Esophageal CancerEsophageal Cancer

Akshra Verma, MD, MSAkshra Verma, MD, MS

Dr. Sohail A. Chaudhry MDDr. Sohail A. Chaudhry MD

EpidemiologyEpidemiology

~ 13,900 new cases each year ~ 13,900 new cases each year (2003)(2003)

~ 13,000 deaths each year~ 13,000 deaths each year Seventh leading cause of deathSeventh leading cause of death Risk increases with ageRisk increases with age

Mean age at diagnosis 67yrsMean age at diagnosis 67yrs

Lifetime riskLifetime risk 0.8% for men0.8% for men 0.3% for women 0.3% for women

Changing trendsChanging trends

Until the 1970sUntil the 1970s– Squamous Cell Ca 75%Squamous Cell Ca 75%– AdenoCa 25% AdenoCa 25%

Past 20-30yrs Past 20-30yrs – Incidence of SCC has decreased both in AA Incidence of SCC has decreased both in AA

and Caucasianand Caucasian– Incidence of AdenoCa increased by 450% in Incidence of AdenoCa increased by 450% in

Caucasian men and 50% in black AA menCaucasian men and 50% in black AA men– In 1994 60% of all esophageal cancers were In 1994 60% of all esophageal cancers were

adenocarcinoma.adenocarcinoma.

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Progression of Barrett’s Progression of Barrett’s EsophagusEsophagus

4% per year

1% per year

0.5 % per year

Clinical SymptomsClinical Symptoms DysphagiaDysphagia OdynophagiaOdynophagia Weight lossWeight loss Less often: Dyspnea, cough, hoarseness Less often: Dyspnea, cough, hoarseness

and pain in retro-sternal, back or right and pain in retro-sternal, back or right upper abdominal upper abdominal

Metastatic Disease: Lymphadenopathy Metastatic Disease: Lymphadenopathy (Virchow’s node), hepatomegaly, (Virchow’s node), hepatomegaly, pleural effusionpleural effusion

Esophageal CarcinomaEsophageal Carcinoma

Adenocarinoma : 75% in distal Adenocarinoma : 75% in distal esophagusesophagus

Squamous Cell Ca: evenly distributed in Squamous Cell Ca: evenly distributed in middle and lower thirdmiddle and lower third

AT DIAGNOSIS: More than 50% have AT DIAGNOSIS: More than 50% have unresectable tumors or radiographically unresectable tumors or radiographically visible metastasisvisible metastasis

Esophagogram Showing a Esophagogram Showing a Malignant Esophageal Malignant Esophageal

StrictureStricture

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Transmural Adenocarcinoma of the Transmural Adenocarcinoma of the Esophagus Associated with Barrett's Esophagus Associated with Barrett's

EsophagusEsophagus

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Cancer of the Distal Esophagus with Cancer of the Distal Esophagus with Metastasis to a Paraesophageal Lymph Metastasis to a Paraesophageal Lymph

NodeNode

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Current AJCC 2002 stagingCurrent AJCC 2002 staging

PredictorsPredictors of prognosis.of prognosis.

Staging of disease at diagnosisStaging of disease at diagnosis WeightWeight loss of more than 10 percent loss of more than 10 percent

of body massof body mass DysphagiaDysphagia LargeLarge tumorstumors Advanced ageAdvanced age lymphatic micrometastases (identifiedlymphatic micrometastases (identified

by immunohistochemical analysis) areby immunohistochemical analysis) are

TreatmentTreatment

Surgical resection is the standard treatment for early Surgical resection is the standard treatment for early esophageal cancer : Stages I, II and some cases of IIIesophageal cancer : Stages I, II and some cases of III

During the past decade, outcomes with surgery have During the past decade, outcomes with surgery have improved resulting in a better 5 year survival due to:improved resulting in a better 5 year survival due to:– Better staging techniquesBetter staging techniques– Improved surgical techniqueImproved surgical technique

Recent DataRecent Data– Rate of curative resection : 54 to 69%Rate of curative resection : 54 to 69%– Rate of operative mortality :4 to 10%Rate of operative mortality :4 to 10%– perioperative complications : 26 to 41%perioperative complications : 26 to 41%

Types of esophagectomiesTypes of esophagectomies TranshiatalTranshiatal ** ** Exposure is provided by an Exposure is provided by an

upper midline laparotomy upper midline laparotomy and a left neck incision.and a left neck incision.

