Introduction
Materials and methods
Protocol and reporting
Data sources and search strategy
Eligibility criteria and study selection
Data extraction
First author (year, country) | Study period | Study design | No. of patients | Median follow-up (months) | ER definition (months) | Overall recurrence rate (%) | ER rate (%) | 5-year OS in ER group (%) | Inclusion criteria | Exclusion criteria |
---|---|---|---|---|---|---|---|---|---|---|
Bhogal,2015 [18],UK | 2004–2006 | PC | 243 | 58 | 18 | 52.7 | 38.3 | - | LR for CRLM | - |
Chen,2022 [19], China | 2008–2020 | RC | 144 | - | 11 | - | - | - | Histologic CRLM, LR after NAC; | NAR, lack of f/p data |
Dai,2021 [15], China | 2012–2019 | RC | 202 | - | 6 | 77.7 | 43.6 | - | Synchronous CRLM, adenocarcinoma, curative-intent surgery | recurrent CRLM or remnant lesions, lack of f/p data |
Deng,2023 [20], China | 2008–2020 | RC | 323 | - | 13 | - | - | - | Clinical or histological CRLM; simultaneous curative-intent resection | Lack of f/p data, other severe diseases |
Finkelstein, 2008 [21],USA | 1995–2002 | PC | 100 | 31 | 12 | 52 | 30.0 | - | LR for CRLM | Extrahepatic disease |
Imai,2016 [22],France | 1990–2012 | PC | 846 | 57.6 | 8 | 78.8 | 44.8 | 11.1 | Curative surgery for CRLM, a f/u > 2 years | Died of postoperative complications |
Inoue,2020 [23], Japan | 2001–2017 | RC | 295 | - | 6 | 64.1 | 29.8 | 45 | LR for CRLM | Noncurative resection |
Jung,2016 [24], Korea | 1990–2011 | RC | 277 | 45.1 | 6 | - | 10.8 | 33.8 | LR for CRLM | R2 resection |
Kaibori,2012 [14], Japan | 1993–2007 | RC | 119 | 31 | 24 | 53.8 | 45.4 | 24.2 | Curative resection for CRLM | R2 resection |
Lalmahomed,2015 [25], Netherlands | 2008–2012 | RC | 151 | 28 | 12 | 76.2 | 54.3 | - | Adult, adenocarcinoma, CRLM, LR or open RFA | Noncurative resection, extrahepatic metastasis, lack of f/p data |
Lin,2018 [26], China | 1999–2016 | RC | 307 | 31.7 | 6 | 57.3 | 16.0 | - | CRLOM, adenocarcinoma, R0 resection, a f/u > 6 months | Extrahepatic metastasis, R1 or R2 resection, loss to f/p |
Liu,2015 [27], China | 2000–2014 | RC | 303 | 40 | 12 | 63.4 | 47.9 | 16 | LR for CRLM | - |
Malik,2007 [28], UK | 1993–2003 | PC | 430 | 33 | 6 | 66.7 | 20.0 | 22 | LR for CRLM, a f/u > 2 years | NAC, repeated LR |
Mao,2017 [29],China | 2007–2015 | PC | 255 | 28.6 | 6 | 65.1 | 34.1 | 11.8 | Curative-intent LR for histological CRLM, a f/u > 6 months | Extrahepatic metastases, R2 resection, RFA, died within 90 days after surgery, repeated LR |
Narita,2015, [30]Japan | 2007–2009 | PC | 184 | - | 6 | 49.5 | 22.3 | - | R0 LR for CRLM | Extrahepatic recurrence within 6 months, R1/R2 resection |
Sakai,2021 [16],Japan | 2001–2016 | RC | 229 | - | 12 | 73.4 | 42.4 | - | Initial LR for CRLM | R2 resection |
