NEOADJUVANT CHEMORADIOTHERAPY AND SURGERY COMPARED WITH SURGERY ALONE IN SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS

ANDREOLLO, Nelson Adami; TERCIOTI Jr., Valdir; LOPES, Luiz Roberto; COELHO-NETO, João de Souza

doi:10.1590/S0004-28032013000200016

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Sumário

Original Articles • Arq. Gastroenterol. 50 (2) • April-June 2013 • https://doi.org/10.1590/S0004-28032013000200016 copy

NEOADJUVANT CHEMORADIOTHERAPY AND SURGERY COMPARED WITH SURGERY ALONE IN SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS

Radioterapia e quimioterapia neoadjuvantes e cirurgia comparado com a cirurgia no tratamento do carcinoma epidermoide do esôfago

SCIMAGO INSTITUTIONS RANKINGS

Context

Despite progress in recent years in methods of diagnosis and surgical treatment of esophageal cancer, there is still controversy about the benefits from neoadjuvant chemoradiotherapy.

Objective

To analise the survival of patients submitted to esophagectomy for squamous cell carcinoma of the esophagus with or without neoadjuvant chemoradiotherapy.

Method

A retrospective, non-randomized study conducted using the medical charts of patients operated for squamous cell carcinoma of the esophagus at the School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil between 1979 and 2006. The Kaplan-Meier analysis was used to calculate survival curves and the log-rank test to compare data in each group. The significance level was settled as 5%.

Results

A total of 123 patients were evaluated in this study, divided into three groups: I - 26 (21.2%) patients submitted to esophagectomy alone; II - 81 (65.8%) patients submitted to neoadjuvant radiotherapy plus esophagectomy and III - 16 (13%) patients submitted to neoadjuvant chemoradiotherapy plus esophagectomy. A statistically significant survival was recorded between the groups (log rank = 6.007; P = 0.05), survival being greatest in the group submitted to neoadjuvant chemoradiotherapy, followed by the group submitted to neoadjuvant radiotherapy compared to the group submitted to esophagectomy alone as the initial treatment of choice.

Conclusion

Radiotherapy and chemotherapy neoadjuvants in patients with squamous cell carcinoma of the esophagus offers benefits and increases survival.

Esophageal neoplasms; Carcinoma, squamous cell; Esophagectomy; Chemotherapy, adjuvant; Radiotherapy, adjuvant

Stage	Surgery alone		Neoadjuvant radiotherapy		Neoadjuvant radiotherapy + chemotherapy
Stage	n	%	n	%	n	%
0	0	0	13	16.04	5	31.25
I	6	23.07	7	8.64	3	18.75
IIA	11	42.3	34	41.98	4	25
IIB	3	11.55	16	19.76	2	12.5
III	6	23.08	11	13.58	2	12.5
IV	0	0	0	0	0	0

Complications	Surgery alone		Neoadjuvant radiotherapy		Neoadjuvant radiotherapy + chemotherapy
Complications	n	%	n	%	n	%
Intraoperative hemorrhage	0	0	4	4.93	1	6.25
Chest drainage	14	53.84	64	79	12	75
Bronchopneumonia	3	11.53	18	22.22	4	25
Anastomotic fistula/stenosis	12	46.15	32	39.5	11	6.25
Perioperative deaths	3	11.54	10	12.35	1	6.25

	Surgery	Surgery + radiotherapy	Surgery + radiotherapy + chemotherapy
No. of patients	23	71	15
No. of late deaths	12	23	3
Percentage of deaths	52.2	32.4	20.0
Mean time of follow-up (months)	32.43	65.75	87.28
Standard error	7.81	9.43	12.21
95% confidence interval	17.12-47.74	47.26-84.23	63.34–111.22
P-value	Surgery versus surgery + radiotherapy		0.05
	Surgery versus surgery + radiotherapy + chemotherapy		0.04
	Surgery + radiotherapy versus Surgery + radiotherapy + chemotherapy		0.27

