Intensive follow-up vs conventional follow-up for patients with non-metastatic colorectal cancer treated with curative intent: A meta-analysis

Table 1 The baseline characteristics of included trials and recruited patients

Ref.	Region	Sample size	Age (yr)	Male (%)	Stage (A/B/C)	Tumor location (C/R)	Treatments	Intervention	Control	Follow-up duration
Mäkelä et al[23], 1995	Finland	106	66.0	49.1	(A/B/C) 28/48/30	75/31	Radical resection denotes surgical removal of all macroscopic tumor tissue with microscopically evaluated clearance of the surgical margins	Flexible sigmoidoscopy with video imaging every 3 mo, colonoscopy at 3 mo, then annually. They also had ultrasound of the liver and primary site at 6 mo, then annually	Rigid sigmoidoscopy and barium enema annually	5.0 yr
Ohlsson et al[24], 1995	Sweden	107	65.6	47.7	(A/B/C) 19/47/41	71/36	Resection with curative intent and early postoperative colonoscopy	Performed at each visit were clinical exam, rigid proctosigmoidoscopy, CEA, alkaline phosphatase, gamma-glutaryl transferase, faecal haemoglobin, and CXR. Examination of anastomosis was performed at 9, 21, and 42 mo. Colonoscopy was performed at 3, 15, 30, and 60 mo. CT of the pelvis was performed at 3, 6, 12, 18, and 24 mo	Written instructions recommending that they leave faecal samples with the district nurse for examination every 3 mo during the first 2 yr then once a year. They contact the surgical department if they had any symptoms	5.5-8.8 yr
Kjeldsen et al[25], 1997	Denmark	597	< 76.0	54.6	(A/B/C) 138/293/166	314/283	Radical primary surgery and no residual neoplasia was detected by complete colonoscopy or incomplete colonoscopy plus double-contrast barium enema, chest radiograph, histological examination of all resection margins in surgical specimens, biopsy of lesions, and inspection and palpation of the liver during surgery	Examinations at 6, 12, 18, 30, 36, 48, 60, 120, 150, and 180 mo after radical surgery (medical history, clinical examination, digital rectal examination, gynaecological examination, Haemoccult-II test, colonoscopy, CXR, haemoglobin level, erythrocyte sedimentation rate, and liver enzymes)	Examinations at 60, 120, and 180 mo (medical history, clinical examination, digital rectal examination, gynaecological examination, Haemoccult-II test, colonoscopy, CXR, haemoglobin level, erythrocyte sedimentation rate, and liver enzymes)	5.0-10.0 yr
Pietra et al[26], 1998	Italy	207	63.3	53.6	(A/B/C) 0/122/85	139/68	Curative resection defined as one in which no macroscopic tumor remained at the end of the operation and in which histopathologic examination of the operative specimen showed no tumor at the lines of resection	Examinations at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 mo, then annually thereafter. There was clinical examination, ultrasound, CEA, and CXR at each visit. Annual CT of the liver and colonoscopy were performed	Examinations at 6 and 12 mo, then annually. At each visit, clinical examination, CEA, and ultrasound were performed. They had annual CXR, yearly colonoscopy, and CT scan	5.0 yr
Schoemaker et al[27], 1998	Australia	325	68.0	63.7	(A/B/C) 71/153/101	238/87	Curative resection	Yearly CXR, CT of the liver, and colonoscopy	Clinical grounds or after screening test abnormality, and at 5 yr of follow-up, to exclude a reservoir of undetected recurrences	5.0 yr
Secco et al[28], 2002	Italy	337	65.1	48.4	(A or B/C) 201/136	NA	Putative curative surgery alone, which defined as macriscopic excision of the primary tumour, peritumoral tissues and palpable locoregional lymph nodes	Clinic visits and serum CEA, abdomen/pelvic US scans, and CXR. Participants with rectal carcinoma had rigid sigmoidoscopy and CXR	Minimal follow-up programme performed by physicians	4.0-5.1 yr
Rodríguez-Moranta et al[29], 2006	Spain	259	68.0	62.2	(II/III) 157/102	194/65	Curative resection, complete colon study was achieved with colonoscopy to determine the presence of synchronous lesions. If colonoscopy of the entire bowel could not be performed before resection, a postoperative colonoscopy was warranted	Seen with history, examination, and bloods (including CEA) at 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, and 60 mo; US/CT at 6, 12, 18, 24, 30, 36, 42, 48, and 56 mo; CXR and colonoscopy at 12, 24, 36, 48, and 56 mo	Seen with history, examination, and bloods (including CEA) at 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, and 60 mo	4.0 yr
