Salvage surgery after failure of non surgical therapy for advanced head and neck cancer

doi:10.4236/ojst.2011.14029

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Open Journal of Stomatology, 2011, 1, 189-194

doi:10.4236/ojst.2011.14029 Published Online December 2011 (http://www.SciRP.org/journal/ojst/ OJST

Published Online December 2011 in SciRes. http://www.scirp.org/journal/OJST

Salvage surgery after failure of non-surgical therapy for

advanced head and neck cancer

Didier Dequanter1, N. Vercruysse2, M. Shahla1, P. Paulus1, P. Lothaire1

1Department of Head and Neck Surgery, CHU Charleroi, Montigny le Tilleul, Belgium;

2Department of Plastic Surgery, CHU Charleroi, Montigny le Ti lleul, Belgium.

Email: [email protected]

Received 25 July 2011; revised 2 September 2011; accepted 15 September 2011.

ABSTRACT

Introduction: for organ and function preservation,

chemoradiotherapy is ga ining popularity for primary

treatment of advanced head and neck cancer, re-

serveing surgery for salvage. Methods: Retrospective

outcome analysis to determine the results of salvage

surgery after failure of primary treatment of advan-

ced head and neck cancer by chemora d iothe rapy. 104

patients with advanced head and cancer were initially

treated by chemoradiotherapy. Follow-up was evalu-

ated in 27 patients undergoing salvage surgery for re-

current tumor (larynx n = 13; oral cavity n = 9; hypo-

pharynx n = 5). The initial tumor is stage T3 in 11

cases and T4 in 16 cases. 10 patients had primary

tumors stage III and 17 patients had tumors stage IV.

Results: One postoperative death occured following

surgery. The overall incidence of complications was 9/

27 (%). Recurrent disease developed at the primary

initially treated in 25 cases and in the neck in 2 cases

after a mean follow-up of 11 months (3 - 136 months).

After salvage surgery, loco-regional recurrence and/

or distant disease developed in 10/27 patients after a

mean follow- up of 4 mo nths . 6/10 (60 %) pa tient s died

after re-recurrence despite salvage chemotherapy.

Conclusion: Salvage surgery after failure of initial

chemoradiotherapy is burdened with high morbi-

dity and bad oncological outcome. We demonstrated

that it is difficult to salvage locally recurrent head

and neck cancer especially at more advanced T-st ages

or when tumor recur. The limited effect of surgical

salvage for recurrent tumor need to be addressed

when choosing the initial treatment plan.

Keywords: Head and Neck Cancer; Salvage Surgery;

Advanced Disease

1. INTRODUCTION

Chemoradiation therapy is gaining popularity for pri-

mary treatment of advanced head and neck cancer, re-

serving surgery for salvage. Chemoradiotherapy is in-

creasingly used for organ and function preservation. In a

substantial amount of patients, chemoradiation failure is

seen. Approximatively, 13% - 24% of patients will, in

reality, requ ire salvage surgery [1].

Data about outcome after salvage surgery is necessary

to assess its value as a second line tool. The two main

aspects for an analysis concern the oncological outcome

on one hand and the morbidity on the other hand. Both

have been reported with broad variation in results among

different groups [1 -4].

This study aims to examine the outcome of salvage

surgery as an additional treatment option in a determined

group.

2. METHODS

104 patients initially treated by chemoradioth erapy were

retrospectively reviewed in order to determine the clini-

cal course of patients treated by salvage surgery after

failure of primary treatment. In presence of a locoregio-

nal recurrence, the option of salvage surgery was ana-

lyzed. Absence of distant metastases and feasibility of

complete surgical resection with acceptable postoperative

functional outcome are premises for the indication of

salvage surgery. In case of local recurrence, the surgical

strategy depends on the result of microlaryngoscopy and

CT scan. If possible, partial laryngectomy is taken in to

consideration, otherwise total (pharyngo) laryngectomy

is indicated. The neck was treated simultaneously by

neck dissection of the levels II-V in all cases of local

recurrence. In presence of a persisting neck mass and

radiological suspicious lymph nodes, microlaryngos-

copy and CT scan of the neck are performed in order to

exclude oral, laryngeal or hypopharyngeal recurrence.

Then, neck dissection of the levels II-V was performed

based on the clinical suspicion and without further pre-

operative lymph node biopsy. The patients with previ-

ously untreated T3 and T4 head and neck tumor were

D. Dequanter et al. / Open Journal of Stomatology 1 (2011) 189-194

190

treated for curative intent by chemoradiotherapy. Suc-

cessful surgical salvage was defined as no evidence of

recurrent cancer at 2 years after salvage surgery and con-

tinuously thereafter. All patients undergoing salvage sur-

gery were analyzed for postoperative morbidity.

