This document discusses treatment options for cancer of the esophagus. It covers staging, endoscopic resection options for early stage cancers, preoperative chemoradiation followed by surgery as standard treatment for locally advanced cancers, and types of surgery and postoperative care. Chemotherapy regimens including cisplatin and fluorouracil provide response rates of 20-30% for metastatic cancers. Overall, the document provides an overview of current guidelines and evidence for endoscopic, surgical, radiation, and chemotherapy approaches to esophageal cancer treatment based on tumor stage.

1. Cancer of the Esophagus
Treatment Options
www.aboutcancer.com

3. NCCN.org

5. Staging System, T and N for
Esophagus Cancer
Tis T1
T1
submucosal
intramucosal
aorta
T3 T4
T2
N0
N1
1-2 nodes
Mucosa
N2
3-6 nodes
N3
7+nodes
Submucosa
Muscularis
propria

6. Tis
Endoscopic
Resection or
Ablation
Esophagectomy

7. EMR Endoscopic Mucosal
Resection

9. EMR (endoscopic mucosal
resection)

10. EMR

11. Photodynamic Therapy

12. Endoscopic
Resection
EMR (endoscopic mucosal resection) or ESD
(endoscopic submucosal dissection) or ablation
(e.g. RFA or radiofrequency ablation or
cryoablation or photodynamic therapy)
Goal is the complete removal and eradication of
all cancer in early stage disease (Tis or T1a)

13. One of the largest studies with long-term follow-up
included 402 patients with superficial esophageal
squamous carcinoma
The patients were treated either with EMR (48 percent)
or ESD (52 percent) The overall survival rates was 84
percent.
Survival was highest among patients whose tumors did
not invade beyond the lamina propria (five-year survival
rate of 91 percent).
The five-year survival rate was 71 percent both for
patients with involvement of the muscularis mucosa and
for patients with involvement of the submucosa.
Am J Gastroenterol. 2013;108(4):544.

14. EMR or ESD
• A meta-analysis of 15 studies found that ESD,
compared with EMR, had higher en bloc and curative
resection rates as well as lower rates of local
recurrence for malignant and premalignant lesions of
the gastrointestinal tract. Similar results were noted in
two other meta-analyses
• In a retrospective study of 300 patients with squamous
cell cancer of the esophagus, patients who underwent
resection with ESD had significantly higher en bloc
resection rates and lower local recurrence rates
compared with patients who underwent EMR (100
versus 53 percent and 1 versus 10 percent,
respectively)

15. T1a
Endoscopic
Resection plus
Ablation
Esophagectomy

16. T1bN0 Esophagectomy
For superficial T1b adenocarcinoma consider endoscopic resection

17. French FFCD 9901 trial, which randomly assigned 195
patients with stage I or II esophageal or EGJ cancer to
preoperative chemoradiotherapy
(fluorouracil plus cisplatin and concurrent RT [45 Gy])
versus surgery alone
Results Chem/Rad/Sug Surgery Alone
Survival 32 mos 44 mos
Adverse Events 65% 35%%
Mortality 7.3% 1.1%
J Clin Oncol 2010; 28:302s

18. T1bN+ or
T2-T4a
Squamous
PreOp
Chemoradiation
then Surgery
Chemoradiation
Esophagectomy
low risk

19. .
A meta-analysis of randomized controlled trials that compared
neoadjuvant chemoradiation and surgery to surgery alone for
resectable esophageal cancer.
Urschel JD, Vasan H Am J Surg.2003 Jun;185(6):538-43
Compared with surgery alone,
neoadjuvant chemoradiation and
surgery improved 3-year survival and
reduced local-regional cancer
recurrence.

20. Preoperative chemoradiotherapy for oesophageal cancer: a
systematic review and meta-analysis.
Gut.2004 Jul;53(7):925-30.
In patients with resectable oesophageal
cancer, chemoradiotherapy plus surgery
significantly reduces three year mortality
(OR = 0.53) compared with surgery alone.
However, postoperative mortality was
significantly increased (OR = 2.10) by
neoadjuvant chemoradiotherapy.

