VATS vs. offene Lobektomie

Patienten

Patienten (m/w) mit NSCLC im Stadium I/II mit Indikation zur anatomischen Resektion (Lobektomie)

Intervention

VATS-Lobektomie

Kontrolle

offene Lobektomie

Zielkriterien (Outcomes)

rezidivfreies Überleben

Gesamtüberleben

postoperative Komplikationsraten (incl. Letalität) innerhalb von 30 Tagen postoperativ

Studiendesign

Systematische Übersichtsarbeiten mit Volltextveröffentlichung ab 2019

RCTs mit Volltextveröffentlichung ab 2008

NSCLC: Non-small cell lung cancer; RCT: Randomisierte kontrollierte Studie; VATS: video-assistierte thoraskopische Lobektomie

1

mVATS lobectomy may be associated with improved overall survival compared to open lobectomy.

C-LD

II-B

2

mVATS may have similar disease-free survival when compared to open lobectomy.

C-LD

II-B

3

mVATS may be associated with a lower recurrence rate, primarily related to distant recurrence when compared to open lobectomy.

C-LD

II-B

4

rVATS has no difference in overall survival and recurrence when compared to mVATS lobectomy.

C-EO

II-B

5

Open lobectomy results in an increase in nodal upstaging when compared to mVATS.

C-LD

II-A

6

mVATS, uVATS, and rVATS may be equivalent in terms of number of lymph nodes harvested and nodal upstaging.

B-NR

II-B

7

mVATS may facilitate the completion of adjuvant chemotherapy when compared to open lobectomy.

C-LD

II-B

8

mVATS lobectomy for the treatment of NSCLC is associated with a decreased risk of adverse events when compared to open lobectomy.

C-LD

II-A

9

mVATS, uVATS, and rVATS may be associated with similar rates of adverse events.

C-LD

II-B

10

mVATS can improve postoperative pain (Class IIA, Level B-R), and may be associated with improved quality of life (Class IIB, Level B-R), and overall function (Class IIB, Level C-EO) when compared to open lobectomy.

B-R und C-EO

II-A und B

11

uVATS lobectomy may reduce early postoperative pain and analgesic requirements compared with mVATS.

C-LD

II-B

12

mVATS and rVATS may be associated with a decreased length of stay when compared to open lobectomy.

C-LD

II-B

13

There is no significant difference in length of stay between mVATS, uVATS, and rVATS.

C-LD

II-B

14

mVATS is associated with reduced costs when compared to open lobectomy.

B-NR

II-A

15

rVATS is associated with higher costs when compared to mVATS lobectomy.

B-NR

II-A

mVATS: multiport video-assisted thoracic surgery; rVATS: robotic video-assisted thoracic surgery; uVATS: uniportal video-assisted thoracic surgery

Evidenzgrade:

B-R: randomized (moderate-quality evidence from 1 or more RCTs or meta-analyses of moderate-quality RCTs)

B-NR: nonrandomized (moderate-qaulity evidence from 1 or more well-designed, well-executed nonrandomized studies, observational studies, or registry studies or meta-analyses of such studies)

C-LD: limited data (randomized or nonrandomized observational or registry studies with limitations of design or execution, meta-analyses of such studies or physiological or mechanistic studies in human subjects)

C-EO: expert opinion (consensus of expert opinion based on clinical experience

Empfehlngsgrade:

IIa: moderate Empfehlung (benefit >> risk)

IIb: schwache Empfehlung (benefit ≥ risk)

Bendixen 2016

(7)

10/2008 to 08/2014

Denmark

NCT 01278888

Single-center RCT

Efficacy of VATS versus open surgery on postoperative pain and quality of life in stage I NSCLC 

Inclusion Criteria:

· Adult (≥ 18 yrs)  patients with NSCLC, stage I

· scheduled or lobectomy

· diagnosed and staged in accordance with national guidelines (PET-CT and invasive mediastinal staging by EBUS-FNA

· performance status 0/1

Exclusion Criteria:

· comorbidities were not a reason for exclusion

· except for alcoholism or ability to ambulate freely

· history of malignant disease

· daily use of any type of analgesics

· previous chest surgery, planned lung resections other than lobectomy

· pregnancy, breast feeding,

· contra indications for non-steroidal anti-inflammatory drugs

· previous CT, RT, or both, or any planned major surgery in the subsequent 12 month period.

n=206

median age (IQR): 66 (62-72) vs. 66 (60-72)

BMI: 24 (23-27) vs. 26 (23-29)

males: 48 %

smoker: 84 %

Adenocarcinoma: 61 %

Squamous: 24 %

Others: 15 %

pT stage (1/1a/1b/2/2a/2b/3/4): 7/22/17/11/18/7/7/<1 %

Four-port VATS (n=103)

vs.

