Background
Methods
Publication Search
Inclusion and Exclusion Criteria
Data Extraction
Statistical Analysis
Results
Search Results
Baseline characteristics of identified studies
First author (year of publication) (reference) | Country of origin | CTC+ patients (marker used) | CTC+ controls (marker used) | Patient age (years) | Tumor histology | Tumor location | Tumor stage (AJCC) | Rate of CTC+ stage ≤II pts (marker used) | Rate of CTC+ stage III-IV pts (Marker used) | |
---|---|---|---|---|---|---|---|---|---|---|
Median (range) | Mean (range) | |||||||||
Gazzaniga (2005)[37] | Italy | 11/19 (Tenascin C), 11/19 (EGFR) | 0/40 (Tenascin C) 0/40 (EGFR) | NR | NR | NR | B | I-IV | NR | NR |
Ribal (2006)[23] | Spain | 23/70 | 0/22 | 65 (44-81) | - | TCC | B | 0a-IV | 4/31 | 17/39 |
Champelovier (1999)[38] | France | 3/4 | 21/29 | NR | NR | NR | B | NR | NR | NR |
Okegawa (2004)[39] | Japan | 25/108 (UP II), 31/108 (CK-20) | Healthy volunteers: 0/20 for either marker; nonmalignant bladder disease patients: 0/10 for UP II and 2/10 for CK-20 | Bladder cancer and nonmalignant bladder patients: 57 (42-75); healthy volunteers: 41 (21-52) | - | TCC | B | 0a-IV | 20/91 (CK-20) 14/91 (UP II) | 11/17 (CK-20) 11/17 (UP II) |
Retz (2001)[24] | Germany | 2/20 | 0/10 (isolated PBMN) | (34-79) | - | NR | B | 0a-IV | 0/14 | 2/6 |
Gudemann (2000)[16] | Germany | 12/49 | Healthy volunteers: 0/22; urocystitis patients: 0/6; benign renal tumor patients: 0/6; patients with prior history of urothelial cancer but no evidence of recurrence: 0/4 | Cancer patients: 68 (60-75); urocystitis patients: 72 (68-74) | - | TCC | B: 48/49 U/P: 1/49 | 0a-IV | 5/35 | 7/14 |
Li (1999)[40] | U.S.A. | 3/60 | 0/10 | NR | NR | TCC | B | NR | NR | NR |
Soria (2002)[25] | France | 27/30 | 0/17 | Patients: 68.5 (49-99); controls: (26-58) | - | NR | B | 0-IV | 14/15 | 13/15 |
Desgrandchamps (1999)[41] | U.K. | 1/31 | 0/2 (initially thought to have malignant bladder disease, one patient was found to have nonspecific inflammation and one schistosomiasis) | NR | NR | TCC | B | 0a-IV | 0/25 | 1/6 |
Naoe (2007)[18] | Japan | 8/26 | No controls assessed | 70.5 (55-85) | - | TCC | B: 22/26 U: 3/26 P: 1/26 | 0a-IV | 0/8 | 8/18 |
Kinjo (2004)[19] | Japan | 18/38 | 0/18 (UTI n = 6; BPH n = 7; other benign conditions n = 5) | Cancer patients: 67 (35-87); controls:56 (18-78) | - | TCC:36/38; TCC+sq:1/38; TCC+ad:1/38 | B | 0a-IV | 13/33 | 5/5 |
Guzzo (2009)[26] | U.S.A. | 9/43 | No controls assessed | - | 67.5 (46-83) | TCC | B | 0a-IV | 2/17 | 7/26 |
