ASCO GU 2023: Evaluation of a Novel Transcriptomic Tumor Signature (PROSTest) as Response Biomarker for 177Lu-PSMA Therapy in Advanced Prostate Cancer

( On the first day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2023 focussing on prostate cancer, Dr. Alin Chirindel presented in Poster Session A on the evaluation of a novel biomarker for response to lutetium-177 PSMA (Lu-PSMA) advanced prostate cancer.

Based on a number of prospective trials, radionuclide therapy targeting the prostate specific membrane antigen (177Lu-PSMA therapy) has proven to be an effective treatment in men with metastatic castration resistant prostate cancer (mCRPCs). Despite representing a significant therapeutic breakthrough, there remains a critical unmet need in 177Lu-PSMA therapy to identify a prognostic biomarker for treatment optimization given that conventional imaging and standard biomarkers have limited value. The PROSTest is a new 27-gene algorithmic signature originally developed for prostate adenocarcinoma diagnosis (0 to 100, positive score ≥20). We hypothesized that PROSTest would be elevated in patients with mCRPC and could have utility as a biomarker for mCRPC management.

The authors prospectively enrolled 113 men with mCRPC to receive 177Lu-PSMA therapy (KlbB-5338-0302021 study). The authors acquired pathology, clinical and biomarker data, and PSMA-PET/CT imaging data. Prior to the start of therapy, blood samples were collected for PROSTest. Using these samples, target genes were isolated and amplified using qPCR. PROSTest scores (0-100) were obtained following algorithmic analysis. Scores were correlated with mCRPC diagnosis and baseline information. Scores and standard clinical measures were evaluated as prognostic factors with survival as endpoint. Mann-Whitney U-test, Kaplan-Meier survival and Cox proportional hazards regression analysis were utilized. All data: median (IQ range).


Among the 113 enrolled men, 89 (79%) patients were evaluable. The median age was 75 (68-80) years. In terms of disease characteristics at time of diagnosis, 70% of patients had Gleason scores 8-10 disease. In terms of staging, 67% of patients had T4 tumors, 53% had N1 disease and, 45% were M1 at diagnosis. At the time of therapy all patients were metastatic and all exhibited PSMA-positive disease. The highest tumor SUVmax was 51 (28-78). PSA levels were 69ng/mL (18-305). The PROSTest score was 89 (81-92). PROSTest scores were weakly correlated with age (r=0.33, p=0.0015) but not with baseline histopathological parameters (e.g., Gleason score, TNM) or pretreatment imaging results (e.g., SUVmax). During follow-up, 24 of 89 patients (27%) patients died.

Currently, treatment and follow-up are ongoing with a median follow-up to date of 5 months (range 3 to 18 months). The mOS is 15 months.

The authors found that only the PROSTest score was associated with mortality: PROSTest scores ≥79 (based on ROC analysis) were associated with significantly increased risk for mortality (HR: 2.9, 95% CI: 1.5-7.4). The mOS was 14 months in patients with pre-therapy PROSTest scores >79 compared to mOS not reached for PROSTest scores <79 (p=0.02). In the COX model, baseline PROSTest was found to to be significantly predictive of death (p=0.01).

Thus, the authors conclude that the PROSTest blood gene expression score is elevated in mCRPCs, though levels are not associated with baseline clinical, histopathological, pretreatment PSA or imaging parameters. Elevated expression (≥79) of this biomarker prior to treatment was associated with a lower survival and could be used to predict survival in patients undergoing 177Lu-PSMA.

Presented by: Alin Chirindel, MD, University Hospital Basel