Adenocarcinoma of the esophagus and esophagogastric junction in patients older than 70 years: Results of neoadjuvant radiochemotherapy followed by transthoracic esophagectomy

Journal of Visceral Surgery (2012) 149, e203—e210

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ORIGINAL ARTICLE

Adenocarcinoma of the esophagus and esophagogastric junction in patients older than 70 years: Results of neoadjuvant radiochemotherapy followed by transthoracic esophagectomy A. Camerlo, X.B. D’Journo ∗, M. Ouattara, D. Trousse, C. Doddoli , P.A. Thomas Service de chirurgie thoracique et des maladies de l’œsophage, hôpital Nord, Assistance publique—Hôpitaux de Marseille, Aix-Marseille université, chemin des Bourrely, 13915 Marseille cedex 20, France

KEYWORDS Adenocarcinoma; Esophagus; Aged patients; Neoadjuvant therapy; Esophagectomy; Surgery

∗

Summary Aim: The standard treatment of locally-advanced esophageal adenocarcinoma consists of neoadjuvant radiochemotherapy followed by surgical resection. Very little data are available concerning the feasibility of this strategy in patients older than 70 years of age. Patients and methods: Between 1996 and 2008, 118 patients underwent transthoracic esophagectomy with lymphadenectomy for adenocarcinoma of the esophagus and gastric cardia (Siewert I and II). These were divided into three groups for comparison: Group I (age less than 70 years, neoadjuvant treatment followed by surgery; n = 66); Group II (age greater or equal to 70 years, surgery alone; n = 32); Group III (age greater or equal to 70 years, neoadjuvant treatment followed by surgery; n = 20). Data concerning comorbidities, type of intervention, morbidity, mortality, survival and quality of life were analyzed. Results: There was no difference among the three groups with regard to comorbidity and preoperative evaluation. The patients in Groups I and III had more locally-advanced tumors (P < 0.001). There was some disparity between the types of surgery proposed. The Lewis-Santy esophagectomy was most commonly used (90%, 50%, and 65% respectively). The 90-day mortality was 8%, 15%, and 15% respectively. There was no statistically significant difference in the incidence of postoperative pulmonary, cardiac, or digestive complications among the three groups. No difference was found in 5-year survival and quality of life. Conclusions: Neoadjuvant radiochemotherapy for elderly patients (age above 70 years) with esophageal adenocarcinoma did not seem to increase postoperative morbidity or mortality, nor was there any difference in quality of life, nor any effect on survival, no matter what the age of the patient. © 2012 Elsevier Masson SAS. All rights reserved.

Corresponding author. Tel.: +33 4 91 96 60 01; fax: +33 4 91 96 60 04. E-mail address: [email protected] (X.B. D’Journo).

1878-7886/$ — see front matter © 2012 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jviscsurg.2012.03.006

e204

A. Camerlo et al.

Introduction

Preoperative data

With progressive aging of the French population, the proportion of elderly patients presenting with esophageal adenocarcinoma is increasing [1,2]. The peak incidence of esophageal adenocarcinoma has advanced to lie between 70 and 79 years of age [3]. Several retrospective studies have demonstrated that esophagectomy is feasible for patients above 70, whether for early-stage disease or for locally-advanced tumors. In both young patients and in the elderly, surgery can obtain the same oncologic results with identical operative risks [4—15]. But there are paradoxical results in the literature. While the vast majority of studies have not clearly shown age greater than 70 to be a risk factor for increased postoperative mortality, age does appear as a risk factor in certain predictive scores such as P-POSSUM, O-POSSUM or Steyeberg’s score [16—18]. These predictive scores are based on multivariate analysis assessing postoperative mortality in large numbers of patients undergoing esophagectomy. The scores consider age as an independent risk factor for postoperative mortality with a finite increase of risk for each decade beyond age 50. In addition, very few studies have evaluated multimodality treatment strategies for patients above 70. If neoadjuvant radiochemotherapy is the generally accepted therapy for locally-advanced esophageal adenocarcinoma based on several randomized studies and meta-analyses [19—24], the feasibility of such a strategy for patients above 70 remains to be evaluated, given that such patients were not included in most of the controlled studies. The principal objective of this retrospective study was to analyze the feasibility and value of neoadjuvant radiochemotherapy followed by transthoracic esophagectomy with lymphadenectomy in the management of esophageal adenocarcinoma in patients above 70. The primary end-point was the incidence of morbidity and mortality at 30 and 90 days. Secondary end-points were analysis of the surgical technique, patient response to induction therapy, and survival.