Sun,2014 [31],China | 2000–2013 | PC | 152 | 22 | 6 | 63.1 | 24.9 | - | - | - |
Tabchouri,2018 [32],France | 2000–2016 | PC | 273 | 41 | 6 | 72 | 22.8 | - | Curative-intent LR for CRLM | A f/u < 6 months |
Tanaka,2014 [33], Japan | 1992–2011 | RC | 405 | 31 | 4 | 40.7 | 8.6 | 27.4 | Curative resection for CRLM | R2 resection |
Viganò,2014 [34], Italy, Multicenter | 1998–2009 | PC | 6025 | 34.4 | 6 | 45.4 | 10.6 | 26.9 | LR for CRLM, a f/u > 6 months | R2 resection, f/u < 6 months, two-stage LR, operative mortality |
Viganò,2022 [12], Italy | 2004–2017 | PC | 484 | 34 | 3 | 75.2 | 11.6 | 17.3 | LR for CRLM | Repeated LR, died within 90 days, R2 resection, loss to f/p |
Watanabe,2020 [35], Japan | 2004–2016 | PC | 643 | 44.2 | 6 | 44.3 | 20.7 | 24 | Initial LR for CRLM | R2 resection |
Wong,2022 [36], Australia | 2007–2017 | PC | 194 | 85.3 | 6 | 74.7 | 29.9 | 28.8 | Initial curative‐intent LR for CRLM, a f/u > 6 months | R2 resection, a f/u < 6 months, died within 30 days |
Yamashita,2011 [37], Japan | 1986–2007 | RC | 121 | - | 12 | 67.8 | 43.0 | 20 | Initial curative‐intent LR for CRLM | RFA or MCT |
Risk-of-bias assessment
Statistical analysis
Evidence strength assessment
Result
Study selection
Study characteristics
Definition of early recurrence
Prognostic factors
First author, year | Median age (years) | Male (%) | CEA | CA199 |
---|---|---|---|---|
Bhogal,2015 [18] | - | - | - | - |
Chen,2022 [19] | 55.0 | 67.3 | - | - |
Dai,2021 [15] | 62.7 | 66.7 | 24.2%, > 100 ng/mL | 30.3%, > 320 U/ml |
Deng,2023 [20] | - | 66.8 | 5.0%, > 200 ng/mL | - |
Finkelstein,2008 [21] | - | - | - | - |
Imai,2016 [22] | - | 61.5 | 44.8%, > 10 ng/mL | 29.8%, > 60 U/ml |
Inoue,2020 [23] | 66.0 | 64.8 | 14.9 ng/mL, med | 27.7 U/ml, med |
Jung,2016 [24] | - | 66.7 | 53.3%, ≥ 50 ng/mL | - |
Kaibori,2012 [14] | - | 59.2 | 50%, > 6 ng/mL | 35.2%, > 30 ng/dl |
Lalmahomed,2015 [25] | 63.0 | 63.4 | - | - |
Lin,2018 [26] | - | 65.3 | 52.1%, > 10 ng/mL | 37.5%, > 35 U/ml |
Liu,2015 [27] | - | 44.6 | 47.8%, > 200 ng/mL | - |
Malik,2007 [28] | 62.0 | 55.8 | 25.0 ng/mL, med | 34.0 U/ml, med |
Mao,2017 [29] | 57.0 | 56.3 | 39.1%, > 30 ng/mL | - |
Narita,2015 [30] | 56.5 | 53.3 | 79.8 ng/mL, med | - |
Sakai,2021 [16] | - | - | - | - |
Sun,2014 [31] | 58.2 | 50.0 | 79.1 ng/mL, med | - |
Tabchouri,2018 [32] | - | - | - | - |
Tanaka,2014 [33] | 61.6 | 51.4 | 235.3 ng/mL, med | - |
Viganò,2014 [34] | - | 58.2 | 10.2%, > 200 ng/mL | - |
Viganò,2022 [12] | - | 55.4 | 8.9%, > 200 ng/mL | - |
Watanabe,2020 [35] | 62.0 | 55.0 | 11.1 ng/mL, med | 18.4 U/ml, med |
Wong,2022 [36] | 66.6 | 50.0 | - | - |
Yamashita,2011 [37] | 59.0 | 59.6 | 26.9%, > 50 ng/mL | - |
