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. 2025 Feb 12;26(4):1548.
doi: 10.3390/ijms26041548.

Circulating Epithelial Tumor Cells (CETC/CTC) in Prostate Cancer: Potential Prognostic Marker for the Risk of Recurrence During Radiotherapy

Affiliations

Circulating Epithelial Tumor Cells (CETC/CTC) in Prostate Cancer: Potential Prognostic Marker for the Risk of Recurrence During Radiotherapy

Dorothea Schott et al. Int J Mol Sci. .

Abstract

Prostate cancer is a leading cause of cancer-related mortality in men, with radiotherapy (RT) playing a pivotal role in treatment. However, reliable biomarkers for assessing relapse risk following RT remain scarce. This study aimed to evaluate circulating epithelial tumor cells (CETC/CTC) as potential biomarkers for assessing relapse risk in prostate cancer patients undergoing RT. Peripheral blood samples were collected from 52 prostate cancer patients, and CETC/CTC were detected using the EpCAM surface marker. Patients received definitive, adjuvant, or salvage RT, and CETC/CTC counts were measured before, at mid-treatment, and at the end of RT. The association between changes in CETC/CTC counts and relapse risk was examined. CETC/CTC were detected in 96% of patients prior to RT. A significant reduction in CETC/CTC counts during RT, particularly in patients who had undergone surgery, was associated with a lower relapse risk. In contrast, an increase in CETC/CTC counts during or after RT was associated with a higher relapse risk (hazard ratio = 8.8; p = 0.002). Furthermore, 36% of patients receiving adjuvant RT and 14% of those receiving definitive RT relapsed, with a higher risk observed in patients showing increasing CETC/CTC counts during RT. Among patients receiving salvage RT, 18% relapsed, though changes in CETC/CTC counts were less significantly associated with relapse. Monitoring CETC/CTC levels during RT offers important prognostic insights into relapse risk in prostate cancer patients. While changes in CETC/CTC counts correlated with relapse, PSA levels measured during the study did not reliably reflect relapse risk in this cohort. CETC/CTC shows promise as a prognostic marker, though further studies are required to validate its clinical superiority over PSA.

Keywords: PSA; circulating epithelial tumor cells; prognostic biomarker; prostate cancer; radiotherapy; risk stratification.

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Conflict of interest statement

KP is the holder of the patents for the herein described method maintrac® to detect CETC/CTC. The other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of the metastatic process.
Figure 2
Figure 2
Kaplan-Meier estimates of PSA-relapse-free survival in prostate cancer patients treated with definitive, adjuvant, or salvage radiation. Dots represent censored patients.
Figure 3
Figure 3
Boxplot diagram of PSA values before and after RT as a function of recurrence during the observation period.
Figure 4
Figure 4
Boxplot diagram of CETC/CTC counts as a function of (A): surgical intervention or (B): androgen deprivation therapy. * corresponds to statistical significance.
Figure 4
Figure 4
Boxplot diagram of CETC/CTC counts as a function of (A): surgical intervention or (B): androgen deprivation therapy. * corresponds to statistical significance.
Figure 5
Figure 5
(A): Boxplot diagram of the mean number of CETC/CTC in patients after surgery during RT. (B): More than a twofold increase in CETC/CTC numbers was observed in 2 patients after surgery from midterm to the end of RT. * corresponds to statistical significance.
Figure 5
Figure 5
(A): Boxplot diagram of the mean number of CETC/CTC in patients after surgery during RT. (B): More than a twofold increase in CETC/CTC numbers was observed in 2 patients after surgery from midterm to the end of RT. * corresponds to statistical significance.
Figure 6
Figure 6
(A): Boxplot diagram showing the mean number of CETC/CTC in patients undergoing definitive RT. (B): More than a twofold increase in CETC/CTC numbers in eight patients receiving definitive radiotherapy from midterm to the end of RT.
Figure 6
Figure 6
(A): Boxplot diagram showing the mean number of CETC/CTC in patients undergoing definitive RT. (B): More than a twofold increase in CETC/CTC numbers in eight patients receiving definitive radiotherapy from midterm to the end of RT.
Figure 7
Figure 7
Boxplot diagram showing the mean number of CETC/CTC in patients undergoing salvage RT. The error bar for the midterm determination exceeds the scale. In order to keep the scales comparable, the scale was not expanded.
Figure 8
Figure 8
Kaplan-Meier survival curved for prostate cancer patients who received definitive or adjuvant radiotherapy, comparing those with decreasing (upper curve) and increasing (lower curve) CETC/CTC numbers (p = 0.002). Dots represent censored patients.
Figure 9
Figure 9
Circulating epithelial tumor cells. (a) Viable CETC/CTC: In viable cells, the cell membrane is well preserved, preventing the nuclear dye PI (red) from entering the cell. (b) Dead CETC/CTC: In apoptotic cells, the cell membrane becomes permeable, allowing the nucleus to be stained with PI.

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