Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Chidambaram, 2022

PS. Study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of cohort studies

Literature search up to July 2021

A: Abate, 2009

B: Antonowicz, 2015

C: DeSouza, 2018

D: Jiang, 2020

E: Lou, 2013

F: Sisic, 2017

G: Elliot, 2020

Study design:

A: Retrospective cohort study

B: Retrospective cohort study

C: Retrospective cohort study

D: Retrospective cohort study

E: Retrospective cohort study

F: Retrospective cohort study

G: Prospective cohort study

Setting and Country:

Not reported

Source of funding and conflicts of interest:

Not reported

Inclusion criteria SR:

- RCT’s, quasi-randomized trials, cohort studies, case control studies;

- Investigating the use of surveillance protocol in patients who had undergone surgery for gastric or esophageal cancer or compared factors between symptomatic and asymptomatic recurrence;

- Surveillance included any form such as regular clinical follow-up (history and examination), blood tests, radiological investigations and endoscopy;

- Studies with any type of surgery carried out with a curative intent;

- Studies involving patients who underwent surgery alongside adjuvant or neoadjuvant chemotherapy

Exclusion criteria SR:

- Review articles and case reports;

- Studies with no comparative group;

- Comparative studies with no outcome data provided for the control or intervention group

- Studies with post-surgery surveillance in a cohort of patients who would have required monitoring regardless, such as patients with hereditary syndromes

- Studies which included patients who did not undergo surgery but underwent only other curative therapies and if other cancer types were included

Regarding the scope of this data extraction, only 6 studies regarding patients with esophageal cancer, were included

Important patient characteristics at baseline:

N; mean age

A: 174 patients; I: 56 years, C: 69 years

B: I: 17 patients, C: 44 patients; I: 61 years, C: 64 years

C: 273 patients; NR

D: 210 patients; 64.1 years

E: 1147 patients; NR

F: 587, 63 years

Sex (males):

A: 16%

B: I: 94%, C: 86%

C: 84%

D: 73%

E: NR

F: I: 72.4%, C: 72.7%

Stage:

A: NR

B: T1: 8%, T2: 21%, T3: 67%, T4: 2%

C: NR

D: T1: 7%, T2: 17%, T3: 22%, T4: 54%

E: T1: 32%, T2: 30%, T3: 25%

F: T1: I: 4.2%, C: 12.4%; T2: I: 18.8%, C: 30.4%; T3: I: 64.6%, C: 46.8%; T4: I: 9.4%, C: 4.6%

Operation:

A: Transthoracic en bloc, transhiata, vagal-sparing or minimally invasive

B: Open: 21%, minimally invasive: 74%, transhiatal: 5%

C: Esophagectomy

D: Esophagectomy: 12%, Gastrectomy: 47%, Esophago-gastrectomy: 41%

E: Esophagectomy

F: Subtotal gastrectomy, total gastrectomy, THG, Ivor Lewos procedure or other.

Other forms of treatment:

A: 27% had neoadjuvant therapy

B: 67.4% had neoadjuvant chemotherapy

C: 75.4% had chemotherapy, 72% had radiotherapy

D: Surgery + adjunctive therapy: 71%

E: 63% had neoadjuvant chemotherapy

F: Neoadjuvant treatment: I: 64.6%, C: 32.2%

Groups comparable at baseline: No

Describe intervention:

A: History and physical examination, complete blood count, serum chemistry tests, CEA level and contrast-enhanced CT scan of chest and abdomen every 3 months for first 3 years, every 6 months for next 2 years and yearly thereafter. PET-scans were done yearly.

B: History and physical examination at 6 weeks, 3 months, 6 months, 1 year, 18 months, 2 years than annually to 5 years. CT-scanning at 6 months, 1 year then annually to 5 years.

C: CT scanning every 3 months for the first year, every 6 months for the 2^nd year, then annually from the 3^rd year forward until the 5^th year postoperatively

D: Bloodwork, imaging, or EGD’s were performed at the discretion of treating physicians. Interval of £ 4 months with respect to imaging at any time during surveillance period

E: History, physical examination and chest and abdominal CT scan every 4-6 months for the first 2 years after surgery and then yearly thereafter.

F: Standardized follow-up protocol every 3 months during first 2 years, every 6 months during 3^rd and 4^th year and after 12 months in the 5^th year. Follow-up examinations included CT-scan and endoscopy.

G: Routine annual CT/PET-CT along with clinical assessment during the first three postoperative years

Describe control:

A: Unplanned surveillance

B: Unplanned CT following urgent referral due to symptoms

C: Unplanned surveillance

D: Bloodwork, imaging, or EGD’s were performed at the discretion of treating physicians. Interval of > 4 months

E: Endoscopy every 6 months for 2 years and then yearly thereafter

F: Individual follow-up by other physicians

G: Investigation as clinically indicated

Follow-up:

A: Median 18 months

B: Minimum 37 months

C: 24 months

D: Median 38.3 months

E: Median 31 months

F: Median 64.5 months

G: Median 60 months

For how many participants were no complete outcome data available?

