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Table 2 Subgroup analyses of diagnostic accuracy variables

From: Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer: systematic review and meta-analysis

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%)
  1. aPooled analysis performed by including results of single marker (either the most specific or the most sensitive in cases with equal specificity) in cases where multiple markers were assessed per study.
  2. bData in parentheses are 95% confidence intervals.
  3. cSubgroup analyses of the different tumor markers used in PCR-based methods included and compared data from all markers in those studies where multiple assays were used.
  4. NR, not reported/retrievable; RBC, red blood cells; TCC, transitional cell cancer.