Identification of Biomarkers Predictive of Successful Salvage Surgery in Prostate-specific Membrane Antigen Positron Emission Tomography-positive Oligorecurrent Prostate Cancer: Results from the BioPoP Trial.

BACKGROUND AND

OBJECTIVE

Prostate-specific membrane antigen (PSMA) radioligand imaging allows early detection of recurrence of prostate cancer (PC). While circulating tumor cells (CTCs) have proven prognostic value in metastatic castration-resistant PC, data for the hormone-sensitive setting are limited. The prospective BioPoP study investigated the prognostic value of CTCs before PSMA-based radioguided salvage surgery (PSMA-RGS) in patients with oligorecurrent PC after radical prostatectomy.

METHODS

The prospective study cohort included 148 patients undergoing 99mTc-based PSMA-RGS between 2020 and 2024. CTCs were measured preoperatively using a CellSearch system. The primary endpoint was the complete biochemical response (cBR; prostate-specific antigen [PSA] <0.2 ng/ml) rate at 6 mo after PSMA-RGS. Secondary endpoints included biochemical recurrence-free survival (BCR-FS) and PC-specific treatment-free survival (TFS).

KEY FINDINGS AND LIMITATIONS: Median PSA before surgery was 0.58 ng/ml (interquartile range [IQR] 0.35-1.08). Most patients exhibited one positive lesion (67%) located within the pelvis (81%). Only 21 patients (14%) were CTC-positive, and three patients had five or more CTCs/7.5 ml blood. The median number of lymph node metastases was 2 (IQR 1-3). The cBR rate at 6 mo was 53% (95% confidence interval [CI] 46-62%) overall, and 51% in CTC-positive group versus 65% in the CTC-negative group (p > 0.05). Median BCR-FS was 7.1 mo (95% CI 4.9-12.4) and median TFS was 42.4 mo (95% CI 37.4-not reached). Exploratory analyses revealed that the group with five or more CTCs/7.5 ml had worse TFS (10.7 vs 42.2 mo for less than five CTCs/7.5 ml). The main limitations are the small number of patients with higher CTC counts and the single-arm design.

CONCLUSIONS AND CLINICAL IMPLICATIONS: High CTC counts may potentially predict inferior outcomes after salvage lymph node dissection. As high counts are rare in early oligorecurrent PC, more sensitive CTC technologies and additional biomarkers are needed. The BioPoP study is registered on ClinicalTrials.gov as NCT04324983.