Surveillance strategies following curative resection and non-operative approach of rectal cancer: How and how long? Review of current recommendations

Table 1 Randomized controlled trials: Different surveillance strategies following curative colorectal cancer resection

Ref.	Surveillance strategy	No. of patients randomized	Significant benefit
Ohlsson et al[44], 1995	Total	107	No
	None (FOBT)	54
	Intensive follow-up: examinations, FOBT, CEA, endoscopy, CXR, CT	53
Mäkelä et al[37], 1995	Total	106	No
	Standard	54
	More intensive examinations, FOBT, CEA, colonoscopy, CXR, liver US, CT	52
Kjeldsen et al[16], 1997	Total	597	No
	Standard	307
	More intensive examinations, blood tests, FOBT, CXR, colonoscopy	290
Schoemaker et al[38], 1998	Total	325	No
	Standard: examinations, blood test, CEA, FOBT	158
	Intensive: standard plus CXR, CT, colonoscopy	167
Pietra et al[57], 1998	Total	207	Yes (increased curative reoperation; increased survival)
	Standard	103
	More intensive examinations, CEA, colonoscopy, CXR, liver US, CT	104
Secco et al[48], 2002	Total	358 (21 drop out)	Yes (increased curative reoperation; increased survival)
	Minimal: examinations yearly and on demand	145
	Risk-adapted	192
	-Low risk: less frequent examinations, CEA, rectosigmoidoscopy, CXR, US	84
	-High risk: more frequent examinations, CEA, rectosigmoidoscopy, CXR, US	108
Wattchow et al[58], 2006	Different settings no different tests	203 (46 lost fu)	No
	General Practitioner	81
	Surgeon visit	76
Rodríguez-Moranta et al[39], 2006	Total	259	Yes (increased curative reoperation, increased survival only for stage II colon tumor and rectal tumor)
	Standard: examinations, blood tests and CEA. Colonoscopy only if history of HNPCC and synchronous neoplasm	127
	Intensive: standard plus annual colonoscopy, CXR, US and CT	132
Sobhani et al[59], 2008	Total	130	Yes (increased curative reoperation; number of patients too small to evaluate survival)
	Standard: examinations, CEA, CXR, US and CT	65
	Intensive: standard plus 18FDG-PET	65
Wang et al[47], 2009	Total	326	Yes (increased curative reoperation; no increased survival)
	Standard: examinations, CEA, colonoscopy, CXR, liver US and CT	161
	Intensive: standard plus more frequent colonoscopy	165
Strand et al[60], 2011	Different settings no different tests	110	No
	Nurse	54
	Surgeon visit	56
Augestad et al[61], 2013	Different settings no different tests	110	No
	General Practitioner	55
	Surgeon visit	55
Primrose et al[34] (FACS), 2014	Total	1202	No
	Minimal follow-up: no scheduled follow-up except a single CT scan at 12-18 mo	301
	CEA follow-up: CEA every 3 mo for 2 yr, then every 6 mo for 3 yr, with a single CT scan at 12-18 mo	300
	CT follow-up: CT scan every 6 mo for 2 yr, then annually for 3 yr	299
	CEA and CT follow-up: combined CEA and CT imaging as above	302
Treasure et al[62] (the CEA Second-Look trial), 2014	Total	Tot 216	No
	Standard: CEA monitoring with no further action even in case of CEA rising	108
	Aggressive: CEA monitoring followed by second-look operation and possible resection in case of CEA rising	108
Verberne et al[35] (CEAwatch)1, 2015	Total	3223	Yes (increased curative reoperation; no increased survival)
	Standard: CEA every 3 mo, examinations, liver US and CXR every 6 mo	1182
	Intensive: CEA every 2 mo, examinations and CT annually. If CEA rise, repeat CEA after 1 mo. If two consecutive CEA rise, CT scan	316
	Standard and Intensive: patients participated both in the standard protocol and in the intensive protocol	1725
Rosati et al[49] (GILDA), 2016	Total	1228	No
	Standard: examinations, CEA, colonoscopy, CXR, liver imaging (US or CT scan)	613
	Intensive: standard plus CA19-9, blood test, more frequent colonoscopy, CXR and liver imaging (US or CT), CT abdomen-pelvis	615
Wille-Jørgensen et al[63] (COLOFOL), 2018	Total	2509	No
	Standard: CEA, CT chest, abdomen and pelvis at 12 and 36 mo	1256
	Intensive: CEA, CT chest, abdomen and pelvis every 6 mo for 2 yr, then at 36 mo	1253

¹During the study period, hospitals changed from a standard follow-up schedule to the intensive follow-up schedule every 3 months. CEA: Carcinoembryonic antigen; CT: Computed tomography; CXR: Conventional chest radiography; FOBT: Fecal occult blood test; HNPCC: Hereditary non-polyposis colorectal cancer; mo: months; US: Ultrasonography; yr: years.

