Abstract

Background: Dosimetry can tailor prostate-specific membrane-antigen-targeted radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC). However, whole-body tumor dosimetry is challenging in patients with a high tumor burden. We evaluate a simplified index-lesion-based single-photon emission computed tomography (SPECT) dosimetry method in correlation with clinical outcome. Methods: 30 mCRPC patients were included (median 71 years). The dosimetry was performed for the first cycle using quantitative 177Lu-SPECT. The response was evaluated using RECIST 1.1 and PERCIST criteria, as well as changes in PSMA-positive tumor volume (PSMA-TV) in post-therapy PSMA-PET and biochemical response according to PSA changes after two RLT cycles. Results: Mean tumor doses as well as index-lesion doses were significantly higher in PERCIST responders compared to non-responders (10.2 ± 12.0 Gy/GBq vs. 4.0 ± 2.9 Gy/GBq, p = 0.03 and 13.7 ± 14.2 Gy/GBq vs. 5.9 ± 4.4 Gy/GBq, p = 0.04, respectively). No significant differences in mean tumor and index lesion doses were observed between responders and non-responders according to RECIST 1.1, PSMA-TV, and biochemical response criteria. Conclusion: Compared to mean tumor doses on a patient level, single index-lesion-based SPECT dosimetry correlates equally well with the response to PSMA-RLT according to PERCIST criteria and may represent a fast and feasible dosimetry approach for clinical routine.

Highlights

  • Prostate-specific-membrane-antigen (PSMA) targeted theranostic approaches for metastatic castration-resistant prostate cancer are of rising clinical importance [1]

  • The median whole-body tumor dose was 14.1 Gy in patients with prostate-specific antigen (PSA) decline ≥ of 50% compared to patients with a PSA decline of less than 50% with a median dose of only 9.6 Gy, providing a rationale for individualized dosimetry during PSMA-RLT

  • This study aimed to evaluate and compare an easy and feasible, index-lesion-based single-photon emission computed tomography (SPECT) dosimetry method with mean tumor doses in multiple tumor lesions on a patient level and to correlate dosimetry data with clinical outcome after 177Lu-PSMA RLT

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Summary

Introduction

Prostate-specific-membrane-antigen (PSMA) targeted theranostic approaches for metastatic castration-resistant prostate cancer (mCRPC) are of rising clinical importance [1]. According to a recent meta-analysis on the efficacy and safety of 177Lu-PSMA RLT, including 17 articles and 744 patients, biochemical response with a prostate-specific antigen (PSA) decline >50% is observed in 46% (95% CI: 40–53%) despite progressive disease after exhaustion of approved therapy options [11]. This study aimed to evaluate and compare an easy and feasible, index-lesion-based SPECT dosimetry method with mean tumor doses in multiple tumor lesions on a patient level and to correlate dosimetry data with clinical outcome after 177Lu-PSMA RLT. We evaluate a simplified index-lesion-based single-photon emission computed tomography (SPECT) dosimetry method in correlation with clinical outcome. Conclusion: Compared to mean tumor doses on a patient level, single index-lesion-based SPECT dosimetry correlates well with the response to PSMA-RLT according to PERCIST criteria and may represent a fast and feasible dosimetry approach for clinical routine

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