Wattchow et al[30], 2006	Australia	203	NA	53.6	(A/B/C) 47/96/60	203/0	Curative surgery and completion of postsurgical chemotherapy	Every 3 mo for the first 2 yr postoperatively, then every 6 mo for the next 3 yr	Asking a list of set questions about symptoms, physical examination, annual faecal occult blood testing, and colonoscopy every 3 yr	2.0 yr
Sobhani et al[31], 2008	France	130	60.1	NA	IV: 17	75/55	Curative surgery, compliance with adjuvant chemotherapy, and the absence of disease progression and/or missed synchronous metastases were checked	PET performed at 9 and 15 mo and conventional follow-up	Conventional follow-up	2.0 yr
Wang et al[32], 2009	China	326	54.5	54.3	(A/B/C) 100/133/93	171/155	Curative surgery, which was defined as one in which no macroscopic tumor remained at the end of the operation and in which histopathologic examination of the operative specimen demonstrated no tumor at the margins of resection	Colonoscopy at each visit	Colonoscopy at 6 mo, 30 mo, and 60 mo from randomisation	5.3-6.5 yr
Strand et al[33], 2011	Sweden	110	68.0	53.6	(I/II/III/IV) 26/40/36/8	0/110	Curative surgery, all patients had a first postoperative visit with the surgeon for information on histology and adjuvant therapy. Consecutive patients were asked to participate at various postoperative controls starting after the adjuvant chemotherapy was terminated	Surgeon-led follow-up	Nurse-led follow-up	5.0 yr
Augestad et al[34], 2013	Norway	110	65.4	59.1	(A/B/C) 24/55/32	110/0	Surgery and received postsurgical adjuvant chemotherapy	Surgeon follow-up	GP follow-up	2.0 yr
Primrose et al[35], 2014	United Kingdom	1202	69.2	61.2	(A/B/C) 254/553/354	811/359	Curative surgery, and adjuvant treatment if indicated, with no evidence of residual disease on investigation	CEA testing every 3 mo for 2 yr, then every 6 mo for 3 yr with a single CT scan of the chest/abdomen/pelvis if requested at study entry by clinician; CT scan of the chest/ abdomen/pelvis every 6 mo for 2 yr, then annually for 3 yr, plus colonoscopy at 2 yr; CEA and CT follow-up: Both blood and imaging as above, plus colonoscopy at 2 yr	No scheduled follow-up except a single CT scan of the chest/ abdomen/pelvis if requested at study entry by a clinician	3.4 yr
Treasure et al[36], 2014	United Kingdom	216	63.0	59.3	(A/B/C) 10/95/101	NA	Curative resection for adenocarcinoma of the colon or rectum and who were fit and willing to adhere to the postoperative monitoring routine	CEA rise triggered the “second-look” surgery, with intention to remove any recurrence discovered	Conventional follow-up	2.0 yr
Rosati et al[37], 2016	Italy	1228	63.9	60.7	(B/C) 617/611	933/295	Curative intent, with adjuvant radio-chemotherapy if indicated	4, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 60 monthly office visits and history and clinical examination, FBC, CEA, and CA 19-9; colonoscopy and CXR at 12, 24, 36, 48, and 60 mo; liver US at 4, 8, 12, 16, 24, 36, 48, and 60 mo; for rectal participants, pelvic CT at 4, 12, 24, and 48 mo	4, 8, 12, 16, 20, 24, 30, 42, 48, and 60 monthly office visits, including history, examination, and CEA; colonoscopy at 12 and 48 mo; liver US at 4 and 16 mo; rectal cancer participants in addition had rectoscopy at 4 mo, CXR at 12 mo, and liver US at 8 and 16 mo. A single pelvic CT was allowed if a radiation oncologist required it as baseline following adjuvant treatment	5.2 yr
Wille-Jørgensen et al[38], 2018	Denmark and Uruguay	2509	64.9	55.0	(II/III) 1352/1157	884/1625	Curative intent, with adjuvant treatment if indicated, a colon and rectum free of neoplasia verified by perioperative barium enema or a colonoscopy within 3 mo after surgery	Multislice contrast-enhanced CT of the thorax and abdomen and CEA at 6, 12, 18, 24, and 36 mo after surgery	Multislice contrast-enhanced CT of the thorax and abdomen and CEA at 12 and 36 mo after surgery	3.0 yr
Rahr et al[39], 2019	Denmark	196	70.0	63.8	(I/II/III/IV) 47/66/49/16	140/56	Elective surgery for verified or suspected CRC were screened by a study nurse for cardiopulmonary comorbidity at the preoperative visit	Routine follow-up with one extra medical visit and additional visits to the Cardiology and Respiratory Medicine Clinics 1 and 3 mo postoperatively	Routine follow-up	1.0 yr
Monteil et al[40], 2021	France	365	65.0	54.8	(I/II/III/IV) 2/176/185/2	290/75	Curative surgery, with adjuvant treatment if indicated	PET/CT and conventional follow-up every 3 mo	CEA, liver echography, and alternated between lung radiography and CT scans	3.0 yr

PET-CT: Positron emission tomography/computed tomography; CXR: Chest radiography; CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen; US: Ultrasound.