Ann Surg Oncol
https://doi.org/10.1245/s10434-018-6648-6
ORIGINAL ARTICLE – GASTROINTESTINAL ONCOLOGY
Cervical Esophageal Cancer Treatment Strategies: A Cohort
Study Appraising the Debated Role of Surgery
Michele Valmasoni, MD, PhD1,2 , Elisa Sefora Pierobon, MD1, Gianpietro Zanchettin, MD, PhD1,
Dario Briscolini, PhD1, Lucia Moletta, MD1,2, Alberto Ruol, MD1, Renato Salvador, MD1,2, and Stefano Merigliano,
MD1,2
1
Department of Surgical, Oncological and Gastroenterological Sciences, Center for Esophageal Disease, University of
Padova, Padua, Italy; 2University Hospital, Padua, Italy
ABSTRACT
Background. Few studies have examined optimal treat-
ment specifically for cervical esophageal carcinoma. This
study evaluated the outcome of three common treatment
strategies with a focus on the debated role of surgery.
Methods. All patients with cervical esophageal cancer
treated at a single center were identified and their outcomes
analyzed in terms of morbidity, mortality, and recurrence
according to the treatment they received, i.e. surgery alone,
definitive platinum-based chemoradiation (CRT), or CRT
followed by surgery.
Results. The study population included 148 patients with
cervical esophageal cancer from a prospective database of
3445 patients. Primary surgery was the treatment of choice
for 56 (37.83%) patients, definitive CRT was the treatment
of choice for 52 (35.13%) patients, and CRT followed by
surgery was the treatment of choice for 40 (27.02%)
patients. CRT-treated patients obtained 36.96% complete
clinical response, with overall morbidity and mortality
rates of 36.95 and 2.17%, respectively. Surgical complete
resection was achieved in 71.88% of surgically treated
cases, with morbidity and mortality rates of 52.17 and
6.25%, respectively. No significant survival difference
existed among the three treatments, but patients who
underwent surgery alone had a significantly lower stage of
disease (p = 0.031). Compared with patients with complete
response after CRT, surgery did not confer any significant
survival benefit, and overall 5-year survival was lower than
Ó Society of Surgical Oncology 2018
First Received: 6 September 2017
M. Valmasoni, MD, PhD
e-mail: michele.valmasoni@unipd.it
definitive CRT alone. In contrast, surgery improved sur-
vival significantly in patients with non-complete response
after definitive CRT (p = 0.023).
Conclusions. Definitive platinum-based CRT should be
the treatment of choice for cervical esophageal cancer.
Surgery has a role for patients with non-complete response
as it adds significant survival benefit, with accept-
able morbidity and mortality.
Cervical esophageal cancer accounts for approximately
5% of esophageal carcinomas.1 The histotype is mainly
squamous cell carcinoma (SCC) and is often locally
advanced at diagnosis, infiltrating anatomical local struc-
tures such as hypopharynx, larynx, trachea, thyroid gland,
or laryngeal nerves.2 Such biological behavior requires
aggressive and often mutilating surgery. For such reasons,
definitive radiation (RT; from experience with head and
neck SCC) and chemoradiation therapies (CRT; from
randomized trials on SCC treatments of the thoracic
esophagus) remain alternatives to surgery, with the promise
of avoiding significant surgical morbidity and mortality. In
many patients, definitive regimens fail, and persistent or
recurrent cancer is frequent, with surgery often remaining
the only treatment option. With no strong evidence
regarding the best treatment for cervical esophageal cancer,
it is instead managed on clinical practice, and, even if
definitive chemoradiation (CRT) is recommended,3,4
neoadjuvant RT or CRT followed by surgery, RT or CRT
with salvage surgery, and surgery alone or followed by
adjuvant chemotherapy and RT have been reported.5–14
In this study, we aimed to evaluate the outcomes of three
treatment strategies (surgery alone, definitive CRT, and
CRT followed by surgery) in a single-center cohort, with a
focus on the debated role of surgery.