Preoperative patient data that had been prospectively recorded and the oncologic characteristics of the tumor were extracted. All patients were capable of self-care in the preoperative geriatric assessment (Katz score less or equal to 1 mini-dependence assessment [MDA] less or equal to 1). The indications for neoadjuvant therapy were discussed in a multidisciplinary conference. Some of the patients had been referred from other hospitals for surgery, having already undergone induction therapy. The therapeutic strategy and the choice of surgical technique were based on the patient’s general condition, the particular surgeon’s preference, and on the tumor stage (clinical stages greater or equal to IIb or III). Neoadjuvant therapy consisted of 45 Gray of radiation therapy in 25 fractional doses with concomitant chemotherapy consisting of two to four courses of 5FU-cisplatin. Patients undergoing salvage surgery, that is, after radiochemotherapy, were not included.

Operative findings All esophagectomies were performed through a transthoracic approach. A gastric esophagoplasty was used for reconstruction except in one patient who required coloplasty after total gastrectomy. The mediastinal lymphadenectomy performed during the thoracic stage included dissection of the peri-esophageal, lateral tracheal, and subcarinal lymph nodes. Abdominal lymphadenectomy included nodes from the lesser curvature, the left gastric artery, the common hepatic artery and the splenic artery. Data concerning operative duration, blood loss, and perioperative blood transfusion were recorded.

Postoperative data

Materials and methods

Postoperative pain control was usually obtained by epidural catheter infusion, paravertebral nerve block, or morphine patient-controlled anesthesia (PCA). Early extubation and ambulation and pulmonary physical therapy were performed in all patients. Patients were allowed to resume eating on the 7th postoperative day after an upper GI series with water-soluble contrast study confirmed the absence of leaks. The level and performance of postoperative care was identical in all three groups.

Patients

Follow-up and quality of life

Between January 1996 and December 2008, 342 patients underwent transthoracic esophagectomy with two-field lymphadenectomy for esophageal cancer in our unit. Data on these patients were retrospectively extracted from our prospective database. Patients with squamous cell carcinoma (n = 154) were excluded from the analysis. The remaining 188 patients presented with adenocarcinoma of the esophagus or esophagogastric junction classified as Siewert I or II. Patients younger than 70 who had undergone resection without neoadjuvant treatment (n = 70) were also excluded from the study. The remaining patients comprised three groups: • Group I (age greater than 70 with neoadjuvant therapy followed by surgery, n = 66); • Group II (age greater or equal to 70 with surgery alone, n = 32); • Group III (age greater or equal to 70 with neoadjuvant therapy followed by surgery, n = 20).

Patient follow-up was by clinical examination at 1 month, 3 months, and thereafter every 6 months for 5 years. A thoraco-abdomino-pelvic CT scan with IV contrast was performed every 6 months for the first 2 years, and then yearly for 3 more years. ‘‘Quality of life’’ was assessed at followup visits according to the following criteria: ability to return home after hospital discharge, need for rehospitalization, occurrence of anastomotic stenosis requiring endoscopic dilatation, symptomatic reflux (heartburn or regurgitation), self-evaluation of digestive comfort (on a scale of 0—10), and weight loss.

Statistical analysis Statistical analysis was performed with SPSS software, version 12.0. We performed intergroup comparisons of Group III (more than 70 years with preoperative neoadjuvant RT-CT) with Group II (more than 70 years, surgery alone) and Group

Adenocarcinoma of the esophagus and esophagogastric junction

e205

I (less than 70 years, with preoperative neoadjuvant RT-CT). Qualitative variables were compared using the Chi2 test and Fisher’s test if n < 30. Quantitative variables were compared using the t Student test or the Mann-Whitney U test (if n ≤ 30 or for non-Gaussian distribution. Survival curves were calculated by the Kaplan-Meier method and comparison between survival curves was made using the log-rank test. Statistical significance was defined as a P value of 0.05.

