A Gap in Colorectal Cancer Surveillance
Colorectal cancer (CRC) is one of the most common and deadly cancers worldwide and yet, some of the most critical clinical questions in its management remain unanswered by current diagnostic tools.
- After surgery with curative intent, how do we know if residual disease remains?
- During treatment, how do we assess whether therapy is truly working?
- After remission, how do we detect recurrence at its earliest, most treatable stage?
Conventional imaging and tissue biopsy are simply not equipped to answer these questions in real time. This study makes the case for a more powerful approach: CTC-based PD-L1 profiling as a dynamic surveillance tool in colorectal cancer patients.
The Clinical Significance of PD-L1 on CTCs in Colorectal Cancer
When tumour cells overexpress PD-L1 on their surface, they gain the ability to evade immune elimination, effectively cloaking themselves from the body’s T cell defences and establishing dormancy in circulation. In the context of colorectal cancer, this has two critical implications.
First, PD-L1-positive CTCs may signal incomplete tumour resection indicating that residual disease remains even when surgical margins appear clear. Second, their presence in circulation, particularly in early-stage or post-treatment patients may reveal cell dormancy that conventional monitoring would entirely miss, until the cancer returns at an advanced stage.
Our Study: 666 Colorectal Cancer Patients
In a retrospective analysis of 666 colorectal cancer patients (63.06% male, 36.94% female) spanning early to late-stage disease, peripheral blood samples were analysed for CTC presence, CTC clusters, and PD-L1 expression using the CDSCO-approved OncoDiscover platform, processing just 1.5 mL of blood per patient. CTCs were confirmed as EpCAM+ve, CK18+ve, DAPI+ve, and CD45-ve using an automated Zeiss Microscope.
What We Found
The results demonstrate the significant clinical potential of CTC-PD-L1 profiling in colorectal cancer:
- 74.25% of patients (n=591) showed ≥1 CTCs per 1.5 mL of blood at baseline confirming that circulating tumour burden is detectable in the vast majority of colorectal cancer patients, even in early-stage disease
- Of those with detectable CTCs, 74.62% (n=441) showed PD-L1 expression, underscoring the scale of immune evasion activity occurring in circulation in this patient population
- The 61–70 age group carried the highest CTC burden, accounting for 25.86% of all CTC-positive cases
- 13% of patients (n=156) showed CTC clusters and notably, the majority of CTC clusters were observed at follow-up rather than baseline, suggesting that cluster formation may be associated with disease progression or treatment response
- Mean CTC count including clusters was 1.71, with mean PD-L1-positive CTCs at 1.02
Why This Matters
The high rate of PD-L1 expression on CTCs in this colorectal cancer cohort carries profound clinical implications, both for surveillance and for treatment selection.
- PD-L1-positive CTCs that evade immune elimination and establish dormancy in circulation represent one of the most plausible mechanisms of late recurrence in colorectal cancer: a phenomenon that currently has no reliable blood-based marker.
- Integrating CTC-PD-L1 profiling into routine post-surgical and post-treatment surveillance could help oncologists identify patients at highest risk of recurrence before it becomes clinically or radiologically apparent enabling earlier intervention and better outcomes.
This study adds to a growing body of evidence that CTC profiling is not just a diagnostic tool; it is a window into tumour biology that has the potential to fundamentally reshape how we monitor and manage colorectal cancer.
Published at the ASCO Annual Meeting 2025 | DOI: 10.1200/JCO.2025.43.16_suppl.e15038
Presented by Aravindan Vasudevan | Actorius Innovations and Research | Publication Only: Developmental Therapeutics:- Molecularly Targeted Agents and Tumor Biology