PATIENTS AND METHODS
All procedures were carried out according to our
research and ethical guidelines. This study was approved
by the Research Committee of the Department of Surgical,
Oncological, and Gastroenterological Sciences at the
University of Padova. All patients provided written consent
for use of their data for research purposes.
Patient Selection
To select the study cohort, we reviewed our prospec-
tively maintained esophageal cancer database. All patients
treated for cervical esophageal cancer, defined as cancer
having its epicenter in the cervical tract of the esophagus,
were considered for inclusion in this study (1992–2010).
Selection criteria were squamocellular carcinoma of the
cervical esophagus, no metastatic disease, definitive CRT
with platinum-based chemotherapy, or primary surgery
with curative intent, with no missing data. We reviewed all
medical records for data consistency and completeness.
Pretreatment Study
All patients underwent staging with esophagogastro-
duodenoscopy (EGDS), endoscopic ultrasound, computed
tomography (CT) scan, and positron emission tomography
(PET)/CT scan (from 2005).9 Fine-needle aspiration
cytology of cervical nodes was performed when indicated,
and laryngoscopy and bronchoscopy were part of the
workup. Cancer stage was classified according to American
Joint Committee on Cancer (AJCC) staging, 7th edition.15
Treatments
Treatment plans were tailored for each patient by mul-
tidisciplinary consensus, based on tumor characteristics
and extension, knowledge at the time of the decision,
patient age and comorbidities, and informed patient’s
decision. The need for laryngectomy was a strong indica-
tion for CRT.
Chemoradiation
Chemotherapy regimens were based on the association
of cisplatin with 5-fluorouracil, with a cisplatin 100 mg/m2
infusion on day 1 and a 5-fluorouracil 1000 mg/m2 con-
tinuous infusion from days 1 to 5, for three or more cycles.
In some patients, taxanes or epirubicin were used based on
tolerability, comorbidities, and performance status. RT
therapy was performed according to the Italian Association
of Oncologic Radiotherapy (AIRO)16 in 1.8 Gy daily
M. Valmasoni et al.
doses, for 5 days a week, for a total dose of at least 50.4 Gy
concurrently with chemotherapy.
CRT toxicity was classified according to the World
Health Organization (WHO) toxicity grading scale,17 and
response to treatments was tested according to Response
Evaluation Criteria in Solid Tumors (RECIST).18
Surgery
Operative approaches included three-incision
esophagectomy or pharyngo-laryngo-esophagectomy,
using either a gastric or colon conduit. In some cases, we
performed pharyngo-laryngectomy with partial esophageal
resection and reconstruction with jejunal autotransplant.
After definitive CRT, esophageal resection was offered
to all patients fit for surgery, even if a clinical complete
response was achieved with CRT. Postoperative morbidity
was classified according to the Clavien–Dindo classifica-
tion19 and mortality within 30 days from surgery was
deemed postoperative.20
Follow-Up and Outcome
All patients had a minimum follow-up of 5 years.
Overall survival and time to recurrence for complete
response or radical surgery were calculated from surgery or
the beginning of CRT. Recurrence was defined as local if
involving the anastomotic region and/or cervical or upper
mediastinal nodes, and as systemic if involving distant
nodes or other organs.
Statistical Analysis
The study cohort was analyzed according to the intent to
treat (CRT or surgery) and then divided into three groups
based on overall treatment, i.e. patients who underwent
primary surgery only (SURG group), patients treated with
definitive CRT (CRT group), and patients undergoing
surgery after CRT (CRT/SURG group). The CRT/SURG
group included both those who underwent salvage surgery
and those who underwent planned surgery.
Descriptive results are shown as mean ± standard
deviation for continuous variables, and size and frequency
for categorical variables. Correlations were evaluated using
the Fishers, Mann–Whitney, and Kruskal–Wallis tests, and
the Sidàk correction for multiple comparisons was applied
when indicated.21 Survival analysis was performed using
the Cox proportional hazard model adjusted for baseline
variables (tumor stage, age, American Society of Anes-
thesiologists score) with the corrected group prognosis
method.22 A p value \ 0.05 was considered statistically
significant. Analyses were performed using JMP statistical
software version 11.0 (SAS Institute Inc., New York, NY,
Treatments for Cervical Esophageal Cancer
USA) and R statistical software version 3.4.3 (The R