Anterolateral thoracotomy (n=103)

One patient crossed

from VATS to thoracotomy

Primary:  postoperative pain (NRS scale)

quality of life (EQ5D and EORTC QLQ-C30) over the entire follow up period

cost-utility (WPAI)

Secondary:

perioperative blood loss

length of the surgical procedure

chest tube duration

postoperative complications

length of hospital stay

67  % of questionnaires on pain and quality of life returned, 60 % of all, 89 % of returned had complete data

Postoperative pain:

· proportion of patients with clinically relevant pain (NRS ≥3) was lower during the first 24 h after VATS:

· 38 % (95%CI 0·28–0·48) vs. 63 % (95%CI 0·52–0·72)  (p=0.0012).

· During 52 weeks of follow-up, episodes of moderate-to-severe pain were less frequent after VATS (p<0.0001)

· Quality of life:

· EQ5D better after VATS (p=0.014).

· No differences were shown with QLQ-C30 (p=0.13).

Postoperative surgical complications (grade 3–4 adverse events):

· similar between the two groups, consisting of:

· prolonged air leakage over 4 days (14 vs. 9 patients)

· re-operation for bleeding (2 vs 0)

· twisted middle lobe (1 vs.3) or

· prolonged air leakage over 7 days ( 5 vs. 6)

· arrhythmia (1 vs. 1)

· neurological events (1 vs 2)

Mortality:

Nine (4 %) patients died during the 1-yr follow-up period (3 vs. 6)

2b

Abwertung aufgrund von geringer Präzision und Indirektheit

Zusammenfassende Beurteilung

Schlussfolgerungen der Autoren der Studie: “VATS is associated with less postoperative pain and better quality of life than is anterolateral thoracotomy for the fi rst year after surgery, suggesting that VATS should be the preferred surgical approach for lobectomy in stage I non-small-cell lung cancer.”

 Schlussfolgerung der Begutachterin: Monozentrische, in Dänemark durchgeführte Studie unter Einschluss von 206 NSCLC Patienten im Stadium I zum Vergleich der Schmerzen, Lebensqualität und des Kosten-Nutzen-Verhältnisses einer Operation mittels VATS und offener Lobektomie. Randomisierung und doppelte Verblindung werden adäquat beschrieben. Geplant war der Einschluss von 294 Patienten, von denen in 6 Jahren nur 206 (70 %) rekrutiert werden konnten und 201 ausgewertet wurden. Die Operationen wurden von 4 erfahrenen Chirurgen durchgeführt (daher Abwertung aufgrund eingeschränkter Übertragbarkeit / Indirektheit). Insgesamt 60 % der Patienten beantworteten die Lebensqualitätsfragebögen vollständig und berichteten deutlich weniger Schmerzen nach VATS. Auch die Lebensqualität scheint nach VATS etwas besser zu sein (keine genaue Aussage möglich aufgrund geringer Präzision, daher Abwertung der Qualität der Evidenz). Die Studie wurde durch öffentliche Mittel unterstützt.

Long 2017

(8)

01/2008 to 03/2014

China

NCT 01102517

Multicentre RCT

Non-inferiority of VATS vs. open operation for early stage

NSCLC on short-term and oncologic efficacy

Inclusion Criteria:

· patients (18 to 75 yrs) with early-stage NSCLC (pulmonary suspicious lesion without mediastinal lymphadenopathy, clinical stage I and II)

· adequate organ function to tolerate pulmonary resection

Exclusion criteria:

· tumor invasion into neighboring organs, extensive pleura adhesion

· predicted postoperative FEV1 or diffusing capacity of lung for carbon monoxide <40 %

· previous thoracotomy; high-dose RT on the chest

· pregnant or lactating female patients

· history of other malignancies in the past 5 years except for nonmelanoma skin cancer, cervix cancer in situ, or early-stage prostate cancer

· intraoperative pleural adhesion or technical

· challenge to achieve hemostasis that make conversion from VATS to thoracotomy

· occult pleural metastasis;

