state of the art standard of care for resectable nsclc ... · tnm classification for lung cancer...

state‐of‐the‐art

standard of care for resectable NSCLC

surgical approach for resectable NSCLC

Dominique H. Grunenwald, MD, PhD

Professor Emeritus in Thoracic and Cardiovascular surgery

Pierre & Marie Curie University. Paris. France

surgical approach for resectable nsclc

•which patient ?

-which resection ?

-which technique ?

-which surgeon ?

standard of care

guidelines

recommendations

what do we expect from the surgery?

• the best local control

• i.e. a complete therapeutic response

• i.e. a chance of cure

• provided it could remain a harmless procedure

• a better survival and quality of life than

– no treatment

− other treatments

– no surgery in the context of multimodal therapy

surgery = extirpation

questions before considering surgery

depends on

operable patient? clinical performance

resectable tumour? TNM staging

type of resection? local invasion

which approach? tumour size and location

therapeutic pathway? state of the art

definitions

• an "operable" patient has an acceptable risk of

death or morbidity

• a "resectable" tumour can be completely excised by

surgery with clear pathological margins

does the patient have the functional

pulmonary reserve to tolerate the

proposed resection to maintain a

reasonable quality of life?

surgical resection offers little benefit if

the patient suffers postoperative

pulmonary insufficiency … or death

risks from surgery increase with age and comorbidities

because

assessment by a multidisciplinary team (MDT)

thoracic surgery

pulmonology

oncology

imaging

nuclear medicine

pathology

consideration of the patient’s general condition

comorbidity

cardiac condition

lung condition

diagnostic and therapeutic indications

Tripartite risk assessment (SCTS-BTS)

Eric Lim et al. Thorax 2010;65:iii1-iii27Copyright © BMJ Publishing Group Ltd & British Thoracic Society. All rights reserved.

assessment by a multidisciplinary team (MDT)

the thoracic surgeon

pulmonology

oncology

imaging

nuclear medicine

pathology

consideration of the patient’s general condition

comorbidity

lung condition

cardiac condition

diagnostic and therapeutic indications

and acceptance

definitions

• an "operable" patient has an acceptable risk of death or

morbidity

• a "resectable" tumour can be completely excised by

surgery with clear pathological margins

"early stage"

what is early stage lung cancer?

this refers to cancers that are caught early enough that

they have the potential to be cured with surgery

Goldstraw P, et al. J Thorac oncol 2007;2:706-14

the TNM stage influences

survival after surgery

TNM Classification for Lung Cancer (8th Edition)

T Classification: importance of tumor size highlighted

T1 T1a (≤1 cm), T1b (>1 to ≤2 cm), and T1c (>2 to ≤3 cm)

T2 T2a (>3 to ≤4 cm) and T2b (>4 to ≤5 cm)

T3 (>5 to ≤ 7cm)

T4 > 7 cm (prev. T3)

T2 involvement of main bronchus regardless of distance from carina (prev. T2/3)

T2 partial and total atelectasis/pneumonitis (prev. T2/3)

T4 diaphragm invasion (prev. T3)

deletion of mediastinal pleural invasion as a T descriptor

N Staging unchanged, new descriptors proposed for prospective testing and validation

p N1 single (pN1a) and multiple (pN1b) nodal station involvement

pN2 pN2a1 (single pN2 nodal station involvement without pN1 disease, “skip

metastasis”

pN2a2 with single station pN2 and pN1 involvement

pN2b with involvement of multiple pN2 nodal stations

M Staging

M1a unchanged

M1b single metastasis in a single organ

M1c multiple metastases

stage groupings (8th edition)

Stage IA N0 and ≤ 3 cm

IA1, IA2, IA3 (a category for each cm in size)

