Table 2. Summary of included studies for esophageal cancer.
| Study | Level of evidence | Quality score | Number | Population | Age (years) | Outcome measure | Time to surgery/delay groups | Follow up | Worse outcome | Summary finding |
|---|---|---|---|---|---|---|---|---|---|---|
| Chiu et al., 2013 (18) | 2b | 7 | 276 | Esophagectomy after nCRT | ≤8 weeks: 56.8; >8 weeks: 53.5 | pCR, OS | ±8 weeks | Yes | No | pCR: ≤8 weeks 26%, >8 weeks 20% (P=0.16); OS: ≤8 weeks 29% >8 weeks 23% (P=0.3) |
| Franko et al., 2016 (19) | 2b | 8 | 4,284 | Esophagectomy after nCRT | 60±9.4 | OS | <5, ≥5–7, ≥7–9, ≥9 weeks | 41 months | Yes | OS: <5 weeks ref; ≥5–7 weeks HR 1.001 (0.869–1.154); ≥7–9 weeks HR 0.991 (0.856–1.148); ≥9 weeks HR 1.194 (1.032–1.380) |
| Franko et al., 2018 (20) | 2b | 8 | 1,244 | Esophagectomy after nCRT | Mean 60.5 | OS | Continuous interval | NS: 5-year survival | No | OS: TTS does not affect survival (P=0.769) |
| Furukawa et al., 2018 (21) | 2b | 7 | 134 | Esophagectomy after nCRT | NS | DFS, OS | ±8 weeks | NS: 5-year survival | No | DFS and OS did not significantly differ between the two groups (P=0.2) |
| Grotenhuis et al., 2010 (22) | 2b | 6 | 491 | Primary esophagectomy | Median 65 | OS | From symptoms ±3 months; from diagnosis <5, 5–8, >8 weeks | NS: 5-year survival | No | OS: from symptoms ≤3 vs. >3 months: 24% vs. 29.3% (P=0.10); from diagnosis <5 vs. 5–8 vs. >8 weeks: 24.7% vs. 21.7% vs. 32.3% (P=0.12) |
| Haisley et al., 2016 (23) | 2b | 8 | 234 | Esophagectomy after nCRT | Median age 64 (IQR 58–70) | pCR, OS | 0–42, 43–56, 57–70, 71–84, 85–98, >99 days | NS | No | pCR 85–98 vs. 0–42 days: OR 5.46 (1.16–25.68); OS: no difference between groups |
| Kathiravetpillai et al., 2016 (24) | 2b | 7 | 190 | cT1–3N0–3M0 with esophagectomy after nCRT | NR | pCR, OS | ±8 weeks | NS: 5-year survival | No | pCR: ≤8 vs. >8 weeks: 31.1% vs. 25.6% (P=0.43); OS: ≤8 vs. >8 weeks: 42% vs. 37% (P=0.430) |
| Kim et al., 2012 (25) | 2b | 6 | 266 | Esophagectomy after nCRT | ≤8 weeks mean 57; >8 weeks mean 60 | pCR, OS | ±8 weeks | Median 55 months | No | pCR: ≤8 vs. >8 weeks: 21% vs. 22% (P=0.79); OS: ≤8 weeks vs. >8 weeks 53 vs. 39 months (P=0.23) |
| Klevebro et al., 2019 (26) | 2b | 8 | 643 | Esophagectomy after nCRT with esophageal/GEJ cancer | Median: ≤49 days: 64; >49 days: 65 | pCR, OS | ±49 days | NS: 5-year survival | No | pCR: >49 days: 0.99 (0.64–1.53); OS: >49 days: HR 0.99 (0.79–1.24) |
| Lee et al., 2016 (27) | 2b | 8 | 5,393 | Esophagectomy after nCRT | Median 62 (range, 20–89) | pCR, OS | ≤40, 41–50, 51–63, ≥64 days | NS: 8-year survival | Yes | pCR: ≤41 days: ref; 41–50 days: OR 1.23 (0.95–1.61); 51–63 days: OR 1.42 (1.09–1.84); ≥64 days: OR 1.53 (1.19–1.98); OS: ≤41 days: ref; 41–50 days: HR 0.97 (0.84–1.11); 51–63 days: HR 1.05 (0.91–1.20); ≥64 days: HR 1.16 (1.01–1.33) |
| Raman et al., 2019 (28) | 2b | 7 | 2,495 | cT1N0M0 esophageal adenocarcinoma with primary surgery | Median: <50 days: 64; 50–100 days: 66, >100:65 | OS | <50, 50–100, >100 days | NS: 5-year survival | Yes | OS: <50 days: HR 0.99 (0.98–1.00); 50–100 days: ref; >100 days: HR 1.00 (1.00–1.01) |