Allard (2004)[43] | U.S.A. | 6/7 | 8/145 healthy pre- and post-menopausal women had 1 CTC; 14/199 women with benign breast diseases had 1 CTC (none had ≥2 CTCs) | NR | NR | NR | B | IV | NR | NR |
Lu (2000)[20] | Japan | 15/56 | 0/10 healthy volunteers; 0/10 patients with renal cell cancer | 71.5 (35-87) | 69.41 | TCC | B: 42/56 B/U: 1/56 U: 9/56 P: 4/56 | 0a-IV | 4/34 | 11/22 |
Osman (2004)[45] | U.S.A. | 21/48 (UP Ia), 10/48 (UP Ib), 25/48 (UP II), 11/48 (UP III), 26/48 (EGFR)a
| 5/14 (UP Ia), 7/14 (UP Ib), 5/14 (UP II), 10/14 (UP III), 10/14 (EGFR)a
| 64 (42-88) | - | NR | B | III-IV | NR | NR |
Rink (2011)[27] | Germany | 20/55 | 1/10 | Patients: 67 (44-89); healthy volunteers: 45 | Patients:66; healthy volunteers: 46 | TCC | B | 0a-IV | NR | NR |
Fujii (1999)[21] | Japan | 9/40 | 0/25 | NR | NR | TCC | B: 27/40 U/P: 12/40 Urethra: 1/40 | 0a-IV | NR | NR |
Okegawa (2010)[22] | Japan | 11/36 | No controls assessed | Stages I-II patients: 71; stage III-IV patients: 68 | - | TCC | B: 28/36 U/P: 8/36 | I-IV | 0/16 | 11/20 |
Gradilone (2010)[48] | Italy | 24/54 (CD45-/CK8+), 22/54 (survivin) | 0/20 | 57.5 (51-64) | - | NR | B | I | NR | NR |
Meye (2002) | Germany | 18/34 | 0/20 | NR | NR | TCC | B | NR | NR | NR |
Gazzaniga (2001)[50] | Italy | 20/27 (EGFR); 17/27 (UP II); 11/27 (CK-19); 4/27 (CK-20) | Healthy volunteers: 0/30 (EGFR), 0/30 (UP II), 6/30 (CK-19), 4/30 (CK-20); cystitis patients: 0/9 (EGFR), 3/9 (UP II), 3/9 (CK-19), 2/9 (CK-20) | NR | NR | TCC | B | Oa-IV | 2/8 (EGFR) 7/8 (UP II) 1/8 (CK-19) 1/8 (CK-20) | 18/19 (EGFR) 3/19 (UP II) 10/19 (CK-19) 3/19 (CK-20) |
CTC Diagnostic Value
Parameter | Subgroupsa
| Sensitivityb
| Specificityb
| Positive likelihood ratiob
| Negative likelihood ratiob
|
---|---|---|---|---|---|
Country of origin | Germany (n = 4) | 32.9% (25.7 to 40.8%; I2 = 77.8%) | 98.7% (93.1 to 100%; I2 = 28.6%) | 6.86 (1.99 to 23.63; I2 = 0) | 0.72 (0.57 to 0.92; I2 = 75.1%) |
Italy (n = 3) | 55.0% (44.7 to 65.0%; I2 = 70.0%) | 100% (96.3 to 100%; I2 = 0) | 37.15 (7.53 to 183.47; I2 = 0) | 0.43 (0.26 to 0.71; I2 = 74.7%) | |
Japan (n = 4) | 27.7% (22.1 to 33.8%; I2 = 64.1%) | 100% (96.1 to 100%; I2 = 0) | 13.79 (3.45 to 55.22; I2 = 0) | 0.74 (0.65 to 0.83; I2 = 47.8%) | |
USA (n = 3) | 29.6% (21.4 to 38.8%; I2 = 95.4%) | 92.7% (89.5 to 95.1%; I2 = 82.2%) | 3.25 (0.27 to 38.72; I2 = 95.4%) | 0.60 (0.18 to 1.97; I2 = 93.4%) | |
