Tumor Volume on PSMA PET as a Prognostic Biomarker in Prostate Cancer Patients Treated With Cabazitaxel

PURPOSE The aim of this study was to evaluate the prognostic value of 68Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT in metastatic castration-resistant prostate cancer patients receiving second-line chemotherapy with cabazitaxel. METHODS All patients with metastatic castration-resistant prostate cancer who underwent a PSMA PET/CT within 8 weeks before initiating the cabazitaxel treatment were retrospectively evaluated. The whole-body PSMA total tumor volume (PSMA-TV) was measured for each patient. Other factors such as prostate-specific antigen, hemoglobin, lactate dehydrogenase, and alkaline phosphatase were recorded. A log-rank cutoff finder was used to define the PSMA-TV optimal cutoff. Survival analyses were performed using Cox regression and Kaplan-Meier methods. RESULTS In total, 32 patients were included, receiving a median of 6 cycles of cabazitaxel (range, 2-10). After a median follow-up of 12 months, 28 patients presented disease progression, and 18 died. Baseline PSMA-TV presented a significant association with progression-free survival (PFS) and overall survival (OS; P = 0.035 and P = 0.002, respectively). Optimal PSMA-TV cutoffs were 515 mL for PFS and 473 mL for OS. Patients with low volume presented longer PFS and OS than those with high volume: median PFS, 21 versus 12 weeks, respectively (hazard ratio, 0.33; P = 0.017); and median OS, 24 versus 8.5 months, respectively (hazard ratio, 0.21; P = 0.002). On the multivariable analyses, PSMA-TV remained an independent predictor of OS (P = 0.016). CONCLUSION Our results show that total tumor volume measured on PSMA PET/CT is a prognostic biomarker in patients treated with cabazitaxel. High PSMA-TV before treatment initiation is associated with shorter PFS and OS.

[1]  K. Pantel,et al.  Aggressive variants of prostate cancer: underlying mechanisms of neuroendocrine transdifferentiation , 2022, Journal of Experimental & Clinical Cancer Research.

[2]  P. Flamen,et al.  68Ga-PSMA PET/CT for Response Assessment and Outcome Prediction in Metastatic Prostate Cancer Patients Treated with Taxane-Based Chemotherapy , 2021, The Journal of Nuclear Medicine.

[3]  K. Rahbar,et al.  Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. , 2021, The New England journal of medicine.

[4]  U. Haberkorn,et al.  E-PSMA: the EANM standardized reporting guidelines v1.0 for PSMA-PET , 2021, European Journal of Nuclear Medicine and Molecular Imaging.

[5]  M. Stockler,et al.  [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial , 2021, The Lancet.

[6]  S. Larson,et al.  Quantification of Metastatic Prostate Cancer Whole-Body Tumor Burden with 18F-FDG PET Parameters and Associations with Overall Survival After First-Line Abiraterone or Enzalutamide: A Single-Center Retrospective Cohort Study , 2021, The Journal of Nuclear Medicine.

[7]  Henk G van der Poel,et al.  EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II-2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer. , 2020, European urology.

[8]  K. Rahbar,et al.  PSMA PET total tumor volume predicts outcome of patients with advanced prostate cancer receiving [177Lu]Lu-PSMA-617 radioligand therapy in a bicentric analysis , 2020, European Journal of Nuclear Medicine and Molecular Imaging.

[9]  A. Buck,et al.  Metabolic Tumour Volume from PSMA PET/CT Scans of Prostate Cancer Patients during Chemotherapy—Do Different Software Solutions Deliver Comparable Results? , 2020, Journal of clinical medicine.

[10]  K. Rahbar,et al.  Semiautomatically Quantified Tumor Volume Using 68Ga-PSMA-11 PET as a Biomarker for Survival in Patients with Advanced Prostate Cancer , 2020, The Journal of Nuclear Medicine.

[11]  D. Murphy,et al.  Prognostic biomarkers in men with metastatic castration-resistant prostate cancer receiving [177Lu]-PSMA-617 , 2020, European Journal of Nuclear Medicine and Molecular Imaging.

[12]  J. Carles,et al.  Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. , 2019, The New England journal of medicine.

[13]  Roger Slavik,et al.  18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. , 2019, The Lancet. Oncology.

[14]  P. Flamen,et al.  68Ga-PSMA-11 PET/CT in a patient with non-PSA-secreting undifferentiated prostate cancer before and after treatment with cabozantinib , 2019, European Journal of Nuclear Medicine and Molecular Imaging.

[15]  John O. Prior,et al.  Radiolabelled choline versus PSMA PET/CT in prostate cancer restaging: a meta-analysis. , 2019, American journal of nuclear medicine and molecular imaging.

[16]  Min Young Yoo,et al.  Prognostic value of metabolic tumour volume on baseline 18F-FDG PET/CT in addition to NCCN-IPI in patients with diffuse large B-cell lymphoma: further stratification of the group with a high-risk NCCN-IPI , 2019, European journal of nuclear medicine and molecular imaging.

[17]  Bjoern H Menze,et al.  qPSMA: Semiautomatic Software for Whole-Body Tumor Burden Assessment in Prostate Cancer Using 68Ga-PSMA11 PET/CT , 2019, The Journal of Nuclear Medicine.

[18]  P. Flamen,et al.  Validation of Metabolically Active Tumor Volume and Total Lesion Glycolysis as 18F-FDG PET/CT–derived Prognostic Biomarkers in Chemorefractory Metastatic Colorectal Cancer , 2019, The Journal of Nuclear Medicine.

[19]  D. Bailey,et al.  A prospective randomized multicentre study of the impact of gallium‐68 prostate‐specific membrane antigen (PSMA) PET/CT imaging for staging high‐risk prostate cancer prior to curative‐intent surgery or radiotherapy (proPSMA study): clinical trial protocol , 2018, BJU international.

[20]  David F Jarrard,et al.  Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  Tobias L. Ross,et al.  Initial Experience with Volumetric 68Ga-PSMA I&T PET/CT for Assessment of Whole-Body Tumor Burden as a Quantitative Imaging Biomarker in Patients with Prostate Cancer , 2017, The Journal of Nuclear Medicine.

[22]  Bernd J. Krause,et al.  68Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0 , 2017, European Journal of Nuclear Medicine and Molecular Imaging.

[23]  G. Salles,et al.  Baseline Metabolic Tumor Volume Predicts Outcome in High-Tumor-Burden Follicular Lymphoma: A Pooled Analysis of Three Multicenter Studies. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  Oliver Sartor,et al.  Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  H. Heinzer,et al.  Initial Experience of (68)Ga-PSMA PET/CT Imaging in High-risk Prostate Cancer Patients Prior to Radical Prostatectomy. , 2016, European urology.

[26]  N. Tunariu,et al.  Visceral disease in castration-resistant prostate cancer. , 2014, European urology.

[27]  A. Armstrong,et al.  Prognostic model predicting metastatic castration-resistant prostate cancer survival in men treated with second-line chemotherapy. , 2013, Journal of the National Cancer Institute.

[28]  J. Machiels,et al.  Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial , 2010, The Lancet.

[29]  E. Adang,et al.  The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. , 2008, Clinical radiology.

[30]  Torsten Hothorn,et al.  On the Exact Distribution of Maximally Selected Rank Statistics , 2002, Comput. Stat. Data Anal..