Background Reports of long-term survivors (≥5 years) of locally advanced esophageal cancer (LAEC) have focused mainly on HRQL or GI symptoms Only

BackgroundReports of long-term survivors (≥5 years) of

locally advanced esophageal cancer (LAEC) have

focused mainly on HRQL or GI symptoms

Only a handful of studies examined long term

oncological outcomes and causes of death beyond 5

years

Are patients with LAEC “truly” cured of their

disease?

AATS 95th ANNUAL MEETING, 2015

Objectives

1.To determine overall and CSS in patients with LAEC surviving at least 5 years 2.To determine the frequency and outcome of recurrent EC in 5 year survivors 3.To determine predictors of recurrence and mortality beyond the 5 year time point4.To determine the incidence of second primary cancers5.To determine competing causes of death


Study Design Retrospective review of prospectively collected EC

database of esophagectomy for clinical T2N0 or higher disease

(1988 - 2009)


Methods

• Definition of recurrence:• Local if luminal or intramural • Regional if in any nodes in dissected bed• Distant visceral or nodes beyond dissected

fields

• OS and CSS calculated from the landmark time of 5th postoperative year using KM method

• Multivariable analysis performed for factors affecting recurrence and survival

Recurrence in entire cohort (198/355)

AATS 95th ANNUAL MEETING, 2015Weill Cornell Medical College


Patient Demographics (Long-term survivors, n=140)

Patients’ Characteristics No. of patients140 (%)

Age at esophagectomy median years (IQR)

63 (55-70)

Gender Male Female

107 (76.4)33 (23.6)

Charlson Comorbidity Index CCI = 0 CCI = Above 0

74 (52.9)66 (47.1)

Performance Status PS = 0 PS = 1,2

91 (65)49 (35)

Pulmonary Comorbidities Absence Presence

106 (75.7)34 (24.3)

Clinical Staging


cTNM stages Number (%)

T1 N1 M0T1 N2 M1

2 (1.4%)1 (0.7%)

T2 N0-1 M0 39 (27.9%)

T3 N0-1 M0T3 N1 M1

86 (61.4%)8 (5.7%)

T4a N0 M0 T4a N1 M1

3 (1.2%)1 (0.7%)

Treatment details

Patients’ Characteristics No. of patients = 140 (%)

Neoadjuvant therapy Surgery alone Adjuvant therapy

74 (52.9)50 (35.7)16 (11.4)

En bloc resection 2-field 3-field

116 (82.9)41 (29.3)75 (53.6)

Histological cell type Adenocarcinoma SCC

87 (62.1)53 (37.9)

Residual tumor status R0 R1, R2

138 (98.6)

2 (1.4)

No. of LN median (IQR) 30 (21 – 41)


Pathological Staging


pTNM stagesNeoadjuvant

therapySurgery

T0 N0T0 N+

123

--

T1 N0T1 N+

74

133

T2 N0T2 N+

611

117

T3/4 N0 T3/4 N+

1415

822

TanyNanyM+ 3 2

Incidence and patterns of recurrence in patients surviving

5 or more years


Patients developing recurrent EC: n=32• Prior to 5 years: 24

• After 5 years: 8

Incidence first recurrence after 5 years: • 8/116 (7%)

Annualized incidence of recurrence until year 10:• 1.4% per year

(10 of 24 disease free at year 5)

10

Pattern of recurrent EC in LAEC surviving at least 5

years

Local only : 3 (2%) Regional only : 11 (7.9%)

Distant : 16 (11.4%)

Regional/distant 2 (1.4%)

After 5 years:1

1

6


MVA Predictors of Recurrence (n=140)

Independent Variables

HR 95% CI ‘p ’ Values

Performance status PS = 0 (n=91) PS = 1 or 2 or 3 (n=49)

1.000.57 0.24 – 1.33 0.192

Neoadjuvant therapy Neo-adjuvant (n=74) Surgery alone (n=66)

1.000.72 0.33 – 1.53 0.386

Pathological T class. T0, Tis, T1 (n=44) T2, T3, T4 (N=96) 1.37 0.53 – 3.53 0.510

Pathological N class. N0 (n=71) N1, N2, N3 (n=69) 3.00 1.28 – 7.06 0.012

Treatment of recurrence

Treatment type Patients Surviving ≥5 after recurrence

Chemotherapy only 14 3

ChemoRT only 9 4

Surgery +/- CT/RT 9 4

6 patients remain disease free > 5 years after treatment of recurrent EC

Cancer Specific Survival (CSS) n=140


Survival years

7 years

10 years

15 years

N=140 88% 84% --

Patients at risk

91 49 22

Median f/u = 101 months from surgery and 41 months

from 5 year point

Overall Survival (OS) n=140


Survival years

7 years

10 years

15 years

N=140 86% 70% 51%

Patients at risk

91 49 22

Causes of Death

Pulmonary diseases (Pneumonia = 5, Respiratory failure = 3, and Pulmonary embolism = 2)


Causes of Death No. of patients (n = 47)

Recurrence of Esophageal cancer

20 (42.6%)

Pulmonary diseases 10 (21.3%)

Cardiac diseases 7 (15%)

Second primary cancer 4 (8.5%)

Stroke 2 (4.3%)

Renal failure 1 (2.1%)

Unknown cause 3 (6.4%)

Second Primary Cancers (16.4%)


Second Primary cancer No. of patients (n = 23)

Prostate cancer 6 (4.3%)

