Arturo Dela Peña, MD FPCS FACS

Esophageal Carcinoma
 Prevalence increasing by 10%/year
 Association of GERD/Barrett’s
Esophagus/Adenocarcinoma
( Metaplasia----Dysplasia------Carcinoma)
ESOPHAGEAL CANCER
 Ranks 21st in both sexes (0.9 % of all
cases)
 CR 1.5 in males (647)
0.8 in females (345)
 Majority Epidermoid CA
 992 cases in 2005
 873 deaths in 2005
ESOPHAGEAL CANCER
 Rising incidence worldwide (lifetime risk
for men (0.8) and for women (0.3)
 Characterized by early spread and poor
prognosis (5-yr survival for all stages 14%)
 0.8% worldwide deaths (446,000 in 2002)
ADVANCES IN ESOPHAGEAL CANCER
 Diagnosis / Staging
 Treatment
 Surgical approach
 Adjuvant treatment
ESOPHAGEAL CANCER (Diagnostic Imaging)
 Organ confined vs Non-organ confined
disease
 Map extent of disease
 Detect response to treatment or
progression
ESOPHAGEAL CANCER (Diagnostic Imaging) - IMPORTANCE

 Overstaging (≈30%) – deny potential

curative surgery
 Understaging – futile surgery that
affect palliation, don’t change long
term outcome, increase health costs
CT SCAN
 Remains the single most widely
applied non-invasive imaging
 Cost effective and with acceptable
accuracy for locoregional and distant
spread
ENDOSCOPIC ULTRASOUND (EUS) with FNA
 Most accurate for locoregional (T2N)
staging of Esophageal CA
 Almost 90% accurate

Saltzman Jr (2003)
Hölscher et al (1994)
Eloubeidi et al (2001)
Reed et al (1999)
Giovanni et al (1994)
LIMITATIONS OF EUS / FNA
 Non-transversality of tight strictures
or stenotic tumors (20-38%)
 Subjective / operator dependent (75-
100 exams)
ENDOSCOPIC ULTRASOUND
 Highly accurate for determining depth
of tumor invasion and status of regional
lymph nodes (65-95%)
 As tumor progresses from T1 to T4,
more accurate than CT even with newer
helical models
 With FNA - almost 100% in staging
coeliac lymph nodes
IMPORTANCE OF ACCURATE STAGING
 Finding of T4 confers very poor
prognosis / identify patients not good
candidate for resection / for
neoadjuvant treatment
 Presence of coeliac lymph nodes –
associated with poor long term
survival
POSITRON EMISION TOMOGRAPHY (PET)
and PET/CT IN ESOPHAGEAL CANCER
 Highly accurate – detection / staging /
assessment of response to
neoadjuvant chemotherapy /
recurrence (65-100%)

Flanagan (1997)
Rankin (1998)
Reed and Eloubeidi (2002)
Kato et al (2007)
 Obviates need for staging surgery
and can prevent futile curative
surgery

Reed and Eloubeidi (2002)

Kato et al (2002)
LIMITATION OF PET SCAN IN ESOPHAGEAL
CANCER
 Limited spatial resolution (makes
localization and discrimination of
nodal disease difficult)
 Combine PET / CT
 SUGGESTED ALGORITHM FOR STAGING
OF ESOPHAGEAL CANCER
Primary diagnosis / pathology

CT and / or PET
No metastasis Distant metastasis

EUS and FNA Non-surgical or salvage treatment

Stage I-IIa Stage IIb, III Stage IV

T2 Neoadjuvant chemotherapy Re-staging CT

(optional – PET / EUS-PET)

T1 and T2 Surgery
ENDOSCOPIC TREATMENT OF SCCA OF ESOPHAGUS
(ENDOSCOPIC MUCOSAL RESECTION – EMR)

 Indications
Depth M1 (Epithelium) / M2 (Lamina propria)
Size < 3 cm
Circumference <¾
Histologic type Well and/or moderately differentiated
Location Middle / distal 3rd
Lateral and posterior
EMR RESULTS AND COMPLICATIONS

AUTHOR N 5-YR SURVIVAL COMPLICATIONS

RATE
Perforation (0.7 %)
Inolle 142 100 %
Stenosis (0.7 %)

Makauuchi 249 97.9 % not mentioned

META-ANALYSIS OF RCT’s OF NEOADJUVANT TREATMENT FOR RESECTABLE
CANCER OF THE ESOPHAGUS AND G-E JUNCTION
(KAKLANOS et al- Annals of Surgical Oncology 10:7, 2003)