Stage IB N0 and >3 to ≤ 4 cm

Stage IIA N0 and >4 to ≤ 5cm

Stage IIB N0 and >5 to ≤ 7 cm

or N1 and smaller tumors

Stage IIIA N0 and > 7cm or others T4

N1 and T3-T4

N2 and T1a-T2b

Stage IIIB N2 and T3-4

N3 and T1a-T2b

Stage IIIC N3 and T3-T4

Stage IVA Any T Any N with M1a and M1b

Stage IVB > 1 extrathoracic metastasis (M1C)

stage IA : IA 1 T1a N0 M0 (≤1 cm)

very early IA2 T1b N0 M0 (>1 to ≤ 2cm)

IA3 T1c N0 M0 (>2 to ≤3cm)

stage IB : T2a N0 M0 (>3 to ≤ 4cm)

stage IIA : T2b N0 M0 (>4 to ≤ 5 cm)

stage IIB : T3 N0 M0 (>5 to ≤ 7cm)

early T1a-c N1 M0

T2a-b N1 M0

stage IIIA: T4 N0 M0

locally advanced T3-4 N1 M0

T1a-2b N2 M0

stage IIIB T3-4 N2 M0

locally advanced T1a-T2b N3 M0

stage IVA-B : Any T, any N, M1a-b-c

surgery

no

surgery

early stage lung cancer in the TNM 8th edition

questions

depends on

operable patient? clinical performance YES

resectable tumour? TNM staging YES

type of resection? local invasion



type of resection depends on tumor size

and/or location (T factor)wedge resection

segmentectomy

lobectomy

pneumonectomy

along with systematic en-bloc dissection of mediastinal lymph node stations!

type of resection depends on local invasion

(T factor)

lobectomy

+ extended resection

extended

pneumonectomy

bilobectomy

(right side)

indication

parenchyma

bronchus

LSD

LMLID

LIG

LSG


very early IA2 T1b N0 M0 (>1 to ≤ 2cm)

IA3 T1c N0 M0 (>2 to ≤3cm)




early T1a-c N1 M0

T2a-b N1 M0



T1a-2b N2 M0




surgery

no

surgery

which resection for stage I tumours ?

potential to be cured with surgery… alone

Ginsberg RJ and Rubinstein LV 1995

the gold standard in stage I

is an anatomic lobar resection

(Lung Cancer Study Group)

remains an area of evolution

several situations where sublobar resection should be

reasonably considered as primary treatment for early-stage nsclc

patients with limited pulmonary reserve

poor physical conditions

multiple primary nsclcs

butthe extent of parenchymal resection

Asamura H. and Donington J. J Thorac Oncol 2017;12:1188-9

1995 LCSG consensus : lobectomy = gold-standard (stage I nsclc)

enhancements in imaging technology

screening programs

minimally invasive surgical resection

reduced perioperative morbidity and mortality

equivalent oncologic effectiveness to open surgery

challenging lobectomy as a standard for small tumors

Blasberg JD, et al. J Thorac Oncol 2010;5:1583-93

sublobar resection: a movement from the

Lung Cancer Study Group

larger cohorts of

localized early-stage

disease

an evolving paradigm?

sublobar resection ?

wedge resection

anatomical segmentectomy

(Surveillance, Epidemiology, and End Results registry)

2,090 patients

limited resect. (segment. or wr) 688 (33%)

no difference in outcomes among patients treated with

lobectomy vs limited resection

overall survival

HR : 1.12 (95% CI: 0.93-1.35)

lung cancer-specific survival

HR: 1.24 (95% CI: 0.95-1.61)

Kates M, et al. Chest 2010

survival following lobectomy and limited resection

for the treatment of stage I nsclc <= 1cm in size: a

review of SEER data

in favor

sublobar resection is equivalent to lobectomy for

clinical stage 1A lung cancer in solid nodules

(International Early Lung Cancer Action Program)

nsclc with a diameter of 30 mm or less (stage 1) n=347

10-yr survival sublobar res. (n=53) 85%

lobectomy (n=294) 86% P = .86

cancers 20 mm or less in diameter P = .45

equivalent survival for patients with clinical stage IA

nsclc in the context of computed tomography screening

for lung cancer

Altorki NK, et al. J Thorac Cardiovasc Surg 2014;147:754-62 (I-ELCAP)

in favor

16 papers / 116 (1 meta analysis, 1 RCT)

represented the best evidence to answer the clinical question.