Table 2 Meta-analyses of follow-up studies with different surveillance strategies

Ref.	Studies included and number of patients	Benefit on survival
Bruinvels et al[19], 1993	7 nonrandomized	Yes
	3283 patients
Rosen et al[67], 1998	2 RCTs, 3 nonrandomized	Yes
	2005 patients
Renehan et al[64], 2002	5 RCTs	Yes
	1342 patients
Figueredo et al[68], 2003	6 RCTs	Yes
	1679 patients
Tjandra et al[65], 2007	8 RCTs	Yes
	2923 patients
Pita-Fernández et al[66], 2015	11 RCTs	Yes
	4055 patients
Mokhles et al[69], 2016	11 RCTs	No
	4515 patients
Jeffery et al[70], 2016	15 RCTs	No
	5403 patients

RCT: Randomized controlled trial.

Table 3 Summary of current surveillance guidelines from specialty societies

Guideline	MH & PE	CEA	Abdomen imaging	Chest imaging	Colonoscopy
ASCO[13]	Every 3-6 mo for 5 yr	Every 3-6 mo for 5 yr	CT of abdomen and pelvis annually for 3 yr, for high-risk patients every 6-12 mo for 3 years and then annually for 2 yr	CT of chest annually for 3 yr, for high-risk patients every 6-12 mo for 3 yr	Colonoscopy at 1 yr, subsequently according findings and every 5 yr if normal. Rectosigmoidoscopy every 6 mo for 5 yr in rectal cancer not irradiated
ASCR[4]	Every 3-6 mo for 2 yr, then every 6 mo for 3 yr	Every 3-6 mo for 2 yr, then every 6 mo for 3 yr	CT of abdomen and pelvis 2 times in 5 yr, for high-risk patients annually for 5 yr	CT of chest 2 times in 5 yr, for high-risk patients annually for 5 yr	Colonoscopy at 1 yr, subsequently according findings and every 5 yr if normal. Rectosigmoidoscopy (+/- ERUS) every 6-12 mo for 3 to 5 yr for patients treated with TME; every 6 mo in patients treated with local excision
ESMO[12]	Every 6 mo for 2 yr	Every 6 mo for 3 yr	CT of abdomen and pelvis 2 times within 3 yr	CT of chest 2 times within 3 yr	Colonoscopy every 5 yr up to age 75
ACPGI[11]	No recommendation for frequency	Every 6 mo for 3 yr	CT of abdomen and pelvis 2 times within 3 yr	CT of chest 2 times within 3 yr	Colonoscopy at 1 yr subsequently according findings and every 5 yr if normal
NCCN[14]	Every 3-6 mo for 2 yr, then every 6 mo for 3 yr for stage II or greater	Every 3-6 mo for 2 yr, then every 6 mo for 3 yr for stage II or greater	CT of abdomen and pelvis every 3-6 mo for 2 yr, then every 6-12 mo for 3 yr	CT of chest every 3-6 mo for 2 yr, then every 6-12 mo for 3 yr	Colonoscopy at 1 yr, repeat in 3 yr then every 5 yr, Proctoscopy (with ERUS or MRI) every 3-6 mo for 2 yr, then every 6 mo for 3 yr for patients treated with transanal excision
ESCP[15]	No recommendation for frequency. Until 5 yr after surgery with a more frequent regimen in the first 2 yr to 3 yr	Every 3–6 mo for 2–3 yr, then every 6-12 mo until 5 yr after surgery	CT abdomen alternating with US for at least 5 yr with a more frequent regimen in the first 2-3 yr	CT of chest alternating with CXR every 3-12 mo for at least 5 yr after surgery	No recommendation for colonoscopy and proctoscopy

ACPGI: The association of Coloproctology of Great Britain and Ireland; ASCO: American Society of Oncology; ASCRS: American Society of Colon Rectal Surgeon; CEA: Carcinoembryonic antigen; CT: Computed tomography; CXR: Conventional chest radiography; ERUS: Endorectal ultrasound; ESMO: European Society for Medical Oncology; ESCP: European Society of Coloproctology; mo: months; MH & PE: Medical history and physical examination; MRI: Magnetic resonance imaging; NCCN: National Comprehensive Cancer Network; TME: Total mesorectal excision; US: Ultrasonography; yr: years.