Foundation, Vienna, Austria; https://www.r-project.org).
RESULTS
Patients
Of 3445 patients, 363 were diagnosed with cervical
esophageal cancer. After the exclusion of patients not
meeting the enrollment criteria, the final cohort included
148 patients (mean age 61.43 ± 8.96 years, 81.08% males,
18.91% females). Fifty-six (37.83%) patients were treated
with primary surgery alone (SURG group), 52 (35.13%)
were treated with definitive CRT (CRT group), and 40
(27.02%) were treated with definitive CRT followed by
surgery (CRT/SURG group) (see Fig. 1a for patient
selection criteria, and Table 1 for patient and tumor
characteristics).
Chemoradiation
Definitive CRT was the treatment of choice for 92
(62.16%) patients (CRT and CRT/SURG groups). The
CRT regimens were cisplatin ? 5-fluorouracil ? RT for
78 (84.7%) patients, cisplatin ? epirubicin or taxane ± 5-
fluorouracil ? RT in 10 (10.8%) cases, and cisplatin ? RT
in 4 (4.3%) patients.
Eighty-four (91.3%) patients underwent three to six
treatment cycles, while 8 (8.7%) patients stopped
chemotherapy after one or two treatment cycles due to
toxicity. Mean RT dose was 50.44 ± 10.53 Gy. Overall
morbidity was 36.95%, WHO 1 toxicity was registered in
five (5.43%) patients, WHO 2 toxicity was registered in six
(6.52%) patients, WHO 3 toxicity was registered in nine
(9.78%) patients, and WHO 4 toxicity was registered in 14
(15.22%) patients. CRT mortality was 2.17%.
At the end of CRT, clinical response was complete
response in 34 (36.96%) patients, partial response in 42
(45.65%) patients, stable disease in 6 (6.52%) patients, and
progressive disease in 10 (10.87%) patients. Mean RT dose
was 52.64 ± 8.42 Gy for complete response patients,
49.85 ± 11.14 Gy for partial response and stable disease
patients, and 45 ± 13.54 for progressive disease patients
(p = 0.189); the mean number of chemotherapy cycles was
3.75 ± 1.14 for patients obtaining a complete response,
3.36 ± 1.01 in cases of partial response or stable disease,
and 3.28 ± 1.60 for progressive disease (p = 0.345).
Patients with stage I–II disease had a 65% complete
response rate, while patients in stage III–IV had a complete
response rate of 29.17% (p = 0.003).
After CRT, 40 of 92 (43.47%) patients underwent sur-
gery—29 (72.5%) because of incomplete response or
disease progression (salvage surgery), and 11 (27.5%) with
complete clinical response, per the patient’s preference
(planned surgery) (see Table 2 for CRT results).
Surgery
Surgery was performed on 96 (64.86%) patients (SURG
and CRT/SURG groups)—in 56 (58.33%) patients as the
first choice and in 40 (41.67%) patients after definitive
CRT. Surgical complete resection (R0) was achieved in 69
(71.88%) patients, with pharyngo-laryngectomy being
necessary in 36 (41.38%) patients. The mean number of
harvested lymph nodes was 13.4 ± 9.02.
The reconstruction technique was esophago-gastroplasty
in 47 (48.95%) patients, esophago-coloplasty in 2 (2.08%)
patients, pharyngo-gastroplasty in 28 (29.1%) patients,
pharyngo-coloplasty in 11 (11.45%) patients, and jejunal
transplant in 2 (2.08) patients; in 6 (6.25%) cases, recon-
struction was not performed.
We registered recurrent nerve lesion in 11 (11.45%)
patients, tracheal lesion in 1 (1.04%) patient, and other
intraoperative complications in 5 (5.20%) patients. Post-
operative morbidity was 52.17%. Anastomotic leak
occurred in 13 (13.68%) patients, and stenosis occurred in
16 (16.84%) patients. Postoperative mortality was 6.25%,
and 90-day mortality was 9.37% (see Table 3 for surgery
results).
Tumor Recurrence
Tumor recurrence rates were 39.29% for the SURG
group (50% local recurrence), 48.08% for the CRT group
(84% local), and 50% for the CRT ? SURG group (55%
local), with a significantly higher local recurrence rate for
the CRT group (p = 0.024). The mean time of recurrence
(in months) was 10.05 ± 7.15 for the SURG group,
8.85 ± 7.19 for the CRT group, and 14.46 ± 10.57 for the
CRT ? SURG group (p = 0.264).
Survival Analysis
The overall survival rate was 21.8%. No significant
differences were noted in the 5-year overall survival rates
according to the treatment plan (SURG group: 12.6%; CRT
group: 26.7%; CRT ? SURG group: 30.7%; p = 0.088).
For patients who underwent surgery, in the SURG group
radical surgery complete resection (R0) had a significant
impact on survival (p = 0.006), while in the CRT ? SURG
group, R0 was not significant (p = 0.378). For patients who
underwent CRT (CRT and CRT ? SURG groups) com-
plete clinical response after therapy was highly significant
for a better 5-year survival (complete response: 46.2%;
 M. Valmasoni et al.