104 patients with advanced head and neck cancer re-

ceived concomitant chemoradiotherapy (CRT) as an ini-

tial treatment. At the end of the follow-up, loco-regional

recurrence was observed in 32 patients. 5 patients with

non-responding tumors the proposal salvage surgery.

To determine the significance of clinical factors (such

as age, gender, primary tumor site, TN stage, pTN stage

on the recurrence, the chi-square test was used. A p <

0.05 was considered statistically significant.

3. RESULTS

Of the 104 patients, 27 patients with recurrent head and

neck cancer tumor were reviewed. The primary site was

the larynx in 13 cases, the oral cavity in 9 cases and the

hypopharynx in 5 cases. The T stage at initial pr e sen t at io n

was T3 in 11 cases, T4 in 16 cases. 10 patients were

stage III and stage IV in 17 cases (Table 1). One postop-

erative death occured following salvage surgery. The

patient died from hepatic disease without showing evi-

dence of tumor.

Recurrence developed at the primary in 25 cases (lar-

ynx in 13 cases, or al cavity in 7 cases and hypopharynx

in 5 cases) and at the neck in 2 cases after a mean fol-

low-up of 11 mont hs (3 - 13 6 months).

Total laryngectomy was needed in 11 cases, a partial

laryngectomy in only 2 cases, a pharyngolaryngectomy

in 3 cases, a buccopharyngectomy in 7 cases and a pha-

ryngectomy in 2 cases. A radical neck dissection as sal-

vage treatment was done in 2 cases. The overall inci-

dence of complications was 9/27 (37.5%). Among the 9

patients, eight patients (who underwent complete (phary-

ngo) laryngectomy developed a pharyngocutaneous fis-

tula. In four cases, the fistula closed spontaneously. In 5

Table 1. Patient characteristics.

Characteristics No. patients

Gender Mal e/Female 22/5

Age (years)

30 - 50 8

51 - 70 16

71+ 3

Stage

III 10

IV 17

Primary tumor location

Pyriform sinus 5

Larynx 13

Oral cavity 9

cases, surgical closure of the fistula was needed.

The last patient developed a cervical abcess that re-

solved spontaneously.

After the salvage treatment, loco-regional recurrence

and/or distant metastases developed in 10/27 (42%) pa-

tients after a mean follow-up of 4 months. Recurrence

was diagno sed in the neck and the pr imary site in 2 cases,

in the neck alone in 3 cases, in the neck and with distant

metastases in one case, at the primary site in 4 cases.

Among the 10 patients who developed recurrence af-

ter salvage surgery, 6 patients (60%) died despite salvage

chemotherapy.

4. DISCUSSION

Concomitant chemoradiation (CRT) is gaining popular-

ity for primary treatment of advanced head and neck

cancer, reserving surgery for salvage. However, it has

been reported that the feasibility of salvages therapies

following tumor recurrence is generally low. In his series,

Taki et al. [5] reported that the local recurrence rate of

hypopharyngeal cancer was 43.7% in patients with T2 -

T4 disease after treatment with RT (CT) but salvage

surgery is often the only curative option for recurrent

cancer.

Patients undergoing salvage surgery can be divided into

two groups: patients with local recurrences on one hand

and patients with persistent lymph node metastases but no

evidence of persistent primary tumor on the other hand.

One the hand, surgical therapy of local recurrence re-

quires radical removal with or without neck dissection.

In our study, the tumor recurrence seemed suitable for

partial laryngectomy in only two cases while in 11 cases

complete laryngectomy was indicated. On one hand, this

is due to the initially advanced tumor stage and one the

other hand, the diagnosis of recurrence is delayed by the

oedema occurring after irradiation.

However, in recent decades, partial laryngectomy has

been used successfully in such patients [3,4]. There is

evidence that salvage surgery following (chemo) radio-

therapy for early stage laryngeal carcinoma gives better

survival rates and enables more often partial resections

than in the presence of advanced initial stages [5-9].

But considering the bad overall survival for salvage

surgery in advanced laryngeal and hypopharyngeal can-

cer, total laryngectomy must be considered the main

procedure for failure after CRT [10]. In our study, partial

pharyngolaryngectomy with or without reconstruction

was done for 11 patients. Of the 11 patients, recurrences

were seen in patients with tumors of the pyriform sinus.

