5. Characteristics of non‐randomized studies.
| Author year | Type of cancer | Type of surgery | Intervention 1 (n) | Intervention 2 (n) | Control (n) | Endpoint | Statistical method | Result* | Date of surgery | Follow‐up until |
| Exadaktylos 2006 | Breast CA | Mastectomy + LND | GA + paravertebral catheter (50) |
‐ | GA (79) | Time to tumour recurrence (local or metastasis) | Adjusted Cox regression | HR 0.21 (0.06‐0.71) | 2001‐2002 | 2005 |
| Ismail 2010 | Cervical CA | First brachytherapy (of several) | SPA or EC (63) |
‐ | GA (69) | 1. Time to tumour recurrence 2. Overall survival |
Adjusted Cox regression | 1. HR 0.95 (0.54‐1.67) 2. HR 1.46 (0.81‐2.61) |
1996‐2003 | nr |
| Gupta 2011b | Colon CA | Colorectal cancer surgery (open) | GA + EC preop (302) |
‐ | GA (58) | Overall mortality | Adjusted Cox regression with stratification on propensity score | HR 0.82 (0.30‐2.19) | 2004‐2009 | 2009 |
| Rectal CA | Colorectal cancer surgery (open) | GA + EC preop (260) |
‐ | GA (35) | Overall mortality | Adjusted Cox regression with stratification on propensity score | HR 0.45 (0.22‐0.90) | 2004‐2009 | 2009 | |
| Vogelaar 2012 (abstract) | Colon CA | Surgery for colon CA | EC 'perioperative' (407) |
‐ | GA (198) | Overall survival | Adjusted Cox regression | HR 0.93 (0.93‐0.98) | 1995‐2003 | 2011 |
|
Luo 2010 (abstract) |
Colon CA | Primary colon surgery | GA + EC (182) |
‐ | GA (931) | Tumour recurrence | Univariable | HR 1.33 (0.94‐1.87) | 2001‐2006 | 2009 |
| Gottschalk 2010 | Colorectal CA | Colorectal cancer surgery | GA + EC preop (256) |
‐ | GA (253) | Time to tumour recurrence | Adjusted Cox model with stratification on propensity score quintiles | HR 0.74 (0.45‐1.22) | 2000‐2007 | 2008 |
| Cummings 2012 | Colorectal CA w/no metastases | Open colectomy | EC (Medicare code) (9670) |
‐ | No EC (Medicare code) (32481) |
1. Overall survival 2. 4‐Year tumour recurrence |
1. Adjusted marginal Cox model with propensity score as co‐variate 2. Adjusted logistic regression |
1. HR 0.92 (0.88‐0.96) 2. OR 1.05 (0.95‐1.15) |
1996‐2005 | 2009 |
| Day 2012 | Colorectal CA | Laparoscopic resection | EC preop (107) |
SPA (144) |
GA + PCA (173) |
1. Overall survival 2. Disease‐free survival |
KM estimate, log‐rank test | 1. P value 0.622 2. P value 0.490 |
2003‐2010 | |
| Lai 2012 | Hepatocellular CA | Percutaneous radiofrequency ablation | GA + EC preop (62) |
‐ | GA (117) |
1. Recurrence‐free survival 2. Overall survival |
Adjusted Cox model with propensity score as co‐variate |
1. 3.66 (2.59‐5.15) 2. 0.77 (0.50‐1.18) |
1999‐2008 | 2011 |
| Gottschalk 2012 | Malignant melanoma | Lymph node dissection | SPA (52) | ‐ | GA (221) | Long‐term survival | Mean survival (months) of matched pairs (52 pairs) |
95.9 (81.2‐110.5) SPA 70.4 (53.6‐87.1) GA P value 0.087 |
1998‐2005 | 2009 |
| Seebacher 1990 | Malignant melanoma | Melanoma resection | Local anaesthesia (376) |
‐ | GA (190) | Survival | KM estimate, log‐rank test | P value 0.51 (stage pT1/2, n = 237) P value 0.006 (stage pT3a, n = 195) in favour of local anaesthesia P value 0.47 (stage pT3b/4, n = 134) |
Control: 1972‐1980 Intervention: 1981‐88 |
1988 |
| Schlagenhauff 2000 | Malignant melanoma w/no metastases | Primary melanoma excision | Local anaesthesia (2185) | ‐ | GA (2136) | Survival | Log‐rank test on matched pairs (1501 pairs) | P value < 0.01 in favour of local anaesthesia | 1976‐1986 | nr |
| De Oliveira 2011 | Ovarian CA | Surgery for ovarian cancer | GA + EC preop (26) |
GA intraop/EC postop (29) |
GA (127) |
1. Overall survival 2. Time to recurrence |
