[177Lu]Lu-PSMA SPECT/CT for early response assessment using quantitative RECIP 1.0.

PURPOSE: This study evaluates the prognostic value of early response assessment using the Response Evaluation Criteria in PSMA imaging (RECIP 1.0) applied to 24-hour post-therapy SPECT/CT at the second cycle of lutetium-177 (177Lu) labeled PSMA radioligand therapy (RLT).

METHODS

This analysis included 136 metastatic castration-resistant prostate cancer (mCRPC) patients treated with ≥ 2 cycles of [177Lu]Lu -PSMA-I&T. Different clinical and biological factors were recorded. Imaging parameters (SUVmean, SUVmax, total tumor volume [TTV]) were measured on 24 h SPECT/CT at cycles 1 and 2 (C1, C2). Patients were classified into progressive disease (RECIP-PD) or non-progressive disease (RECIP-non-PD). Uni and multivariable analysis were performed using Cox regression and Kaplan-Meier curves for progression-free survival (PSA-PFS) and overall survival (OS).

RESULTS

After a median follow-up of 23 months, median PSA-PFS was 6.4 months and median OS was 16.6 months. Regarding imaging parameters, increase in SUVmean (HR = 1.02, p < 0.001), TTV increase ≥ 20% (HR = 3.5, p < 0.001) and appearance of new lesions (NL) (HR = 2.6, p < 0.001) were significantly associated with shorter PSA-PFS, while only TTV increase ≥ 20% (HR = 1.8, p = 0.023) and NLs (HR = 2.3, p = 0.0016) were associated with OS. The combination of both categories using RECIP 1.0 demonstrated that RECIP-PD patients (n = 16/136) had significantly reduced median PSA-PFS (HR = 3.6, p < 0.001) and OS (HR = 3.1, p < 0.001) compared to RECIP-non-PD. The most consistent prognostic accuracy was achieved using RECIP 1.0 (Harrell's C-index: PSA-PFS = 0.80, OS = 0.78).

CONCLUSION

Our study demonstrates that quantitative RECIP 1.0 applied on C2 [177Lu]Lu-PSMA SPECT/CT is an independent prognostic tool for early identification of mCRPC patients unlikely to benefit from continued [177Lu]Lu-PSMA-RLT. The clinical significance of this finding must be prospectively validated before implementation for changes in therapeutic management.