ASCO 2023: Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography Disease Extent and Overall Survival in Patients with High-Risk Nonmetastatic Castration-Resistant Prostate Cancer: An International Multicenter Retrospective Study

(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2^nd and June 6^th was host to a prostate, testicular, and penile cancers poster discussion session. Dr. Boris Hadaschik presented the results of an international, multicenter retrospective study evaluating Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography (PSMA-PET/CT) disease extent and overall survival (OS) outcomes in patients with high-risk, non-metastatic castrate-resistant prostate cancer (nmCRPC) on conventional imaging.

nmCRPC is defined by a rising PSA level in the setting of castrate testosterone levels and with no evidence of metastasis on conventional imaging. Despite negative findings on conventional imaging, a prior study by Fendler et al. has demonstrated that PSMA-PET/CTs are positive in 98% of patients overall, with 55% demonstrating evidence of M1 disease.¹ However, to date, the associations between PSMA-PET/CT findings/parameters and oncologic outcomes in conventional imaging-defined nmCRPC remain unclear. As such, the objective of this study was to evaluate the prognostic utility of PSMA-PET/CT disease extent findings for overall and new metastases-free survivals.

The authors included 200 patients with nmCRPC patients from five centers and with disease characteristics similar to those observed in the SPARTAN, PROSPER, and ARAMIS trials:

• PSA doubling time ≤10 months and/or Grade Group 4 or 5 disease
• No pelvic nodes ≥2 cm in the short axis
• No evidence of distant metastases on conventional imaging

All patients underwent a PSMA-PET/CT. Images were interpreted by one unblinded local reader and two central readers who were aware of the patients’ most recent PSA values and prior treatment but were blinded to other imaging findings and clinical data. Whole-body PSMA-positive tumor volume segmentation was performed with qPSMA software. The primary endpoint was overall survival, defined as the time from PSMA-PET to death from any cause. Secondary endpoints included:

• New metastases-free survival, defined as time from PSMA-PET to either death from any cause or detection of new metastases using any imaging modality, including PSMA-PET
• 1^st and 2^nd line treatment following PSMA-PET

Time-to-event analyses using Kaplan Meier curves and univariable Cox regression analyses were performed to evaluate the associations between baseline patient characteristics/PET findings and survival outcomes.

The study cohort included 200 patients. The median follow-up was 74 months, during which 28% of patients died and 42% had evidence of new metastases. The median overall survival in the cohort was 74 months, similar to that observed in the apalutamide arm of SPARTAN.²

On univariable analysis, worse overall survival was observed among patients with ≥5 PET-detected distant lesions and those with a ≥8.4 SUVmax (i.e., higher PSMA avidity), with only polymetastatic disease (≥5) lesions remaining significant on multivariable analysis.

The median new metastases-free survival was significantly shorter in patients with polymetastatic disease (5+ lesions: 38 months versus <5 lesions: 60 months):

With regards to impact on management, locoregional and targeted therapy was most prevalent in patients with either none/local ((miTxN0M0) or locoregional disease (miTxN1M0). ADT was continued in all groups, and systemic treatment (ARSI, PARPi, chemotherapy, radioligand therapy, other) was intensified most frequently in patients with distant-only (miM1) or combined locoregional and distant disease (miN1M1). 

Presented by: Boris A. Hadaschik, MD, Professor, Chairman, Department of Urology, University Hospital Essen, Essen, Germany

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.

1. Fendler WP, et al. Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography in Men with Nonmetastatic Castration-Resistant Prostate Cancer. Clin Cancer Res 2019;25(24):7448-54.
2. Smith MR, Saad F, Chowdhury S, et al. Apalutamide and Overall Survival in Prostate Cancer. Eur Urol. 2021 Jan;79(1):150-158.