PDF EN Jornal Brasileiro de Pneumologia 6 7 english

* Study carried out in the Department of Thoracic Surgery of the São Lucas Hospital. Pontifícia Universidade Católica do Rio Grande do Sul – PUCRS, Pontifical Catholic University of Rio Grande do Sul – Porto Alegre (RS) Brazil.

1. Resident in the Department of Thoracic Surgery of the São Lucas Hospital. Pontifícia Universidade Católica do Rio Grande do Sul – PUCRS, Pontifical Catholic University of Rio Grande do Sul – Porto Alegre (RS) Brazil.

2. Thoracic Surgeon at the São Lucas Hospital. Pontifícia Universidade Católica do Rio Grande do Sul – PUCRS, Pontifical Catholic University of Rio Grande do Sul – Porto Alegre (RS) Brazil.

3. Fellow in the Department of Thoracic Surgery. University of Toronto, Toronto, Ontario, Canada.

4. Adjunct Professor in the Department of Thoracic Surgery. Pontifícia Universidade Católica do Rio Grande do Sul – PUCRS, Pontifical Catholic University of Rio Grande do Sul – School of Medicine, Porto Alegre (RS) Brazil.

5. Full Professor in the Department of Thoracic Surgery. Pontifícia Universidade Católica do Rio Grande do Sul – PUCRS, Pontifical Catholic University of Rio Grande do Sul – School of Medicine, Porto Alegre (RS) Brazil.

Correspondence to: Pedro Augusto Reck dos Santos. Rua Sofia Veloso, 104, apto 903, Cidade Baixa, CEP 90040-150, Porto Alegre, RS, Brasil. Tel 55 51 3407-4120. E-mail: pedroreck78@gmail.com

Submitted: 1 December 2006. Accepted, after review: 3 April 2007.

Concordance between cl

i

_n

i

_{cal and patholog}

i

_{cal stag}

i

_ng

i

_{n pat}

i

_{ents w}

i

_{th stages}

I

_or

II

_{non-small cell lung}

cancer subjected to surg

i

_{cal treatment*}

Pedro Augusto Reck dos Santos1_{, Rodrigo Sponchiado da Rocha}1_,

Mauríci_{o P}i_pki_n1_{, Marner Lopes da Silveira}2_{, Marcelo Cypel}3_,

Jayme Oli_vei_{ra R}i_os4_{, José Antonio Lopes de Figueiredo Pinto}5

Abstract

Objective: To compare cli_ni_{cal and patholog}i_{cal stag}i_ng i_{n pat}i_{ents w}i_{th non-small cell lung cancer subm}i_{tted to surg}i_{cal treatment, as well}

as to i_denti_{fy the causes of d}i_{scordance. Methods: Data related to pat}i_{ents treated at the Department of Thorac}i_{c Surgery of the Pont}i_fi_cal

Catholi_{c Un}i_versi_{ty of R}i_{o Grande do Sul São Lucas Hosp}i_{tal were analyzed retrospect}i_{vely. Sens}i_ti_vi_{ty, spec}i_fi_ci_{ty, pos}i_ti_{ve pred}i_cti_{ve value,}

negati_{ve pred}i_cti_{ve value, and accuracy were calculated for cl}i_ni_{cal stages} I_A, I_{B, and} II_{B. The kappa} i_{ndex was used to determ}i_{ne the}

concordance between cli_ni_{cal and patholog}i_{cal stag}i_{ng. Results: Of the 92 pat}i_{ents stud}i_{ed, 33.7% were class}i_fi_{ed as cl}i_ni_{cal stage} I_{A, 50%}

as I_{B, and 16.3% as} II_{B. The concordance between cl}i_ni_{cal and patholog}i_{cal stag}i_{ng was 67.5% for stage} I_{A, 54.3% for} I_{B, and 66.6% for} II_{B. The accuracy of the cl}i_ni_{cal stag}i_{ng was greater for stage} I_{A, and a kappa of 0.74,} i_{n th}i_{s case, conf}i_{rmed a substant}i_{al assoc}i_ati_{on w}i_th

pathologi_{cal stag}i_{ng. The d}i_ffi_culty i_{n evaluat}i_{ng nodal metastat}i_{c d}i_sease i_{s respons}i_{ble for the low concordance} i_{n pat}i_{ents w}i_{th cl}i_ni_cal

stage I_B. Conclusions: The concordance between cli_ni_{cal and patholog}i_{cal stag}i_ng i_{s low, and pat}i_{ents are frequently understaged (}i_{n the}

present study, only one case was overstaged). Strategi_{es are necessary to} i_{mprove cl}i_ni_{cal stag}i_{ng and, consequently, the treatment and}

prognosi_{s of pat}i_{ents w}i_{th non-small cell lung cancer.}

neoplasti_{c d}i_{sease and for whom surgery} i_{s not} i_ndi_cated.

The objecti_{ve of th}i_{s study was to determ}i_ne

the concordance between CS and PS, i_{n add}i_ti_{on to} i_denti_fyi_{ng the causal factors that lead to d}i

scord-ance between them.