The thoracic esophagus is The thoracic esophagus is bluntly dissected, and a bluntly dissected, and a cervical anastomosis cervical anastomosis created; thoracotomy is created; thoracotomy is not required. not required.

Drawbacks: inability to Drawbacks: inability to perform a full thoracic perform a full thoracic lymphadenectomy, and lymphadenectomy, and lack of visualization of the lack of visualization of the midthoracic dissection.midthoracic dissection.

Transthoracic Transthoracic The Ivor Lewis The Ivor Lewis

esophagectomy combines a esophagectomy combines a laparotomy with right laparotomy with right thoracotomy, and produces thoracotomy, and produces an intrathoracic an intrathoracic anastomosis. anastomosis.

This technique permits This technique permits direct visualization of the direct visualization of the thoracic esophagus, and thoracic esophagus, and allows the surgeon to allows the surgeon to perform a limited perform a limited lymphadenectomy. lymphadenectomy.

However formal dissection However formal dissection of lymph nodes is not of lymph nodes is not performedperformed

**Lower rate of peri-operative complications (mainly fewer pulmonary complication, lower incidence of chylous leakage)

Five-Year Survival Rates for Five-Year Survival Rates for Esophageal CarcinomaEsophageal Carcinoma

Role of RadiotherapyRole of Radiotherapy

Radiotherapy : In pt with SCC of Radiotherapy : In pt with SCC of esophagaus and poor surgical candidatesesophagaus and poor surgical candidates– Advantage: avoidance of perioperative Advantage: avoidance of perioperative

morbidity and mortalitymorbidity and mortality– Not as effective palliative maneuver as Not as effective palliative maneuver as

surgery for dysphagia and odynophagiasurgery for dysphagia and odynophagia– higher probability of local complications like higher probability of local complications like

esophagotracheal fistulaesophagotracheal fistula Preoperative Radiotherapy: No survival Preoperative Radiotherapy: No survival

advantageadvantage

Role of ChemotherapyRole of Chemotherapy

Preoperative Chemotherapy Preoperative Chemotherapy (Cisplatin and Fluorouracil) : possible (Cisplatin and Fluorouracil) : possible small benefitsmall benefit

Preoperative Chemotherapy and Preoperative Chemotherapy and Radiation therapyRadiation therapy

Comparing Preoperative Chemotherapy and Radiotherapy with Comparing Preoperative Chemotherapy and Radiotherapy with Surgery AloneSurgery Alone

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Surgery alone Vs Combined Surgery alone Vs Combined modality therapy. Phase III modality therapy. Phase III

studystudy

RandomizeN=113Adeno

SurgeryN=55

Cis/5FUXRT

SurgeryN=58

Median Survival: 11m1 yr survival: 44%2 yr survival: 26%3 yr survival 6%

Median Survival :16m 1 yr survival 52%2 yr survival37%3 yr survival 32%

Two courses of chemotherapy in weeks 1 and 6 5 FU 15 mg per kg daily for five daysCisplatin, 75 mg per square m2 on day 7Radiotherapy, 40 Gy, administered in 15 fractions over a 3-week period, beginning concurrently with the first course of chemotherapy.

Walsh et al NEJMWalsh et al NEJM

Walsh et alWalsh et al

Kaplan–Meier Plot of Kaplan–Meier Plot of Survival of Patients Survival of Patients with Esophageal with Esophageal Adenocarcinoma, Adenocarcinoma, According to the According to the Intention-to-Treat Intention-to-Treat AnalysisAnalysis. .

