The prognostic value of post-treatment PSMA and FDG PET/CT in metastatic, castration-resistant prostate cancer treated with ¹⁷⁷LuPSMA-617 and NOX66 in a phase I/II trial (LuPIN).

Abstract

BACKGROUND: ¹⁷⁷Lutetium PSMA-617 (¹⁷⁷LuPSMA-617) therapy has shown high prostate specific antigen (PSA) response rates in men with metastatic castration-resistant prostate cancer (mCRPC). However early treatment resistance is common. This LUPIN sub-study aimed to determine the prognostic value of post-treatment quantitative PET for PSA progression free (PSA-PFS) and overall survival (OS) with ¹⁷⁷LuPSMA-617 therapy. METHODS: 56 men with progressive mCRPC were enrolled in LuPIN trial and received up to 6 doses of ¹⁷⁷LuPSMA-617 and a radiation sensitizer (NOX66). ⁶⁸Ga-PSMA-11 and ¹⁸F-FDG PET/CT, diagnostic CT and bone scan were performed at study entry and exit. Quantitative analysis tracked change (Δ) in total tumour volume (TTV) and standardised uptake value (SUV). Univariable and multivariable analyses were conducted to examine the association of ΔTTV (continuous and > 30%), SUV_max, PSA and radiographic progression with PSA-PFS and OS. RESULTS: All men (37/56) who underwent both screening and post treatment molecular imaging were analyzed. 70% (26/37) had a PSA response >50%, median PSA-PFS was 8.6 months and median OS 22 months. Clinical progression had occurred at trial exit in 54% (20/37). 95% (35/37) demonstrated reduced PSMA SUV_max and 68% (25/37) reduced PSMA-TTV in response to treatment. An increase in PSMA-TTV ≥30% was associated with worse OS (median OS 10.2 vs 23.6 months, p 0.002). Change in PSMA-SUV_max was not associated with PSA-PFS or OS. FDG-SUV_max was reduced in 51% (18/35) and FDG -TTV in 67% (22/35). Increased FDG-SUV_max was associated with worse OS (median OS 20.7 vs. 25.7 months, p<0.01). Increased FDG-TTV > 30% was associated with short PSA-PFS (median PFS 3.5 vs 8.6 months, p<0.001) but not OS. Both PSA and radiographic progression were associated with shorter OS (median 14.5 vs 25.7 months, p<0.001, and 12.2 vs 23.6 months, p 0.002). On multivariable analysis, only increased PSMA-TTV and PSA progression remained independently prognostic of OS (HR 5.1 (95%CI 1.5-17.1), p 0.008 and HR 3.5 (95%CI 1.1-10.9), p 0.03 respectively). CONCLUSION: Change in quantitative PSMA-TTV has strong potential as a prognostic biomarker with ¹⁷⁷LuPSMA-617 therapy, independent of FDG-PET parameters, PSA or radiographic progression. Further research into the value of post-treatment PET as imaging biomarker is warranted.