Methods

Between January of 2002 and January of 2006, 125 pati_{ents, all of whom were d}i_{agnosed w}i_th

NSCLC vi_{a f}i_beropti_{c bronchoscopy, percutaneous}

puncture, thoracoscopy, or i_ntraoperati_{ve b}i_opsy,

underwent surgi_{cal treatment} i_{n the Department}

of Thoraci_{c Surgery of the Pontifícia Universidade}

Católica do Rio Grande do Sul (PUCRS, Ponti_fi_cal

Catholi_{c Un}i_versi_{ty of R}i_{o Grande do Sul) São}

Lucas Hospi_{tal. Those pat}i_{ents were cl}i_ni_cally

staged by computed tomography (CT) of the chest and abdomen, CT of the skull (i_{n the presence of}

neurologi_{cal symptoms), or bone sc}i_nti_{graphy (}i_n

the presence of related symptoms). Cervi_{cal med}

i-asti_{noscopy was the method used to evaluate the}

paratracheal and subcari_{nal lymph nodes. The}

pati_{ents w}i_{th tumors located} i_{n the left upper lobe}

underwent parasternal medi_asti_{notomy for the}

evaluati_{on of the subaort}i_{c and aortopulmonary}

wi_{ndow stat}i_{ons. Thoracoscopy was used for the} i_nvesti_gati_{on of pleural effus}i_on.

All pati_{ents underwent thoracotomy w}i_th

standard resecti_{on for NSCLC, accord}i_{ng to resp}

i-ratory functi_{on, w}i_{th systemat}i_{c lymph node}

di_ssecti_{on (paratracheal, subcar}i_{nal, and h}i_{lar lymph}

nodes on the ri_{ght s}i_{de; and subaort}i_c,

aortopul-monary wi_{ndow, subcar}i_{nal, and h}i_{lar lymph nodes}

on the left si_{de). The postoperat}i_ve

anatomopatho-logi_{cal analys}i_{s revealed a part}i_{cular PS, wh}i_{ch was}

then compared to the CS i_{n order to} i_denti_{fy where}

there was di_scordance.

There were 92 pati_{ents w}i_{th CS} I _or II_{, data}

collecti_{on be}i_{ng performed retrospect}i_{vely. Pat}i_ents

wi_th i_{ncomplete CS or PS, those w}i_{th h}i_{stology other}

than NSCLC, those wi_{th CS} III _or IV _submi_{tted to}

surgi_{cal treatment, and those subm}i_{tted to}

neoadju-vant therapy were excluded. Thi_{s study was approved}

by the Ethi_cs i_{n Human Research Comm}i_{ttee of the}

PUCRS São Lucas Hospi_tal.

The data related to the pati_{ents were analyzed}

usi_{ng M}i_{crosoft Off}i_{ce Excel 2003, and the stat}i

s-ti_{cal analys}i_{s was performed us}i_{ng the R for}

Introduct

i

_on

Lung cancer i_{s the most common cause of death}

from mali_{gnant neoplas}i_a, i_{n males and females}

ali_{ke. In add}i_ti_on, i_{t accounts for 28% of all cancer}

deaths, and only breast cancer has a hi_gher i_nc

i-dence. There are approxi_{mately 180,000 new cases}

of pulmonary neoplasi_a i_{n the Un}i_{ted States each}

year.(1)

The prognosi_{s of pat}i_{ents w}i_{th pulmonary}

neoplasi_{a depends on early d}i_agnosi_{s and}

accu-rate oncologi_{c stag}i_{ng. The type of treatment used}

di_{ffers accord}i_{ng to the t}i_{me (stage) at wh}i_{ch the}

neoplasi_a i_{s d}i_{agnosed. Therefore,} i_t i_s i_mportant

to i_denti_{fy subgroups of pat}i_{ents w}i_{th the same}

prognosi_{s and def}i_{ne treatment strateg}i_{es for each}

subgroup.

The current stagi_{ng system for non-small cell}

lung cancer (NSCLC) i_{s tumor-node-metastas}i_s

(TNM) stagi_ng,(2) _{which provides only a definition}

of the anatomi_{c extent of the neoplas}i_{a: s}i_ze,

loca-ti_{on, and extent of the pr}i_{mary les}i_{on; presence and}

locati_{on of the locoreg}i_{onal lymph node}

metas-tasi_{s; and system}i_{c metastat}i_{c d}i_{sease. Th}i_{s system} i_{s recogn}i_{zed as hav}i_{ng s}i_gni_fi_{cant l}i_mi_tati_{ons, such}

as that of not consi_deri_{ng cl}i_ni_{cal aspects (}i_ncludi_ng

the general status of the pati_{ent, we}i_{ght loss,}

func-ti_{onal capac}i_{ty, and the h}i_stologi_{c subtype of the}

tumor) or the i_{nfluence of prognost}i_{c factors that}

are pri_mari_{ly b}i_ologi_{cal (such as the mutat}i_on i_{n the}

p53 gene).

From thi_{s results a spec}i_{al problem,}

under-stagi_{ng, wh}i_ch i_{s caused by the l}i_mi_tati_ons i_{n the}

sensi_ti_vi_{ty of the var}i_{ous d}i_agnosti_{c methods used} i_{n the preoperat}i_{ve stag}i_{ng. The stag}i_{ng obta}i_ned

after all tests, i_nvasi_{ve or not, that are performed}

pri_{or to pulmonary resect}i_on i_{s des}i_{gnated cl}i_ni_cal

stagi_{ng (CS). For pat}i_{ents undergo}i_{ng surgery, CS} i_s

confi_{rmed or rev}i_{ewed accord}i_{ng to the operat}i_ve

fi_ndi_{ngs. Patholog}i_{cal stag}i_{ng (PS)} i_{s determ}i_{ned by}

the analysi_{s of the surg}i_{cal sample, and th}i_{s result}

plays an i_{mportant role} i_{n the subsequent}

thera-peuti_{c dec}i_si_ons.