Results Preoperative data Demographic data concerning comorbidities, general patient health and preoperative pulmonary evaluation are summarized in Table 1. Mean age in the three groups was 56, 75, and 73 years respectively. There was no significant difference in comorbidities or general patient health among the three groups. Only a difference in Body Mass Index (BMI) between Group II and Group III was noted. The interval between the end of induction CT-RT and surgery was 37 ± 8 days in Group I, and 39 ± 22 days in Group III (P = 0.66). Three patients in Group I and one patient in Group III were unable to complete the neoadjuvant therapy (30 Grays radiotherapy and only two courses of chemotherapy) because of intolerance to radiotherapy.

Operative data Operative data are presented in Table 2. The Lewis-Santy procedure was the most commonly performed esophagectomy technique (90% in Group I). A left thoraco-abdominal esophagectomy (Sweet) or a Lewis-Santy procedure combined with abdominal laparoscopy was more commonly performed in the older patients (50% and 35% respectively in groups II and III) than in the younger patients (10% in Group I). Analysis of perioperative data found only one significant difference among the groups: there was a higher rate of blood transfusion in Groups I and III.

Tumoral characteristics: preoperative assessment and final pathological assessment

Figure 1. mortality.

Overall survival in the three groups including operative

surgical complications. Ninety-day mortality was 7%, 16%, and 15% respectively in Groups I, II and III.

Survival The average duration of follow-up was 22.5 ± 24 months (median 12 months, range 0—112 months). The median overall survival (including postoperative deaths) in Groups I, II and III was 44 months (range: 3—85), 30 months (range 0—56), and 23 months (range: 0—57) (P = 0.304) respectively. The median disease-free survival (including postoperative deaths) in Groups I, II and III was 29 months (range: 10—32), 21 months (range: 0—59), and 22 months (range: 0—47) (P = 0.807) respectively. The survival curves are presented in Figs. 1 and 2.

Quality of life Information concerning ‘‘quality of life’’ was gathered in all patients older than 70 and is summarized in Table 5. No

The preoperative assessment of tumoral extension and the final pathological staging are summarized in Table 3. The patients in Groups I and III presented with more advanced tumors than those in Group II, based on preoperative assessment. Neoadjuvant treatment resulted in a significant tumoral response since, patients in Groups I and III, 6% and 10% of patients respectively had tumors classified as stage 0, I or IIA before treatment against 65% and 58% on final histological staging. A complete histological response was observed in respectively 21% and 10% of patients in groups I and III. The average number of lymph nodes analyzed did not differ between groups (18 ± 13, 19 ± 11, 13 ± 8 respectively in groups I, II and III).

Morbidity and mortality Morbidity and mortality are summarized in Table 4. Overall postoperative morbidity was similar in the three groups. Respiratory complications occurred most commonly but were no more frequent in the older patients than in the younger patients. No significant difference was found in the rate of

Figure 2. Disease-free survival in the three groups including operative mortality.

e206 Table 1

A. Camerlo et al. Preoperative patient data. Group I n = 66 (%)

Group II n = 32 (%)

Group III n = 20 (%)

Comparison Group I and III

Comparison Groups II and III

56 ± 10

75 ± 3

73 ± 2

0.001

0.04

9/1

9/1

9/1

0.93

0.57

20 (30)

13 (40)

6 (30)

0.97

0.31

Past history of cancer

2 (3)

4 (12.5)

2 (10)

0.19

0.57

Hypertension

24 (37)

15 (46)

9 (45)

0.48

0.56

COPD

9 (14)

4 (12.5)

3 (15)

0.87

0.55

Diabetes General health

5 (8)

6 (19)

4 (20)

0.11

0.59

BMI Performance index WHO 0

23 ± 3

25 ± 4

23 ± 3

0.22

0.02

32 (48)

16 (50)

10 (50)

0.32

0.44

1

28 (42)

12 (37)

5 (25)

2

6 (9)

4 (13)

5 (20)

13 (20)

6 (18)

0

0.17

0.55

2

38 (58)

23 (71)

14 (70)

3

15 (22)

3 (9)

6 (30)

38 (57)

13 (40)

12 (60)

0.2

0.09

VC (liters)

4 ± 0.8

3.4 ± 0.8

3.7 ± 0.8

0.76

0.15

FEV1/CV (%)

77 ± 9

72 ± 10

73 ± 8

0.93

0.90

Demographic data Age mean Sex ratio (M/F) Comorbidities Cardiac disease

ASA score 1

Respiratory parameters NYHA Score (stage 2)

Group I (patients under 70 years with neoadjuvant treatment); Group II (patients above or equal to 70 years with surgery alone — no neoadjuvant therapy); Group III (patients above or equal to 70 with neoadjuvant treatment); BMI = body mass index; VC: vital capacity; FEV1: Forced expiratory volume at 1 s.

difference was seen between Groups II and III except for the mode of hospital discharge.

