy monitoring to fully exploit the potential of the theranostic concept.…”