21. Survival after neoadjuvant chemotherapy or chemoradiotherapy
for resectable oesophageal carcinoma: an updated meta-analysis.
Lancet Oncol.2011 Jul;12(7):681-92.
The HR for all-cause mortality for neoadjuvant
chemoradiotherapy was 0.78. The HR for the overall
indirect comparison of all-cause mortality for
neoadjuvant chemoradiotherapy versus neoadjuvant
chemotherapy was 0.88.
This updated meta-analysis provides strong evidence
for a survival benefit of neoadjuvant chemoradiotherapy
or chemotherapy over surgery alone in patients with
oesophageal carcinoma

22. 157 esophageal cancer patients at the University
of Texas M.D. Anderson Cancer Center The
treatment approaches included preoperative
chemotherapy, n = 76 or preoperative C/RT, n =
81
Preoperative C/RT demonstrated increased
pathologic complete response (28% versus 4%)
and overall survival (3 years, 48% versus 29%)
Ann Thorac Surg. 2010 Sep;90(3):892-8;

23. Preoperative Chemoradiotherapy for Esophageal or
Junctional Cancer
P. van Hagen for the CROSS Group
N Engl J Med 2012; 366:2074-2084
randomly assigned patients with resectable tumors to
receive surgery alone or weekly administration of
carboplatin and paclitaxel for 5 weeks and concurrent
radiotherapy (41.4 Gy), followed by surgery.
Results Chem/Rad/Surg Surgery Alone
R0 Resection 92% 69%
Path CR 19%
Hospital Mortality 4% 4%
Median Survival 49.4 mos 24.0 mos
Survival/5y 47% 34%

24. Survival
CRT + Surgery
Surgery
Months

25. Surgery Alone Versus Chemoradiotherapy Followed by
Surgery for Stage I and II Esophageal Cancer: Final Analysis
of Randomized Controlled Phase III Trial FFCD 9901
Christophe Mariette. J Clin Onc 2014: 2416
randomly assigned to surgery alone or NCRT followed by
surgery. CRT protocol was 45 Gy with concomitant
chemotherapy composed of fluorouracil and cisplatin
Results Chemo/Rad/Sug Surgery Alone
Survival/3 y 47.5% 53.0%
PostOp Mortality 11.1% 3.4%

26. Comparison of Preoperative Chemotherapy Compared With
Chemoradiotherapy
Arm B chemoradiotherapy and surgery):
median survival time 33.1 months, 3-
year survival rate 47.7%.
Arm A chemotherapy and surgery median
survival time 21.1 months, 3-year survival rate
27.7%.
JCO February 20, 2009vol. 27 no. 6 851-856

27. Trial of Preoperative Oxaliplatin, Docetaxel, and Capecitabine With
Concurrent Radiation Therapy (45Gy) in Localized Carcinoma of
the Esophagus
pCR rate, 49%; Sixty-nine percent of patients underwent surgery.
median disease-free survival (DFS) and overall survival (OS) were 16.3
and 24.1 months, respectively. Two-year DFS and OS were 45.1% and
52.2%, respectively.
Over all Survival
Spigel J Clin Onc 2010:28:2213
Months

28. T1bN+ or
T2-T4a
Squamous
PreOp
Chemoradiation
then Surgery
Chemoradiation
Esophagectomy
low risk

29. Chemoradiotherapy of locally advanced esophageal
cancer: long-term follow-up of a prospective
randomized trial (RTOG 85-01).
JAMA.1999 May 5;281(17):1623
Squamous cell or adenocarcinoma of the esophagus,
T1-3 N0-1 M0. Combined modality therapy: 50 Gy plus
cisplatin and fluorouracil, compared with RT only : 64 Gy
in 32 fractions over 6.4 weeks.
Results Chemo-Radiation Radiation
Survival/5Y 14 – 26% 0%

30. RTOG 94-05
J Clin Onc 2002;20:1167
5-FU + cisplatin + radiation (64.8Gy or
50. 4Gy)
Results High Dose Low Dose
Median survival 13.0 mos 18.1 mos
Surv/2y 31% 40%
Local Failure 56% 52%

31. Survival from 94-05
50.4Gy
64.8Gy
Months

32. Randomized Trial of Two Nonoperative Regimens of
Induction Chemotherapy Followed by
Chemoradiation in Patients With Localized
Carcinoma of the Esophagus: RTOG 0113
assigned to receive either induction with fluorouracil,
cisplatin, and paclitaxel and then fluorouracil plus
paclitaxel with 50.4 Gy of radiation (arm A) or induction
with paclitaxel plus cisplatin and then the same
chemotherapy with 50.4 Gy of radiation (arm B)
The median survival time was 28.7 months for patients
in arm A and 14.9 months for patients in arm B (18.8
months for patients in RTOG 9405). The 2-year survival
rate was 56% for arm A and 37% for arm B.

33. ChemoRadiation Alone,
RTOG
Survival
Months
RTOG 0113
RTOG 9405
JCO 2008;28:4551

34. Survival with ChemoRadiation
versus Esophagectomy
Chan. IJROBP ;1999:45:265

35. 10y Survival Chemoradiation
with or without Surgery
No Surgery
2 4 6 8 10
Years
Surgery
Bidoli. Cancer 2002:94:352

36. Chemoradiation with and without surgery in patients
with locally advanced squamous cell carcinoma of
the esophagus.
Stahl. J Clin Oncol. 2005 Apr 1;23(10):2310-7
locally advanced squamous cell carcinoma (SCC) of the
esophagus were randomly allocated to either
Induction chemotherapy followed by chemoradiotherapy
(40 Gy) followed by surgery (arm A),
or the same induction chemotherapy followed by
chemoradiotherapy (at least 65 Gy) without surgery (arm
B).