| Ranney et al., 2017 (29) | 2b | 7 | 2,444 | Stage II or III with Esophagectomy after nCRT | Median age 61 (IQR: 55–67) | Downstage, OS | ±56 days | NS: 5-year survival | Yes | Downstaging: ≥56 days: OR 1.38 (1.02–1.85); OS ≥56 days: HR 1.44 (1.22–1.71) |
| Ruol et al., 2010 (30) | 2b | 7 | 129 | Esophagectomy after nCRT | Median 60.4 | OS | ≤30, 31–60, 61–90 days | NS: 5-year survival | No | OS: 5-year survival ≤30 days: 0%; 31–60 days: 43%; 61–90 days: 35.9% (P=0.13) |
| Shaikh et al., 2015 (31) | 2b | 6 | 88 | Esophagectomy after nCRT | 61 (range, 36–80) | pCR, OS | 26–45, 46–50, 51–63, ≥64 days | Median 87.7 months | No | pCR: ≤45 days ref; 46–50 days: OR 1.75 (0.34–8.95); 51–63 days: OR 2.06 (0.43–9.87); ≥64 days: OR 4.85 (1.11–21.26); OS: no difference in OS between groups (P=0.24) |
| Shapiro et al., 2014 (32) | 2b | 7 | 325 | Esophagectomy after nCRT | 60 (IQR: 55–67) | pCR, DFS, OS | Continuous interval | NS: 5-year survival | No | pCR: each add. weeks >45 days OR 1.35 (P=0.0004); DFS: each add. weeks HR 0.98 (P=0.620); OS: each add. weeks HR 1.03 (P=0.465) |
| Singla et al., 2018 (33) | 2b | 7 | 226 | Esophagectomy after nCRT | Mean 61 | pCR, OS | ±50 days | Median 52 months | No | OS: ≤50 vs. >50 days: 48.9 vs. 42.6 months (P=0.73); pCR: ≤50 vs. >50 days: 26.9% vs. 19% (P=0.24) |
| Tessier et al., 2014 (34) | 2b | 7 | 257 | Esophagectomy after nCRT | Median: 59 (range, 38–77) | pCR, OS | ±7 weeks | Median 28.4 months | No | pCR: ≥7 weeks: OR 0.8 (0.5–1.4); OS: ≥7 weeks OR 1.0 (0.7–1.4) |
| Tsang et al., 2017 (35) | 4 | 6 | 107 | Esophagectomy after nCRT | Mean ≤64 days: 61; >64 days: 66 | pCR, OS | ±64 days | NS: 5-year survival | No | pCR ≤64 vs. >64 days: 35% vs. 24.5% (P=0.23); OS: ≤64 vs. >64 days: 61.5% vs. 46.2% (P=0.09) |
| van der Wilk et al., 2018 (36) | 2b | 8 | 3,102 | Esophagectomy after nCRT | NS | pCR | 0–5, 6–7, 8–9, 10–12, 13–14, >15 weeks | No | No | pCR: >10 vs. <5 weeks for adenocarcinoma OR 1.35 (1.00–1.95); >13 vs. <5 weeks for squamous cell carcinoma OR 2.86 (1.23–6.65) |
| van der Wilk et al., 2019 (37) | 4 | 7 | 98 | Esophagectomy after nCRT with pCR, active surveillance vs. immediate surgery | Median age: delay: 72; immediate: 70 | DFS, OS | Delay: mean 10 months; immediate: mean 3 months | NS: 3-year survival | No | DFS: delayed resection: HR 1.08 (0.44–2.67); OS: delayed resection: HR 0.41 (0.14–1.20) |
| Visser et al., 2016 (38) | 2b | 7 | 137 | Primary esophagectomy (subgroup of study) | Mean 64±9.9 | DFS, OS | Continuous interval | 56 months | No | DFS: TTS HR 1.03 (0.95–1.12); OS: TTS HR 1.06 (0.99–1.13) |
| Visser et al., 2017 (39) | 2b | 8 | 1,250 | Primary esophagectomy (subgroup of study) | Mean 65±9.5 | Upstaging, OS | ≤5, 5–8, ≥8 weeks | Median 78 months | No | Upstaging: No effect; OS: ≤5 weeks: ref; 5–8 weeks: HR 0.92 (0.76–1.13); ≥8 weeks: HR 1.00 (0.76–1.13) |
| Wang et al., 2015 (40) | 2b | 6 | 665 | Esophagectomy after nCRT | 54±9.4 | OS | <30, 30–59, 60–89, >90 days | NS: 3-year survival | Yes | OS: <30 days: HR 1.15 (0.71–1.86); 30–59 days: HR ref; 60–89 days: HR 0.89 (0.57–1.37); ≥90 days: HR 2.01 (1.14–3.54) |
NS, not stated; OR, odds ratio; HR, hazard ratio; TTS, time to surgery; DFS, disease-free survival; OS, overall survival; ref, reference group; nCRT, neoadjuvant chemoradiotherapy.