Non‐surgical versus surgical treatment for oesophageal cancer

Lawrence MJ Best; Muntzer Mughal; Kurinchi Selvan Gurusamy

doi:10.1002/14651858.CD011498.pub2

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Figure 1

Study flow diagram.

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Figure 2

'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies.

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Figure 3

'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.

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Analysis 1.1

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 1 Short‐term mortality.

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Analysis 1.2

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 2 Long‐term mortality (binary).

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Analysis 1.3

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 3 Long‐term mortality (time‐to‐event).

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Analysis 1.4

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 4 Proportion with a serious adverse event within 3 months.

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Analysis 1.5

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 5 Short‐term health‐related quality of life.

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Analysis 1.6

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 6 Medium‐term health‐related quality of life.

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Analysis 1.7

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 7 Long‐term recurrence (binary).

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Analysis 1.8

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 8 Long‐term recurrence (time‐to‐event).

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Analysis 1.9

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 9 Local recurrence (binary).

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Analysis 1.10

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 10 Proportion with any adverse event within 3 months.

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Analysis 1.11

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 11 Length of hospital stay (days).

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Analysis 1.12

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 12 Dysphagia at maximal follow‐up.

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Analysis 1.13

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 13 Long‐term mortality (time‐to‐event): stratified by treatment.

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Analysis 1.14

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 14 Long‐term mortality (binary): definitive chemoradiotherapy versus surgery with neoadjuvant chemotherapy.

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Analysis 1.15

Comparison 1 Surgical versus non‐surgical treatment of oesophageal cancer, Outcome 15 Long‐term mortality (time‐to‐event): definitive chemoradiotherapy versus surgery with neoadjuvant chemotherapy or chemoradiotherapy.

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Summary of findings for the main comparison. Non‐surgical versus surgical treatment of oesophageal cancer (primary outcomes)

Non‐surgical versus surgical treatment of oesophageal cancer
Patient or population: people with oesophageal cancer Settings: secondary or tertiary care Intervention: non‐surgical treatment Comparison: surgical treatment
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)
	Assumed risk	Corresponding risk
	Surgical treatment	Non‐surgical treatment
Short‐term mortality All‐cause mortality either in‐hospital or within 3 months	78 per 1000¹	30 per 1000 (9 to 105)	RR 0.39 (0.11 to 1.35)	689 (5 studies)	⊕⊝⊝⊝ very low^2,3
Long‐term mortality (binary outcome) All‐cause mortality for the duration of follow‐up	691 per 1000¹	712 per 1000 (636 to 788)	RR 1.03 (0.92 to 1.14)	511 (3 studies)	⊕⊕⊝⊝ low²
Long‐term mortality (time‐to‐event outcome): chemoradiotherapy versus surgery All‐cause mortality for the duration of follow‐up	349 per 1000¹	314 per 1000 (278 to 357)	HR 0.88 (0.76 to 1.03)	602 (4 studies)	⊕⊕⊝⊝ low²
Long‐term mortality (time‐to‐event outcome): radiotherapy versus surgery All‐cause mortality for the duration of follow‐up	350 per 1000¹	451 per 1000 (398 to 507)	HR 1.39 (1.18 to 1.64)	512 (3 studies)	⊕⊝⊝⊝ very low^2,3
Long‐term mortality (binary): definitive chemoradiotherapy versus surgery with neoadjuvant chemotherapy All‐cause mortality for the duration of follow‐up	740 per 1000	769 per 1000 (688 to 858)	RR 1.04 (0.93 to 1.16)	431 (2 studies)	⊕⊝⊝⊝ low²
Long‐term mortality (time‐to‐event): definitive chemoradiotherapy versus surgery with neoadjuvant chemotherapy or chemoradiotherapy All‐cause mortality for the duration of follow‐up	349 per 1000	346 per 1000 (284 to 418)	HR 0.99 (0.78 to 1.26)	431 (2 studies)	⊕⊝⊝⊝ very low^2,4
Proportion with a serious adverse event within 3 months Serious adverse event within 3 months as defined by ICH‐GCP International Conference on Harmonisation ‐ Good Clinical Practice guideline (ICH‐GCP 1996) or reasonable variations thereof	273 per 1000¹	166 per 1000 (68 to 401)	RR 0.61 (0.25 to 1.47)	80 (1 study)	⊕⊝⊝⊝ very low^2,4
Short‐term health‐related quality of life Any validated scale	The mean short‐term health‐related quality of life in the control groups was 7.52	The mean short‐term health‐related quality of life in the intervention groups was 0.93 higher (0.24 to 1.62 higher)	‐	165 (1 study)	⊕⊝⊝⊝ very low^2,5
Medium‐term health‐related quality of life Any validated scale	The mean medium‐term health‐related quality of life in the control groups was 8.76	The mean medium‐term health‐related quality of life in the intervention groups was 0.95 lower (2.1 lower to 0.2 higher)	‐	62 (1 study)	⊕⊝⊝⊝ very low^2,5
The basis for the assumed risk* is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio; HR: hazard ratio.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.
¹The basis for control risk is the event rate across all studies (i.e. the sum of all events in the surgical group across all studies reporting the outcome divided by the sum of all people in the surgical group in the trials reporting the outcome) for all outcomes except long‐term mortality (time‐to‐event) where a control group risk of 0.35 was used (based on similar control group risks at 2 years in a number of trials included in this analysis) and long‐term recurrence (time‐to‐event) where a control group risk of 0.4 was used (based on similar control group risk at 2 year in a trial included for this analysis). ²Downgraded two levels due to significant bias within the trials. ³Downgraded two levels due to inconsistency in the results across the studies. ⁴Downgraded one level due to wide CIs (overlaps 1 and 0.75 or 1.25). ⁵Downgraded one level due to wide CIs (overlaps 0 and 0.25 and −0.25).