a study cohort selection

(Period 1992-2010)
3445
Esophageal Cancer
Patients

167 pts.
363 pts. Head and neck cancer or
Cancer involving the thoracic esophagus or
cervical esophagus not clear origin, involving
cervical esophagus

48 pts.
196 pts. Exclusion Criteria:
Cancer originating from no SCC
cervical esophagus no Available Data
no Study Treatment

Study cohort
148 pts.
Chemoradiation and/or
Surgery

b treatment flow-chart
56 pts. SURGERY ALONE

148 pts. 40 pts. SURGERY

CERVICAL ESOPHAGUS SCC (29 pts. for cPR/cPD/Recurrence,
11 pts. with cCR for patients choice)

92 pts. DEFINITIVE CRT

56 pts. NO SURGERY

FIG. 1 a Study cohort selection and b treatment flowchart. SCC squamous cell carcinoma, cPR clinical partial response, cPD clinical
progressive disease, cCR clinical complete remission, CRT chemoradiation

partial response/stable disease: 16%; progressive disease: DISCUSSION

11%; p = 0.009).
Considering patients with complete clinical response
after CRT, there was no significant difference in survival in
the CRT ? SURG group compared with the CRT group
(p = 0.176) (Fig. 2a). For patients with partial response,
stable disease, or progressive disease, the CRT ? SURG
group had a significantly higher survival compared with the
CRT group (p = 0.023) (Fig. 2b). Comparison between
patients in the CRT group with complete response and
patients in the SURG group with R0 resection showed a
significantly better survival for the CRT group (p = 0.001).
Cervical esophageal cancer represents 2–10% of all
esophageal malignancies. It is frequently considered along
with cancer of the hypopharynx, even though these are two
separate pathological entities.23–26 Nevertheless, it is dif-
ficult to distinguish tumor origin when patients present
with advanced-stage disease. Published series mainly
report data regarding the two neoplasms together and
patients who underwent heterogeneous treatment strate-
gies, making any comparison difficult.27–32 This
Treatments for Cervical Esophageal Cancer

TABLE 1 Patient and tumor SURG (n = 56) CRT (n = 52) CRT ? SURG (n = 40) p value
characteristics
Sex
Male 44 (78.57) 43 (82.69) 33 (82.5) 0.832
Female 12 (21.43) 9 (17.31) 7 (17.5)
Age, years (mean [SD]) 61.11 [8.71] 62.50 [9.1] 60.49 [9.2] 0.535
Karnofsky score
[ 80 36 (67.92) 34 (65.38) 29 (78.38) 0.498
B 80 17 (32.08) 18 (34.62) 8 (21.62)
Location
Cervical 34 (60.71) 35 (67.31) 28 (70) 0.878
Thoracic extension 8 (14.29) 7 (13.46) 4 (10)
Hypopharynx extension 14 (25) 10 (19.23) 8 (20)
ASA score
1 4 (7.14) 1 (1.92) 3 (7.5) 0.086
2 38 (67.86) 26 (50) 21 (52.5)
3 13 (23.21) 22 (42.31) 16 (40)
4 1 (1.79) 3 (5.77) 0 (0)
Tumor length, mm (mean [SD]) 43.82 [19.77] 50 [23.3] 54.53 [27.3] 0.097
cStagea
1–2 23 (41.07) 13 (25) 7 (17.5) 0.031
3–4 33 (58.93) 39 (75) 33 (82.5)
cN
Negative 31 (55.36) 15 (28.85) 9 (22.5) 0.001
Positive 25 (44.64) 37 (71.15) 31 (77.5)
Data are expressed as n (%) unless otherwise specified
SD standard deviation, ASA American Society of Anesthesiologists, SURG surgery alone, CRT definitive
chemoradiation, CRT ? SURG chemoradiation followed by surgery, cN lymph node status
a
According to the American Joint Committee on Cancer, 7th edition