First author, year | Poor tumor diff-erentiation (%) | LNM (%) | T3-4 (%) | Rectal tumor (%) |
---|---|---|---|---|
Bhogal,2015 [18] | - | - | - | 30.1 |
Chen,2022 [19] | 28.8 | 77.9 | 95.2 | 47.1 |
Dai,2021 [15] | - | 77.3 | - | 25.8 |
Deng,2023 [20] | 34.9 | 83.0 | 94.2 | 44.8 |
Finkelstein,2008 [21] | 30.0 | 70.0 | - | 33.3 |
Imai,2016 [22] | - | 62.3 | 80.2 | 24.6 |
Inoue,2020 [23] | - | 81.8 | - | 42.0 |
Jung,2016 [24] | 66.7 | 63.3 | 63.3 | 40.0 |
Kaibori,2012 [14] | 5.6 | 68.5 | 87.0 | 29.6 |
Lalmahomed,2015 [25] | - | 59.8 | 84.1 | 28.0 |
Lin,2018 [26] | 28.6 | 72.7 | - | 34.7 |
Liu,2015 [27] | - | 54.6 | 47.5 | 47.6 |
Malik,2007 [28] | - | 58.1 | - | - |
Mao,2017 [29] | 28.7 | 81.6 | 96.6 | - |
Narita,2015 [30] | - | 63.3 | - | 36.7 |
Sakai,2021 [16] | - | - | - | - |
Sun,2014 [31] | - | 80.0 | - | 56.7 |
Tabchouri,2018 [32] | - | 77.8 | - | - |
Tanaka,2014 [33] | 11.4 | - | - | 34.3 |
Viganò,2014 [34] | - | 68.8 | 90.8 | 35.6 |
Viganò,2022 [12] | - | 67.9 | 83.9 | 28.6 |
Watanabe,2020 [35] | 6.1 | 76.3 | 87.8 | 37.4 |
Wong,2022 [36] | - | 74.1 | - | 31.0 |
Yamashita,2011 [37] | - | 42.3 | 65.4 | 32.7 |
First author, year | Synchronous metastases (%) | More metastases (%) | Diameter (median, cm) | Bilobar- distribution (%) | Extrahepatic metastases (%) | Initial un- resectable (%) |
---|---|---|---|---|---|---|
Bhogal,2015 [18] | - | - | - | - | - | - |
Chen,2022 [19] | 91.3 | - | 3.0 | 60.6 | 11.5 | - |
Dai,2021 [15] | 78.8 | 42.4 | 2.7 | 40.9 | - | - |
Deng,2023 [20] | - | 66.8 | - | 47.7 | 14.1 | - |
Finkelstein,2008 [21] | 66.7 | 40.0 | - | 26.7 | - | - |
Imai,2016 [22] | 71.8 | 54.0 | 66.7 | 23.0 | 45.2 | |
Inoue,2020 [23] | 63.6 | 64.8 | 3.2 | - | - | - |
Jung,2016 [24] | 93.3 | 56.7 | - | 46.7 | - | - |
Kaibori,2012 [14] | 68.5 | 44.4 | - | 44.4 | - | - |
Lalmahomed,2015 [25] | - | - | 2.8 | 32.9 | - | - |
Lin,2018 [26] | 63.3 | 14.3 | - | 34.7 | - | - |
Liu,2015 [27] | 22.2 | 60.6 | - | 57.3 | 45.5 | - |
Malik,2007 [28] | 47.7 | 36.0 | 4.5 | - | - | - |
Mao,2017 [29] | 80.5 | 82.0 | 3.0 | 50.6 | - | 69.0 |
Narita,2015 [30] | - | 66.7 | - | 43.3 | - | - |
Sakai,2021 [16] | - | - | - | - | - | - |
Sun,2014 [31] | 68.3 | - | 4.1 | - | - | - |
Tabchouri,2018 [32] | - | - | - | - | - | - |
Tanaka,2014 [33] | 74.3 | 54.3 | 5.2 | 74.2 | 14.3 | - |
Viganò,2014 [34] | 63.4 | 29.1 | - | 39.8 | 8.1 | 20.7 |
Viganò,2022 [12] | 78.6 | 92.9 | - | - | 23.2 | - |
Watanabe,2020 [35] | 75.6 | - | 3.0 | - | - | - |
Wong,2022 [36] | 70.6 | - | 3.1 | 44.8 | - | - |
Yamashita,2011 [37] | 82.7 | 36.5 | 3.7 | 28.8 | - | - |
First author, year | Laparoscopic resection (%) | Simultaneous resection (%) | Major hepatectomy (%) | R1 resection (%) | Preoperative chemotherapy (%) | Postoperative chemotherapy (%) | Blood transfusion (%) | Postoperative complications (%) |