37. Chemoradiation with and without surgery in patients
with locally advanced squamous cell carcinoma of
the esophagus.
Stahl. J Clin Oncol. 2005 Apr 1;23(10):2310-7
overall survival to be equivalent between the two
treatment groups
Local progression-free survival was better in the surgery
group (2-year progression-free survival, 64.3%) than in
the chemoradiotherapy group (2-year progression-free
survival 40.7%
Treatment-related mortality was significantly increased
in the surgery group than in the chemoradiotherapy
group (12.8% v 3.5%)

38. Survival
J Clin Oncol. 2005 Apr 1;23(10):2310-7
Years
Surgery
Radiation

39. Chemoradiation followed by surgery compared with
chemoradiation alone in squamous cancer of the esophagus:
FFCD 9102.
Bedenne.
J Clin Oncol. 2007 Apr 1;25(10):1160-8.
Patients received fluorouracil (FU) and cisplatin and either
conventional (46 Gy) or split-course (15 Gy X 2) concomitant
radiotherapy. Then randomly assigned to surgery (arm A) or
continuation of chemoradiation (arm B;FU/cisplatin and either
conventional [20 Gy] or split-course [15 Gy] radiotherapy).
Results Surgery Radiation
Survival/2y 34% 40%
Median Surv 17.7 mos 19.3 mos
Local Control 66% 57%
Stent 5% 32%

40. Chemoradiation followed by surgery compared with chemoradiation
alone in squamous cancer of the esophagus: FFCD 9102.
Bedenne.
J Clin Oncol. 2007 Apr 1;25(10):1160-8.

41. What to Do after PreOp
Chemoradiation?
No evidence
of Disease
Surveillance
Esophagectomy

42. What to Do after PreOp
Chemoradiation?
Persistent
Disease
Esophagectomy
Palliative Care

43. PostOperative Therapy
Types of Resection Based on
Pathology Findings
R0 = No cancer at Resection Margins
R1 = Microscopic Residual at Margins
R2 = Macroscopic (obvious) residual
or Metastases

44. PostOperative Therapy
Squamous
R0 = Surveillance
R1 = Observation or Chemoradiation
R2 = Chemoradiation or Palliation

45. PostOperative Therapy
Adenocarcinoma
R0 = Surveillance for T1N0
consider chemoradiation for others
and for all N+
R1 = Chemoradiation
R2 = Chemoradiation or Palliation

46. Surgery

47. Surgery
remove replaced

49. Surgery
Esophagus Esophagus
Esophagus
joined to
stomach
Cancer
Cancer
removed
Stomach Stomach

50. Principles of Surgery
All patients who are fit enough to undergo major
resection (esophagectomy) should be considered for
surgery unless:
Tumor is < 5cm from the cricopharyngeus (too high in
the neck)
Superficial (Tis or Ta) enough that endoscopic surgery
would be an option
Too locally advanced (inoperable or bulky lymph nodes
or metastatic)

51. T4b
Chemoradiation
Chemo alone or
Radiation alone
Palliative Care

52. Single Agent Chemotherapy
Drug Response Rate
5-FU 17%
Doxorubicin 0%
Cisplatin 19%
Methotrexate 13%
Paclitaxel 15-32%
Docetaxel 20%
Irinotecan 14%

53. Chemotherapy
Cisplatin-fluorouracil , response rates of
20 – 30% , median survival of 8 months,
and 30%/1 year survival
ECF (epirubicin, cisplatin, fluorouracil)
ECX (capecitiabine) EOF (oxaliplatin) or
EOX response rate was 40 to 48%,
survival was 17 to 19 months, and 1 year
survival 37 to 47%
N Engl J Med 2008; 358:36-46

54. Chemotherapy
PreOp ChemoRadiation Protocols
• Paclitaxel (Taxol) and Carboplatin
• Cisplatin and Fluorouracil (or
Capecitabine (Xeloda)
• Oxaliplatin (Eloxatin) and Fluorouracil

55. Chemotherapy
Metastatic Protocols
• DCF (docetaxel (Taxotere), cisplatin,
fluorouracil
• ECF (epirubicin, oxaliplatin, fluorouracil)
• Other drugs: trastuzumab (Herceptin),
irinotecan (Camptosar), Ramucirumab
(VEGFR2)

56. Cancer of the Esophagus
Treatment Options
www.aboutcancer.com