Preoperative therapy in locally advanced esophageal cancer

Table 3 Salient features of randomized controlled trials addressing the role of preoperative chemoradiotherapy followed by surgery vs surgery alone in the management of esophageal cancer

Trial	Study period	Treatment	No. of patients	Histology	Completed treatment	R0	pCR	pN+	LRR	Median survival (mo)	OS	Treatment related mortality	DFS median/proportions	Conclusion
Apinop et al[31], 1994	1986-1992	FC + 40 Gy RT + Surgery	35	SCC	26	NA	26.9%	NA	NA	NA	NS	NS	NA	No statistically significant difference in OS, complication rate, mortality
		Surgery	34	SCC	-	NA	-	NA	NA	NA	NS	NS	NA
Le Prise et al[32], 1994	1988-1991	Sequential FC-20 Gy RT-FC + Surgery	41	SCC	39	51.0%		NA	17.9%	10	19.2 (3 yr)	8.5%	7.6 mo	No change in operative mortality or survival time
		Surgery	45	SCC	42	36.0%	-	NA	21.4%	10	13.8 (3 yr)	7%	5 mo
Walsh et al[33], 1996	1990-1995	FC + 40 Gy RT + Surgery	58	AC	53	NA	25%	42	NA	32	37 (3 yr)	3%	NA	Multimodal treatment superior to surgery alone
		Surgery	55	AC	54	NA	-	82	NA	11	07 (3 yr)	2%	NA
Lee et al[34], 2004	1999-2002	FC + 45.6 Gy RT + Surgery	51	SCC	35	100%	43%	37	22.8%	28.2	55 (2 yr)	8.5%	49% (2 yr)	CRT induced high clinical and pathological response, but no statistically significant benefit in OS and DFS
		Surgery	50	SCC	48	87.5%	-	78	10.8%	27.3	57 (2 yr)		51%(2 yr)
Burmeister et al[35], 2005	1994-2000	FC + 35 Gy RT + Surgery	128	45 SCC + 80 AC + 3 others	105	80.0%	16%	43	11%	22.2	NS	4.7%	16 mo	No significant improvement in PFS or OS
		Surgery	128	50 SCC+ 78 AC	110	59.0%	-	67	14%	19.3	NS	5.4%	12 mo
Tepper et al[36], 2008 (CALGB 9781)	1997-2000	FC+ 50.4 Gy RT + Surgery	30	7 SCC + 23 AC	29	84.6%	40%	12	13.7%	53.7	39 (5 yr)	5 yr	28% (5 yr)	Long-term survival advantage supports trimodality therapy as a standard of care
		Surgery	26	7 SCC+ 19 AC	26	88.4%	-	NA	15.3%	21.4	16 (5 yr)	3.8%	15% (5 yr)
Lv et al[37], 2010	1997-2004	2 Cis, Pacli+ 40 gy + Surgery	80	SCC	80	97.4%	NA	NA	11.3%	53	24.5 (10 yr)	3.4%	61.3% (3 yr)	Rational application of pre-op or post-op CRT can improve PFS, OS
		Surgery	80	SCC	80	80.0%	-	NA	35%	36	12.5 (10 yr)	0%	49.3% (3 yr)
Van Hagen et al[38], 2012 (CROSS trials)	2004-2008	5 Pacli, Carbo + 41.4 Gy + Surgery	178	41 SCC + 134 AC + 3 other	168	92.0%	29%	13	3.3%	49.4	47 (5 yr)	5.9%	not reached	Improved survival with acceptable adverse-event rates
		Surgery	188	43 SCC + 141 AC + 4 other	186	69.0%	-	75	9.3%	24	34	6.9%	24.2 mo
Mariette et al[39], 2014	2000-2009	2 Cis, 5FU + Surgery	98	67 SCC + 30 AC+ 1 other	84	93.8%	33.3%	30.8	22.1%	31.8	41 (5 yr)	11.1%	35.6% (5 yr)	No effect on R0 resection rate or survival but enhanced postoperative mortality
		Surgery	97	70 SCC + 27 AC	91	92.1%	-	52.8	28.9%	41.2	33.8	3.4%	27.7% (5 yr)

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