Lung cancer 3 (2.1%)

Gastric cancer 2 (1.4%)

Head and Neck cancers 2 (1.4%)

Breast cancer 2 (1.4%)

Ovarian carcinoma 2 (1.4%)

Skin cancers (melanoma and SCC)

2 (1.4%)

Urinary bladder cancer 2 (1.4%)

Colon cancer 1 (0.7%)

Meningioma 1 (0.7%)

Predictors of Mortality >5 Y. (n=140)

Independent Variables

HR 95% CI ‘p ’ Values

Neoadjuvant therapy Neo-adjuvant (n=74) Surgery alone (n=66) 0.76 0.41 – 1.39 0.369

Extent of resection en bloc (n=116) non-en bloc (n=24) 4.17 1.69 – 10.30 0.002

Pathological N class. N0 (n=71) N1, N2, N3 (n=69) 1.04 0.50 – 2.18 0.914

Recurrence No recurrence (n=108) Recurrences (n=32) 4.65 2.42 – 8.93 <0.001


Conclusions The majority of patients with LAEC who do not

recur by 5 years are, in fact, cured of their disease

A small subset of patients (<10%) remain at risk for recurrent EC Nodal disease is the only independent

variable for EC recurrence Patients cured of EC are at risk for second

primary cancers Pulmonary disease leads to at least 20% of non

–cancer deaths


Recommendations

Careful follow up for patients with LAEC surviving 5 years should be continued due to the risk of late recurrence and second primary cancers

Therapy can be advocated for selected patients with recurrences

Because aspiration may be an important long term sequela of esophagectomy, patients need careful follow-up by physicians familiar with the management of esophageal diseases


Thank youThank you

Conclusion

Despite surviving at least 5-years after esophagectomy for LAEC, a small subset of patients at risk for Recurrence of esophageal cancerSecond primary cancersPulmonary disease possibly related to esophagectomy

Careful follow-up and surveillance are mandatory for LAEC patients even after 5-years follow-up


Overall Survival for Neoadjuvant vs. Surgery alone (OS) n=140


Survival years 7 years 10 years 15 years

Neoadjuvant(n=74) 83% 62% 48%

Surgery alone (n=66) 88% 74% 58%

Patients at risk 7 years 10 years 15 years

Neoadjuvant 39 15 5

Surgery alone 48 30 11

Disease Free Survival for Neoadjuvant vs. Surgery alone (DFS) n=140



Neoadjuvant(n=74) 72% 56% 45%

Surgery alone (n=66)

78% 69% 56%

Patients at risk 7 years 10 years 15years

Neoadjuvant 33 12 3


Cancer Specific Survival for Neoadjuvant vs. Surgery alone (CSS) n=140



Neoadjuvant(n=74) 83% 80% --

Surgery alone (n=66) 92% 87% --


Neoadjuvant 39 15 4


Overall Survival for pT0,pTis,pT1 vs. pT2-4



Path Tis,T0,T1 (n=44) 97% 77% 69%

Path T2,T3,T4 (n=96) 80% 65% 49%


Path Tis,T0,T1 (n=44) 26 10 3

Path T2,T3,T4 (n=96) 61 35 13

Disease Free Survival for pT0,pTis,pT1 vs. pT2-4



Path Tis,T0,T1 (n=44) 86% 73% 63%

Path T2,T3,T4 (n=96) 69% 58% 46%


Path Tis,T0,T1 (n=44) 24 9 2

Path T2,T3,T4 (n=96) 52 31 12

Cancer Specific Survival for pT0-1,pTis vs. pT2-4



Path Tis,T0,T1 (n=44) 97% -- --

Path T2,T3,T4 (n=96) 84% 78% --


Path Tis,T0,T1 (n=44) 26 10 3

Path T2,T3,T4 (n=96) 61 35 13

Overall Survival for pN0 vs. pN1-3



Path N0 (n=71) 94% 79% 60%

Path N1-3 (n=69) 78% 60% 48%


Path N0 (n=71) 44 23 9

Path N1-3 (n=69) 43 22 7

Disease Free Survival for pN0 vs. pN1-3



Path N0 (n=71) 89% 74% 55%

Path N1-3 (n=69) 60% 51% 45%


Path N0 (n=71) 43 22 8

Path N1-3 (n=69) 33 18 3

Cancer Specific Survival for pN0 vs. pN1-3



Path N0 (n=71) 94% -- --

Path N1-3 (n=69) 82% 75% --


Path N0 (n=71) 44 23 9

Path N1-3 (n=69) 43 22 7

Follow-up and Recurrence


Median follow-up for 5-year survivors was 101 months (60-270 m.)

For entire cohort (n=140): 198 developed recurrent EC in the entire cohort (n=355) 96 % occurred prior to the 5th postoperative year. 107 in the first year (54%), 43 (22%) patients in year 2, 27 (14%) in

year 3, 7 (4%) in year 4, 6 (3%) in year 5, and 8 (4%) after year 5.

In 5-year survivors (n=140): 32 (23%) developed recurrence. Local in 3 patients (2%), Regional in 11 (7.9%), Distant in 16

(11.4%) and both regional and distant in 2 (1.4%) patients. 11 patients survived at least 5 years after treatment of their recurrence.

Recurrence in entire cohort (n=355)


Documents

Background Reports of long-term survivors (≥5 years) of locally advanced esophageal cancer (LAEC) have focused mainly on HRQL or GI symptoms Only