Di_spari_ti_{es between CS and PS occur frequently,}

thus compromi_si_{ng the des}i_{gn of cl}i_ni_{cal stud}i_es

and, more i_{mportantly, the} i_ndi_vi_{dual treatment}

of pati_{ents, s}i_nce i_{nadequate stag}i_{ng can result} i_{n los}i_{ng the benef}i_{t of the neoadjuvant therapy}

left upper lobe i_{n 32.6% of the pat}i_{ents and} i_{n the}

ri_{ght upper lobe} i_{n 27.5% of the pat}i_ents.

Wi_{th regard to CS, 33.7% of the pat}i_{ents were}

classi_fi_{ed as} I_{A, 50% as} I_{B, and 16.3% as} II_B

(Table 2). All pati_{ents class}i_fi_{ed as} II_{B were so}

clas-si_fi_{ed because tomograph}i_{c f}i_ndi_{ngs led to the}

suspi_ci_{on of thorac}i_{c wall or par}i_{etal pleura} i

nva-si_{on, s}i_{nce there were no pat}i_{ents w}i_{th CS} II_B

- T2N1M0.

In relati_{on to CS} I_{A, the concordance between}

CS and PS was 67.5%. There were 4 pati_{ents who}

mi_{grated to PS} I_{B due to v}i_{sceral pleura} i_nvasi_on,

1 who mi_{grated to} II_{A due to the presence of a}

metastati_{c h}i_{lar lymph node, 1 who m}i_{grated to} II_B

due to pari_{etal pleura} i_nvasi_{on, 2 who m}i_{grated to} III_{A due to the presence of metastat}i_{c d}i_sease i_n i_psi_{lateral med}i_asti_{nal lymph node, 1 who m}i_grated

to III_{B because there was another les}i_on i_{n the same}

lobe, and 1 who mi_{grated to} IV _{due to the presence}

of a lesi_on i_{n another lobe.} I_{n the group of pat}i_ents

classi_fi_{ed as CS} I_B, i_{n wh}i_{ch most of the changes}

occurred, the concordance was 54.3%, and there were 12 pati_{ents who m}i_{grated to PS} II_{B, 9 due to}

the presence of pathologi_{cal N1 lymph nodes and the}

remai_ni_{ng 3 due to prev}i_{ously undetected par}i_etal

pleura i_nvasi_{on. However, there were 9 pat}i_{ents who}

mi_{grated to PS} III_{, 8 to stage} III_{A because there was}

metastasi_s i_{n N2 gangl}i_{a and 1 to} III_{B due to the}

presence of another lesi_on i_{n the same lobe.} I_{n the}

group of pati_{ents class}i_fi_{ed as CS} II_{B, the}

concord-ance was 66.6%, and there was 1 pati_{ent who}

mi_{grated to PS} I_{B s}i_{nce no par}i_{etal pleura} i_nvasi_on

was found. Of the remai_ni_{ng pat}i_{ents, 2 m}i_grated

to III_{A (neoplas}i_{a w}i_{th costal} i_nvasi_{on and presence}

of a metastati_{c N1 lymph node), 1 m}i_{grated to} III_B,

agai_{n due to the presence of another les}i_on i_{n the}

lobe resected, and 1 mi_{grated to} I_{V, also due to the}

presence of another lesi_{on, albe}i_t i_{n another lobe}

(Table 2 and Fi_{gure 1).}

A classi_fi_cati_{on of CS} I_{A had a sens}i_ti_vi_{ty of}

100%, speci_fi_ci_{ty of 85%, pos}i_ti_{ve pred}i_cti_{ve value}

of 67%, negati_{ve pred}i_cti_{ve value of 100%, and a}

qui_{te h}i_{gh accuracy (89%). The power of}

concord-ance, calculated usi_{ng the kappa} i_{ndex, was 0.74.}

Sensi_ti_vi_{ty for stage} I_{B was 98%, w}i_{th a low}

speci_fi_ci_{ty of 35%, pos}i_ti_{ve pred}i_cti_{ve value of 66%,}

and negati_{ve pred}i_cti_{ve value of 93%. Accuracy was}

70%, and the kappa i_{ndex was 0.33.}

Fi_{nally, the pat}i_{ents w}i_{th CS} II_{B presented}

low sensi_ti_vi_{ty (43%) and h}i_{gh spec}i_fi_ci_{ty (92%).}

Wi_{ndows software.}(3) _{Sensitivity, specificity, pos}

i-ti_{ve pred}i_cti_{ve value, negat}i_{ve pred}i_cti_{ve value, and}

accuracy were calculated for CS I_{A (T1N0M0), CS} I_{B (T2N0M0), and CS} II_{B (T3N0M0). None of the}

pati_{ents w}i_{th CS} II_{B were found to present T2N1M0}

preoperati_{ve stag}i_{ng. Cohen’s kappa} i_{ndex was used}

to determi_{ne the power of concordance between CS}

and PS i_{n the stages stud}i_ed.(4)