Author	Type of study	Number of patients	Mean survival (months)	P-value
Le Prise et al.1994⁽¹²⁾12. Le Prise E, Etienne PL, Meunier B, Maddern G, Ben Hassel M, Gedouin D, Boutin D, Campion JP, Launois B. A randomized study of chemotherapy, radiation therapy, and surgery versus surgery for localized squamous cell carcinoma of the esophagus. Cancer 1994;73:1779-84.	Randomized	41 (chemo) vs 45	11	0.56
	Randomized	(surgery)	11	0.56
Bosset et al.1994⁽³⁾3. Bosset JF, Gignoux M, Triboulet JP, Tiret E, Mantion G, Elias D, Lozach P, Ollier JC, Pavy JJ, Mercier M, Sahmoud T. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med. 1997;337:161-7.	Randomized	143 (chemo) vs	18.6	0.78
	Randomized	139 (surgery)	18.6	0.78
Ancona et al.2001⁽²⁾2. Ancona E, Ruol A, Santi S, Merigliano S, Sileni VC, Koussis H, Zaninotto G, Bonavina L, Peracchia A. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esopagheal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer. 2001;91:2165-74.	Randomized	47 (chemo) vs	25	0.01
	Randomized	47 (surgery)	24	(only complete pathological response)
Urba et al.2001⁽²⁵⁾25. Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol. 2001;19:305-13.	Randomized	50 (chemo) vs	17.6	0.15
	Randomized	50 (surgery)	16.9	0.15
El Nakadi et al.2001⁽⁸⁾8. El Nakadi I, Van Laethem JL, Houben JJ, Gay F, Closset J, Van Houtte P, Danhier S, Limbosch JM, Lambilliotte JP, Gelin M. Squamous cell carcinoma of the esophagus: multimodal therapy in locally advanced disease. World J Surg. 2002;26:72-8.	Non-randomized	38 (surgery) vs	Unavailable	0.19
	Non-randomized	61 (radio + chemo)	21	0.19
Urschel et al.2002⁽²⁶⁾26. Urschel JD, Vasan H. A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer. Am J Surg. 2003;185:538-43.	Meta-analysis of nine	1116 (total)	Odds ratio:	0.016
	randomized studies	surgery vs	0.79 (1st year)	(3rd year)
		(radio + chemo)	0.77 (2nd year)
		(radio + chemo)	0.66 (3rd year)
Makary et al.2003⁽¹⁴⁾14. Makary MA, Kiernan PD, Sheridan MJ, Tonnesen G, Hetrick V, Vaughan B, Graling P, Elster E. Multimodality treatment for esophageal cancer: the role of surgery and neoadjuvant therapy. Am Surg. 2003;69:693-700.	Non-randomized	76 (surgery) vs	17.2 vs	0.01
	Non-randomized	40 (radio + chemo)	35.7	0.01
Liao et al.2004⁽¹³⁾13. Liao Z, Zhang Z, Jin J, Ajani JA, Swisher SG, Stevens CW, Ho L, Smythe R, Vaporciyan AA, Putnam JB Jr, Walsh GL, Roth JA, Yao JC, Allen PK, Cox JD, Komaki R. Esophagectomy after concurrent chemoradiotherapy improves locoregional control in clinical stage II or III esophageal cancer patients. Int J Radiat Oncol Biol Phys. 2004;60:1484-93.	Non-randomized	72 (surgical) vs	12 vs	<0.05
	Non-randomized	60 (radio + chemo)	62	<0.05
Malaisrie et al.2004⁽¹⁵⁾15. Malaisrie SC, Untch B, Aranha GV, Mohideen N, Hantel A, Pickleman J. Neoadjuvant chemoradiotherapy for locally advanced esophageal cancer: experience at a single institution. Arch Surg. 2004;139:532-8.	Non-randomized	65 (surgical) vs	28.7 vs	0.14
	Non-randomized	31 (radio + chemo)	24.1	0.14
Fiorica et al.2004⁽⁹⁾9. Fiorica F, Di Bona D, Schepis F, Licata A, Shahied L, Venturi A, Falchi AM, Craxì A, Cammà C. Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis. Gut. 2004;53:925-30.	Meta analysis of six	390 (surgery) vs	Odds ratio:	0.03
	randomized studies	388 (radio + chemo)	0.53 (3rd year)	(3rd year)
Greer et al.2005⁽¹⁰⁾10. Greer SE, Goodney PP, Sutton JE, Birkmeyer JD. Neoadjuvant chemoradiotherapy for esophageal carcinoma: a meta-analysis. Surgery. 2005;137:172-7.	Meta-analysis	364 (surgery) vs	Odds ratio:	0.74
	(6 randomized studies)	374 (radio + chemo)	0.86	0.74
Zhang et al.2005⁽²⁹⁾29. Zhang X, Watson DI, Jamieson GG, Bessell JR, Devitt PG. Neoadjuvant chemoradiotherapy for esophageal carcinoma. Dis Esophagus. 2005;18:104-8.	Non-randomized	59 (surgery) vs	19.3% (4 years) vs	<0.05
	Non-randomized	56 (radio + chemo)	33.3% (4 years)	<0.05
Morgan et al.2007⁽¹⁸⁾18. Morgan MA, Lewis WG, Crosby TD, Escofet X, Roberts SA, Brewster AE, Harvard TJ, Clark GW. Prospective cohort comparison of neoadjuvant chemoradiotherapy versus chemotherapy in patients with oesophageal cancer. Br J Surg. 2007:94:1509-14.	Non-randomized	117 (chemo) vs	24 vs	0.03
	Non-randomized	88 (radio + chemo)	43	0.03
Andreollo et al.2012	Non-randomized	23 (surgery) vs	32.4	0.05
		71 (radio) vs	65.4
		16 (radio + chemo)	87.2

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[1] Correspondence: Prof. Nelson Adami Andreollo - Departamento de Cirurgia da Faculdade de Ciências Médicas da UNICAMP - Cidade Universitária s/n° - Barão Geraldo - 13083-970 - Campinas, SP, Brazil. E-mail:nandreollo@hotmail.com