· major protocol violation; clinician decides the patient should not continue the trial according to individual condition; patient withdraws

n=481, 425 (88 %) analysed

males: 50 %

age: 58±9yrs

smoking history: 33 %

pulmonary /other comorbidity: 9.2 /52 %

presentation:

incidential finding: 53.4 %

cough:32.7 %

chest pain: 5.6 %

histology:

adenocarcinoma: 79.8 %

SCC: 10.6 %

median tumor size: 25 (IQR 17-32) vs. 30 (20-40) mm

pathological stage (IA, IB, IIA,IIB/IIIA/IIIB): 40/28/10/4/16/1 %

VATS (anatomic lobectomy, visualization only by thoracoscope and non–rib-spreading technique, number of ports according to surgeons preference) (n=236, 223 analysed)

vs.

axillary thoracotomy (n=245, 210 analysed)

Eight VATS procedures

were converted to open operation intraoperatively

(3.72%)

Primary:

5-year

overall and disease-free survival (not yet reached)

Secondary (only short-term and perioperative outcomes): 

death (28 days)

morbidity (28 days)

operation time, intraoperative blood loss

duration and volume of chest drainage

length of

stay

completeness of operation

yield of lymph

nodes

complications (Postoperative haemorrhage, pneumonia, air leak)

Short-term and perioperative outcomes:

Complete resection: 99.55 vs. 99.05 %

Surgical margin:

Negative: 99.07 vs. 97.62 %

Positive: 0.47 vs. 2.38 %

Median operation time: shorter with VATS:  150 (IQR 117-200) vs. 166 (IQR 130-205) minutes (p=0.009)

less intraoperative blood loss with VATS: 100 (IQR 50-150) vs. 100 (100-200) ml (p=0.001)

no difference for postoperative pleural drainage (median 4, IQR 3-6 days), length of hospitalization (median 14, IQR 12-19 days)

Postoperative complications: 10.31 vs. 10.95 %:

No differences shown for frequency and severity of haemorrhage, pneumonia, air leak, arrhythmia, atelectasis, respiratory failure

Incidental stage III disease identified in 34 patients (15.81%) vs.  39 patients (18.57

Cancer residual margins in 1 patient vs. 5 patients (p= 0.128)

Similar yield of lymph nodes from either surgical approach (p=0.389)

1b-

Abwertung aufgrund von Studienlimitationen

Zusammenfassende Beurteilung

Schlussfolgerungen der Autoren der Studie: “In conclusion, the ancillary analysis of our RCT provided evidence that VATS lobectomy is a safe and reliable procedure for the treatment of clinically early-stage NSCLC, and it may be superior to axillary thoracotomy approach in terms of operation time and intraoperative blood loss. However, long-term follow-up is warranted to verify the superior or equivalent oncologic outcome of VATS lobectomy. The report could be expected by the end of 2019.“

Schlussfolgerung der Begutachterin: Multizentrische, in China durchgeführte Nichtunterlegenheitsstudie unter Einschluss von 481 NSCLC Patienten in den klinischen Stadien I und II mit dem primären Ziel, das Überleben (Gesamt- und krankheitsfrei) von Patienten nach einer Operation mittels VATS und einer Lobektomie durch einen axilliären Zugang zu vergleichen. Patienten und das Personal waren nicht verblindet, es existiert ein registriertes Protokoll, aber es fehlt eine Veröffentlichung der Ergebnisse zum Überleben nach 5 Jahren der in den Jahren 2008 bis März 2014 rekrutierten Patienten (daher Abwertung aufgrund von Studienlimitationen). Bisher liegen Ergebnisse der Operation (Komplette Resektion, Operationszeit, Blutverlust) und zu postoperativen Komplikationen vor, welche auf einen geringeren Blutverlust und eine geringere Operationszeit mit VATS hindeuten. Die Studie wurde durch öffentliche Mittel der Krankenhäuser und Universität unterstützt.

Ng 2019

(5)

Search from 2000-01/2018

Systematic review

optimal surgical approach for lobectomy compared to conventional open lobectomy to improve clinical and resource outcomes

Inclusion criteria:

· RCTs and non-randomized observational studies (prospective or retrospective cohort and case–control studies)

· Adult patients undergoing upfront lobectomy for stages I–III NSCLC

· Studies comparing VATS  to conventional open thoracotomy, as well as studies that compared different VATS systems

· any VATS lobectomy using more than one port was considered to be multiport VATS

· studies reporting mixed lung resection procedures, whe data  extraction and analysis of outcomes for lobectomy for NSCLC patients could be segregated out.