Not reported

Outcome measure-1

Defined as detection of recurrence

Effect measure: OR [95% CI]:

A: 25.00 [14.23-43.94]

B: 0.32 [0.17-0.58]

C: 2.07 [1.47-2.91]

D: 1.31 [0.74-2.31]

E: 1.27 [0.89-1.80]

F: 1.27 [0.89-1.80]

Pooled effect (random effects model):

1.76 [95% CI 0.78 to 3.97] favoring the intervention (planned surveillance)

Heterogeneity (I²): 96%

Outcome measure-2

Defined as post-recurrence survival

Effect measure: MD [95% CI]:

A: NR

B: -1.00 [-1.65- -0.35]

C: NR

D: 12.30 [10.95-13.65]

E: NR

F: 8.00 [6.72-9.28]

Pooled effect (random effects model):

6.42 [95% CI -2.16 to 14.99] favoring the intervention (planned surveillance)

Heterogeneity (I²): 99%

Outcome measure-3

Defined as overall survival

B: I: 15 months, C: 20 months

D: I: 36.2 months, C: 23.7 months

G: HR 0.90

Risk of bias (NOS score):

Tool used by authors:

A: 8/9 (high quality)

B: 8/9 (high quality)

C: 8/9 (high quality)

D: 8/9 (high quality)

E: 8/9 (high quality)

F: NR

G: 8/9 (high quality)

Brief description of author’s conclusion: Our study shows that there is still no consensus regarding monitoring patients after their operation. Our study highlights that planned surveillance had good survival benefit for patients with esophageal cancer.

Bjerring, 2019

Type of study: RCT

Setting and country: Single center, Odense Denmark

Funding and conflicts of interest: Authors declare no conflict of interest

Inclusion criteria:

- Patients who underwent radical resection for adenocarcinomas in the gastro-oesophageal junction (GOJ), stomach and pancreas at Odense University Hospital

- Patients who were fit for oncological treatment (Eastern Cooperative Oncology Group performance status score < 3) at time of assessment 1 month after surgery

- Written informed consent

Exclusion criteria:

- Not reported

N total at baseline:

Intervention: 90

Control: 93

Important prognostic factors²:

Mean age in years:

I: 63 (95%CI 61-65)

C: 67 (95%CI 66-69)

Sex:

I: 60% M

C: 59% M

Location of cancer:

GOJ:

I: 32%

C: 41%

Stomach:

I: 24%

C: 34%

Pancreas:
I: 43%

C: 25%

Preoperative chemotherapy:
I: 43%

C: 59%

Postoperative chemotherapy:

I: 71%

C: 73%

Groups comparable at baseline: No

Describe intervention:

Follow-up at 3, 6, 9, 12, 18 and 24 months after surgery with clinical assessment in combination with FDG-PET/CT and endoscopic ultrasonography (EUS) at all time points.

Describe control:

Standard follow-up with regular visits to the outpatients clinical at 3, 6, 9, 12, 18 and 24 months after surgery. Standard follow-up included a clinical assessment. Diagnostic tests were undertaken only when there was a clinical suspicion of recurrent disease.

Length of follow-up:

Regular follow-up: 24 months

Chart review follow-up: 8 years (June 2017)

Loss-to-follow-up:

No loss-to-follow-up reported

Incomplete outcome data:

Not reported

Outcome measures and effect size (include 95%CI and p-value if available):

Overall survival

I: Median 46 months (95%CI 29-not reached)

C: Median 36 months (95%CI 21-50)

Re-interventions (number of patients receiving chemotherapy for recurrence)

I: N=29/52 (56%)

C: N=19/50 (38%)

Disease recurrence

I: N=48 (53.3%)

C: N=42 (45.2%)

Detection of isolated locoregional recurrences

I: N=13 (14.4%)

C: N=4 (4%)

Brief description of author’s conclusion: It was hypothesized that the addition of imaging at the follow-up visits would detect recurrences earlier after surgery. Although the time from surgery to the detec- tion of recurrence was not statistically significantly differ- ent between the two groups, most patients in the imaging group were asymptomatic at the time of recurrence detec- tion (33 of 42 patients).

Study reference

(first author, publication year)

Was the allocation sequence adequately generated?

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?

Were patients blinded?

Were healthcare providers blinded?

Were data collectors blinded?

Were outcome assessors blinded?

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measure

LOW

Some concerns

HIGH

Bjerring, 2019

Definitely yes;

Reason: Central randomization with computer generated random numbers

Definitely yes;

Reason: Group allocation labels were placed in non-transparent envelopes. Randomization sequence was unknown to doctors responsible for patient enrolment

Definitely no;

Reason: Patients and health care providers were not blinded. PET-CT radiologists were not offered any clinical information about the patients or EUS data

Probably yes;

Reason: No loss to follow-up reported

Definitely yes;

Reason: All relevant outcomes were reported

Probably no;

Reason: Groups were not comparable at baseline regarding age and location of cancer

Some concerns

Reference

Reason for exclusion

Bišof V, Juretić A, Stančić-Rokotov D, Rustemović N, Miletić D, Boban M, Omrčen T, Razumović JJ, Pavlović I, Fröbe A, Čonkaš M, Rakušić Z, Gugić D. [CLINICAL RECOMMENDATIONS FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH ESOPHAGEAL AND ESOPHAGOGASTRIC JUNCTION CANCERS]. Lijec Vjesn. 2016 Sep-Oct;138(9-10):233-9. Croatian. PMID: 30148543.

Wrong language

Bjerring OS, Hess S, Petersen H, Fristrup CW, Lundell L, Mortensen MB. Value of regular endosonography and [18F]fluorodeoxyglucose PET-CT after surgery for gastro-oesophageal junction, stomach or pancreatic cancer. BJS Open. 2021 Mar 5;5(2):zraa028. doi: 10.1093/bjsopen/zraa028. PMID: 33688946; PMCID: PMC7944502.

Wrong design: Narrative article regarding to EUFORO study Bjerring (2019)