Early response monitoring during [177Lu]Lu-PSMA I&T therapy with quantitated SPECT/CT predicts overall survival of mCRPC patients: subgroup analysis of a Swiss-wide prospective registry study

• Published in: European journal of nuclear medicine and molecular imaging Vol. 51; no. 4; pp. 1185 - 1193
• Main Authors: Neubauer, Moritz C., Nicolas, Guillaume P., Bauman, Andreas, Fani, Melpomeni, Nitzsche, Egbert, Afshar-Oromieh, Ali, Forrer, Flavio, Rentsch, Cyril, Stenner, Frank, Templeton, Arnoud, Schäfer, Niklaus, Wild, Damian, Chirindel, Alin
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2024; Springer Nature B.V
• Subjects: Biomarkers; Cancer therapies; Cardiology; Castration; Computed tomography; Confidence intervals; Data analysis; Dipeptides - therapeutic use; Drug dosages; Heterocyclic Compounds, 1-Ring - therapeutic use; Humans; Image analysis; Image processing; Imaging; Lutetium - therapeutic use; Lutetium isotopes; Male; Medical imaging; Medicine; Medicine & Public Health; Metastases; Metastasis; Nuclear Medicine; Oncology; Original; Original Article; Orthopedics; Patients; Prostate cancer; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant - diagnostic imaging; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - radiotherapy; Radiology; Rank tests; Retrospective Studies; Single photon emission computed tomography; Single Photon Emission Computed Tomography Computed Tomography; Software; Subgroups; Survival; Switzerland; Therapy; Thigh; Treatment Outcome; Tumors; Urea - analogs & derivatives; Working groups; Switzerland; Response monitoring; Lu]Lu-PSMA I&T; Metastatic prostate cancer; [; Quantitative SPECT/CT; [177Lu]Lu-PSMA I&T
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-023-06536-2

Purpose To assess early tumor response with quantitated SPECT/CT and to correlate it with clinical outcome in metastatic castration–resistant prostate cancer (mCRPC) patients treated with 177 Lutetium-PSMA I&T therapy. Methods Single-center, observational study, part of the prospective Swiss national cancer registry study investigating the safety and efficacy of [ 177 Lu]Lu-PSMA I&T (EKNZ: 2021–01271) in mCRPC patients treated with at least two cycles of [ 177 Lu]Lu-PSMA I&T 6-weekly. After the first and second cycle quantitated SPECT/CT (Symbia Intevo, Siemens) was acquired 48 h after injection (three fields of view from head to thigh, 5 s/frame) and reconstructed using xQuant® (48i, 1 s, 10-mm Gauss). Image analysis: The PSMA-positive total tumor volumes (TTV) were semi-automatically delineated using a SUV threshold of 3 with MIMencore® (version 7.1.3, Medical Image Merge Software Inc.). Changes in TTV, highest tumor SUVmax, and total tumor SUVmean between cycles 1 and 2 were calculated and grouped into a) stable or decrease and b) increase. Serum PSA levels were assessed at each therapy cycle and at follow-up until progression or death. Changes in TTV, PSA, SUVmax, and SUVmean were correlated with PSA-progression-free survival (PSA-PFS) and the overall survival (OS) using the Kaplan–Meier methodology (log-rank test). Results Between 07/2020 and 04/2022, 111 patients were screened and 73 finally included in the data analysis. The median follow-up was 8.9 months (range 1.4–26.6 months). Stable or decreased TTV at cycle 2 was associated with longer OS (hazard ratio (HR) 0.28, 95% confidence interval (CI) 0.09–0.86, p  < 0.01). Similar, stable, or decreased PSA was associated with longer OS (HR 0.21; CI 0.07–0.62, p  < 0.01) and PSA-PFS (HR 0.34; 95% CI 0.16–0.72, p  < 0.01). Combining TTV and PSA will result in an augmented prognostic value for OS (HR 0.09; CI 0.01–0.63; p  < 0.01) and for PSA-PFS (HR 0.11; CI 0.02–0.68; p  < 0.01). A reduction of SUVmax or SUVmean was not prognostically relevant, neither for OS ( p 0.88 and 0.7) nor for PSA-PFS ( p 0.73 and 0.62, respectively). Conclusion Six weeks after initiating [ 177 Lu]Lu-PSMA I&T, TTV and serum PSA appear to be good prognosticators for OS. Combined together, TTV + PSA change demonstrates augmented prognostic value and can better predict PSA-PFS. Larger studies using TTV change prospectively as an early-response biomarker are warranted for implementing management change towards a more personalized clinical practice.