Exclusion criteria:

· Studies that assessed other types of surgery (segmentectomy, bilobectomy, sleeve lobectomy, pneumonectomy, and wedge resection)

· studies where patients received neoadjuvant chemotherapy or radiation

· studies that included patients with advanced lung cancer

· studies that included patients with benign neoplasm or infectious disease

N=145 studies, n=369793

N=7 RCTs with n=1276

N=138 non-RCTs (cohort and case-control studies) with n=368517

142 studies published in English

N=13 with propensity score matching

Most studies were conducted in the United States, China, Japan, and South Korea, but also in several European countries and one South American country

Risk of bias:

All RCTs were rated as high risk of bias for blinding.

N=138 non-RCTs were rated with Newcastle-Ottawa scale (range 0-9, 9 indicates high methodological quality). Most studies have reasonably good quality, all studies were at risk for performance or detection bias because it was not possible to blind physicians, patients and personnel to the intervention,

many of the outcomes are objective in nature,

no clear evidence of publication bias, but inadequate power for some clinical outcomes

minimally invasive surgical (MIS) approaches (multiport

video-assisted thoracic surgery (mVATS), uniportal video-assisted thoracic surgery (uVATS), and robotic video-assisted

thoracic surgery (rVATS))

vs.

conventional open lobectomy

mVATS vs. open lobectomy (N=115)

mVATS vs. rVATS (N=9)

mVATS vs. uVATS (N=13)

rVATS vs. open lobectomy (N=1)

mVATS to rVATS vs. open lobectomy (N=4)

combined mVATS / rVATS vs. open lobectomy (N=2)

Primary:

Overall survival. Secondary: Recurrence-free survival

local or distant

tumor recurrence

lymph node evaluation, pathological upstaging

adverse events

length of stay

postoperative pain

scores

quality of life

ability to return to normal activities

respiratory function*

cost-effectiveness*

*not extracted

Survival and recurrence:

·       5-year-survival (N=30, n=16200): higher with mVATS (72 % vs. 67 %; OR 1.35; 95%CI 1.17 to 1.56) with substantial heterogeneity between studies (I²=60 %)

·       5-year DFS (N=14, n=4108): no difference shown (no recurrence in 65 vs. 61%; OR 1.15; 95%CI 0.94 to 1.40) with moderate heterogeneity between studies (I²=48 %)

·       Overall disease recurrence (N=22, n=6176): lower with mVATS (15 vs. 19 %; OR 0.73; 95%CI 0.61 to 0.87) with small heterogeneity between studies (I²=24 %)

·       Local recurrences (N=14, n=3691): no differences shown (5 vs. 6 %; OR 0.77; 95%CI 0.58 to 1.03) with small heterogeneity between studies (I²=0 %)

·       Distant recurrences (N=14, n=3691): lower with mVATS (6 vs. 10 %; OR 0.67; 95%CI 0.52 to 0.85) with small heterogeneity between studies (I²=0 %)

Lymph node evaluation and pathological upstaging:

No difference in lymph nodes (N=28; n=29341) and lymph node stations (N=15; n=6714) dissected

·       Reduced odds of nodal upstaging with mVATS (11 vs. 14%; OR 0.71; 95%CI 0.58 to 0.97) with moderate heterogeneity between studies (I²=57 %)

Complications and adverse events:

All less frequent with mVATS:

·       Complications (N=53, n=88 460): (36 vs. 42 %; OR 0.64; 0.59 to 0.71) with substantial heterogeneity between studies (I²=64 %)

·       Cardiopulmonary (N=17, n=143 390): (OR 0.60; 0.48 to 0.75) with substantial heterogeneity between studies (I²=74 %)

·       Atrial fibrillation (N=23, n=12 246): (OR 0.62; 0.45 to 0.84) with moderate heterogeneity between studies (I²=46 %)

·       Prologed air leak (N=33, n=18 762): (OR 0.78; 0.67 to 0.90) with small heterogeneity between studies (I²=12 %)

·       Wound infection (N=13, n=52 234): (OR 0.50; 0.36 to 0.68) with small heterogeneity between studies (I²=0 %)

·       30-day mortality (N=15, n=23 629): (OR 0.77; 0.62 to 0.95) with small heterogeneity between studies (I²=0 %)

·       No differences shown for 90-day mortality (N=6, n=12 479): (OR 0.78; 0.56 to 1.07) with small heterogeneity between studies (I²=13 %)

Pain and quality of life:

Less postoperative pain (measured with VAS) with mVATS on days 1,7,14,30 and 90

Higher quality of life (1 RCT, n=201, EQ5D) at week 2, 8, 12, 26 and 52 and higher quality of life (N=3, n=332, Global QoL tool) at 1 year and better activities of daily lifing (N=1, n=103)