there is evidence that wedge resections, compared to

segmentectomies and lobectomies, lead to lower survival and

higher recurrence rates

lobectomy is still recommended for younger patients with

adequate cardiopulmonary function. against

CALGB 140503

JCOG0802/WJOG4607L

expected results of clinical trials

will see !

questions

depends on

operable patient? clinical performance YES

resectable tumour? TNM staging YES

type of resection? local invasion DECIDED



approach depends on tumor size and location…

• open thoracotomy

• vats

• uniportal vats

• robotic

• others (transmanubrial, …)

… and $$$ as well

Grunenwald D, et al. Ann Thorac Surg 1997;63:563-6

video-assisted thoracic surgery (VATS) has become a common

surgical technique

VATS generally means operating by using thoracoscopy with a

minimal number of small incisions and without rib spreading

assumption that it has an oncologic outcome equivalent to that of

open thoracotomy but is a less invasive method

scientifically supported comparisons between VATS and open

thoracotomy with randomized controlled trials have been

scarcely reportedAsamura H. and Donington J. J Thorac Oncol 2017;12:1188-9

minimally invasive lobectomy

open or mis* ?

safety?

* mini-invasive surgery

intraoperative vascular risks

Watanabe A : 21 pulmonary artery injuries / 185 vats (11%) *

Tatsumi A : 1 death from intraoperative bleeding / 118 vats **

*Watanabe A. et al. Kyobu Geka 2003;56:943-8

**Tatsumi A. et al. Jpn Journal Thorac Cardiovasc Surg 2003;51:646-50**

Gopaldas RR, et al. Ann Thorac Surg 2010;89:1563-70

video-assisted thoracoscopic versus open thoracotomy

lobectomy in a cohort of 13,619 patients

Nationwide Inpatient Sample database

lobectomy thoracotomy (n = 12,860)

vats (n = 759)

vats = higher incidence of intraoperative complications

(p = 0.04)

minimal incision = delay in control of bleeding

vats worse?

open thoracotomy 24,811 (95.1%)

VATS 1,278 (4.9%)

end points vats

30-day postop. death ns

atelectasis and pneumopathy reduced

other postoperative complications ns

hospital length of stay decreased from 2.4 days

os and dfs not influenced

Pagès PB, et al. et al. Ann Thorac Surg 2016;101:1370-8

propensity score analysis comparing videothoracoscopic

lobectomy with thoracotomy: a french nationwide

study

vats equivalent ?

propensty matched groups n=2721

lobectomy thoracotomy vats p

no. % no. %

patients 2721 2721

total complications 792 29 863 32 0.0357

major CP complic. 316 16 435 20 0.0094

atelectasis (bronchosc.) 65 2.4 150 5.5 <0.0001

initial ventilation < 48h 18 0.7 38 1.4 0.0075

wound infection 6 0.2 17 0.6 0.0218

in-hosp. mortality 27 1 50 1.9 0.0201

postop. hospital stay (days) 7.8 9.8 0.0003

VATS is associated with a lower incidence of complications compared with

thoracotomy.Falcoz PE, et al. Eur J Cardiothorac Surg 2016;492:602-9

video-assisted thoracoscopic surgery versus open

lobectomy for primary nsclc: a propensity-matched

analysis of outcome from the ESTS database

(28771 patients)

vats better ?

open lobectomy 3058 patients (58.6%)

thoracoscopic lobectomy 2164 (41.4%)propensity matching produced 1848 patients in each group

5-year OS rates for open lobectomy 65.5%

for thoracoscopic lobectomy 68.7% ns

similar long-term survival in the setting of lung cancer

thoracoscopic lobectomy is an acceptable surgical treatment of

lung cancer

Wang BY, et al. J Thorac Oncol 2016;11:1326-34

thoracoscopic lobectomy produces long-term survival

similar to that with open lobectomy in cases of nsclc:

a propensity-matched analysis using a population-based

cancer registry (5222 patients)

vats equivalent ?