TABLE 2 Chemoradiation CRT total (n = 92) CRT (n = 52) CRT ? SURG (n = 40) p value
results
RT dose, Gy (mean [SD]) 50.44 [10.53] 49.99 [10.93] 51.01 [10.14] 0.678
CRT toxicitya
No 58 (63.04) 28 (53.85) 30 (75) 0.083
WHO 1 5 (5.43) 2 (3.85) 3 (7.5)
WHO 2 6 (6.52) 4 (7.68) 2 (5)
WHO 3 9 (9.78) 8 (15.38) 1 (2.5)
WHO 4 14 (15.22) 10 (19.23) 4 (10)
CRT responseb
CR 34 (36.96) 23 (44.23) 11 (27.5) 0.031
PR 42 (45.65) 17 (32.69) 25 (62.5)
SD 6 (6.52) 5 (9.62) 1 (2.5)
PD 10 (10.87) 7 (13.46) 3 (7.5)
Data are expressed as n (%) unless otherwise specified
Statistical difference expressed as p for CRT versus CRT ? SURG
SD standard deviation, CRT definitive chemoradiation, CRT ? SURG chemoradiation followed by surgery,
RT radiotherapy, CR complete response, PR partial response, SD stable disease, PD progressive disease,
RECIST Response Evaluation Criteria in Solid Tumors, WHO World Health Organization
a
Toxicity classified according to the WHO
b
Response to therapy classified according to RECIST
 M. Valmasoni et al.

TABLE 3 Results of surgery

SURG total (n = 96) SURG (n = 56) CRT ? SURG (n = 40) p value

Surgical radicality
R0 69 (71.87) 41 (73.21) 28 (70) 0.668
R1–2 27 (28.13) 15 (26.79) 12 (30)
Type of reconstruction
EGP 47 (48.95) 25 (44.64) 22 (55) 0.156
ECP 2 (2.08) 0 (0) 2 (5)
PGP 28 (29.1) 19 (33.36) 9 (22.5)
PCP 11 (11.45) 6 (10.71) 5 (12.5)
Jejunal interposition 2 (2.08) 2 (3.58) 0 (0)
No reconstruction 6 (6.25) 4 (7.14) 2 (5)
Pharyngo-laryngectomy
No 51 (58.62) 25 (51.02) 22 (64.71) 0.214
Yes 36 (41.38) 24 (48.98) 12 (35.29)
Intraoperative complications
No 75 (79.79) 42 (77.78) 33 (82.5) 0.504
Recurrent nerve lesion 11 (11.7) 7 (12.96) 4 (10)
Tracheal lesion 1 (1.06) 0 (0) 1 (2.5)
Other 5 (5.32) 4 (7.4) 1 (2.5)
Harvested lymph nodes
Mean nodes [SD] 13.4 [9.02] 12.55 [8.92] 14.65 [9.16] 0.293
Mean positive nodes [SD] 1.04 [2.19] 0.88 [1.61] 1.28 [2.87] 0.458
Negative 58 (60.42) 34 (60.71) 24 (60) 0.943
Positive 38 (39.58) 22 (39.29) 16 (40)
Vascular invasion
No 20 (42.55) 13 (44.83) 7 (36.8) 0.484
Yes 27 (57.45) 15 (51.72) 12 (63.16)
Postoperative complications
No 44 (47.83) 24 (42.86) 20 (55.56) 0.233
Yes 48 (52.17) 32 (57.14) 16 (44.44)
Anastomotic leak
No 82 (86.32) 46 (83.64) 36 (90) 0.365
Yes 13 (13.68) 9 (16.36) 4 (10)
Anastomotic stenosis
No 79 (83.16) 44 (80) 35 (87.5) 0.328
Yes 16 (16.84) 11 (20) 5 (12.5)
Statistical difference expressed as p for SURG versus CRT ? SURG
SD standard deviation, SURG surgery alone, CRT ? SURG chemoradiation followed by surgery, EGP esophago-gastroplasty, ECP esophago-
coloplasty, PGP pharyngo-gastroplasty, PCP pharyngo-coloplasty

