Prognostic value of pretherapeutic ⁶⁸Ga-PSMA-11-PET based imaging parameters in mCRPC patients treated with PSMA radioligands

Abstract

Purpose

This study aims to evaluate the prognostic significance of various previously reported PSMA-PET parameters in patients undergoing ¹⁷⁷Lu-PSMA radioligand therapy (RLT). While individual studies have investigated the prognostic value of one or few of these factors, comprehensive analyses are rare.

Methods

Data of 82 patients undergoing ¹⁷⁷Lu-PSMA-radiologand-therapy (RLT) were analyzed. Total tumor volume (tumor volume), average SUVmean of all tumor lesions (SUVmean) and the quotient of sum of SUVmean of all tumor lesions to SUVmean of the parotid glands (tumor-parotid-ratio; TPR) and of the kidneys (tumor-kidney-ratio; TKR) were included in analysis.

Results

This study showed that a tumor volume of <290.6 ml is associated with a better survival in patients undergoing PSMA-RLT (median PFS: 4.2, median OS: 13.2 months) compared to patients with higher tumor volume (median PFS: 3.4,median OS: 6.2 months; p-value = 0.01 for PFS and <0.001 for OS). The average SUVmean correlated inversely with survival. Patients with a SUVmean > 10.7 had a median PFS of 4.2 and OS of 11.4 months while patients with SUVmean <10.7 had a median PFS of 1.6 and OS of 5 months (p-value <0.001 for both). The assessment of TPR showed no significant difference regarding OS and PFS. TKR showed a better PFS in patients with ratio > 0.33 (p-value 0.009) but no significant difference regarding OS.

Conclusion

The present study confirms that pretherapeutic PSMA-PET before RLT with ¹⁷⁷Lu-PSMA has a prognostic value.

Keywords

PSMA - mCRPC - Radioligand therapy

Publication History

Received: 29 April 2024

Accepted after revision: 06 August 2024

Article published online:
29 August 2024

• References

• 1 Bray F, Ferlay J, Soerjomataram I. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424
• 2 Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract 2011; 65: 1180-1192
• 3 Mansinho A, Macedo D, Fernandes I. et al. Castration-Resistant Prostate Cancer: Mechanisms, Targets and Treatment. Adv Exp Med Biol 2018; 1096: 117-133
• 4 Sadaghiani MS, Sheikhbahaei S, Werner RA. et al. (177) Lu-PSMA radioligand therapy effectiveness in metastatic castration-resistant prostate cancer: An updated systematic review and meta-analysis. Prostate 2022; 82: 826-835
• 5 Hofman MS, Violet J, Hicks RJ. et al. (177)Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial. Lancet Oncol 2018; 19: 825-833
• 6 Fendler WP, Kratochwil C, Ahmadzadehfar H. et al. 177Lu-PSMA-617 therapy, dosimetry and follow-up in patients with metastatic castration-resistant prostate cancer. Nuklearmedizin 2016; 55: 123-128
• 7 Sartor O, de Bono J, Chi KN. et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2021; 385: 1091-1103
• 8 Rahbar K, Schmidt M, Heinzel A. et al. Response and Tolerability of a Single Dose of 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer: A Multicenter Retrospective Analysis. J Nucl Med 2016; 57: 1334-1338
• 9 Ahmadzadehfar H, Eppard E, Kurpig S. et al. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Oncotarget 2016; 7: 12477-12488
• 10 Rahbar K, Bode A, Weckesser M. et al. Radioligand Therapy With 177Lu-PSMA-617 as A Novel Therapeutic Option in Patients With Metastatic Castration Resistant Prostate Cancer. Clin Nucl Med 2016; 41: 522-528
• 11 Kessel K, Seifert R, Schafers M. et al. Second line chemotherapy and visceral metastases are associated with poor survival in patients with mCRPC receiving (177)Lu-PSMA-617. Theranostics 2019; 9: 4841-4848
• 12 Brauer A, Grubert LS, Roll W. et al. (177)Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging 2017; 44: 1663-1670
• 13 Fendler WP, Eiber M, Beheshti M. et al. PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0. Eur J Nucl Med Mol Imaging 2023; 50: 1466-1486
• 14 Seifert R, Kessel K, Schlack K. et al. PSMA PET total tumor volume predicts outcome of patients with advanced prostate cancer receiving [(177)Lu]Lu-PSMA-617 radioligand therapy in a bicentric analysis. Eur J Nucl Med Mol Imaging 2021; 48: 1200-1210
• 15 Hartrampf PE, Huttmann T, Seitz AK. et al. SUV(mean) on baseline [(18)F]PSMA-1007 PET and clinical parameters are associated with survival in prostate cancer patients scheduled for [(177)Lu]Lu-PSMA I&T. Eur J Nucl Med Mol Imaging 2023; 50: 3465-3474
• 16 Seifert R, Herrmann K, Kleesiek J. et al. Semiautomatically Quantified Tumor Volume Using (68)Ga-PSMA-11 PET as a Biomarker for Survival in Patients with Advanced Prostate Cancer. J Nucl Med 2020; 61: 1786-1792
• 17 Scher HI, Morris MJ, Stadler WM. et al. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol 2016; 34: 1402-1418
• 18 Wahl RL, Jacene H, Kasamon Y. et al. From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. J Nucl Med 2009; 50: 122S-150S
• 19 Seifert R, Kessel K, Schlack K. et al. Total tumor volume reduction and low PSMA expression in patients receiving Lu-PSMA therapy. Theranostics 2021; 11: 8143-8151
• 20 Kuo P, Hesterman J, Rahbar K. [68Ga]Ga-PSMA-11 PET baseline imaging as a prognostic tool for clinical outcomes to [177Lu]Lu-PSMA-617 in patients with mCRPC: A VISION substudy.
• 21 Buteau JP, Martin AJ, Emmett L. et al. PSMA and FDG-PET as predictive and prognostic biomarkers in patients given [(177)Lu]Lu-PSMA-617 versus cabazitaxel for metastatic castration-resistant prostate cancer (TheraP): a biomarker analysis from a randomised, open-label, phase 2 trial. Lancet Oncol 2022; 23: 1389-1397
• 22 Hohberg M, Reifegerst M, Drzezga A. et al. Prediction of Response to (177)Lu-PSMA Therapy Based on Tumor-to-Kidney Ratio on Pretherapeutic PSMA PET/CT and Posttherapeutic Tumor-Dose Evaluation in mCRPC. J Nucl Med 2023; 64: 1758-1764
• 23 Hotta M, Gafita A, Murthy V. et al. PSMA PET Tumor-to-Salivary Gland Ratio to Predict Response to [(177)Lu]PSMA Radioligand Therapy: An International Multicenter Retrospective Study. J Nucl Med 2023; 64: 1024-1029
• 24 Roll W, Schindler P, Masthoff M. et al. Evaluation of (68)Ga-PSMA-11 PET-MRI in Patients with Advanced Prostate Cancer Receiving (177)Lu-PSMA-617 Therapy: A Radiomics Analysis. Cancers (Basel) 2021; 13
• 25 Michalski K, Ruf J, Goetz C. et al. Prognostic implications of dual tracer PET/CT: PSMA ligand and [(18)F]FDG PET/CT in patients undergoing [(177)Lu]PSMA radioligand therapy. Eur J Nucl Med Mol Imaging 2021; 48: 2024-2030