Length of hospital stay (N=35, n=36 776):

·       shorter with mVATS (MD -1.95; 95%CI -3.1 to 0.73) with substantial heterogeneity between studies (I²=97 %)

2a-

Abwertung aufgrund von Indirektheit und Studienlimitationen, Aufwertung aufgrund hoher Präzision

 Zusammenfassende Beurteilung

Schlussfolgerungen der Autoren der Studie: “In conclusion, we have performed an extensive systemic review and meta-analysis comparing mVATS to open lobectomy, and the most popular MIS approaches to each other. mVATS has been reported for over 25 years and a large number of studies with several thousand patients have been included in comparisons between mVATS and open lobectomy. However, only 7 of the 145 included studies were randomized trials. In addition to the general limitations of meta-analysis, it is hard to control for surgeon specific biases (e.g., treating smaller and peripheral tumors with an MIS approach), and institutional biases where some surgeons will use an open and others an MIS approach. With these limitations in mind, our analysis suggests that the mVATS approach is superior to thoracotomy, particularly with respect to adverse events, pain control and perhaps improved survival. With respect to the optimal MIS approach, fewer studies are available to make definitive statements. Robotic VATS may be more expensive than mVATS, but otherwise does not demonstrate superiority or inferiority compared to mVATS. There is a suggestion that uVATS may be associated with lower adverse events and pain. It is our goal that the extensive analysis provided in the manuscript and appendix will assist future investigators in planning new trials to explore differences between these techniques.”

Schlussfolgerung der Begutachterin: Systematische Übersicht zum Vergleich minimal invasiver Operationstechniken (mVATS, uVATS, rVATS) mit einer offenen Lobektomie unter Einschluss von RCTs und vergleichenden Beobachtungsstudien (Kohorten- und Fall-Kontrollstudien) mit einer Suche bis Januar 2018. Einschluss von 145 Studien mit 369 793 Studienteilnehmern mit NSCLC der Grade I-III (davon 7 randomisierte Studien und 13 Studien mit Propensity-Score-Matching), von denen die meisten in Asien durchgeführt wurden und viele Patienten in einem frühen Erkrankungsstadium einschließen (deshalb und wegen Einbezug der Grade I-III Abwertung aufgrund von eingeschränkter Übertragbarkeit). Die systematische Übersichtsarbeit weist eine moderate Einschränkung der Qualität auf (fehlendes Protokoll, Informationen zur Suche in Registern und zum Screenen der Referenzen, keine Heterogenitätsbetrachtungen), die Studien sind nicht verblindet (Durchführungs- und Beobachtungsbias kann nicht ausgeschlossen werden (daher Abwertung aufgrund von Studienlimitationen). Es wird die Wirksamkeit einer minimal invasiven Operation auf das Überleben (substantielle Heterogenität, aber 25/30 Studien zeigen Vorteil von mVATS) und krankheitsfreie Überleben sowie das Auftreten von Rekurrenzen, ein Upstaging aufgrund der Lymphknotenuntersuchung, dem Auftreten postoperativer Komplikationen (auch hier substantielle Heterogenität, aber in 51/53 Studien weniger Komplikationen mit mVATS im Vergleich zur Thorektomie), das Auftreten von Schmerzen, die Lebensqualität und die Länge des Krankenhausaufenthaltes gezeigt. Insgesamt wird die Qualität der Evidenz aufgrund der aus der hohen Anzahl von Studien und Teilnehmern und der aussagekräftigen Ergebnisse zu Überleben und Komplikationen um einen Grad von 2a (Systematische Übersicht auf Grundlage von Kohortenstudien) auf 2a- abgewertet.

Palade 2013

(9)

05/2008 to 12/2011

Germany

Single center RCT

Completeness of the hilar and mediastinal lymphadenectomy for clinical stage I NSCLC treated with

VATS lobectomy vs. open lobectomy

Inclusion Criteria:

• adult (age > 18 yrs) with NSCLC in clinical Stage I (cT1–2, cN0)

• Tumour size <5 cm (on CT)

• 2 cm distance to the lobar orifice (on chest CT)

• CT or PET-CT

•Endobronchial ultrasound/mediastinos-copy for CT/PET-positive

lymph node

n=66

age: 66±8 yrs

males: 68.8 %

Right upper/lower lobe: 41/11 %

Middle lobe: 8 %

Left upper/lower lobe: 10/20 %

Squamous cell: 23 5

Adenocarcinoma: 64  %

Large cell: 6 %

Tumour size: 2.4±1.4 cm

VATS (n=34) with three incisions and an anterior approach

vs.