a national study of nodal upstaging after thoracoscopic

versus open lobectomy for clinical stage I lung cancer

(nodal upstaging occurs when unsuspected lymph node metastases are

found during the final evaluation of surgical specimens)

Danish Lung Cancer Registry

1,513 pts VATS 717 (47%)

thoracotomy 796 (53%)

nodal upstaging 281 pts (18.6%)

thoracotomy higher N1 upstaging (13.1% vs 8.1%; p<0.001)

N2 upstaging (11.5% vs 3.8%; p<0.001)

no difference in OS between VATS and thoracotomy

(hazard ratio, 0.98; 95% confidence interval, 0.80 to 1.22, p=0.88).

Licht PB, et al. Ann Thorac Surg 2013;96:943-9

a national study of nodal upstaging after thoracoscopic

versus open lobectomy for clinical stage I lung cancer

(nodal upstaging occurs when unsuspected lymph node metastases are

found during the final evaluation of surgical specimens)

Danish Lung Cancer Registry

1,513 pts VATS 717 (47%)

thoracotomy 796 (53%)

nodal upstaging 281 pts (18.6%)

thoracotomy higher N1 upstaging (13.1% vs 8.1%; p<0.001)

N2 upstaging (11.5% vs 3.8%; p<0.001)

no difference in OS between VATS and thoracotomy

(hazard ratio, 0.98; 95% confidence interval, 0.80 to 1.22, p=0.88).

Licht PB, et al. Ann Thorac Surg 2013;96:943-9

vats worse?

vats equivalent ?

retrospective review

c-stage 1a p-stage 1a p

thoracotomy 1964 36,4% 30.5% 0.0002

vats 500 47,4% 38% 0.0002

thoracotomy VATS p

overall nodal upstaging (%) 9.9 4.8 0.0002

increased survival was found with VATS 0.0042

selection bias may play a role

the improved quality of life measures associated with VATS may

explain survival improvement despite lower surgical upstaging

Martin JT, et al. Ann Thorac Surg 2016;101:238-44

nodal upstaging during lung cancer resection is

associated with surgical approach!

retrospective review

c-stage 1a p-stage 1a p

thoracotomy 1964 36,4% 30.5% 0.0002

vats 500 47,4% 38% 0.0002

thoracotomy VATS p

overall nodal upstaging (%) 9.9 4.8 0.0002

increased survival was found with VATS 0.0042

selection bias may play a role

the improved quality of life measures associated with VATS may

explain survival improvement despite lower surgical upstaging

Martin JT, et al. Ann Thorac Surg 2016;101:238-44

nodal upstaging during lung cancer resection is

associated with surgical approach!

vats worse?

vats better ?

nodal upstaging more frequent in the open group (12.8% vs.

10.3%; p < 0.001)propensity score matching : 4437 patients in each group

upstaging remained more common for open approaches

however, in academic/research facility, the difference in nodal

upstaging no longer significant (12.2% vs. 10.5%, p = 0.08)

Medbery RL, et al. J Thorac Oncol 2016;11:222-33

nodal upstaging is more common with thoracotomy

than with vats during lobectomy for early-stage

lung cancer: an analysis from the national cancer

data base (16,983 patients)

vats worse?

vats equivalent ?

large national or regional databases

VATS lower incidence of postoperative complications

shorter length of hospital stay by 1 to 2 days

some reports

higher incidence of nodal upstaging observed in open

possibility of insufficient nodal evaluation in VATS

these conclusions were derived from retrospective studies

therefore, harbor hidden biases that may affect the outcome

further randomized studies required to demonstrate the

prognostic equivalence and any differences in QOL or

postoperative complications

. Asamura H. and Donington J. J Thorac Oncol 2017;12:1188-9

to conclude on vats lobectomy

retrospectively reported to be equivalent to VATS in all measures

of quality for treatment of lung cancer

no randomized trials have reported the comparative data between

RATS and VATS/thoracotomy for lung cancer

robot-assisted thoracic surgery (RATS)