1. Median survival time (months), log‐rank test 2. Adjusted Cox model |
1. 71 m (62‐80) for GA 96 m (84‐109) for EC intraop 70 m (58‐83) for EC postop P value 0.01 for GA vs EC intraop (favours EC intraop) 2. HR 0.37 (0.19‐0.73) for intraop EC HR 0.86 (0.52‐1.41) for postop EC |
2000‐2006 | 2009 |
| Lin 2011 | Ovarian CA | Surgery for ovarian cancer | EC only preop (106) |
‐ | GA (37) | Survival time | Adjusted Cox regression on propensity matched pairs (29 pairs) | HR 0.83 (0.67‐0.99) | 1994‐2006 | 2008 |
|
Koensgen 2013 (abstract) |
Ovarian CA | Primary radical tumour debulking | EC preop + GA (72) | GA (33) |
1. Recurrence‐free survival 2. Overall survival |
KM estimate, log‐rank test |
1. HR 1.52 (1.4‐1.56), P value 0.008 2. nr |
2003‐2010 | nr | |
| Lacassie 2013 | Ovarian cancer (Figo IIIc‐IV) |
Exploratory laparotomy | EC preop or postop + GA (37) | GA (43) | 1. Time to recurrence 2. Cancer‐specific survival |
Adjusted Cox regression with propensity score weighting | 1. HR 0.65 (0.40‐1.08) 2. HR 0.59 (0.32‐1.08) |
2000‐2011 | nr | |
| Kienbaum 2010/Alexander 2009 (abstracts) | Pancreatic CA | Radical pancreatic tumour resection | GA + EC (71) |
‐ | GA (29) | Overall survival | Log‐rank | P value 0.05 (P value 0.025 in favour of control for participants receiving high‐dose epidural opioids) |
2005‐2008 | nr |
| Biki 2008 | Prostate CA | Open radical prostatectomy | GA + EC preop (102) | ‐ | GA (123) | BCR‐free survival | Univariable Cox regression on propensity matched pairs (71 pairs) | HR 0.48 (0.23‐1.00) | 1994‐2003 | 2006 |
| Forget 2011 | Prostate CA w/no metastasis | Radical prostatectomy | GA + EC preop (578) |
‐ | GA (533) | BCR‐free survival | Adjusted Cox model | HR 0.84 (0.52‐1.17) | 1993‐2006 | 2006 |
| Wuethrich 2010 | Prostate CA (all stages) | Open radical retropubic prostatectomy w/LND | GA + EC preop (103) |
‐ | GA (158) | 1. BCR‐free survival 2. Clinical progression‐free survival 3. Cancer‐specific survival 4. Overall survival |
Adjusted Cox model with propensity score as co‐variate | 1. HR 0.82 (0.50‐1.34) 2. HR 0.40 (0.20‐0.79) 3. HR 0.95 (0.36‐2.47) 4. HR 1.01 (0.44‐2.32) |
Intervention: 1994‐1997 Control: 1997‐2000 |
nr |
| Wuethrich 2013 | Prostate CA (pT3/4) | Retropubic radical prostatectomy w/LND | GA + EC preop (67) |
‐ | GA (81) | 1. BCR‐free survival 2. Local recurrence‐free survival 3. Distant recurrence‐free survival 4. Cancer‐specific survival 5. Overall survival |
Univariable Cox regression on matched pairs (67 pairs) | 1. HR 1.00 (0.69‐1.47) 2. HR 1.16 (0.41‐3.29) 3. HR 0.56 (0.26‐1.25) 4. HR 0.96 (0.45‐2.05) 5. HR 1.17 (0.63‐2.17) |
1994‐2000 | nr |
Several statistical methods were used in most studies. We weighted reported results in the following descending order: adjusted regression with propensity score or matched pairs, adjusted regression, univariable analysis. Only the highest weighted analysis is reported in the table.
HR = hazard ratio, defined as intervention/control.
*HR < 1 denotes advantage for the intervention group, HR > 1 denotes advantage for the control group. We adjusted the HR derived from individual trials accordingly, as needed.
bold font denotes significant results in favour of the intervention group (EC).
italic font denotes significant results in favour of the control group (GA).
CA = cancer.
pT = pathological tumour staging.
EC = epidural catheter.
SPA = spinal anaesthesia.
GA = general anaesthesia.
LND = lymph node dissection.
preop = preoperatively.
postop = postoperatively.
n = number of participants.
OR = odds ratio.
n.s. = non‐significant.
BCR = biochemical recurrence.
nr = not reported.
m = months.