Clinical evidence and practical value of circulating tumor cells (CTCs) in colorectal cancer
Provide actionable signals for personalized risk stratification, treatment monitoring, and recurrence early warning for colorectal cancer patients.
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If you or a loved one is facing colorectal cancer, CTC testing is not a magic bullet, but it has real, actionable clinical value in four key areas:
- Risk stratification
- Treatment response monitoring
- Early warning of recurrence
- Supporting immunotherapy decisions
It works best after diagnosis, around surgery, and during systemic therapy (chemo/targeted/immunotherapy). It does not replace colonoscopy, imaging, or CEA, but it often gives an earlier, more dynamic signal. In oncology, that earlier signal can be the difference between months or years of survival. (SEER; American Cancer Society)
Colorectal cancer 5-year relative survival is heavily stage-dependent: overall ~65%, but drops to ~14% once distant metastases appear (stage IV). From a patient’s view, the message is brutally simple: catch it early and keep watching aggressively. CTCs are one of the best tools we have for the “keep watching” part.
Conclusion
Q1: Do early-stage colorectal cancer patients even have CTCs?
Yes — but detection rates vary. In non-metastatic disease, CTCs can already be found in a proportion of patients depending on platform and timing. A negative result does not mean you are tumour-free; a positive result, however, significantly raises risk and justifies tighter surveillance. Bottom line: treat CTCs as part of your personal risk map, not a pass/fail exam. (Scientific Reports 2017; BMC Cancer 2017)
Absolutely — this is one of the strongest real-world settings. Multiple meta-analyses show CTC positivity strongly correlates with shorter progression-free and overall survival. Persistent or rising CTCs during/after treatment are a red flag for residual disease and metastatic potential. Practically: imaging is done every 8–12 weeks; CTC is one blood draw and can be repeated far more often with almost no burden. Falling or undetectable CTCs = good news. Rising CTCs = trigger earlier intervention, often before scans worsen. (BMC Cancer 2015; PLOS ONE 2022)
Q2: I’ve already been diagnosed — is CTC still useful now?
Q3: I’m already monitoring CEA — do I still need CTC?
Yes — they are complementary, not competitive. CEA has limited sensitivity, especially for early recurrence or small-volume disease. CTCs often move before CEA. Multivariate analyses repeatedly show CTC retains independent prognostic power even after adjusting for stage, CEA, and tumour burden. Translation for patients: “CEA normal but CTC high” doesn’t mean panic today — it means tighter follow-up tomorrow (shorter scan intervals, lower threshold for action).
Q4: I’m having (or just had) surgery — can CTC predict recurrence?
Strong evidence says yes. The highest-risk signal is strongest around 1–4 weeks post-op.
- Pre-op positive + post-op still positive → dramatically higher recurrence risk
- Pre-op positive → post-op negative → favourable biology Many centres now use perioperative CTC to re-stratify stage II/III patients and decide intensity of adjuvant therapy or surveillance. (PLOS ONE 2022; BMC Cancer 2017)
Q5: I’m on (or just finished) chemotherapy — can CTC show if it’s working?
Yes, and often earlier than imaging. Persistent low/declining CTCs during chemo → significantly better survival curves. Rising CTCs despite stable scans → hidden progression or emerging resistance → trigger early regimen change or additional imaging. In practice, this is how you avoid wasting months on ineffective treatment.
Q6: My scans say “stable disease” — do I still need CTC?
This is exactly where CTC shines — as an early-warning radar. Rising CTCs in the face of stable imaging is a recognised high-risk scenario and often prompts earlier scans or treatment escalation. Conversely, persistently negative CTCs support continuing current therapy and can safely space out imaging, reducing unnecessary radiation and anxiety.
Q7: I’m considering immunotherapy — does CTC (especially PD-L1 on CTC) help?
Promising but still supplementary. Immunotherapy in colorectal cancer is mainly for MSI-high/dMMR tumours. In MSS/pMMR (the majority), response rates remain low. Emerging data show that PD-L1 expression on CTCs and CTC dynamics can help predict benefit or resistance, but it is not yet a definitive decision gate. Treat PD-L1-CTC as a helpful tie-breaker rather than the sole ticket. (KEYNOTE-177; AJCP 2022; JITC 2022–2023)
Practical Patient Playbook — How to Actually Use CTC
Positioning Think of CTC as one zipper tooth in your monitoring chain alongside imaging, CEA, pathology, and molecular markers. You want convergence, not reliance on any single marker.
