Table 1.
Study | Country | Patient number | Sampling time | Median follow-up (months) | Disease stage | Cancer type | Detection method | Blood volume (mL)a | RT-PCR marker | Detection rate, % (n/N)b | Cut-off of CTC-positive | Diagnostic specificity, % (n/N)c | Outcomes | HR estimation | Multivariate adjustment |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Hardingham11 | Australia | 94 | Preoperative | 14.8 | Dukes’A-C | CRC | RT-PCR | 10 | CK19, CK20, MUC1, MUC2 | 20 (19/94) | — | 100 (18/18) | OS | Reported | No |
31 | Preoperative | 14.8 | Dukes’s C | CRC | RT-PCR | 10 | CK19, CK20, MUC1, MUC2 | 42 (13/31) | — | 100 (18/18) | OS | Reported | No | ||
Bessa20 | Spain | 32 | Preoperative | 42 | TNM II | CRC | RT-PCR | 20 | CEA | 38 (12/32) | — | NR | DFS | Extrapolated | No |
27 | Preoperative | 42 | TNM III | CRC | RT-PCR | 20 | CEA | 41 (11/27) | — | NR | DFS | Extrapolated | No | ||
Ito21 | Japan | 99 | Postoperative | NR | TNM I-III | CRC | RT-PCR | 5–7 | CEA | 26 (26/99) | — | 100 (20/20) | DFS | Extrapolated | No |
Bessa22 | Spain | 66 | Postoperative | 36 | TNM I-III | CRC | RT-PCR | 20 | CEA | 55 (36/66) | — | NR | RFS; OS | Extrapolated | No |
24 | Postoperative | 36 | TNM III | CRC | RT-PCR | 20 | CEA | 58 (14/24) | — | NR | RFS | Extrapolated | No | ||
Sadahiro23 | Japan | 99 | During surgery | 59 | TNM I-III | CRC | RT-PCR | NR | CEA | 39 (39/99) | — | NR | RFS | Reported | Yes |
Douard24 | France | 89 | Preoperative | NR | TNM I-III | CRC | RT-PCR | 10 | CGM2 | 44 (39/89) | — | NR | RFS | Extrapolated | No |
Koch12 | Germany | 82 | Postoperative | 58 | TNM II | CRC | RT-PCR | 10 | CK20 | 34 (28/82) | — | 100 (98/98) | RFS; CRS | Reported | Yes |
Allen-Mersh13 | UK | 113 | Postoperative | 46.4 | Dukes’A-C | CRC | RT-PCR | 14 | CEA/CK20 | 30 (34/113) | — | 98 (199/203) | RFS | Reported | Yes |
Sadahiro29 | Japan | 200 | Postoperative | 52 | TNM I-III | CRC | RT-PCR | NR | CEA | 22 (44/200) | — | NR | DFS; OS | Reported | Yes |
Koyanagi14 | USA | 34 | Preoperative | 34 | TNM I-III | CRC | RT-PCR | 9 | c-MET, MAGE-A3, GalNAc-T, CK20 | 47 (16/34) | — | 100 (47/47) | OS | Reported | Yes |
Uen15 | China | 438 | Preoperative and postoperative | 44 | TNM I-III | CRC | RT-PCR | 4 | hTERT, CK19, CK20, CEA | 31 (137/438) | — | NR | RFS | Reported | Yes |
287 | Preoperative and postoperative | 44 | TNM I-III | Colon cancer | RT-PCR | 4 | hTERT, CK19, CK20, CEA | 32 (92/287) | — | NR | RFS | Extrapolated | No | ||
151 | Preoperative and postoperative | 44 | TNM I-III | Rectal cancer | RT-PCR | 4 | hTERT, CK19, CK20, CEA | 30 (45/151) | — | NR | RFS | Extrapolated | No | ||
Iinuma (training)16 | Japan | 420 | Preoperative | NR | Dukes’B-C | CRC | RT-PCR | 10 | CEA, CK19, CK20, CD133 | 25 (106/420) | — | NR | DFS; OS | Reported | Yes |
176 | Preoperative | NR | Dukes’B | CRC | RT-PCR | 10 | CEA, CK19, CK20, CD133 | 23 (41/176) | — | NR | DFS; OS | Reported | Yes | ||
150 | Preoperative | NR | Dukes’C | CRC | RT-PCR | 10 | CEA, CK19, CK20, CD133 | 38 (57/150) | — | NR | DFS; OS | Reported | Yes | ||
268 | Preoperative | NR | Dukes’B-C | Colon cancer | RT-PCR | 10 | CEA, CK19, CK20, CD133 | 26 (69/268) | — | NR | DFS; OS | Extrapolated | No | ||