Other (n = 4) | 40.0% (31.7 to 48.8%; I2 = 95.0%) | 70.0% (57.9 to 80.4%; I2 = 94.2%) | 3.34 (0.11 to 104.66; I2 = 90.6) | 0.55 (0.22 to 1.38; I2 = 89.0%) | |
Histologic tumor type | TCC ± other components (n = 11) | 28.9% (25.2 to 32.8%; I2 = 87.5%) | 99.6% (97.6 to 100%; I2 = 0) | 8.42 (3.5 to 20.29; I2 = 15.6%) | 0.71 (0.61 to 0.83; I2 = 82.1%) |
Not reported (n = 7) | 53.8% (46.3 to 61.2%; I2 = 85.7%) | 89.9% (86.8 to 92.4%; I2 = 93.7%) | 5.89 (1.61 to 21.62; I2 = 89.2%) | 0.49 (0.28 to 0.85; I2 = 89.2%) | |
Sampling time | Pretreatment or ≥7 days post-chemotherapy (n = 11) | 31.0% (27.0 to 35.2%; I2 = 50.0%) | 95.8% (93.8 to 97.4%; I2 = 53.1%) | 11.57 (7.28 to 18.40; I2 = 1.3%) | 0.71 (0.62 to 0.81; I2 = 71.2%) |
NR or miscellany (n = 7) | 43.2% (36.9 to 49.7%; I2 = 93.8%) | 83.1% (76.2 to 88.7%; I2 = 93.1%) | 5.69 (1.16 to 27.97; I2 = 86.7%) | 0.52 (0.30 to 0.89; I2 = 94.2%) | |
Blood sample volume | ≤7.5 ml (n = 8) | 31.3% (26.6 to 36.4%; I2 = 89.2%) | 88.8% (83.5 to 92.8%; I2 = 92.8%) | 8.16 (1.17 to 56.83; I2 = 85.8%) | 0.64 (0.49 to 0.85; I2 = 89.7%) |
> 7.5 ml (n = 10) | 38.4% (33.5 to 43.5%; I2 = 89.9%) | 94.7% (92.4 to 96.5%; I2 = 69.6%) | 7.15 (2.52 to 20.32; I2 = 71.2%) | 0.67 (0.54 to 0.83; I2 = 82.4%) | |
Collection of two consecutive blood samples | Yes (n = 6) | 41.2% (35.2 to 47.5%; I2 = 90.3%) | 100% (97.1 to 100%; I2 = 0) | 15.32 (4.91 to 47.84; I2 = 0) | 0.61 (0.46 to 0.81; I2 = 87.6%) |
No (n = 12) | 31.6% (27.6 to 36.0%; I2 = 89.0%) | 91.6% (89.0 to 93.7%; I2 = 90.3%) | 5.33 (1.93 to 14.68; I2 = 83.0%) | 0.69 (0.56 to 0.85; I2 = 85.4%) | |
Cell separation method | Ficoll-Hypaque centrifugation ± further methods (n = 8) | 34.4% (29.2 to 39.9%; I2 = 90.5%) | 87.9% (82.0 to 92.3%; I2 = 92.5%) | 6.99 (0.88 to 55.73; I2 = 85.9%) | 0.69 (0.56 to 0.84; I2 = 76.8%) |
RBC lysis protocols (n = 3) | 35.1% (28.4 to 42.2%; I2 = 87.0%) | 91.9% (82.2 to 97.3%; I2 = 87.9%) | 5.74 (0.50 to 65.75; I2 = 75.8%) | 0.69 (0.52 to 0.91; I2 = 66.4%) | |
Other protocols or NR (n = 7) | 35.5% (29.5 to 41.9%; I2 = 91.3%) | 95.1% (92.8 to 96.9%; I2 = 56.8%) | 10.77 (4.92 to 23.56; I2 = 19.9%) | 0.57 (0.36 to 0.92; I2 = 94.3%) | |
Molecular detection technique | RT-PCR based (including nested RT-PCR; n = 13) | 32.0% (28.3 to 36.0%; I2 = 85.8%) | 91.7% (88.1 to 94.5%; I2 = 90.6%) | 7.75 (2.38 to 25.24; I2 = 80.2%) | 0.70 (0.61 to 0.81; I2 = 81.8%) |
Other (n = 5) | 45.9% (37.9 to 54.0%; I2 = 93.7%) | 94.1% (91.3 to 96.3%; I2 = 22.2%) | 7.60 (2.17 to 26.67; I2 = 53.3%) | 0.45 (0.22 to 0.94; I2 = 89.4%) | |