open versus minim. invasive surgery (MIS [VATS and robotic])

propensity score matching: 9,390 patients in each group

MIS have increased 30-day readmission rates p < 0.01

shorter median hospital length of stay p < 0.01

improved 2-yr survival p = 0.04

nodal upstaging ns

30-day mortality ns

Yang CF, et al. Ann Thorac Surg 2016;101:1037-42

VATS versus robotic lobectomy for clinical T1-2, N0 nsclcpropensity score matching : 1,938 patients in each group

no difference with regard to nodal upstaging, 30-day mortality,

and 2-year survival

use and outcomes of minimally invasive lobectomy

for stage I nsclc in the national cancer data base

(30,040 patients)

clinical stage I or stage II nsclc

1,220 robotic lobectomies

12,378 VATS procedures

robotic lobectomy more comorbidities

longer operative times

robotic and vats equivalent complications

hospital stay

30-day mortality

nodal upstaging

Louie BE, et al. Ann Thorac Surg 2016; Sep;102(3):917-24

comparison of video-assisted thoracoscopic surgery

and robotic approaches for clinical stage I and stage

II nsclc using the sts database

uniportal vats

Gonzales-Rivas D. WCLC 2016

the future : uniportal robotic platform

Intuitive Sugical da Vinci Sp Single Port Robotic Surgical system


early IA2 T1b N0 M0 (>1 to ≤ 2cm)

IA3 T1c N0 M0 (>2 to ≤3cm)




early T1a-c N1 M0

T2a-b N1 M0



T1a-2b N2 M0




surgery

no

surgery

surgical resection of lung cancer - standard of care

stage I & II tumours- surgery

- open , vats

- lobar or sublobar?



IA3 T1c N0 M0 (>2 to ≤3cm)




early T1a-c N1 M0

T2a-b N1 M0



T1a-2b N2 M0




no

surgery

surgical resection of lung cancer - standard of care

stage I & II tumours- surgery

- open or vats

- lobar or sublobar?



IA3 T1c N0 M0 (>2 to ≤3cm)




early T1a-c N1 M0

T2a-b N1 M0



T1a-2b N2 M0




surgery

no

surgery

state of the art ? – controversial situations

stage III-N2

surgery or not ?

upfront surgery or induction ?

risks ?

locally advanced –T3/4

surgery ?

is there a role for surgery in locally advanced nsclc ?

what we know from evidence based

medicine in N2 disease

• dramatic benefit with induction chemotherapy compared

to surgery alone in two small-scale studies [Roth, Rosell,

1994]

• no benefit in large european randomized study in stage

IIIA category [Depierre, 2002]

• stage IIIA benefits from adjuvant chemotherapy

following "complete resection" [Arriagada, 2004;

Douillard, 2006]

• nothing on radiotherapy (Lung-ART still ongoing)

• nothing on surgery

N2 disease – paradigms and opinions

• mediastinal downstaging from induction is the most

powerful positive prognostic factor for survival after

surgery [Betticher, 2003; Albain, 2009]

• rt should be considered the preferred locoregional

treatment for pts with stage IIIA-N2 nsclc responders to

induction ct [Van Meerbeck, 2007]

• good candidates for surgery may still be appropriately

managed by using resection rather than radiation

[Vansteenkiste, 2007]

• the role of surgery is not clearly defined [Roy and

Donington, 2007]

N2 disease – paradigms and opinions

• mediastinal downstaging from induction is the most

powerful positive prognostic factor for survival after

surgery [Betticher, 2003; Albain, 2009]

• rt should be considered the preferred locoregional

treatment for pts with stage IIIA-N2 nsclc responders to

induction ct [Van Meerbeck, 2007]

• good candidates for surgery may still be appropriately

managed by using resection rather than radiation

[Vansteenkiste, 2007]

• the role of surgery is not clearly defined [Roy and

Donington, 2007]

no standard of care

case by case discussion

in a tumor board

locally advanced T3-4

superior sulcus tumor

locally advanced nsclc are not "surgical", an evolving paradigm?

