Watch and wait approach in rectal cancer: Current controversies and future directions

Table 1 Time between completion of neoadjuvant therapy and first reassessment in watch and wait clinical studies

Study	Patients (n)	Neoadyuvant therapy		Timing of assessment after CRT
		Radiotherapy schedule	Chemotherapy regimen
Habr-Gama et al[107], 2013	70	54Gy/30	CRT: 5-FU/LV CNCT: 5-FU/LV x3	10 wk
Araujo et al[128], 2015	51	45 Gy/25 or 50, 40 Gy/28	CRT: 5-FU or capecitabine	NS
Smith et al[129], 2012	32	50,4 Gy/28	CRT: 5-FU or capecitabine	4-10 wk
Dalton et al[127], 2012	12	45 Gy/25	CRT: capecitabine	8 wk
Renehan et al[99], 2016	259	45 Gy/25	CRT: 5-FU or capecitabine	≥ 8 wk
Appelt et al[5], 2015	51	60 Gy/30 to tumor + 50 Gy/30 to LNs	Tegafur-uracil (UFT)	6 wk
Vaccaro et al[130], 2016	204	50.4 Gy/28	CRT: 5-FU/LV	8-12 wk
Lai et al[131], 2016	267	45 Gy/25 or 54 Gy/30	CRT: 5-FU/LV	8-12 wk
Martens et al[98], 2016	141	50.4 Gy/28 or 5 Gy/5	CRT: 5-FU	8-20 wk
Creavin et al[132],	362	50-54 Gy/30	CRT: 5-FU	6-8 wk

CRT: Chemoradiation therapy; CNCT: Consolidation chemotherapy; NS: Not stated; 5-FU: 5-fluorouracil; LV: Leucovorin.

Table 2 Tumor regrowth and salvage surgery in watch and wait clinical studies

Study	Patients (n)	Regrowth	Salvage surgery	Distant metastasis	Survival
Habr-Gama et al[161]	90	27 (31%)	93%	13 (14%)	3 yr (88%)
Renehan et al[99]	129	44 (34%)	84%	5 (4%)	3 yr (96%)
Kong et al[162]	370	105 (28.4%)	83.80%
van der Valk et al[102]	1000	250 (25%)	86%	80 (8%)	5 yr (85%)
Chadi et al[165]	602	168 (28%)	89%	60 (10%)	5 yr (87%)
Dattani et al[100]	692	149 (21.6%)	88%	56 (8.2%)	3 yr (93.5%)
On et al[164]	248	37 (15.3%)	68.40%	8 (21%)	92.30%
Nasir et al[160]	78	23 (29.5%)	100%	1 (4.35%)	3 yr (96%)

Table 3 Selected ongoing clinicals trials in patients with rectal cancer in a watch-and-wait program

Clinicaltrials.gov identifier (NCT number)	Study type	Neoadjuvant schedule	Primary outcome	Planned enrollment (n)	Recruitment status
NCT03402477	Observational	Radiotherapy or chemo-radiotherapy (at least 40 Gy) or short-course radiotherapy combined with chemotherapy	Local relapse rate	100	Recruiting
	Prospective
NCT03125343	Interventional	According to the Swedish National	3-yr disease free survival	200	Recruiting
	Non-randomized	Program for rectal cancer
NCT03846726	Observational	Neoadjuvant chemoradiotherapy	Disease free survival	513	Active, not recruiting
	Retrospective
NCT03064646	Interventional	Neoadjuvant chemoradiotherapy or neoadjuvant radiotherapy associated or not with induction chemotherapy	Local relapse rate	30	Recruiting
	Non-randomized
NCT03426397	Observational	Short course of radiation or neoadjuvant chemoradiotherapy	2-yr non-regrowth disease free survival	220	Recruiting
	Prospective
NCT04009876	Interventional	5-FU/LV + Oxaliplatin + nal-IRI for 8 cycles followed by standard chemoradiation (5 wk)	Clinical complete response rate	30	Recruiting
	Non-randomized
NCT03001362	Interventional	54 Gy in 30fx with radiosensitizing chemotherapy as per institutional standard	Local relapse rate	48	Recruiting
	Non-randomized
NCT02704520	Interventional	Experimental arm: 45Gy-55Gy long course radiotherapy with radiosensitizing chemotherapy as per institutional standard	Feasibility phase: To assess the rate of patient recruitment	98	Recruiting
	Randomized
			Phase III trial: 3-years disease free suvival
NCT04095299	Interventional	Experimental arm: 62 Gy to the clinical tumor volume and 50.4 Gy to the elective volume with capecitabine	2-yr rectal preservation	111	Recruiting
	Randomized

An advanced search of ClinicalTrials.gov was performed in March 2020 for “wath and wait in rectal cancer” (retrieved 10 records). These were reviewed and selected based on the status of the study. nal-IRI: Liposomal irinotecan; 5-FU: 5-fluorouracil; LV: Leucovorin.