152 | Preoperative | NR | Dukes’B-C | Rectal cancer | RT-PCR | 10 | CEA, CK19, CK20, CD133 | 24 (37/152) | — | NR | DFS; OS | Extrapolated | No | ||
Iinuma (validation)16 | Japan | 315 | Preoperative | NR | Dukes’B-C | CRC | RT-PCR | 10 | CEA, CK19, CK20, CD133 | 24 (75/315) | — | NR | DFS; OS | Reported | Yes |
143 | Preoperative | NR | Dukes’B | CRC | RT-PCR | 10 | CEA, CK19, CK20, CD133 | 22 (32/143) | — | NR | DFS; OS | Reported | Yes | ||
97 | Preoperative | NR | Dukes’C | CRC | RT-PCR | 10 | CEA, CK19, CK20, CD133 | 36 (35/97) | — | NR | DFS; OS | Reported | Yes | ||
203 | Preoperative | NR | Dukes’B-C | Colon cancer | RT-PCR | 10 | CEA, CK19, CK20, CD133 | 23 (46/203) | — | NR | DFS; OS | Extrapolated | No | ||
112 | Preoperative | NR | Dukes’B-C | Rectal cancer | RT-PCR | 10 | CEA, CK19, CK20, CD133 | 25 (28/112) | — | NR | DFS; OS | Extrapolated | No | ||
Lu17 | China | 141 | Postoperative | 40 | TNM II-III | Colon cancer | RT-PCR | 4 | hTERT, CK19, CK20, CEA | 36 (51/141) | — | NR | RFS; OS | Reported for RFS; Extrapolated for OS | Yes for RFS; No for OS |
Deneve 25 | France | 60 | Preoperative | 36 | M0 | CRC | Epispot | 10–20 | CK19 | 12 (7/60) | 27 CTCs/10–20 mL | 100 (20/20) | CRS | Extrapolated | No |
Lu30 d | China | 90 | Postoperative | 36 | TNM III | Colon cancer | RT-PCR | 4 | hTERT, CK19, CK20, CEA | 23 (21/90) | — | NR | DFS; OS | Reported | Yes |
Bork18 | Germany | 239 | Preoperative | 28 | TNM I-III | CRC | CellSearch | 7.5 | — | 8.8 (21/239) | 1 CTC/7.5 mL | NR | PFS; OS | Reported | Yes |
Sotelo26 | Spain | 472 | Postoperative | 40 | TNM III | CRC | CellSearch | 7.5 | — | 35 (166/472) | 1 CTC/7.5 mL | NR | DFS; OS | Reported | Yes |
van Dalum28 | Netherlands | 183 | Preoperative | 61 | TNM I-III | CRC | CellSearch | 7.5 | — | 24 (44/183) | 1 CTC/30 mL | NR | RFS; CCRD | Reported | Yes |
146 | Postoperative | 61 | TNM I-III | CRC | CellSearch | 7.5 | — | 20 (29/146) | 1 CTC/30 mL | NR | CCRD | Extrapolated | No | ||
Kust27 | Croatia | 82 | Preoperative | 50 | TNM I-III | CRC | RT-PCR | 10 | CK20 | 73 (60/82) | — | 70 (16/23) | RFS; OS | Extrapolated | No |
82 | Postoperative | 50 | TNM I-III | CRC | RT-PCR | 10 | CK20 | 74 (61/82) | — | 70 (16/23) | RFS; OS | Extrapolated | No | ||
Tsai19 | China | 84 | Preoperative | NR | TNM I-III | CRC | CMx platform | 2 | CK20 | 43 (36/84) | 5 CTCs/2 mL | 100 (27/27) | DFS | Reported | Yes |
Abbreviations: NR, not reported; M0, non-metastasis; M1, metastasis; RT-PCR, reverse transcriptase polymerase chain reaction; OS, overall survival; DFS, disease-free survival; RFS, recurrence-free survival; CRS, cancer-related survival; CCRD, colon cancer related death.
aIt referred to the sample blood volume used for CTC isolation in each study.
bIt referred to the number of CTC-positive patients (n) per total number of patients (N) included in each study.
cIt referred to the number of CTC-negative subjects (n) per total number of healthy controls (N) included in each study.
dThe study of Lu (2013) was removed in the overall analysis because it had overlapping cases with the study of Lu (2011), but it was included in the subgroup analysis based on cancer type.