en bloc vertebrectomy / intralesional approach

upfront surgery / induction rt-ct

pers. MDA Toronto

yr 2006 2009 2013

induction none, ct none ct-rt

surg. technique en bloc intralesional en bloc

pts 34 31 48

partial vert. 28 16 38

total vertebr. 6 15 10

R0 res. (%) 88 56 88

mortality (%) 3 5 6

5-yr surv. (%) 24 27 61

1. evidence suggests that

triple modality therapy with

complete resection of

Pancoast tumors with

involvement of the spine

offers an advantage over

other therapeutic modalities

2. given the negative

prognostical influence of

N2 nodal status , those

patients must be precluded

from surgery

3. highly selected centers and

surgical teams

state of the art

what about the surgical quality ?

lymph node dissection as an example

resection without evidence of pathologic nodal involvement

lobectomy 83.9 %

sublobar resection 12.7 %

pneumonectomy 2.8 %

the number of LNs removed correlated with increasing tumor

size and extent of resection

the number of LNs removed correlated with improved survival

removal of <10 LNs was associated with a 12 % increased

risk of death (p < 0.001)

Samavoa AX, et al. Ann Surg Oncol 2016;23(Suppl 5):1005-11

rationale for a minimum number of lymph nodes

removed with nsclc resection: correlating the

number of nodes removed with survival in 98,970

patients

importance of surgical quality measures (QMs) in nsclc was

highlighted in 2016

National Cancer Database

stage I (1) anatomic resection

(2) operation within 8 weeks of diagnosis

(3) R0 resection

(4) more than 10 lymph nodes sampled

99% of resections met at least one QM

only 22% satisfied all four

median OS no QMs 31 months

4 QMs 89 months

compliance with basic QMs was associated with improved OS

Surgical Quality


quality measures (no.) 1 2 3 4

% of patients 99.7 94.9 68.6 22.5

more likely to meet all four measures

income of at least $38,000/year

insurance type (private insurance vs. Medicare)

centers with at least 38 cases/year

academic institutions

clinical stage IB patients

national adherence to quality measures is suboptimal

guideline compliance is strongly associated with survival

efforts should be instituted by national societies to improve adherence.

Samson P, et al. Ann Thorac Surg 2017;103:303-11

quality measures in clinical stage I nsclc : improved

performance is associated with improved survival(133,366 patients)

adherence to four QMs

(1) neoadjuvant therapy

(2) lobectomy or more extensive procedure

(3) R0 resection

(4) >10 lymph nodes sampled

only 12.8% of stage IIIA resections satisfied all QMs

median OS no QMs 12 months

4 QMs 43.5 months

compliance with QMs remained a strong independent

predictor of survival


surgical quality in clinical stage IIIA

recommendations

• ESMO

Postmus PE, et al. Ann Oncol 2017;28(Suppl.4)

• BTS-SCTS

Lim E, et al. Thorax 2010;65:iii1-iii27

• ACCP

Howington JA, et al. Chest 2013;143(5_suppl):e278S-e313S

Suggested algorithm for locoregional lymph node staging

ESMO Clinical Practice guidelines. Postmus PE, et al. Ann Oncol 2017;28(Suppl.4)

treatment of early stages (stages I and II) - surgery


take home messages

1. the therapeutic decision starts in a multidisciplinary tumor

board including a thoracic surgeon

2. detailed TNM staging according to the 8th edition

determines the choice of treatment

3. surgery should be offered to all patients with stage I and II

4. anatomical resection is preferred

5. lymph node dissection should conform to standard

specifications

take home messages (cont'd)

6. surgical approach should be appropriate to the expertise of

the surgeon

7. pneumonectomy should be avoided where possible

8. patients with limited pulmonary reserve can be considered

for sublobar resection as an acceptable alternative to

lobectomy

9. compliance with surgical quality measures is associated with

improved survival

10. cancer surgery must be performed by board-certified

thoracic surgeons

state of the art standard of care for resectable nsclc ... · tnm classification for lung cancer...

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