Evaluation of 177Lu-PSMA SPECT Quantitation as a Response Biomarker within a Prospective 177Lu-PSMA-617 and NOX66 Combination Trial (LuPIN)

Abstract

Background: 177LuPSMA-617 is an effective and novel treatment in metastatic castrate-resistant prostate cancer (mCRPC). Our ability to assess response rates and therefore efficacy may be improved using predictive tools. This study investigates the predictive value of serial 177Lu- PSMA SPECT imaging in monitoring treatment response. Methods: 56 men with progressive mCRPC previously treated with chemotherapy and novel androgen signaling inhibitor (ASI) enrolled in LuPIN trial receiving up to 6 doses of LuPSMA-617 and a radiation sensitizer (NOX66). 68Ga-PSMA-11 and 18FDG PET/CT were performed at study entry and exit, and 177Lu-SPECT/CT (SPECT) vertex to mid thighs was acquired 24hrs following each treatment. SPECT quantitative analysis was undertaken at cycles 1 (baseline) and 3 (week-12) of treatment (C1 and C3). Results: 32/56 men had analyzable serial 177Lu-SPECT/CT imaging at both C1 and C3. In this subgroup, median PSA-PFS was 6.3 months (95%CI 5-10) and median OS 12.3 months (95%CI 12-24). PSA 50% response rate was 63% (20/32). SPECT total tumor volume (SPECT-TTV) was reduced in 68% (22/32, median - 0.20L (-1.4 to -0.001) and increased in 31% (10/32, median 0.36 (0.1-1.4)). Any increase in SPECT-TTV was associated with shorter PSA-PFS (HR 4.1 (95% CI 1.5-11.2), p 0.006). A ≥30% increase in SPECT-TTV was also associated with shorter PSA-PFS (HR 3.3 (95%CI 1.3-8.6), p 0.02). Tumoral SUVmax was reduced in 91% (29/32) and SUVmean in 84% (27/32); neither was associated with PSA-PFS or OS outcomes. PSA progression by week-12 was also associated with shorter PSA-PFS (HR 26.5 (95%CI 5.4-131). In the patients with SPECT-TTV progression at week-12, 50% (5/10) had no concurrent PSA progression (median PSA-PFS 4.5 months (95% CI 2.8-5.6), and 5/10 men had both PSA and SPECT TTV progression at week 12 (median PSA-PFS 2.8 months (95% CI 1.8-3.7). Conclusion: Increasing PSMA-TTV on quantitative 177Lu-SPECT/CT predicts short progression free survival and may play a future role as an imaging response biomarker.