open lobectomy (n=32)

Primary:

Quality of life

Other:

Lymphadenectomy*

Perioperative outcomes

*not extracted

Perioperative outcomes:

Operative time: longer with VATS: 187±38 vs. 158±39 min (p=0.003)

No differences in median

drainage time: 1 (1-11) vs. 4 (2-19 days) and

length of hospital stay: 9 (6-26) vs. 11 (8-36) days

Early postoperative complications:

·       Less complications with VATS: 8 patients with 11 complications vs. 19 patients with 34 complications (p=0.039)

o   Pneumonia: 6.3 vs. 25 % (p=0.039)

o   Acute/chronic respiratory: 3.1/0 vs. 12.5/31.3 % (p=0.162/0.001)

·    Other complications were very rare with no differences between groups (maximum 2 per group)

·    pneumothorax after chest tube removal more frequent with VATS: 12.5 vs 0% (p= 0.039).

·    In all cases, this complication was treated by the insertion of chest drainage, and in 1 case, a blood pleurodesis was necessary to obliterate the persisting air leakage.

·    Reoperation rate: 0 vs. 2 (reopening of the pleural cavity)

·    Operative mortality: 1 vs. 0 (died 32 day postopertively)

2b

Abwertung aufgrund von Studienlimitationen und geringer Präzision

Zusammenfassende Beurteilung

Schlussfolgerungen der Autoren der Studie: „In conclusion, this is one of the few prospective randomized trials that show that hilar and mediastinal lymphadenectomy by

VATS is as effective as the open approach via an anterolateral thoracotomy. Oncological concerns with respect to intraoperative lymph node staging are no longer justified.”

Schlussfolgerung der Begutachterin: Monozentrische, in Deutschland durchgeführte Studie unter Einschluss von 66 NSCLC Patienten im klinischen Stadium I. Primärer Endpunkt war das Überleben. Angaben zur Durchführung der Randomisierung fehlen, die Studie wurde nicht verblindet oder registriert, es existiert keine Fallzahlanalyse und Ergebnisse zum primär geplanten Endpunkt (Überleben) fehlen (daher Abwertung aufgrund von sehr schwerwiegenden Studienlimitationen). Bisher liegen Ergebnisse der Operation (Komplette Resektion, Operationszeit, Blutverlust) und zu postoperativen Komplikationen vor, welche auf eine längere Operationszeit, aber weniger Komplikationen nach der Operation nach VATS hinweisen. Es konnten keine Unterschiede in der Anzahl der untersuchten Lymphknoten gezeigt werden. Aufgrund der geringen Fallzahl wurde die Evidenz aufgrund von geringer Präzision abgewertet. Die Studie wurde durch Karl Storz (führender Hersteller von Endoskopiesystemen) aus Tuttlingen unterstützt.

Wang 2019

(6)

Search in 4 databases until 04/2019

Systematic review

Comparison of VATS vs. MST on perioperative

outcomes in NSCLC

Inclusion criteria:

· patients with NSCLC proven pathologically

· compared the effects between VATS and MST

· RCT or cohort studies with acceptable methodological quality.

Exclusion criteria:

· conference abstracts,

· reviews, letters, book chapters, animal experiments or

· case reports

· baseline characters were incomplete

· insufficient data for meta-analysis

N=10 (1 RCT, 3 prospective and 5 retrospective studies). 3 wit propensity score matching

with 1514 patients

N=7 : clinical stage I

N=2, n=383:  pathological stage I-IV

N=1, n=87: clinical stage I-III

VATS (presented

with a video camera inserted into the pleural

space without rib spreading) (n=711)

vs.

Muscle-sparing thoracotomy (MST: preserving related muscles: latissimus dorsi and serratus anterior were retracted or split in the direction of the fibers) (n=803)

Primary: postoperative complication, intraoperative blood loss, hospital stay, chest tube drainage time

Secondary:

Operative time, resected lymph nodes, mortality, postoperative pain, complications

postoperative complications:

· less frequent with VAS (86/648 vs. 153/707; OR 0.54 (95%CI 0.4 - 0.73); p < 0.001) with no heterogeneity between studies (I²=0 %) (N=8 studies with 1355 patients)

· reduction of intraoperative blood loss in VATS

· (MD: -43.87 ml (95%CI −73.66 to − 14.08); p = 0.004) with substantial heterogeneity between studies (I²=84 %)  (N=4 studies with 536 patients)