We think that advanced tumor stage with metastatic

spread, h ypopharyngeal localisation and previou s radical

radiochemotherapy have contributed significantly to the

unsatisfying results of salvage surgery. Thereby, an ear-

lier detection of persistent and growing tumor tissue

D. Dequanter et al. / Open Journal of Stomatology 1 (2011) 189-194 191

after completion of (chemo) radiotherapy might improve

the prognosis of salvage surgery.

Simultaneous neck dissection has been recommended

in the literature because of neck recurrence in previously

unsuspicious neck [11,12]. However, the oncological

value of simultaneous neck dissection in the absence of

suspect lymph nodes has also been questioned [13]. Te-

mam et al. [2] found lymph nodes metastases only in on e

of the 30 patients undergoing salvage surgery for local

recurrence of initially irradiated carcinoma of the head

and neck with cN0 necks. They therefore recommend li-

mitation of neck dissection according to the in itial N sta-

tus. In our series, mostly, the N status after salvage su rge-

ry for local recurrences including neck dissection was

congruent with the N status before chemorad iotherap y in

cases while in one case an initial cN2b stage turned into

a pN0 stage after salvage surgery. This data suggest a

coherence of initial clinical lymph nod es status with that

in case of local recurrence after CRT in most cases. Thus,

less radical neck surgery in absence of initial and preop-

erative lymph nodes metastases has to be discussed.

On the other hand, neck dissection (ND) for persistent

cervical lymph nodes may be judged an overtreatment

for the majority of our patients when no vital tumor

could be found in the neck specimen. None of our pa-

tients with N0 neck developed regional recurrence dur-

ing the follow-up. The indication for neck dissection

(ND) is based upon the clinical suspicion the main pro-

blem in preoperative verification of a metastasis relies in

the difficulty to distinguish scarred lymph node tissue

from nodes containing vital tumor cells. Patients with

histologically confirmed persistent cervical metastases

had a high tendency of further regional recurrences and

distant metastasis. In the literature, neck dissection after

chemoradiotherapy yielded unfavourable results for his-

tologically proven N+ situations. On the other hand, ND

seems to be inappropiate if no vital tumor tissue is de-

tected after excision of suspicious residual nodes. Some

authors advocate a wait and see policy for persistent ly-

mph nodes in head an neck cancer as long as a decrease

in size can be demonstrated after chemoradiotherapy

[14]. Others are in favor of an immediate ND after RC-

HT for all patient with initial N2-N3 [15] or only in N3

[16-19] neck disease even in presence of complete re-

sponse. We believe that salvage ND for suspicion of re-

sidual disease is of low morbidity and should therefore

be recommended in regard to individual tumor control.

Performance of radical instead of selective ND must be

discussed in this context and shou ld examined further.

But not only the type of salvage surgery must be dis-

cussed, but also the selection of patients candidate to sal-

vage surgery is an important issue.

In our series, 10 of the 27 patients with advanced head

and neck cancer presented locoregional recurrence and/

or distant metastases.

Most patients (8/10) who developed a recurrence had

a tumor staged T4. Clearly, the tumor extension should

be an important factor in the selection of patients candi-

date to salvage surgery. Indeed, Schwartz et al. in his

series [20], showed that individuals with stage I-II pri-

mary tumors had significantly improved salvage time

and total survival time compared with those with stage

III-IV primary tumors (p < 0.005 and p < 0.001). Con-

versely, the stage of the recurrent tu mor was not predict-

tive of either improved salvage time and total survival

time. Patients who underwent salvage surgery had signi-

ficantly improved salvage time and total survival time

compared with those who received chemotherapy and/or

radiation therapy (p < 0.001 and p < 0.002). Neither the

stage of the primary or recurrent tumors nor the type of

salvage treatment received significantly correlated with

an improved cure rate. Patients most likely to benefit

from retreatment are those who have primary tumors

stage I-II, recur greater than 6 months after theri initial

treatment and develop recurrences that are amenable to

salvage surgery. In his series, Gleich [21] confirmed the

limited potential for survival in patients who have a re-

currence after treatment for advanced (T3 or T4) pri-

mary site head and neck cancer. 48 patients underwent

salvage therapy for recurrence. The median time to re-

currence was 14 months and the median survival time

was 26.2 months. Among the 28 patients treated for pri-

mary site recurrence, the mean time for recurrence was

12.6 months and the mean survival time was 27.3

months. Only the 5 of the 28 patients had prolonged sur-

vival. The stage of recurrent disease did not influence

the outcome. Among the 20 patients treated for neck

recurrence, the mean time to recurrence was 14 months

and the mean time survival time was 25 months. Six of

the 20 patients had prol o nged survival.