---|---|---|---|---|---|---|---|---|
Bhogal,2015 [18] | - | - | - | - | - | 92.3 | - | - |
Chen,2022 [19] | - | 73.1 | 84.6 | 46.2 | 61.5 | 59.6 | - | 59.6 |
Dai,2021 [15] | - | - | - | - | - | - | - | - |
Deng,2023 [20] | 15.8 | - | 57.7 | 32.8 | 56.0 | 63.1 | 23.2 | 53.9 |
Finkelstein,2008 [21] | - | - | 13.3 | 3.3 | - | - | - | - |
Imai,2016 [22] | - | - | 57.1 | 53.2 | 100 | 83.3 | 38.9 | 22.2 |
Inoue,2020 [23] | - | 17.0 | - | 21.8 | 34.1 | 38.8 | 18.4 | 28.4 |
Jung,2016 [24] | 0.0 | 30.0 | 20.0 | 63.3 | - | 40.0 | - | - |
Kaibori,2012 [14] | - | - | 37.0 | 24.1 | 37.0 | 55.6 | 37.0 | 37.0 |
Lalmahomed,2015 [25] | - | 32.9 | - | - | - | - | - | - |
Lin,2018 [26] | - | - | - | - | 55.1 | 71.4 | - | - |
Liu,2015 [27] | - | 51.9 | 50.0 | 45.0 | 58.3 | 48.7 | 61.3 | - |
Malik,2007 [28] | - | - | - | 34.9 | - | - | - | - |
Mao,2017 [29] | 4.6 | 60.9 | - | 42.5 | 74.7 | - | 18.4 | 14.9 |
Narita,2015 [30] | - | 56.7 | 33.3 | - | 80.0 | - | 30.0 | - |
Sakai,2021 [16] | - | - | - | 32.0 | - | - | - | - |
Sun,2014 [31] | - | 11.7 | 28.3 | - | 50.0 | 60.0 | - | 33.3 |
Tabchouri,2018 [32] | - | - | - | - | - | - | - | - |
Tanaka,2014 [33] | - | - | - | - | 34.3 | 68.6 | - | - |
Viganò,2014 [34] | 1.7 | - | - | - | - | 47.9 | 24.4 | - |
Viganò,2022 [12] | - | 10.7 | 10.7 | 73.2 | - | - | - | 33.9 |
Watanabe,2020 [35] | - | - | 17.6 | 11.5 | 38.9 | 39.7 | 13.7 | - |
Wong,2022 [36] | - | - | 39.7 | 34.5 | 86.2 | 74.1 | - | - |
Yamashita,2011 [37] | - | - | 34.6 | - | - | - | 32.7 | - |
Assessment on risk-of-bias
Study | 1.Study participation | 2.Study attrition | 3. PF measurement | 4. Outcome measurement | 5. Adjustment for other PF | 6. Statistical analysis and reporting | Overall |
---|---|---|---|---|---|---|---|
Bhogal,2015, [18] | Moda | Modc | Low | Low | Low | Low | Mod |
Chen,2022, [19] | Low | Low | Low | Low | Low | Low | Low |
Dai,2021, [15] | Low | Low | Low | Low | Low | Low | Low |
Deng,2023, [20] | Low | Modc | Low | Low | Low | Low | Low |
Finkelstein,2008, [21] | Moda | Modc | Low | Low | Low | Low | Mod |
Imai,2016, [22] | Low | Modc | Low | Low | Low | Low | Low |
Inoue,2020 [23] | Low | Mod | Low | Low | Low | Low | Low |
Jung,2016, [24] | Low | Modc | Low | Low | Low | Low | Low |
Kaibori,2012 [14] | Modb | Modc | Low | Low | Low | Low | Mod |
Lalmahomed,2015, [25] | Low | Low | Low | Low | Modf | Low | Low |
Lin,2018, [26] | Low | Low | Low | Low | Low | Low | Low |
Liu,2015, [27] | Moda | Modc | Low | Low | Low | Low | Mod |
Malik,2007, [28] | Low | Modc | Low | Low | Low | Low | Low |
Mao,2017, [29] | Low | Modc | Low | Low | Low | Low | Low |
Narita,2015, [30] | Low | Modc | Low | Low | Modf | Low | Mod |