 11 RCT’s / Neoadjuvant Chemo

 2311 patients
 Parameters
 2-year survival
 Treatment related mortality
CONCLUSIONS
 Neoadjuvant Chemotherapy seems to offer modest
Survival Advantage (4.4 % 2-year survival- 95% CI 0.3-
8.5%)
 Increase in treatment-related mortality for
neoadjuvant chemotherapy and neoadjuvant
chemotherapy groups (1.7 % 95 % CI- 0.9-4.3 % and
3.4 % 95% CI 0.1-7.3% respectively).
NEOADJUVANT CHEMOTHERAPY FOR
SCCA OF ESOPHAGUS
 Intergroup Trial (INT 0113) – Kelsen et al
- Chemotherapy followed by surgery vs surgery
alone for localized esophageal cancer (1998)
(N=440)
 Randomized / 3 cycles of Cisplatin / 5-FU before
surgery + 2 cycles post-op
Chemo / Surgery Surgery
(N=213) (N=227)
Median survival 14.9 mos 16.1 mos
2-yr survival rate 35% 37%
NEOADJUVANT CHEMOTHERAPY FOR
SCCA OF ESOPHAGUS
 MRE Trial (OE02) – Lancet 2002; 359 (9519): 1727-1733
(N=802)

Chemo / Surgery Surgery

Median survival 16.8 mos 13.3 mos
2-yr survival rate 43 % 32 %
NEOADJUVANT CHEMOTHERAPY FOR
SCCA OF ESOPHAGUS
 Meta-analysis of preop chemotherapy for
esophageal SCCA
Malthaner & Fenlon – 2004 (11 RCT’s)
(N=2051)
 Neoadjuvant chemotherapy – not alter resection rate,
rate of complete resection, post-op complications
 Clinical response – 36% Pathological response – 3.0%
 3 / 4 / 5 – year survival rate - 21% 24% 44%
 11 patients needed to treat for one extra survivor at 5
years
NEOADJUVANT CHEMOTHERAPY FOR
ESOPHAGEAL SCCA
 May improve long-term outcome ( in surgery of
responders especially complete responders )
 Non-responders – worse prognosis ( probably
due to unnecessary delay to surgery )

Law et al (1997)
Roth et al (1988)
Schlag PM (1992)
Ancona et al (2001)
Kelsen et al (1998)
WHICH IS THE BEST OPERATION
FOR ESOPHAGEAL CARCINOMA?
SURGICAL THERAPY FOR ESOPHAGEAL SCCA
 Non-thoracotomy aproach
 Transhiatal
 Trans-thoracic approach
 En bloc resection
 2-Field Lymphadenectomy
 3-Field Lymphadenectomy (extended)
META-ANALYSIS OF THRANSTHORACIC vs. TRANSHIATAL RESECTION FOR
CANCER OF ESOPHAGUS (Hulscher et al –University of Amsterdam-Annals of
Thoracic Surgery 2001; 72:306-313)

 24 articles (6 prospective comparative studies/ 3

RCT’s)
 7,527 patients (138 patients total in RCT)
RESULTS
 No difference in 3-year survival for all data combined
 In comparative trials
 3-year and 5-year survival in
transthoracic are higher compared to
transhiatal (39 % vs. 24 %- 95 CI 0.83-
1.07)
3-FIELD LYMPHADENECTOMY
 Improved staging
Reduced local recurrence
Possible improved long-term
survival
RATIONALE FOR 3-FIELD (EXTENDED) LYMPHADENECTOMY –
MORE AGGRESSIVE SURGERY
 Lack of biological modifiers (such as
hormonal therapy)
 Relative ineffectiveness of available
chemotherapy
 Absence of evidence of utility of
radiotherapy in adjuvant setting
SURGICAL RESULTS OF 3-FIELD LYMPH NODE DISSECTION
FIVE-YEAR SURVIVAL RATES AFTER TWO-FIELD AND
THREE-FIELD DISSECTION
Authors Two-field (%) Three-field (%) Comment
Isono (1991) 27 (n=2,671) 34 (n=1,740) p<0.001, 96 hospitals, 1983-86

Kato (1991) 34 (n=73) 49 (n=77) p<0.01, RCT, 1985-89

Kakegawa (1991) 36 (n=159) 40 (n=705) ns, 10 hospitals, 1985-89

Iizuka (1992) 45 (n=521) 47 (n=459) ns, 32 hospitals, 1988-1989

Fujita (1993) 33 (n=49) 49 (n=38) p<0.10, 2 hospitals, 1985-89

23 (n=67) p<0.05

Akiyama (1994) 38 (n=283) 53 (n=261) p<0.001, historical, 1973-93

Watanabe (2000) 55 (n=98) 48 (n=141) ns, 1988-94

Altorki (2002) - 51 (n=80) 1994-2001

 RESULTS OF 3-FIELD LYMPHADENECTOMY FOR
ESOPHAGEAL SCCA
Author (N) Mortality Morbidity Overall
5-yr survival
Lerut 174 1.2 % 58 % 41 %

Duranceau 215 2.8 % 43 % 39 %

Moreno-Gonzales 234 2.8 % 41 % 42 %

Sienert 138 1.8 % 32 % 48 %

Horuarth 189 3.4 % 48 % 41 %

Pinotti 368 3.5 % 41 % 43 %

Zhang 724 2.9 % 54 % 51 %

Akiyama 817 1.3 % 51 % 55 %

Isono 1740 2.3 % 44 % 53 %