Nested RT-PCR method | Yes (n = 9) | 30.5% (26.2 to 35.1%; I2 = 71.6%) | 87.4% (82.1 to 91.6%; I2 = 92.3%) | 5.37 (1.58 to 18.27; I2 = 77.7%) | 0.76 (0.70 to 0.82; I2 = 24.7%) |
No (n = 9) | 41.0% (35.5 to 46.6%; I2 = 93.4%) | 95.4% (93.2 to 97.1%; I2 = 52.1%) | 10.08 (3.90 to 26.08; I2 = 43.1%) | 0.49 (0.29 to 0.81; I2 = 94.2%) | |
PCR marker usedc
| CK-20 (n = 7) | 26.4% (21.7 to 31.6%; I2 = 48.8%) | 85.0% (79.1 to 89.7%; I2 = 92.6%) | 3.38 (0.99 to 11.59; I2 = 74.5%) | 0.80 (0.73 to 0.89; I2 = 43.1%) |
UP II (n = 5) | 28.4% (23.4 to 33.9%; I2 = 91.9%) | 92.9% (86.5 to 96.9%; I2 = 78.2%) | 4.15 (1.20 to 14.33; I2 = 62.8%) | 0.75 (0.59 to 0.95; I2 = 85.2%) | |
EGFR (n = 3) | 60.6% (50.0 to 70.6%; I2 = 34.4%) | 89.2% (81.1 to 94.7%; I2 = 95.7%) | 11.94 (0.03 to 4369.8; I2 = 96.2%) | 0.54 (0.23 to 1.28; I2 = 81.1%) | |
Other (n = 6) | 36.0% (29.7 to 42.6%; I2 = 69.4%) | 77.7% (69.9 to 84.3%; I2 = 90.2%) | 1.48 (0.47 to 4.65; I2 = 88.0%) | 0.87 (0.56 to 1.35; I2 = 81.7%) |
Association of CTC detection with disease stage
Parameter | Subgroupa
| ORb
| Parameter | Subgroups | ORb
|
---|---|---|---|---|---|
Country of origin | Japan (n = 5) | 10.48 (4.82 to 22.78; I2 = 0) | Histologic tumor type | TCC (n = 9) | 7.91 (4.60 to 13.61; I2 = 0) |
Other (n = 7) | 5.20 (2.21 to 12.25; I2 = 22.7%) | Not reported or TCC+other components (n = 3) | 3.94 (0.35 to 43.85; I2 = 51.1%) | ||
Cell separation method | Ficoll-Hypaque centrifugation ± further methods (n = 5) | 5.07 (2.48 to 10.35; I2 = 0) | Sampling time | Pretreatment or ≥7 days post-chemotherapy (n = 9 | 8.24 (4.63 to 14.68; I2 = 0) |
CellSearch method (n = 3) | 7.43 (1.52 to 36.25; I2 = 22.4%) | NR or miscellany (n = 3) | 3.95 (0.36 to 43.95; I2 = 71.0%) | ||
Other protocols or NR (n = 4) | 13.57 (5.27 to 34.95; I2 = 0) | ||||
Blood sample volume | ≤7.5 ml (n = 6) | 9.36 (4.65 to 18.86; I2 = 0) | Collection of two consecutive blood samples | Yes (n = 4) | 4.25 (1.56 to 11.62; I2 = 21.1%) |
> 7.5 ml (n = 6) | 5.00 (2.27 to 11.00; I2 = 0) | No (n = 8) | 9.53 (4.88 to 18.62; I2 = 0) | ||
Molecular detection technique | RT-PCR based (including nested RT-PCR; n = 7) | 8.36 (4.62 to 15.13; I2 = 0) | Nested RT-PCR method | Yes (n = 6) | 7.53 (4.09 to 13.85; I2 = 0) |
Other (n = 5) | 4.55 (1.07 to 19.35; I2 = 34.7%) | No (n = 6) | 7.21 (1.66 to 31.28; I2 = 47.0%) | ||
PCR marker usedc
| CK-20 (n = 5) | 5.47 (2.80 to 10.68; I2 = 0) | |||
UP II (n = 3) | 1.59 (0.10 to 25.27; I2 = 89.8%) | ||||
Other (n = 3) | 17.50 (3.98 to 77.03; I2 = 0) |