Summary of findings for the main comparison. Non‐surgical versus surgical treatment of oesophageal cancer (primary outcomes)

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Summary of findings 2. Non‐surgical versus surgical treatment of oesophageal cancer (secondary outcomes)

Non‐surgical versus surgical treatment of oesophageal cancer
Patient or population: people with oesophageal cancer Settings: secondary or tertiary care Intervention: non‐surgical treatment Comparison: surgical treatment
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Surgical treatment	Non‐surgical treatment
Long‐term recurrence (binary outcome) Local recurrence, surgical wound recurrence, or distal metastases	526 per 1000¹	552 per 1000 (458 to 673)	RR 1.05 (0.87 to 1.28)	339 (2 studies)	⊕⊝⊝⊝ very low^2,3	‐
Long‐term recurrence (time‐to‐event outcome) Local recurrence, surgical wound recurrence, or distal metastases	508 per 1000¹	494 per 1000 (433 to 561)	HR 0.96 (0.8 to 1.16)	349 (2 studies)	⊕⊕⊝⊝ low²	‐
Local recurrence (binary)	381 per 1000	339 per 1000 (267 to 427)	RR 0.89 (0.70 to 1.12)	449 (3 studies)	⊕⊝⊝⊝ very low^2,3,4	‐
Proportion with any adverse event within 3 months Any adverse event within 3 months of any severity	386 per 1000¹	668 per 1000 (429 to 1000)	RR 1.73 (1.11 to 2.67)	80 (1 study)	⊕⊝⊝⊝ very low^2,4	‐
Length of hospital stay (days) Including the index admission for oesophagectomy (the hospital admission during which the oesophagectomy is performed) and any surgical complication‐related readmissions	See comment	See comment	Not estimable	342 (2 studies)	⊕⊝⊝⊝ very low^2,5	Significant heterogeneity present (I² statistic = 93%, P = 0.0001) making meta‐analysis inappropriate. The mean hospital stay was 16 days shorter (3 days shorter to 29 days shorter) in non‐surgical treatment than surgical treatment in 1 trial (Bedenne 2007) and 14 days longer (5 days longer to 23 days longer) in non‐surgical treatment than surgical treatment in another trial (Chiu 2005).
Dysphagia at maximal follow‐up	367 per 1000	543 per 1000 (370 to 803)	RR 1.48 (1.01 to 2.19)	139 (1 study)	⊕⊝⊝⊝ very low^2,4	‐
The basis for the assumed risk* is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio; HR: hazard ratio.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.
¹The basis for control risk is the event rate across all studies (i.e. the sum of all events in the surgical group across all studies reporting the outcome divided by the sum of all people in the surgical group in the trials reporting the outcome). ²Downgraded two levels due to significant bias within the trials. ³Downgraded one level due to inconsistency in the results across the studies. ⁴Downgraded one level due to wide CIs (overlaps 1 and 0.75 or 1.25). ⁵Downgraded one level due to wide CIs (overlaps 0 and 0.25 and −0.25).

Summary of findings 2. Non‐surgical versus surgical treatment of oesophageal cancer (secondary outcomes)

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Comparison 1. Surgical versus non‐surgical treatment of oesophageal cancer

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Short‐term mortality Show forest plot	5	689	Risk Ratio (M‐H, Random, 95% CI)	0.39 [0.11, 1.35]

2 Long‐term mortality (binary) Show forest plot	3	511	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.92, 1.14]

3 Long‐term mortality (time‐to‐event) Show forest plot	7	1114	Hazard Ratio (Fixed, 95% CI)	1.09 [0.97, 1.22]

4 Proportion with a serious adverse event within 3 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Short‐term health‐related quality of life Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

6 Medium‐term health‐related quality of life Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

7 Long‐term recurrence (binary) Show forest plot	2	339	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.87, 1.28]

8 Long‐term recurrence (time‐to‐event) Show forest plot	2	349	Hazard Ratio (Fixed, 95% CI)	0.96 [0.80, 1.16]

9 Local recurrence (binary) Show forest plot	3	449	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.70, 1.12]

10 Proportion with any adverse event within 3 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

11 Length of hospital stay (days) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

12 Dysphagia at maximal follow‐up Show forest plot	1	139	Risk Ratio (M‐H, Fixed, 95% CI)	1.48 [1.01, 2.19]

13 Long‐term mortality (time‐to‐event): stratified by treatment Show forest plot	7	1114	Hazard Ratio (Fixed, 95% CI)	1.09 [0.97, 1.22]

13.1 Chemoradiotherapy	4	602	Hazard Ratio (Fixed, 95% CI)	0.88 [0.76, 1.03]
13.2 Radiotherapy	3	512	Hazard Ratio (Fixed, 95% CI)	1.39 [1.18, 1.64]
14 Long‐term mortality (binary): definitive chemoradiotherapy versus surgery with neoadjuvant chemotherapy Show forest plot	2	431	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.93, 1.16]

15 Long‐term mortality (time‐to‐event): definitive chemoradiotherapy versus surgery with neoadjuvant chemotherapy or chemoradiotherapy Show forest plot	2	431	Hazard Ratio (Fixed, 95% CI)	0.99 [0.78, 1.26]

Comparison 1. Surgical versus non‐surgical treatment of oesophageal cancer

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