Discussion Even though age may be an independent risk factor for postoperative mortality after esophagectomy (principally due to pulmonary infections) [16,25], many surgical series have demonstrated the feasibility of performing esophagectomy in patients above 70 without increased mortality [4—13,26]. A review of this literature is detailed in Table 6. Thus esophageal resection in elderly patients seems both reasonable and justified. The actual age limit is the only factor that remains controversial. Esophagectomy for patients above 70 has been extensively reported, and recently, certain authors have reported identical results with patients above 75 years of age [12,26,27] and even older than 80 years of age [15]. It would seem that preoperative patient evaluation for risks of postoperative complications would be more pertinent using scores that integrate patient age and comorbidities (such as the Steyeberg, the P-POSSUM, or the O-POSSUM score) rather than relying simply on age criteria [27].

The role of neoadjuvant treatment in the management of esophageal adenocarcinoma is currently well defined since the report by Gebski et al. [21] in 2007. This meta-analysis confirmed that induction treatment increased 2-year survival with identical postoperative morbidity and mortality when compared with surgical treatment alone. These results have been subsequently confirmed [21—23]. The risk/benefit ratio of neoadjuvant treatment appears to be highest when concomitant radiation therapy is offered and in patients with locally-advanced tumors (stage greater or equal to IIB). Nevertheless, induction therapy is rarely offered to elderly patients due to a presumed increase in postoperative risk, as was seen in most of the surgical series summarized in Table 6. In fact, the percentage of elderly patients who underwent neoadjuvant therapy varied from 0% to 31% while the incidence of locally-advanced tumors ranged from 31% to 75%. In addition, it seems that elderly patients represented only a small fraction of those treated in these different clinical studies [28]; a specific evaluation of this ‘‘under-treated’’ segment of the population therefore seemed necessary. Our study specifically evaluated the impact of a strategy of neoadjuvant induction for esophageal adenocarcinoma based on a variety of criteria and taking age into account

Adenocarcinoma of the esophagus and esophagogastric junction Table 2

e207

Operative data. Group I n = 66 (%)

Group II n = 32 (%)

Group III n = 20 (%)

2 (3)

5 (15)

3 (15)

Lewis-Santy esophagectomy

60 (90)

16 (50)

13 (65)

Lewis-Santy laparoscopic

4 (6)

11 (35)

4 (20)

Esophagoplasty: gastric — colic

65—1

32—0

20—0

318

275

Mean blood loss (mL)

314

Perioperative RBC Transfusion — mean Epidural analgesia

Surgical procedure Sweet esophagectomy

Perioperative data Mean operative duration (minutes)

Hospital stay (HS) HS overall-mean (days) HS in intensive care — mean (days)

Comparison Group I and III

Comparison Groups II and III

0.039

0.52

263

0.29

0.88

444

345

0.85

0.94

2.1

1.9

4.7

0.005

0.03

35 (53)

18 (56)

9 (45)

0.18

0.16

23

29

29

0.49

0.15

6

11

8

0.33

0.86

Group I (patients under 70 years with neoadjuvant treatment); Group II (patients above or equal to 70 years with surgery alone — no neoadjuvant therapy); Group III (patients above or equal to 70 years with neoadjuvant treatment).

Table 3

Tumor stage: preoperative and histological. Group I n = 66

Clinical stage I

Group II n = 32

2 (3)

6 (19)

IIA

2 (3)

19 (60)

IIB

3 (4.5)

III IVa—b Pathologic stage 0

58 (87) 1 (1.5) 14 (21)

I

4 (6)

IIA

1 (1.5)

1 (3) 6 (18) 0 0

Group III n = 20 0 2 (10) 0 18 (90) 0 2 (10)

6 (18)

2 (10)

13 (40)

6 (30)

IIB

19 (29)

1 (3)

III

6 (9)

7 (22)

8 (40)

IVa—b

2 (3)

3 (9)

