The BioPoP study was designed to address this gap by incorporating liquid biopsy into the decision-making process. In our prospective cohort of 148 patients undergoing PSMA-RGS for oligorecurrent disease, we evaluated whether circulating tumor cells (CTCs) — measured preoperatively using the CellSearch® system — could help predict treatment outcomes.
What did we find?
The key finding is nuanced. Overall, CTCs were detectable in only 14% of patients — a markedly lower rate than what is reported in the metastatic castration-resistant (30–50%) or metastatic hormone-sensitive setting (20–25%). This low prevalence itself is clinically meaningful: it reflects the limited tumor burden in this early recurrence setting and underscores that oligorecurrent disease is biologically distinct from more advanced stages.
Importantly, the mere presence of CTCs at low counts (1–3 cells/7.5 ml blood) did not negatively affect outcomes. Patients with low CTC counts had complete biochemical response rates and treatment-free survival comparable to CTC-negative patients. This is reassuring, as it suggests that detecting a few circulating cells should not discourage clinicians from offering salvage surgery to otherwise suitable candidates.
However, in exploratory analyses, the small subgroup of patients with ≥5 CTCs/7.5 ml blood showed worse treatment-free survival (10.7 vs. 42.2 months). While only three patients met this threshold, the signal is biologically plausible: higher CTC counts likely indicate occult systemic disease beyond what PSMA-PET can visualize, suggesting these patients may benefit more from early systemic therapy than from local intervention alone.
What does this mean for clinical practice?
For the urologist counseling a patient with PSMA-PET-positive oligorecurrent disease, our data provides several practical takeaways. First, CTC enumeration alone — at least with current EpCAM-based technologies — is unlikely to become a standalone selection tool in this setting, simply because the vast majority of patients have undetectable or very low counts. Second, in patients in whom surgical metastasis-directed therapy might be considered (or asked for by the patient), but clinical values might point towards an early systemic disease, CTC measurements could be undertaken. When CTC counts are elevated, this should prompt a careful discussion about whether salvage surgery is the right approach or whether systemic treatment should be prioritized.
Where do we go from here?
The sensitivity ceiling of EpCAM-based CTC detection in early-stage recurrence is a clear limitation. Future approaches may need to combine CTC enumeration with other liquid biopsy modalities — particularly circulating tumor DNA — to provide a more comprehensive picture of residual disease. Prospective trials stratifying treatment decisions by liquid biopsy results, similar to what has been recently demonstrated in metastatic breast cancer, will be essential to establish true clinical utility.
Ultimately, the BioPoP study reinforces a broader principle in oligorecurrent prostate cancer management: imaging alone may not tell the whole story, and integrating blood-based biomarkers into our treatment algorithms could help us better identify the patients who stand to gain the most from metastasis-directed surgery.
Written by:
- Sophie Knipper, Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, Vivantes Klinikum am Urban, Berlin, Germany
- Tobias Maurer, Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany