Phase 2 trial of PSMA PET CT versus planar bone scan and CT in prostate cancer patients progressing while on androgen deprivation therapy

John Nikitas; Andrei Gafita; Matthias R Benz; Loïc Djaïleb; Andrea Farolfi; Masatoshi Hotta; Ida Sonni; Rejah Alano; Matthew Rettig; John Shen; Wesley Armstrong; Tristan Grogan; Sandy Liu; Johannes Czernin; Jeremie Calais

doi:10.1038/s41598-024-75589-6

Phase 2 trial of PSMA PET CT versus planar bone scan and CT in prostate cancer patients progressing while on androgen deprivation therapy

Sci Rep. 2024 Oct 18;14(1):24411. doi: 10.1038/s41598-024-75589-6.

Authors

John Nikitas¹, Andrei Gafita², Matthias R Benz³, Loïc Djaïleb³, Andrea Farolfi⁴, Masatoshi Hotta³, Ida Sonni^{3

5

6}, Rejah Alano³, Matthew Rettig^{7

8}, John Shen⁷, Wesley Armstrong³, Tristan Grogan⁹, Sandy Liu¹⁰, Johannes Czernin³, Jeremie Calais¹¹

Affiliations

¹ Department of Radiation Oncology, University of California, Los Angeles, CA, USA.
² Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA.
⁴ Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁵ Department of Radiological Sciences, University of California, Los Angeles, CA, USA.
⁶ Department of Experimental and Clinical Medicine, University Magna Graecia, Catanzaro, Italy.
⁷ Departments of Medicine and Urology, University of California, Los Angeles, CA, USA.
⁸ Hematology-Oncology Section, Medicine Service, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA, USA.
⁹ Department of Medicine Statistics Core, University of California, Los Angeles, CA, USA.
¹⁰ Department of Medical Oncology & Therapeutics Research, City of Hope, Los Angeles, CA, USA.
¹¹ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA. [email protected].

Abstract

For prostate cancer patients who experience biochemical progression during androgen deprivation therapy (ADT), prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has not been prospectively compared to planar bone scan plus CT. This was a single-arm, head-to-head, prospective phase II trial (NCT04928820) designed to enroll 102 men with prostate cancer who experienced biochemical progression (rising prostate-specific antigen [PSA] ≥ 1 ng/mL) during ADT. All patients received 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scans. Each scan was interpreted by three central independent readers. The primary endpoint was the per-patient bone metastasis detection rate of PSMA PET/CT versus planar bone scan and CT. Secondary endpoints compared the number of bone metastases detected per patient and the inter-reader agreement of each imaging modality. Twenty-two men were enrolled between July 2021 and June 2022. Due to slow accrual following approval of PSMA PET radiotracers in the U.S. and a lack of a statistical signal between the two imaging modalities on interim analysis, this trial was closed early on October 2022. Median PSA was 8.5 ng/mL (interquartile range: 1.6-77.6). There was 100% agreement between the two scans. Six patients (27%) had negative findings and 16 patients (73%) had positive findings on both scans. PSMA PET/CT and bone scan plus CT detected an equal number of bone lesions for 14 patients (64%), PSMA PET/CT detected more bone lesions for six patients (27%), and bone scan plus CT detected more bone lesions for two patients (9.1%) (p = 0.092). The inter-reader agreement rates of PSMA PET/CT and bone scan plus CT were 96% and 82%, respectively (p = 0.25). In men with biochemical progression during ADT, 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scan plus CT had identical bone metastasis detection rates. Bone scan plus CT can continue to serve as a cost-effective and readily accessible restaging modality in patients with biochemical progression. ClinicalTrials.gov NCT04928820. Registered 16/06/2021.

Keywords: Androgen deprivation therapy; Biochemical recurrence; Bone metastases; Bone scan; Prostate-specific membrane antigen PET/CT.

Publication types

Clinical Trial, Phase II
Comparative Study

MeSH terms

Aged
Aged, 80 and over
Androgen Antagonists* / therapeutic use
Antigens, Surface / metabolism
Bone Neoplasms* / diagnostic imaging
Bone Neoplasms* / drug therapy
Bone Neoplasms* / secondary
Bone and Bones / diagnostic imaging
Bone and Bones / drug effects
Bone and Bones / metabolism
Bone and Bones / pathology
Disease Progression
Gallium Isotopes
Gallium Radioisotopes
Glutamate Carboxypeptidase II / metabolism
Humans
Male
Middle Aged
Positron Emission Tomography Computed Tomography* / methods
Prospective Studies
Prostate-Specific Antigen / blood
Prostatic Neoplasms* / diagnostic imaging
Prostatic Neoplasms* / drug therapy
Prostatic Neoplasms* / pathology
Radiopharmaceuticals
Tomography, X-Ray Computed / methods

Substances

Androgen Antagonists
FOLH1 protein, human
Prostate-Specific Antigen
Glutamate Carboxypeptidase II
Antigens, Surface
gallium 68 PSMA-11
Gallium Radioisotopes
Radiopharmaceuticals
Gallium Isotopes

Associated data

ClinicalTrials.gov/NCT04928820