Sakai,2021, [16] | Low | Modc | Low | Low | Low | Low | Low |
Sun,2014, [31] | Moda | Low | Low | Low | Low | Low | Low |
Tabchouri,2018, [32] | Low | Low | Low | Low | Low | Low | Low |
Tanaka,2014, [33] | Moda | Modc | Low | Mode | Low | Low | High |
Viganò,2014, [34] | Modb | Modc | Modd | Low | Low | Low | High |
Viganò,2022, [12] | Low | Low | Low | Low | Low | Low | Low |
Watanabe,2020, [35] | Low | Low | Low | Low | Low | Low | Low |
Wong,2022, [36] | Low | Low | Low | Low | Low | Low | Low |
Yamashita,2011, [37] | Low | Low | Low | Low | Low | Low | Low |
Meta-analysis for prognostic factors
Outcome | Studies | Participants | RR & 95%CI | P value | I2 | Egger's test P value | Class of Evidence |
---|---|---|---|---|---|---|---|
1. Patient characteristic | |||||||
1.1 Age | 6 | 1584 | 1.06 [0.90, 1.25] | 0.47 | 36% | - | Class II |
1.2 Male | 17 | 4146 | 0.94 [0.86, 1.03] | 0.16 | 24% | 0.185 | Class I |
1.3 Elevated CEA | 9 | 2417 | 1.56 [1.19, 2.04] | 0.001 | 81% | - | Class II |
1.4 Elevated CA199 | 4 | 1138 | 1.48 [1.20, 1.81] | < 0.001 | 36% | - | Class II |
2. Primary tumor characteristics | |||||||
2.1 Poor differentiation | 6 | 1362 | 1.13 [1.03, 1.25] | 0.01 | 0% | - | Class I |
2.2 Lymph node metastasis | 19 | 4471 | 1.31 [1.17, 1.48] | < 0.001 | 47% | 0.035 | Class II |
2.3 T3-4 | 10 | 2558 | 1.04 [0.93, 1.17] | 0.48 | 0% | 0.623 | Class I |
2.4 Rectal tumor | 17 | 3959 | 1.00 [0.91, 1.11] | 0.93 | 41% | 0.897 | Class I |
3. Liver metastases characteristics | |||||||
3.1 Synchronous metastases | 16 | 3702 | 1.23 [0.89, 1.71] | 0.21 | 90% | 0.121 | Class III |
3.2 More metastases | 13 | 3254 | 1.46 [1.26, 1.68] | < 0.001 | 57% | 0.206 | Class II |
3.3 Larger metastases | 7 | 1862 | 1.18 [1.04, 1.34] | 0.01 | 29% | - | Class I |
3.4 Bilobar distribution | 13 | 2717 | 1.37 [1.21, 1.55] | < 0.001 | 40% | 0.811 | Class I |
3.5 Extrahepatic metastases | 4 | 1332 | 1.13 [0.99, 1.29] | 0.06 | 25% | - | Class I |
4. Surgical procedures and operative outcome | |||||||
4.1 Laparoscopic resection | 3 | 855 | 0.87 [0.72, 1.05] | 0.16 | 0% | - | Class II |
4.2 Simultaneous resection | 8 | 2161 | 1.00 [0.83, 1.21] | 0.98 | 55% | - | Class II |
4.3 Major hepatectomy | 12 | 2588 | 1.16 [1.07, 1.25] | < 0.001 | 0% | 0.329 | Class I |
4.4 Positive surgical margin | 12 | 3187 | 1.33 [1.20, 1.48] | < 0.001 | 34% | 0.505 | Class I |
4.5 Preoperative chemotherapy | 12 | 2606 | 1.12 [0.97, 1.28] | 0.12 | 58% | 0.074 | Class III |
4.6 Postoperative chemotherapy | 12 | 3200 | 0.93 [0.78, 1.11] | 0.40 | 74% | 0.616 | Class II |
4.7 Blood transfusion | 9 | 2319 | 1.10 [0.96, 1.25] | 0.16 | 39% | - | Class I |
4.8 Postoperative complications | 6 | 1731 | 1.28 [1.13, 1.44] | < 0.001 | 30% | - | Class I |