Preoperative therapy in locally advanced esophageal cancer

Table 2 Salient features of randomized controlled trials addressing the role of preoperative/perioperative chemotherapy followed by surgery versus surgery alone in the management of esophageal cancer

Trials	Study period	Treatment	No. of patients	Histology	R0 resection	pCR	pN+	Median follow up	LRR	OS (%)	Conclusions
Roth et al[21], 1988	1982-1986	Periop Cisplatin vindesine, bleomycin + S	19	SCC	35%	6%	NS	30 mo	NS	25 (3 yr)	Prolonged OS in responders in perioperative chemotherapy arm with acceptable toxicity and post-op complications
		Surgery	20	SCC	21%	-	NS	30 mo	NS	05 (3 yr)	No improvement in survival in chemotherapy arm
Nygaard et al[6], 1992	1983-1988	Preop Cisplatin, Bleomycin + S	44	SCC	44%	NS	NS	NA	NS	03 (3 yr)
		Surgery	41	SCC	36%	-				09 (3 yr)
Schlag et al[22], 1992	1980's	Preop FC + S	22	SCC	44%	6%	NA	NA	NS	NS	No influence on resectability or OS in chemotherapy arm. Rather, it results in Increase in side effects and postop mortality rate
		Surgery	24	SCC	45%	-	NA	NA	NS	NS
Maipang et al[19], 1994	1988-1990	Preop Cisplatin Vindesine, Bleomycin + S	24	SCC	NS	0%	NS	NA	NS	31 (3 yr)	Better OS in control group. Poorly nourished patients may tolerate smaller dosages of chemotherapy
		Surgery	22	SCC		-		NA		36 (3 yr)
Law et al[18], 1997	1989-1995	Preop FC + S	74	SCC	67%	6.7%	70	NA	12	44 (2 yr)	Significant downstaging and an increased likelihood of R0 resection in chemotherapy arm. No survival difference but responders fared better
		Surgery	73	SCC	35%	-	88		30	31 (2 yr)
Ancona et al[15], 2001	1992-1997	Preop FC + S	47	SCC	90%	13%	NS	30 mo	32	34 (5 yr)	Significantly improved long term survival in patients with pathologic complete response following preoperative chemotherapy
		Surgery	47	SCC	87%	-		30 mo	34	22 (5 yr)
Cunnigham et al[26], 2006 (Magic trial)	1994-2002	Peri-op ECF + S	37/250	AC	69.3%	NA	NS	49	14.4	36.3 (5 yr)	Peroperative chemotherapy decreased tumor size and stage, and significantly improved PFS, OS
		Surgery	36/253	AC	66.4%	-		47	20.6	23 (5 yr)
Kelsen et al[17], (RTOG 8911, US Intergroup 113) 2007	1990-1995	Preop FC + S	213	SCC - 98, AC - 115	63%	2.5%	NS	8.8 yr	25	23 (3 yr)	No improvement in OS in chemotheray arm.Only R0 resection results in long-term survival, regardless of pre-op chemotherapy
		Surgery	227	SCC - 106, AC - 121	59%	-			19	26 (3 yr)
MRC OEO2 trial, 2009 Allum et al[25]	1992-1998	Preop FC + S	400	SCC - 123, AC - 265, Others - 12	60%	4%	58	5.9 yr	11.5	23 (5 yr)	Preop chemotherapy improves survival and should be considered as a standard of care
		Surgery	402	SCC - 124, AC - 268, Others - 10	54%	-	68	6.1 yr	12.2	17 (5 yr)
Ychou et al[23], 2011	1995-2003	Peri-op FC + S	113	AC	84%	3%	67	8.8 yr	12	38 (5 yr)	Peri-op chemotherapy significantly increased R0 resection rate, DFS, and OS
		Surgery	111	AC	73%	-	80		8	24 (5 yr)
Boonstra et al[16], 2011	1989-1996	Preop Cisplatin, Etoposide + S	85	SCC	71%	7%	43	15 mo	19	26 (5 yr)	Significant improvement in OS in chemotherapy arm
		Surgery	84	SCC	57%	-	46	14 mo	25	17 (5 yr)
Ando et al[24], 2012- JCOG 9907	2000-2006	Preop FC + S	164	SCC	96%	2%	65	62 mo	25	55 (5 yr)	Pre-op chemotherapy can be regarded as standard treatment
		Surgery	166	SCC	91%	-	76	NA	31	43 (5 yr)

Periop: Perioperative; SCC: Squamoous cell cancer; AC: Adenocarcinoma; RT: Radiotherapy; NA: Not available; OS: Overall survival; NS: Not stated; ECF: Epirubicin, cisplatin, 5-FU; S: Surgery.