In our study, among the patients treated for neck re-

currence, the mean time to recurrence was 8 months and

the mean time survival time was 18 months.

In his series, Kim et al. [22] determined the factors

predicting the outcome after salvage surgery with mi-

crovascular flap reconstruction for recurr ent sq ua m ou s c e ll

cancer of the head and neck. They concluded that pa-

tients with early cancers are the best candidates for sal-

vage surgery but patients with T3 and T4 and who con-

tinue to smoke after initial diagnosis and treatment are

poor candidate s to unde rgo sal vage surgery.

For Wong et al. [23], surgical salvage is only feasible

for early recurrent tumor. In this series, published by

Goodwin et al. [24], median disease free survival was

17.9 months in 109 patients, and this correlated strongly

with recurrent stage, weakly with recurrent site, and not

at all with time to presalvage recurrence.

D. Dequanter et al. / Open Journal of Stomatology 1 (2011) 189-194

192

Therefore, Yom et al. [25] proposed for patients with

T3 T4 tumors a planned clinical, radiographic, and

pathologic restaging at 1 to 2 months after initial treat-

ment. This practice produces improved overall local

control and survival rates compared with the literature

reports for delayed attempted salvage with timing base

don the findings of routine clinical surveillance.

In addition, the chance for salvage surgery was more

limited in patients with hypopharyngeal cancers. In this

series [5], when the recurrence became unequivocal,

most T3 and T4 patients were considered unsuitable to

receive surgical salvage. Only two patients of 18 patients

(11%) who experienced local recurrence achieved long

term survival after surgical salvage. All T4 patients died

within 19 months after the local recurren ce was detected.

By contrast, laryngeal cancer offers more chance to un-

dergo salvage surgery for recurrence [26,27].

Finally, some studies report an acceptable frequency

of postoperative complications such as pharyngo-cuta-

neous fistulas after CRT [4,26].

However, some authors report that preoperative che-

moradiotherapy as a cause of increased postoperative

morbidity in laryngeal and hypopharyngeal surgery as

compared to the primary surgery has been postulated [1,

14,28].

Clark et al. [29] showed that irradiation increased the

incidence of postoperative pharyngo-cutaneous fistula

from 24% to 38% while Wakisaka [30] et al. noted that

although the frequency of pharyngocutaneous fistula

after RT or CRT was not high, fistula closure tended to

be delayed. In their series, Taki et al. [5] experienced

severe postoperative complications including pharyngo-

cutaneous fistulas in 25% of patients who underwent

laryngopharyngectomy. Such complications could seve-

rely diminish the quality of life for patients.

However, the frequency of published pharyngocuta-

neous fistulas in salvage surgery ranges from 14% to 92%

[28] depending the applied dose [31] the tumor stage and

localisation [14] and ti me from initial therapy [28]. As a

comparison, pharyngocutaneous fistulas after larynge-

ctomy without previous therapy occurred in about 11%

for hypopharyngeal [32] and in 4% for laryngeal carci-

nomas [33].

However, salvage surgery can be performed with ac-

ceptable rate of postoperative complications. In his se-

ries, Agra et al. [34] after analyzing the frequency and

risk factors for postoperative complications after salvage

surgery for recurrent head and neck cancers demon-

strated that salvage surgery can be performed with ac-

ceptable rates of complications Post operative complica-

tions occurred in 66 patients (53.2%). 53 patients (42.7%)

had minor complications and 23 patients (18.5%) had

major ones. There were 4 postoperative deaths (3.2%)

The major factor associated with the overall occurrence

of postoperative complications was the clinical stage of

the recurrent tumor (p = 0.02) the occurrence of minor

complications correlated with the previous treated site,

with complications occurring more often in patients un-

dergoing locoregional versus local treatment (p = 0.004)

major complications were associated with the time be-

tween initial treatment and salvage surgery (p = 0.05).

Although most patients had good functional outcome

only a select group of patients with recurrent SCC achi-

eved long term survival after salvage surgery. In the lit-

erature, only a few articles have been published that

discuss the treatment of patients with rerecurrence.

In our series, rerecurrence was diagnosed in 10 of the

24 patients. After a short follow up, 6 of the 10 patients

died.

Patients with rerecurrence seems not to be candidate

for salvage treatment and are at a high risk for death.

Indeed, patients with rerecurrence who have under-

gone all modalities of therapy, the chances for salvage

are limited.

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