· shorter hospital stay with VATS (MD: -1.5 days (95%CI −2.28 to −0.73); p = 0.0001) with substantial heterogeneity between studies (I²=68 %)  (N=9 studies with 1421 patients)

· shorter chest tube drainage time with VATS (MD -0.71 days (95%CI − 1.18 to − 0.24); p = 0.003) with moderate heterogeneity between studies (I²=57 %) (N=6, n=845)

· less postoperative pain on days 1 and 2 (MD -1.02 (95 %CI -1.18 to -0.24) and MD -1.42 (95% CI 1.37 to -0.66), p=0.00001) with no heterogeneity between studies (I²=0 %)  (N=0)

· longer operative time with VATS (MD 17.11 min (95%CI 2.38 to 31.85); p= 0.02) with substantial heterogeneity between studies (I²=92 %)  (N=9, n=1276)

· No difference shown on

o   number of resected lymph nodes (MD 1.25 (95%CI − 4.57 to 7.07), p = 0.67) (N=3, n=864)

o   postoperative mortality (OR: 1.03 (95%CI 0.38, 2.80), p = 0.95) with no heterogeneity between studies (I²=0 %)  (N=9, n=1276)

o   pneumonia (OR: 1.11 (95%CI 0.48, 2.55), p = 0.85) with no heterogeneity between studies (I²=0 %)  (N=4)

o   prolonged air leak (OR: 0.79 (95%CI 0.32, 1.93), p = 0.6) with moderate  heterogeneity between studies (I²=55 %)  (N=5)

o   arrhythmia (OR: 0.48 (95%CI 0.21, 1.06), p = 0.07) with no  heterogeneity between studies (I²=0 %)  (N=5)

o   postoperative bleeding (OR: 0.62 (95%CI 0.24, 1.61), p = 0.32) with small  heterogeneity between studies (I²=15 %)  (N=4)

o   chylothorax (OR: 0.52 (95%CI 0.20, 1.33), p = 0.17) with small  heterogeneity between studies (I²=15 %)  (N=4)

2a-

Abwertung aufgrund von Studienlimitationen

Zusammenfassende Beurteilung

Schlussfolgerungen der Autoren der Studie: “In conclusion, this present systematic review and metaanalysis indicates that the benefit of VATS was superior to that of MST in the reduction of intraoperative trauma, postoperative complications and enhanced recovery after surgery for patients with operable lung cancer. In consideration of some limitations of enrolled studies, the conclusion should be carefully applied. Further high-quality randomized controlled trials are needed.“

Schlussfolgerung der Begutachterin:  Systematische Übersicht mit geringen Einschränkungen der methodischen Qualität (fehlendes Protokoll, kein Screening registrierter Studien, fehlende Beschreibung der Ausschlussgründe aller potentiell relevanten Studien), basiert auf 10 Studien (davon 1 RCT und 3 mit Propensity-Score Matching) unter Einschluss von 1514 Patienten. Insgesamt 7 Studien schließen ausschließlich Patienten im klinischen Stadium I ein. In der randomisierten Studie fehlt eine Beschreibung der Randomisierung, der Verblindung der Patienten und von Ausschlussgründen, so dass insgesamt ein hohes Verzerrungsrisiko besteht. Weitere Verzerrungsquellen betreffen die Länge und Angemessenheit der Nachbeobachtungszeit (Abwertung aufgrund von Studienlimitationen und Design der Primärstudien). Zusammenfassend konnte für die mit VATS operierten Patienten eine geringere Anzahl postoperativer Komplikationen, geringere Drainage und Krankenhausaufenthaltszeiten und ein geringerer Blutverlust gezeigt werden, während die Operationszeit zunahm. Die teilweise substantielle Heterogenität der Ergebnisse der Einzelstudien betraf nicht die Gesamtaussage einer geringeren Anzahl postoperativer Komplikationen mit VATS, so dass die Qualität der Evidenz nicht aufgrund von Inkonsistenz abgewertet wurde.

Yang 2019

(10)

01/2013 to 06/2015

China

Single-center RCT

efficacy of VATS versus thoracotomy for radical resection of NSCLC, stage I or II in elderly patients

Inclusion criteria:

· patients (> 60 yrs) with stage I or II NSCLC

· confirmed by imaging and pathological examination

· no involvement of mediastinal and hilar lymph nodes, no lymph node metastasis nor distant metastasis.

