Abstract
Background: 177LuPSMA is an effective treatment in metastatic castrate-resistant prostate cancer (mCRPC). Our ability to assess response rates and adjust treatment may be improved using predictive tools. This study aimed to evaluate change in 177Lu-PSMA-SPECT quantitative parameters to monitor treatment response. Methods: 127 men with progressive mCRPC previously treated with androgen signaling inhibition (99%) and chemotherapy (71%) received a median 3 (IQR 2-5) doses Lu PSMA I&T 8 GBq (IQR 8-8.5). Imaging included 68Ga-PSMA-11 PET-CT (SUVmax >15 at a single site and >10 at all sites > 2cm), diagnostic CT, and 177Lu-SPECT/CT (Lu-SPECT) vertex to mid-thigh (24 hours following treatment). Lu-SPECT quantitative analysis was undertaken at cycle-1 (baseline) and 2 (week 6) of treatment. Clinical and biochemical results were assessed to evaluate PSA progression free (PSA-PFS) and overall survival (OS). Results: 58% (74/127) had PSA reduction > 50%. The median PSA-PFS was 6.1 months [95%CI 5.5-6.7] and OS 16.8 months [95% CI 13.5-20.1]. At time of analysis 41% (52/127) were deceased. 76% (96/127) had analyzable serial 177Lu-SPECT/CT imaging at baseline and week-6. SPECT-total tumor volume (SPECT-TTV) was reduced between baseline and week-6 in 74% (71/96, median -193 (IQR -486 to -41). Any increase in SPECT-TTV between baseline and week-6 was associated with significantly shorter PSA-PFS (HR 2.5 (95%CI 1.5-4.2) p 0.0008) but not OS. Median PSA-PFS in those with an increase in SPECT-TTV was 3.7 months (95%CI 2.8-6.8), compared to 6.7 months (95%CI 5.8-10.6) with no increase in SPECT-TTV. An increase in SPECT-TTV greater than 20% was also associated with PSA-PFS (HR 1.9 (95%CI 1.2-3.0) p 0.008), but less significantly than any change in SPECT-TTV. There was a significant difference in PSA-PFS between patients with both increased PSA and SPECT-TTV vs. those patients with reduced SPECT-TTV and PSA (median 2.8 vs. 9.0 months P < 0.0001). Conclusion: Increasing PSMA SPECT-TTV on quantitative 177Lu-SPECT/CT predicts short progression free survival and may play a future role as an imaging response biomarker, identifying when to cease or intensify Lu-PSMA therapy.
- Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.