Results

Of the 92 pati_{ents stud}i_{ed, 65 (70.6%) were}

male and 27 (29.4%) were female. The mean age was 63.2 years (medi_{an, 67 years). Table 1 shows}

that pulmonary lobectomy (76.1%) was the surgi_cal

procedure most commonly used, followed by

pneumonectomy, conservati_{ve segmentectomy,}

bi_{lobectomy, and wedge resect}i_{on. The predom}

i-nant hi_stologi_{cal type was adenocarc}i_{noma (}i_{n 38%}

of the cases), followed by epi_dermoi_{d carc}i_{noma (}i_n

33.7%). Most of the neoplasms were located i_{n the}

Table 1 - Characteri_sti_{cs of the pat}i_ents.

n(%) Gender

Male 65 (70.6)

Female 27 (29.4)

Procedures

Lobectomy 70 (76.1)

Segmentectomy 6 (6.5)

Pneumonectomy 9 (9.8)

Bi_lobectomy 5 (5.4)

Wedge resecti_on 2 (2.2)

Hi_stology

Adenocarci_noma 35 (38.0)

Epi_dermoi_{d carc}i_noma 31 (33.7)

Adenosquamous carci_noma 9 (9.8)

Bronchi_{al-alveolar carc}i_noma 3 (3.3)

Large-cell carci_noma 6 (6.5)

Others 8 (8.7)

Si_{te affected}

Ri_{ght upper lobe} 25 (27.2)

Mi_{ddle lobe} 3 (3.3)

Ri_{ght lower lobe} 15 (16.3)

Left upper lobe 30 (32.6)

Left lower lobe 15 (16.3)

to medi_asti_{nal lymph node sampl}i_{ng or d}i_ssecti_on

duri_{ng surgery, and th}i_{s comprom}i_{sed the PS. Most}

pati_{ents rece}i_{ved surg}i_{cal treatment only, and} i_t i_s i_{mportant to emphas}i_{ze that,} i_{n stages} II_, III_{, and} I_{V, no adjuvant treatment was used} i_{n 61, 38, and}

37%, respecti_{vely. It becomes ev}i_{dent that there} i_s

lack of consensus on thi_{s po}i_nt.

In our study, 32.2% of the pati_{ents w}i_{th CS} I_A

were reclassi_fi_{ed as be}i_ng i_{n more advanced stages}

when the PS was analyzed. It i_s i_{mportant to h}i

gh-li_{ght that 6.4% of the pat}i_{ents were reclass}i_fi_ed

as PS II_{, and that, desp}i_{te hav}i_{ng undergone the}

standard treatment for the stage, those pati_ents

clearly have a worse prognosi_{s, as has been}

demon-strated by other researchers.(10) _{However, 12.9% of}

the pati_{ents were found to be} i_{n PS} III _or IV _and, i_{n th}i_{s context, lost the benef}i_{ts of the mult}i_modal

treatment or had no i_ndi_cati_{on for surgery at any}

ti_{me dur}i_{ng treatment. Pat}i_{ents w}i_{th small (T1)}

tumors are hardly ever understaged, and, when thi_s

occurs, the tumors are usually reclassi_fi_{ed as T2 due}

to undi_{agnosed v}i_{sceral pleura} i_nvasi_on i_{n the CS.}

Wi_{th regard to stage} I_{B, the concordance}

between CS and PS was sli_{ghtly lower (approx}i_mately

54%). In thi_{s group, 26% of the pat}i_{ents m}i_grated

to PS II_{B, the ma}i_{n reason for th}i_{s be}i_{ng the}

pres-ence of hi_{lar lymph nodes affected by the d}i_sease,

whereas 19.5% of the pati_{ents m}i_{grated to stages} i_n

whi_{ch surgery was not the f}i_{rst therapeut}i_{c opt}i_on.

Approxi_{mately 43% of the T2 pat}i_{ents were}

reclas-si_fi_{ed as be}i_ng i_{n more advanced stages because}

they presented lymph node metastasi_s i_{n N1 or N2}

stati_{ons. We observe, therefore, a def}i_ci_ency i_{n the}

evaluati_{on of nodal metastat}i_{c d}i_{sease dur}i_{ng CS}

usi_{ng the methods currently ava}i_lable.

The reason why 16.3% of the pati_ents

evalu-ated were classi_fi_{ed as CS} II_{B was the susp}i_ci_{on of}

thoraci_{c wall or par}i_{etal pleura} i_nvasi_{on, and the}

Posi_ti_{ve pred}i_cti_{ve value was 66%, and negat}i_ve

predi_cti_{ve value was 83%, w}i_{th an accuracy of}

80%. Concordance, usi_{ng the kappa} i_{ndex, was 0.41}

(Fi_{gure 2).}

D

i

_scuss

i

_on

The PS i_{s the most} i_{mportant factor} i_{n the}

prog-nosti_{c evaluat}i_{on of pat}i_{ents w}i_{th NSCLC subm}i_tted

to surgi_{cal treatment. As some stud}i_{es have shown,}

the benefi_{ts of the neoadjuvant treatment, espec}i_ally i_{n relat}i_{on to the} i_{ncreased surv}i_{val of pat}i_{ents w}i_th

stage III_{A, the preoperat}i_ve i_denti_fi_cati_{on of th}i_s

subgroup of pati_{ents has acqu}i_{red greater s}i_gni_f

i-cance.(5,6)

The i_{mportance of the preoperat}i_ve i_denti_fi

ca-ti_{on of those pat}i_{ents who,} i_{n the PS, proved to}

belong to stage IV _{should also be stressed, s}i_nce

those pati_{ents d}i_{d not benef}i_{t, at any t}i_{me, from}

the surgi_{cal procedure they were subm}i_{tted to.}(7) _In

thi_{s sense, stud}i_{es that determ}i_{ne the concordance}

between CS and PS are of utmost i_mportance.

However, a cli_ni_{cal patholog}i_{cal compar}i_son i_s

only vali_{d for T and N, s}i_{nce thoracotomy, w}i_{th the}

subsequent analysi_{s of the surg}i_{cal sample, does}

not typi_{cally alter the M factor. In general, what} i_s

found i_{s that th}i_{s concordance deter}i_{orates as T and}

N i_{ncrease. Even w}i_{th an appropr}i_{ate CS, the rate}

of exploratory thoracotomy or i_{ncomplete resect}i_on

ulti_{mately ranges from 8 to 10%.}(8)

Thi_{s object}i_{ve has been g}i_{ven cons}i_derable

wei_{ght, as have and the ref}i_{nement of CS and PS.}

However, one group of authors,(9) _{in a series of}

11,668 pati_{ents subm}i_{tted to surg}i_{cal treatment for}

NSCLC, found that only 27% had been submi_tted

to cervi_{cal med}i_asti_{noscopy and that, of th}i_{s group,}

only 46% had undergone lymph node bi_{opsy. In add}

i-ti_{on, only 60% of the pat}i_{ents had been subm}i_tted

Table 2 - Concordance between cli_ni_{cal and patholog}i_{cal stag}i_ng.

Cli_ni_{cal stag}i_{ng Patholog}i_{cal stag}i_ng % of total Probabi_li_{ty CS = PS}

I_A I_B II_A II_B III_A III_B IV Total

I_{A 21 4 1 1 2 1 1 31 33.7 67.54}

I_B 0 25 0 12 8 1 0 46 50.0 54.34

II_B 0 1 0 10 2 1 1 15 16.3 66.6

Total 21 30 1 23 12 3 2 92 100.0 62.82

I_{A, 51.6% for} I_{B, 48.2% for} II_{B, and 33.3% for} III_A. I_{n the analys}i_{s of the med}i_asti_{nal lymph nodes,}

26% of the pati_{ents were class}i_fi_{ed as present}i_ng

cli_ni_{cal N0, when,} i_{n fact, they were pat}i_{ents w}i_th

pathologi_{cal N2. Nevertheless,} i_{n the subgroup of}

pati_{ents w}i_{th patholog}i_{cal N2, 46.3% were found}

to have been correctly staged, and, of those, only 3 had been submi_{tted to preoperat}i_{ve cerv}i_cal

medi_asti_noscopy.

Other researchers,(13) _{by means of a prospective}

analysi_{s of the}i_{r pat}i_{ents us}i_{ng chest CT, found that}

the concordance between CS and PS was 66% for stage I_{, 82% for stage} II_{, and 69% for stage} III_.

The benefi_{ts of h}i_{ghly accurate stag}i_ng i_n

defi_ni_{ng prognos}i_{s should always be emphas}i_zed,

si_{nce the most appropr}i_{ate therapy for the pat}i_ent i_{s thereby determ}i_{ned. In th}i_{s sense, the evaluat}i_on

of the nodal extent of the NSCLC plays an i

mpor-tant role. The removal of all medi_asti_{nal lymph}

nodes allows the extent of the di_{sease to be}

evalu-ated wi_{th h}i_{gh accuracy, as well as be}i_{ng assoc}i_ated

wi_{th lower recurrence and better surv}i_{val, s}i_nce i_t

provi_{des the appropr}i_{ate PS.}(14)

In the study of nodal metastati_{c d}i_sease, i_ts

presence i_{n the h}i_{lar groups has been h}i_ghli_{ghted as}

another factor wi_{th prognost}i_c i_{mportance, show}i_ng

that the group of N1 pati_ents i_{s heterogeneous. The} i_{nvolvement of the h}i_{lar groups} i_{s assoc}i_{ated w}i_th

a 39% fi_{ve-year surv}i_{val, be}i_{ng s}i_gni_fi_{cantly lower} i_{f compared to the} i_{nvolvement of the} i_nterlobar,

lobar, and segmental groups.(15) _{Some authors}(16)

have also demonstrated that the prognosi_s i_{s better}

for pati_ents i_{n whom the lobar N1 was resected}

than for those i_{n whom the h}i_{lar N1 was resected.}

As currently performed, CS has i_{ts problems. In}

general, the li_mi_tati_{ons of chest CT and those of}

cervi_{cal med}i_asti_{noscopy ult}i_{mately contr}i_{bute to}

decreasi_{ng the accuracy of CS. The concordance}

between CS and PS i_{n the evaluat}i_{on of metastat}i_c

di_sease i_{n med}i_asti_{nal lymph nodes us}i_{ng chest CT} i_{s low, w}i_{th a false pos}i_ti_{ve rate of 44% and a false}

negati_{ve rate of 17%.}(17) _{Cervical mediatinoscopy,}

despi_{te hav}i_{ng advantages over chest CT, s}i_nce i_t

determi_{nes the presence of N1 or N3 and prov}i_des

hi_stologi_{cal d}i_agnosi_{s, has} i_{ts range restr}i_{cted to}

the upper lymph node groups and does not fully approach the subcari_{nal stat}i_on,(18) _{as well as having}

ri_{sks and accompany}i_{ng compl}i_cati_{ons. Therefore,}

new procedures have helped to opti_mi_{ze CS.}

concordance between CS and PS was 66.6%, whi_ch

reflects, i_{n our study, the prec}i_si_{on of chest CT} i_n i_denti_fyi_{ng th}i_s i_mpai_{rment. Here, the loss of the}

benefi_{ts of the neoadjuvant therapy or even the}

absence of surgi_cal i_ndi_cati_{on occurred} i_{n 26.6% of}

the cases due to the mi_grati_{on of pat}i_{ents to stages} III_A, III_{B, or} IV_{B. There was only one pat}i_{ent who}

was downstaged, bei_{ng reclass}i_fi_{ed as} I_{B. The kappa} i_{ndex shows that the concordance for CS} I_{A (0.74)}

was much better than that found for CS I_{B (0.33).}

Typi_{cally, concordance decreases as CS} i_{ncreases. In}

our study, the kappa for stage II_{B was greater than}

that for stage I_{B, probably because the former only}

evaluates the T factor, si_{nce there were no pat}i_ents

presenti_{ng CS} II_{B - T2N1M0.}

The relati_{vely low pos}i_ti_{ve pred}i_cti_{ve values}

and the relati_{vely h}i_{gh negat}i_{ve pred}i_cti_{ve values}

found corroborate the results of other studi_{es and}

demonstrate that CS typi_{cally understages pat}i_ents,

rarely overstagi_{ng them. On group of authors,}(11)_in

a study of 2994 pati_{ents w}i_{th pulmonary neoplas}i_a

submi_{tted to surg}i_{cal treatment, found a}

concord-ance of 75% for stages I_{A and} I_{B and of 23.5%}

for stage II_{B, although,} i_{n that study, the pat}i_ents

were submi_{tted to cerv}i_{cal med}i_asti_{noscopy only} i_n

the presence of lymph nodes greater than 1 cm i_n

di_ameter.

Another group of authors,(12) _{by means of a}

retrospecti_{ve analys}i_{s of 180 pat}i_{ents w}i_{th NSCLC}

submi_{tted to surg}i_{cal treatment between 1994}

and 2000, i_{n whom cerv}i_{cal med}i_asti_{noscopy was}

performed only i_{n the presence of lymph nodes}

greater than 1 cm i_{n d}i_{ameter, found that the}

concordance between CS and PS was 77% for stage

0 5 10 15 20 25 30 35 40 45 50

I_A I_B II_A II_B III_A III_B IV

EC EP

Fi_{gure 1 - Results of the compar}i_{son between cl}i_ni_cal

the presence of medi_asti_{nal lymph node metastas}i_s i_{n 42% of the pat}i_ents i_{n whom chest CT f}i_ndi_ngs

were normal.

Endoscopi_{c ultrasonography, a procedure that}

has been i_ntroduced i_{n the evaluat}i_{on of pat}i_ents

wi_{th pulmonary neoplas}i_{a, has contr}i_{buted to better}

CS evaluati_{on. It can v}i_suali_{ze the layers of the}

trachea and bronchii_{n deta}i_{l, thereby d}i_sti_ngui_shi_ng

neoplasti_c i_nvasi_{on from extr}i_nsi_{c compress}i_{on, as}

well as maki_ng i_{t poss}i_{ble to evaluate the}

rela-ti_onshi_{p between extralum}i_{nal pulmonary les}i_ons

and adjacent vessels. It can also faci_li_{tate b}i_opsy

of medi_asti_{nal and h}i_{lar lymph nodes as well as of}

parenchymal lesi_ons.(22)

Thoracoscopy has been used i_{n order to} i_ncrease

CS accuracy. One group of authors,(23) _analyzing

pati_{ents w}i_{th negat}i_{ve cerv}i_{cal med}i_asti_noscopy

results whose T and N were evaluated wi_{th the a}i_d

of thoracoscopy, through pleural lavage cytology, i_n

addi_ti_{on to b}i_{opsy of paraesophageal lymph node}

groups and of the pulmonary li_gament i_{n tumors}

located i_{n lower lobes (when poss}i_{ble, b}i_{opsy of the} i_{nterlobar or} i_{ntersegmental groups was performed,}

and the subcari_{nal and paratracheal lymph nodes}

were only sampled i_{f they had a patholog}i_{cal aspect),}

found that thoracoscopy presented no compli

ca-ti_{ons, be}i_{ng cons}i_{dered more accurate than chest CT}

si_nce i_{t staged 88% of the cases correctly, compared}

wi_{th 42% for CT. Its greatest benef}i_{t was stag}i_ng

the factor T correctly i_{n 96% of the cases.}

The factor N was staged correctly i_{n 74% of the}

cases, reveali_{ng metastat}i_{c d}i_sease i_{n paraesophageal}

and pulmonary li_{gament lymph nodes} i_{n pat}i_ents

wi_{th negat}i_{ve cerv}i_{cal med}i_asti_{noscopy results.}

Despi_{te the l}i_mi_tati_{on of thoracoscopy} i_{n relat}i_on

to the evaluati_{on of the aortopulmonary w}i_ndow i_{n pat}i_{ents w}i_{th large les}i_ons i_{n the left upper lobe,} i_{t was found that} i_{t can} i_denti_{fy mal}i_{gnant pleural}

effusi_{on that} i_{s too small for v}i_suali_zati_{on on chest}

CT, evaluate thoraci_{c wall} i_nvasi_on, i_{n add}i_ti_{on to}

sampli_{ng poster}i_{or subcar}i_{nal lymph nodes, as well}

as pulmonary li_{gament and paraesophageal lymph}

nodes, whi_ch i_{s very} i_mportant i_{n pat}i_{ents w}i_th

negati_{ve cerv}i_{cal med}i_asti_{noscopy results.}

Consi_deri_{ng the mean d}i_{fference of 35%}

between CS and PS, i_t i_{s very d}i_ffi_{cult to compare}

a study that uses CS to one that uses PS. It i_s

always i_{mportant to remember that each} i_nvasi_ve

stagi_{ng method has the potent}i_{al to better evaluate}

di_{fferent lymph node stat}i_{ons. It} i_{s essent}i_{al that}

Posi_{tron em}i_ssi_{on tomography (PET) scan,}

due to i_{ts capac}i_{ty of detect}i_{ng areas w}i_{th greater}

metaboli_{c act}i_vi_ty i_{n the human body,} i_{n add}

i-ti_{on to help}i_{ng d}i_fferenti_{ate between mal}i_gnant

and beni_{gn pulmonary nodules, has also allowed}

better selecti_{on of pat}i_{ents for surg}i_{cal treatment,} i_mprovi_{ng CS, s}i_nce i_{t has h}i_{gher accuracy to}

eval-uate medi_asti_{nal lymph nodes than does chest CT,}

especi_ally i_{n relat}i_{on to spec}i_fi_{c lymph node groups}

such as those of the subaorti_{c, aortopulmonary}

wi_{ndow, and subcar}i_{nal stat}i_ons.(19) _{The PET scan}

does not replace medi_asti_{nal lymph node b}i_opsy,

and surgi_{cal treatment should not be den}i_{ed to any}

pati_{ent based exclus}i_{vely on th}i_{s test. However,} i_ts

si_gni_fi_{cance l}i_es i_{n select}i_{ng areas to be sampled,}

and thi_{s often leads to the} i_denti_fi_cati_{on of lymph}

node di_{sease that was prev}i_{ously unsuspected.}

Another testi_{ng modal}i_{ty that has part}i_ci_pated i_{n th}i_{s sense} i_{s endoscop}i_{c endosonography w}i_th

fi_{ne-needle asp}i_rati_{on. Through the esophagus,}

an echoendoscope i_{s used to access the poster}i_or

medi_asti_{num and adjacent lymph nodes}

(aortop-ulmonary wi_{ndow, subcar}i_{nal, paraesophageal,}

and pulmonary li_{gament lymph nodes), sampl}i_ng

these stati_{ons. It} i_{s a safe method of evaluat}i_ng

the stati_{ons c}i_{ted above, w}i_{th an accuracy of 97%,}

avoi_di_{ng exploratory procedures} i_{n approx}i_mately

57% of the pati_ents,(20) _{a percentage that is greater}

than that achi_{eved through chest CT or PET scan.}

Usi_{ngh th}i_{s test, one group of researchers}(21) _found

0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1

Sens itivi

ty

Specifi city

Positi ve pre

dicti ve v

alue

Nega tive

predi ctive

value Accu

racy Kappa

CS I_{A CS} I_{B CS} II_B

Fi_{gure 2 - Stat}i_sti_{cal evaluat}i_{on of the cl}i_ni_{cal stag}i_ng

6. Albain KS, Rusch VW, Crowley JJ, Rice TW, Turrisi AT 3rd, Weick JK, et al. Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group phase II study 8805. J Clin Oncol. 1995;13(8):1880-92.

7. Spira A, Ettinger DS. Multidisciplinary management of lung cancer.N Engl J Med. 2004;350(4):379-92.

8. Deslauriers J, Gregoire J. Clinical and surgical staging of non-small cell lung cancer. Chest. 2000;117(4 Suppl 1):S96-S103.

9. Little AG, Rusch VW, Bonner JA, Gaspar LE, Green MR, Webb WR, et al. Patterns of surgical care of lung cancer patients. Ann Thorac Surg. 2005;80(6):2051-6; discussion 2056. 10. Naruke T, Tsuchiya R, Kondo H, Asamura H. Prognosis and

survival after resection for bronchogenic carcinoma based on the 1997 TNM-staging classification: the Japanese experience. Ann Thorac Surg. 2001;71(6):1759-64. 11. López-Encuentra A, García-Luján R, Rivas JJ,

Rodríguez-Rodríguez J, Torres-Lanza J, Varela-Simo G, et al. Comparison between clinical and pathologic staging in 2,994 cases of lung cancer. Ann Thorac Surg. 2005;79(3):974-9; discussion 979.