Exclusion criteria:

· surgical contraindications (e.g. coagulation dysfunction, severe renal and hepatic insufficiency)

· received CT, RT  and other targeted therapy before treatment, a history of thoracotomy

· immune system disease, did not actively cooperate in this study or incomplete clinical data

n=100

age: 65±5.9 yrs

65 % males

Adenocarcinoma: 56 %

SCC: 44 %

Tumor size: 3.0±0.9 c

PS(I/II): 53/37 %

Peripheral/central lesion: 78/22 %

Smoking history: 61 %

Hypertension: 51 %

Diabetes: 53 %

VATS (n=50)

Vs.

Thoracotomy (n=50)

perioperative indicators (operative time, the amount of intraoperative blood loss, the number of mediastinal lymph nodes dissected, the time to chest tube removal and the time to ambulation)

rates of cardiopulmonary complications

Tumour-free survival

Perioperative outcomes:

· no difference in the number of mediastinal lymph nodes dissected shown: 10.7±6.8 vs. 11.4±6.2 (p=0.592)

· shorter operative time with VATS: 109.5±42.3 vs. 134.8±55.7min (p=0.012)

· reduced intraoperative bleeding wit VATS: 145.7±49.1 vs. 292.3±65.2 ml (p<0.001)

· shorter time to chest tube removal with VATS: 3.4 ±0.6 vs. 5.3±0.8 days (p<0.001)

· shorter time to ambulation with VATS: 1.4±0.5 vs. 3.2±0.9 days (p<0.001)

cardiopulmonary complications:

· lower rates of overall cardiopulmonary complications: 8 vs. 58 % (p<0.001),

· with less common tachycardia (1 vs. 4 patients), atrial fibrillation (2 vs.3), premature contractions (1 vs.3), atelectasis (2 vs.6), hypoxemia (1 vs.8) and involuntary cough (1 vs.5)

Tumour-free survival:

No differences after 1 yr: 82 vs. 78 %, 2 yrs: 60 vs. 58 % and

3 yrs: 40 vs. 34 %

2b

Abwertung aufgrund von Studienlimitationen und geringer Präzision

Zusammenfassende Beurteilung

Schlussfolgerungen der Autoren der Studie: „In conclusion, radical resection of NSCLC by VATS in elderly patients is more significantly favorable than by conventional thoracotomy in perioperative indicators, cardiopulmonary complications, lung function and immune function. However, there are still some limitations in this study, such as small sample size, single-center study, no results of long-term follow-ups, etc. Prospective randomized controlled trials with larger sample size and long-term follow-up are required in the future research to further validate the advantages of VATS for radical resection of NSCLC in elderly patients.”

Schlussfolgerung der Begutachterin: Monozentrische, in China durchgeführte Studie unter Einschluss von 100 NSCLC Patienten über 60 Jahren in den klinischen Stadien I und II. Angaben zur Durchführung der Randomisierung fehlen, die Studie wurde nicht verblindet oder registriert, es existiert keine Fallzahlanalyse und Spezifizierung eines primären Endpunktes (daher Abwertung aufgrund von sehr schwerwiegenden Studienlimitationen). Es konnten verbesserte perioperative Ergebnisse (kürzere Operationszeit, ein geringerer Blutverlust und kürzere Behandlungsdauern bei geringeren Komplikationsraten, aber keine Unterschiede im krankheitsfreien Überleben über 3 Jahre gezeigt werden. Angaben zur Förderung werden nicht berichtet. Aufgrund der geringen Fallzahl erfolgte eine Abwertung aufgrund geringer Präzision.

AE: Adverse event; CG: Control group; CI: Confidence interval; CRT: Chemo-radiotherapy; CT: Chemotherapy;  d: Tag; EBUS-FNA:  endoscopic bronchial ultrasound guided fine-needle aspiration; EORTC: European Organization for Research and Treatment of Cancer;  EQ5D: EuroQol 5 Dimensions;  HR: Hazard ratio; IG: Intervention group; IQR: Intraquartil range; LLL: Left lower lobe; LUL: Left upper lobe; MD: Mean difference; MIS: minimally invasive surgical systems; MST: Muscle-sparing thoracotomy; n: Number of participants; NSCLC: Non-small cell lung cancer; NR: not reached; NRS: numeric rating scale; OR: Odds Ratio; OS: overall survival; PS: Performance status; QLQ-C30: 30 item Quality of Life Questionnaire; RR: Relative Risk; RLL: Right lower lobe; RML: Right moddle lobe; RUL: Right upper lobe; RT: Radiotherapy; SCC: Squamous cell carcinoma; VATS: Video-assisted thoracoscopic surgery; wks: weeks; yrs: years