2 (10)

14 (21)

—

2 (10)

Grade 2: rare residual cancer cells within fibrosis

17 (26)

—

7 (35)

Grade 3: more fibrosis than cancer

17 (26)

—

5 (25)

Grade 4: more cancer than fibrosis

14 (21)

—

6 (30)

4 (6)

—

Histological response (Mandard Classification) Grade 1: no residual cancer

Grade 5: no tumor regression

0

0

Group I (patients under 70 years with neoadjuvant treatment); Group II (patients above or equal to 70 years with surgery alone — no neoadjuvant therapy); Group III (patients above or equal to 70 with neoadjuvant treatment).

in the analysis of results of patients in our unit. Only two other studies have evaluated this therapeutic strategy in elderly patients [19,20]. No difference in terms of survival or postoperative morbidity and mortality has been

demonstrated. Nevertheless, the patient groups analyzed in these two retrospective studies had differing cancer histologies. Adenocarcinoma and squamous cell carcinoma of the esophagus differ in both their epidemiology and their

e208 Table 4

A. Camerlo et al. Postoperative morbidity and mortality. Group I n = 66 (%)

Group II n = 32 (%)

Group III n = 20 (%)

Comparison Group I and III

Comparison Group II and III

Mortality (%) 30 days

4 (6)

2 (6)

2 (10)

0.42

0.50

Hospital

5 (7)

4 (12)

2 (10)

0.51

0.58

90 days

5 (7)

5 (15)

3 (15)

0.27

0.63

32 (48)

15 (47)

9 (45)

0.78

0.22

18 (27)

8 (25)

7 (35)

0.5

0.32

5 (7)

3 (9)

2 (10)

0.57

0.36

—

0.22

Morbidity Overall Respiratory Cardiovascular Renal (dialysis)

0

3 (9.4)

0

Surgical

7 (22)

10 (15)

3 (15)

0.98

0.40

Anastomotic leak/fistula

3 (4)

5 (15)

2 (10)

0.32

0.44

Re-intervention

0

2 (6)

2 (10)

0.06

0.50

Hemorrhage

0

1 (3)

1 (5)

0.23

0.62

0.58

—

2 (3)

Chylothorax

0

0

Group I (patients under 70 years with neoadjuvant treatment); Group II (patients above or equal to 70 years with surgery alone — no neoadjuvant therapy); Group III (patients above or equal to 70 years with neoadjuvant treatment). Respiratory complications include: pneumonia, atelectasis, acute respiratory distress syndrome; cardiovascular complications include: myocardial infarction, atrial fibrillation, and pulmonary embolus.

response to neoadjuvant therapy [29,30]. The impact of the two histologies in elderly patients should therefore be analyzed separately. Analysis of our results showed, in retrospect, that we had implicitly chosen our surgical technique based on the patient’s age. While the Lewis-Santy technique of esophagectomy is considered the standard resection for younger patients (more than 90% in our experience), we had nevertheless chosen to use a minimally invasive laparoscopically-assisted version of the Lewis-Santy procedure or the Sweet technique for our older patients. The former technique has the advantage of being perfectly standardized, permitting a safe and effective reconstruction and Table 5

Quality of life in patients older than 70. Group II n = 32

Discharge from hospital to home New admission to the hospital Anastomotic stricture/Endoscopic dilatation Reflux Digestive comfort scale (0—10) Weight loss (kg)

Group III n = 20

P

12 (37.5)

2 (10)

0.02

6 (19)

6 (30)

0.27

3 (9)

3 (15)

0.42

2 (6)

5 (25)

0.06

6.50

6.52

0.97

5.46

8.25

0.11

Group II (patients above or equal to 70 years with surgery alone — no neoadjuvant therapy) versus Group III (patients above or equal to 70 years with neoadjuvant treatment).