study contributes to the hypothesis that definitive CRT
should be the treatment of choice for cervical esophageal
cancer.
Cervical esophageal cancer has a dismal prognosis
regardless of treatment; we reported a 5-year survival rate
of 21.8%, similar to that reported in the literature
(18–35%).8,33,34
As far as staging is concerned, our series is similar to
that reported in the literature, with the majority of patients
having advanced disease at diagnosis, and with 70.94% of
patients being stage III and IV and lymph nodes metastases
being present in 62.83% of patients. Likewise, analyzing
the data of hypopharyngeal cancers, Gourin and Terris
Treatments for Cervical Esophageal Cancer

a complete response patients b partial response, stable, progressive disease patients

1.0

1.0
Unadjusted CRT Unadjusted CRT
Adjusted CRT Adjusted CRT
Unadjusted CRT/SURG Unadjusted CRT/SURG
Adjusted CRT/SURG Adjusted CRT/SURG
0.8

0.8
0.6

0.6
Survival

Survival
p=0.176
0.4

0.4
0.2

0.2
p=0.023
number of at-risk number of at-risk
23 21 20 14 13 12 9 29 14 9 4 2 2 2
0.0

0.0
11 9 6 4 4 4 4 29 23 16 10 6 6 6

0 10 20 30 40 50 60 0 10 20 30 40 50 60
Time (months) Time (months)

FIG. 2 Five-year survival (unadjusted and adjusted curves): chemoradiation versus chemoradiation followed by surgery. a Clinical complete
response patients. b Partial response, stable disease, and progressive disease patients. CRT chemoradiation therapy, SURG surgery