Timing
- Baseline before surgery
- ~4 weeks post-op (some centres also at 1 week)
- Before starting chemo/targeted/immunotherapy and every 1–2 cycles thereafter
- Anytime imaging is stable but you or your doctor are uneasy
Interpretation Focus on trend, not single value: Falling → negative = good Persistent high or rising = alarm Discordance with imaging = early warning
Decision-making Rising CTC ≠ immediate drug switch, but it does mean faster risk review (earlier scan, add ctDNA, discuss trials). Negative CTC ≠ you can relax completely, but it does allow safely spacing appointments and scans.
Limitations Different platforms give different numbers — comparability across centres is still limited. Choose a lab with rigorous quality control and have results interpreted by a team experienced in liquid biopsy.
Patient FAQ
- CTC positive = definite metastasis/recurrence? → No. It’s a risk signal, not a death sentence.
- CTC negative = I can stop monitoring? → No. False negatives exist. Keep it in your long-term rhythm.
- PD-L1-CTC before immunotherapy? → Helpful supporting data, but MSI/MMR status remains the primary driver.
- CTC or ctDNA — which one? → Not either/or. ctDNA is ultra-sensitive for minimal residual disease detection; CTC gives live-cell phenotype. Best results come from using both.
Final Word
You don’t need another fancy term — you need earlier, more accurate, more personal clues. The evidence for CTCs in colorectal cancer is now solid enough to claim a permanent seat at the table: risk re-stratification after diagnosis, perioperative recurrence prediction, real-time systemic therapy monitoring, and early radar when scans look quiet. Use it together with imaging, CEA, and molecular markers, and every blood draw becomes actionable intelligence — turning time back into your ally.
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References
- American Cancer Society. (2025). Colorectal cancer survival rates. Retrieved from the American Cancer Society website. Cancer.org
- Huang, X., Gao, P., Song, Y., Sun, J., Chen, X., Zhao, J., Xu, H., & Wang, Z. (2015). Meta-analysis of the prognostic value of circulating tumor cells detected with the CellSearch system in colorectal cancer. BMC Cancer, 15, 202. https://doi.org/10.1186/s12885-015-1218-9 BioMed Central+1
- Lu, Y.-J., Wang, P., Peng, J., Wang, X., Zhu, Y.-W., & Shen, N. (2017). Meta-analysis reveals the prognostic value of circulating tumour cells detected in the peripheral blood in patients with non-metastatic colorectal cancer. Scientific Reports, 7, 905. https://doi.org/10.1038/s41598-017-01066-y Nature
- Wu, J., Li, Z., Zou, J., Li, L., Cui, N., Hao, T., Yi, K., Yang, J., & Wu, Y. (2022). A meta-analysis of the value of circulating tumor cells in monitoring postoperative recurrence and metastasis of colorectal cancer. PLOS ONE, 17(9), e0274282. https://doi.org/10.1371/journal.pone.0274282 PLOS
- Secinti, I. E., Ozgur, T., & Dede, I. (2022). PD-L1 expression in colorectal adenocarcinoma is associated with the tumor immune microenvironment and epithelial-mesenchymal transition. American Journal of Clinical Pathology, 158(4), 506-515. https://doi.org/10.1093/ajcp/aqac077 Oxford Academic
- André, T., Shiu, K.-K., Kim, T. W., Jensen, B. V., Jensen, L. H., Punt, C., … & Diaz, L. A. (2022). Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): Final overall survival analysis. The Lancet Oncology, 23(5), 659-670. https://doi.org/10.1016/S1470-2045(22)00197-8 The Lancet
- National Cancer Institute, Surveillance, Epidemiology, and End Results Program (SEER). (2025). Colorectal Cancer — Cancer Stat Facts. Retrieved from the NCI SEER website. SEER
- Xie, P., Zheng, H., Chen, H., Wei, K., Pan, X., Xu, Q., … & Meng, X. (2021). Tumor response as defined by iRECIST in gastrointestinal malignancies treated with PD-1 and PD-L1 inhibitors and correlation with survival. BMC Cancer, 21, 1246. https://doi.org/10.1186/s12885-021-08944-9 BioMed Central
- (補充參考—液體活檢脈絡) JAMA Oncology Editorial/Analysis (2025). Early ctDNA change and survival in dMMR/MSI-H mCRC treated with ICIs（隨機試驗預先規劃分析）. JAMA Oncology. JAMA Network
- (補充參考—ctDNA 早期預警) Pharmacy Times. (2025). AACR 2025: ctDNA testing identifies recurrence risk within weeks of surgery in colorectal cancer（VICTORI 研究簡報）.