a satisfactory two-field nodal dissection, while the Sweet technique (left thoraco-phrenic approach with intrathoracic anastomosis) has the advantage of rapidity (operative time less than 180 minutes) through a single incision with analgesia successfully managed by epidural catheter. However this technique has two major drawbacks limiting its systematic use: the nodal dissection is limited to the subcarinal area and the anastomosis is located below the carina, which results in a high risk of reflux into the residual esophagus. In our series, overall morbidity was not significantly different among the three groups, varying from 45 to 48%. The most frequent complications were respiratory (25 to 35%) as is commonly reported in the literature (Table 5). Thus, neoadjuvant therapy does not seem to increase overall and specific morbidity after esophagectomy, even in the older population. These results agree with those of two previous studies [19,20], except that Rice’s study [19] showed a higher incidence of atrial fibrillation in elderly patients. Analysis of 90-day mortality showed an increased mortality risk in older patients (15%) compared with younger patients (7%), due principally to respiratory and cardiac medical complications. No difference in 90-day mortality was seen in older patients who received neoadjuvant therapy compared with those who underwent surgery alone. The multimodal approach does not seem to negatively affect patient ‘‘quality of life’’ in older patients compared to surgery alone. Even though patients undergoing combined therapy are more often discharged to a convalescent center rather than to home, the other factors assessed regarding quality of life do not seem to be modified by the performance of neoadjuvant therapy. The only other study evaluating ‘‘quality of life’’ in patients with esophageal cancer treated by differing modalities showed identical results for patients above and below the age of 70 [31].

Literature review: esophagectomy for cancer in elderly patients.

Authors

n

Age

Number of esophageal AdenoCa’s

Clinical Stage IIB—III (%)

Neoadjuvant treatment (%)

EWT (%) Thomas [4] 1996

56

70

31 (8)

18 (32)

3 (5.3)

Jougon [6] 1997

89

70

53 (9.8)

42 (47)

0 (0)

Poon [5] 1998

167

70

3 (1.7)

123 (73)

0 (0)

Fang [8] 2001

79

70

nd

42 (53)

2 (2.5)

Sabel [9] 2002

26

70

18 (15)

13 (50)

7 (27)

Rice [19] 2005

74

70

59 (19)

23 (31)

Ma [11] 2006

60

70

4 (7)

Shimada [12] 2007

55

75

Ruol [20] 2007

31

Internullo [27] 2008 Our series

Mortality 30 days (%)

Intervention

11 (20) 0

Pulmonary complications (%)

Surgical complications (%)

5-year survival (%)

TTE (%) 45 (80) 5 (9)

10 (18)

13 (23)

17

nd

13.3

89 (100) 7 (7.8)

7 (8)

125 (74) 17 (10.1)

66 (39)

26 (16)

26

79 (100) 3 (3.8)

23 (29)

33 (42)

40

4 (16)

22 (84) 1 (3.8)

4 (15)

nd

nd

35 (47)

38 (52)

36 (48) 1 (1.3)

13 (17.5)

28 (38)

nd

45 (75)

19 (31.6)

17 (29)

11 (20)

25 (45)

11 (20)

70

10 (32)

21 (68)

108

75

80 (74)

nd

52

70

52 (100)

24 (46)

42 (26) 0

43 (71)

2 (3.3)

11 (18)

3 (5)

nd

0

55 (100)

3 (5.4)

11 (20)

nd

33

31 (100)

4 (13)

27 (87)

1 (3.2)

10 (32)

45

6 (5.5)

0

108 (100)

6 (5.5)

40 (37)

18 (16.6)

35.7

0

47 (100)

4 (7.6)

15 (29)

13 (25)

33

20 (38)

7 (22.5)

Adenocarcinoma of the esophagus and esophagogastric junction

Table 6

EWT: Esophagectomy without thoracotomy; ETT: transthoracic esophagectomy.

e209

e210 The analysis of overall and disease-free survival in patients who received induction therapy (Groups I and III) found no significant intergroup difference. Neoadjuvant therapy thus seems to offer the same efficacy regardless of age, as is evidenced by the rate of partial and complete tumoral response in the two groups. In addition, no significant difference in overall and disease-free survival was noted in elderly patients whether they received neoadjuvant therapy or surgery alone (Groups II and III), even though their initial stage of disease was not comparable. A strategy incorporating neoadjuvant therapy should be offered to elderly patients with locally-advanced esophageal carcinoma to achieve a survival benefit similar to that seen in younger patients.

Conclusion Despite the small numbers in our series, the multimodal approach to the treatment of esophageal adenocarcinoma in elderly patients does not seem to increase postoperative morbidity and mortality after transthoracic esophagectomy. The choice of a less-invasive surgical technique seems to be a compromise approach to minimize surgical trauma, whether or not neoadjuvant treatment is used.

Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.

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