observed that 60–80% of patients have metastatic lymph
nodes at diagnosis, which are contralateral in 40% of
cases.29
In the 1960s, surgery became the standard treatment for
cervical esophagus and hypopharynx cancer due to the
introduction of pharyngo-laryngo-esophagectomy, which
brought an improvement in outcome.35,36 This surgical
procedure has shown significant drawbacks, with only a
modest improvement in long-term survival. Postoperative
complications can be life-threatening, such as conduit
necrosis or anastomotic leaks, with unacceptably high
mortality. Reported morbidity was 10.5%, which was
similar to our anastomotic leak rate of 13.68%.14,36–39 The
mortality rate in our series was 6.25%, but it has been
reported in the literature to be as high as 50%. Lastly,
quality of life can be greatly worsened due to the frequent
need to perform laryngectomy, thyroidectomy, or
parathyroidectomy.
The introduction of multimodal treatment planning
permits consideration of an organ-sparing approach. In the
neoadjuvant setting, CRT may lead to downstaging of the
disease, allowing a conservative surgery approach such as
larynx-sparing surgery or even, when a complete response
is reached, deferral of surgery. Although concomitant
definitive CRT is considered the optimal treatment, no
supporting level A evidence is available.4
The RTOG 85-01 study, comparing the results of
chemoradiation versus surgery alone for esophageal can-
cer, showed the overall 2-year survival rate was
significantly better for CRT-treated patients (38 vs. 10%),
with lower disease recurrence (16 vs. 24%); these results
have been confirmed at 5-year follow-up.40 The meta-
analysis of six studies by Pottgen and Stuschke,41 including
a total of 929 patients with squamocellular esophageal
cancer, demonstrated that CRT and surgery have similar
survival rates, with better locoregional disease control for
surgery-treated patients at the cost of increased mortality
rates. The best results seem to be obtained with cisplatin
and 5-fluorouracil with concomitant radiotherapy of at least
45 Gy. Wang et al.42 observed a complete response in 63%
of patients treated with this regimen, with an 18.6% 5-year
survival rate.
Burmeister et al.43 reported a complete response rate of
91% and a 5-year survival rate of 55% in 34 patients with
stage I–IIB cervical esophageal cancer treated with
definitive CRT. Nevertheless, 12% of patients showed a
grade 3 toxicity and 44% showed RT-induced stenosis. In a
more recent paper, Gkika et al. 7 reported 25 and 10% 5-
and 10-year survival rates for 55 patients with stage II–III
cervical cancer who underwent definitive CRT with toler-
able toxicity.
Unlike the present study, few studies have only focused
on cervical esophageal cancer. Our results confirm that
cisplatin-based CRT allows a high rate of complete
response with satisfactory survival. In 92 patients treated
with definitive CRT, we registered 36.96% complete
responses and 45.65% partial responses.
Some authors treated cervical esophageal cancer with
more aggressive treatment regimens tailored for head and
neck SCC, with results to lower-dose schedules.34,44,45
As expected, we found that complete response is more
frequent in patients with low-stage disease, and survival
was significantly correlated with complete response. In our
study, patients with a complete response had a 42.6%
5-year survival compared with 16% of patients with partial
response or stable disease. Similar results have been

described by Aoyama et al.,46 who observed that obtaining
a complete response is the most important prognostic factor
following definitive CRT, even if associated with surgery.
For non-complete response, salvage surgery represents
an option with increased, but still acceptable, morbidity
and mortality rates. Swisher et al.47 reported a mortality
rate of 5% for salvage surgery compared with 3% for
planned surgery, and a 5-year survival rate of 32 versus
45%. In our experience, postoperative mortality was 5%
for all patients who underwent surgery after CRT, with a
5-year survival rate of 30.7%.
Among our patients, some strongly preferred to undergo
surgery even after obtaining a complete response, but,
interestingly, our study showed that adding surgery to the
treatment options can have a negative impact on survival
(Fig. 2a). Morbidity and mortality due to surgery is not
counterweighted by a sufficient survival benefit. In con-
trast, for patients with partial or no response to CRT,
surgery adds a significant survival benefit (Fig. 2b). Given
these results, we no longer offer surgery as an option after
achieving a clinical complete response with CRT.
According to the literature, tumor recurrence rates range
from 13.7 to 42% after definitive CRT, and 15.6–48.6%
after surgical treatment alone.26 In our study, there were
seemingly no differences between treatments. Stratifying
these results according to recurrence site, we found that
local recurrence was significantly higher in the CRT group
(CRT 84% vs. SURG 50% and CRT ? SURG 55%;
p = 0.024), underlining the positive effect of surgery in
controlling local disease and the otherwise positive sys-
temic action of chemotherapy.
The treatment of cervical esophageal cancer remains a
highly debated topic due to the lack of a large series and
the inability to design randomized controlled trials as a
result of the scarcity of cases. This study tries to better
clarify the optimal strategy for the treatment of cervical
esophageal cancer. Limitations of the study are its retro-
spective design, the possible non-complete adjustment for
selection bias, and the time interval involved.
CONCLUSIONS
In our practice, we recommend that a patient with cer-
vical esophageal cancer be treated with definitive platinum-
based chemotherapy with at least 50.4 Gy concomitant RT,
and that surgery should only be considered for non-com-
plete response patients as it can add significant survival
benefit with acceptable morbidity and mortality.
DISCLOSURE Michele Valmasoni, Elisa Sefora Pierobon, Gian-
pietro Zanchettin, Dario Briscolini, Lucia Moletta, Alberto Ruol,
Renato Salvador, and Stefano Merigliano have no conflicts of interest
to disclose.
M. Valmasoni et al.
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