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Walsh et al Walsh et al

At the time of surgery: At the time of surgery: – 42 % (23 of 55) of patients treated with 42 % (23 of 55) of patients treated with

preoperative multimodal therapy who could be preoperative multimodal therapy who could be evaluated had positive nodes or metastases evaluated had positive nodes or metastases versusversus

– 82 % (45 of 55) of patients who underwent 82 % (45 of 55) of patients who underwent surgery alone (P<0.001). surgery alone (P<0.001).

25 % of patients who underwent surgery 25 % of patients who underwent surgery after multimodal therapy had complete after multimodal therapy had complete responses, as determined pathologically. responses, as determined pathologically.

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Post op Chemo and Post op Chemo and Radiation Radiation

Role is currently undefinedRole is currently undefined No proven benefit in node negative patientsNo proven benefit in node negative patients Node positive patients may be benefited and Node positive patients may be benefited and

should be enrolled in clinical trials as there is should be enrolled in clinical trials as there is currently no evidence of benefit.currently no evidence of benefit.

Patients with incompletely resected tumors or Patients with incompletely resected tumors or positive margins should receive adjuvant positive margins should receive adjuvant chemoradiation if they can tolerate it, otherwise chemoradiation if they can tolerate it, otherwise only XRTonly XRT

Role of Chemotherapy Role of Chemotherapy Contd..Contd..

Preoperative Chemotherapy (Cisplatin and Preoperative Chemotherapy (Cisplatin and Fluorouracil) : possible small benefitFluorouracil) : possible small benefit

Preoperative Chemotherapy and Radiation Preoperative Chemotherapy and Radiation therapytherapy

Post op Chemotherapy and radiation Post op Chemotherapy and radiation therapy offered to pt with incomplete therapy offered to pt with incomplete resectionresection

Non surgical Chemotherapy and Non surgical Chemotherapy and radiation therapy: Long term survival radiation therapy: Long term survival in 25% of ptsin 25% of pts

Management of Advanced Management of Advanced Stage IV DiseaseStage IV Disease

Chemoradiotherapy for palliation of symptoms Chemoradiotherapy for palliation of symptoms – Infusional 5-FU 1000 mg/m2 per day, days 1 to 4, and 29 to Infusional 5-FU 1000 mg/m2 per day, days 1 to 4, and 29 to

3333– Cisplatin 75 mg/m2, on days 1 and 29Cisplatin 75 mg/m2, on days 1 and 29– Concurrent external beam RT (50.4 Gy in daily 2 Gy fractions)Concurrent external beam RT (50.4 Gy in daily 2 Gy fractions)

Shrinkage of the tumor by atShrinkage of the tumor by at least 50 percent may least 50 percent may occur in 15 to 30% of patients whooccur in 15 to 30% of patients who are treated with are treated with fluorouracil, a taxane (paclitaxel or docetaxel),fluorouracil, a taxane (paclitaxel or docetaxel), or or irinotecanirinotecan

Addition of cisplatin : 35 to 55 percent Addition of cisplatin : 35 to 55 percent

Response to chemotherapyResponse to chemotherapy typically lasts a few typically lasts a few months, and survival rarely exceeds one yearmonths, and survival rarely exceeds one year

Future DirectionsFuture Directions

Cetuximab : Ab that blocks EGFRCetuximab : Ab that blocks EGFR– Synergy with both chemo and rad therapy in Synergy with both chemo and rad therapy in

head & neck Ca and colorectal Cahead & neck Ca and colorectal Ca Trastuzumab, targeted at HER-2/neu Trastuzumab, targeted at HER-2/neu

pathway in addition to cisplatin, paclitaxel pathway in addition to cisplatin, paclitaxel and combined radiotherapy and combined radiotherapy

Bevacizumab, targeted at VEGF ligandBevacizumab, targeted at VEGF ligand Oral agents: inhibits tyrosine kinase Oral agents: inhibits tyrosine kinase

associated with EGFR, OSI-774 and ZD associated with EGFR, OSI-774 and ZD 18391839

Thank You!Thank You!