12. Cetinkaya E, Turna A, Yildiz P, Dodurgali R, Bedirhan MA, Gürses A, et al. Comparison of clinical and surgical-pathologic staging of the patients with non-small cell lung carcinoma. Eur J Cardiothorac Surg. 2002;22(6):1000-5. 13. Cerfolio RJ, Bryant AS, Ojha B, Eloubeidi M. Improving the

inaccuracies of clinical staging of patients with NSCLC: a prospective trial. Ann Thorac Surg. 2005;80(4):1207-13; discussion 1213-4.

14. Moskovitz AH, Rusch VW. Resection and mediastinal lymph node dissection. Op Tech Thorac Cardiovasc Surg. 2005;10(2):166-77.

15. Tanaka F, Yanagihara K, Otake Y, Yamada T, Shoji T, Miyahara R, et al. Prognostic factors in patients with resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC). Eur J Cardiothorac Surg. 2001;19(5):555-61. 16. Yano T, Yokoyama H, Inoue T, Asoh H, Tayama K, Ichinose

Y. Surgical results and prognostic factors of pathologic N1 disease in non-small-cell carcinoma of the lung. Significance of N1 level: lobar or hilar nodes. J Thorac Cardiovasc Surg. 1994;107(6):1398-402.

17. Toloza EM, Harpole L, McCrory DC. Noninvasive staging of non-small cell lung cancer: a review of the current evidence. Chest. 2003;123(1 Suppl):S137-S46.

18. Hoffmann H. Invasive staging of lung cancer by mediastinoscopy and video-assisted thoracoscopy. Lung Cancer. 2001;34(Suppl 3):S3-S5.

19. Cerfolio RJ, Ojha B, Bryant AS, Bass CS, Bartalucci AA, Mountz JM. The role of FDG-PET scan in staging patients with nonsmall cell carcinoma. Ann Thorac Surg. 2003;76(3):861-6.

20. Eloubeidi MA, Cerfolio RJ, Chen VK, Desmond R, Syed S, Ojha B. Endoscopic ultrasound-guided fine needle aspiration of mediastinal lymph node in patients with suspected lung cancer after positron emission tomography and computed tomography scans. Ann Thorac Surg. 2005;79(1):263-8. 21. Wallace MB, Silvestri GA, Sahai AV, Hawes RH, Hoffman BJ,

Durkalski V, et al. Endoscopic ultrasound-guided fine needle aspiration for staging patients with carcinoma of the lung. Ann Thorac Surg. 2001;72(6):1861-7.

these methods be used i_{n conjunct}i_on i_{n order to}

achi_{eve greater concordance between CS and PS.}

For i_deal i_ntrathoraci_{c stag}i_{ng, we suggest the}

followi_{ng measures:}

1) a better defi_ni_ti_{on of tomograph}i_{c cr}i_teri_{a for}

the presence of pathologi_{cal N1 lymph nodes}

and vi_{sceral pleura} i_nvasi_on;

2) performance of cervi_{cal med}i_asti_noscopy i_n

all pati_{ents, even} i_{n those whose}

preopera-ti_{ve tests show no med}i_asti_{nal adenopathy,}

as well as systemati_{c evaluat}i_{on of the}

parat-racheal and subcari_{nal stat}i_{ons; and}

3) performance of thoracoscopy also i_{n all}

pati_{ents for the evaluat}i_{on of the par}

i-etal and vi_{sceral pleurae, as well as for the}

evaluati_{on of the subcar}i_{nal lymph nodes,}

especi_{ally when they are not access}i_ble

through cervi_{cal med}i_asti_noscopy, i_{n add}

i-ti_{on to the paraesophageal group and the}

pulmonary li_gament.

In the present study, the concordance between CS and PS was substanti_{al for stage} I_{A, decreas}i_ng

for I_{B and} II_{B. The pat}i_{ents were understaged,}

except i_{n one case,} i_{n wh}i_{ch the pat}i_{ent was}

over-staged. The mai_{n source of d}i_{scordance was the}

di_ffi_culty i_{n the preoperat}i_{ve evaluat}i_{on of}

meta-stati_{c lymph node} i_{nvolvement. It} i_{s necessary that}

tomographi_{c cr}i_teri_{a for N1 be def}i_{ned and that}

stagi_{ng us}i_{ng surg}i_{cal methods be systemat}i_cally i_ndi_cated i_{n order to} i_{ncrease CS y}i_{eld. Therefore,}

we expect to opti_mi_{ze the treatment and} i_mprove

the prognosi_{s of pat}i_{ents w}i_{th NSCLC.}

Referênc

i

_as

1. Schneider A, Schwartzmann G. Tratamento cirúrgico do carcinoma brônquico. In: Pinto Filho DR, Cardoso PFG, Figueiredo Pinto JAL, Schneider A, editors. Manual de cirurgia torácica. Rio de Janeiro: Editora Revinter, 2001. p. 245-6.

2. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest. 1997;111(6):1710-7.

3. R-project [homepage on Internet]. Vienna: The R Project for Statistical Computing, c2006. [cited 2006 Nov 09]. Available from: http://www.r-project.org

4. Fleiss LJ, Levin B, Paik MC, editors. Statistical methods for rates and proportions. 2nd ed. New York, NY: John Wiley and Sons, Inc.; 1981. p 218.

23. Roberts JR, Blum MG, Arildsen R, Drinkwater DC Jr, Christian KR, Powers TA, et al. Prospective comparison of radiologic, thoracoscopic, and pathologic staging in patients with early non-small cell lung cancer. Ann Thorac Surg. 1999;68(4):1154-8.