Is The Surgical Treatment for Patients with Advanced Lung Cancer beneficial? Pro and Con

April 27, 2007, AntalyaApril 27, 2007, Antalya 11

Is The Surgical Treatment for Is The Surgical Treatment for Patients with Advanced Lung Cancer Patients with Advanced Lung Cancer

beneficial?beneficial?ProPro and Conand Con

Ufuk Yilmaz M.D. Ufuk Yilmaz M.D. Suat Seren Chest Disease and Surgery Training and research Suat Seren Chest Disease and Surgery Training and research

Hospital, Izmir Hospital, Izmir

April 27, 2007, Antalya 2

► In patients with suspected NSCLC;In patients with suspected NSCLC;

The initial evaluation includes both the The initial evaluation includes both the diagnosis of the primary tumor and the diagnosis of the primary tumor and the determination of the extent of tumor spread determination of the extent of tumor spread to regional and distant lymph nodes as well to regional and distant lymph nodes as well as to other structuresas to other structures


► The accurate staging of NSCLC is central to The accurate staging of NSCLC is central to determining the appropriate stage determining the appropriate stage dependent therapeutic choices.dependent therapeutic choices.


► Almost all patients with stage IV non-small Almost all patients with stage IV non-small cell lung cancer (NSCLC) have diffusely cell lung cancer (NSCLC) have diffusely metastatic disease, and therefore, the metastatic disease, and therefore, the standard of care for NSCLC is standard of care for NSCLC is chemotherapy or palliative care. chemotherapy or palliative care.

► These patients are usually considered These patients are usually considered unsuitable for surgery with curative intentunsuitable for surgery with curative intent..


Big QuestionBig Question

►Does these patients be sutiable for curative Does these patients be sutiable for curative surgery?surgery?


Answers, which one?Answers, which one?

►No ?No ?

► Yes ?Yes ?


My answerMy answer

►No No ►These patients does not be sutiable These patients does not be sutiable

for curative surgery.for curative surgery.


►Why no?Why no?


Quality of the evidenceQuality of the evidence

Good = evidence based on good randomized controlled Good = evidence based on good randomized controlled trials or meta-analyses trials or meta-analyses

Fair = evidence based on other controlled trials or Fair = evidence based on other controlled trials or randomized controlled trials with minor flaws randomized controlled trials with minor flaws

Low = evidence based on nonrandomized, case-control, or Low = evidence based on nonrandomized, case-control, or other observational studies other observational studies

Expert opinion = evidence based on the consensus of the Expert opinion = evidence based on the consensus of the carefully selected panel of experts in the topic field. There carefully selected panel of experts in the topic field. There are no studies that meet the criteria for inclusion in the are no studies that meet the criteria for inclusion in the literature review. literature review.


Pitfalls in the interpretation of data Pitfalls in the interpretation of data regarding to the treatment regarding to the treatment

The number of patients studiedThe number of patients studied

Retrospective trialRetrospective trial

BiasBias

Heterogeneous patient Heterogeneous patient populationspopulations

No randomizationNo randomization


From an oncological point of From an oncological point of viewview

► The potential benefit from metastasectomy The potential benefit from metastasectomy and and

Detailed tumor evaluation Detailed tumor evaluation

Distant spread of the primary tumorDistant spread of the primary tumor

The resectability of the metastasesThe resectability of the metastases

The resectability of the primary The resectability of the primary tumortumor

The nodal involvement status The nodal involvement status


► Isolated metastasisIsolated metastasis► Solitary metastasisSolitary metastasis► Soliter metastasisSoliter metastasis►OligometastasisOligometastasis► Single hematogenous distant metastasisSingle hematogenous distant metastasis


To detect of the solitary To detect of the solitary metastasismetastasis(1)(1)

► The FN rate of the clinical evaluation in cI-II The FN rate of the clinical evaluation in cI-II NSCLC pts is <5%NSCLC pts is <5%

► The FN rate of clinical evaluation for pts that The FN rate of clinical evaluation for pts that include cIII NSLC is include cIII NSLC is ~~15-30%15-30%



► The FN rate of a contrast-enhanced brain CT The FN rate of a contrast-enhanced brain CT for metastases in NSCLC pts is <10%for metastases in NSCLC pts is <10%

► The FN rate of a bone scaning for The FN rate of a bone scaning for metastases in NSCLC pts is metastases in NSCLC pts is ~~ 4-6% 4-6%

► The FN rate of a contrast-enhanced liver CT The FN rate of a contrast-enhanced liver CT for metastases in NSCLC pts is <10%for metastases in NSCLC pts is <10%



► The FN rate of the PET scaning for The FN rate of the PET scaning for metastases in NSCLC pts is <8%metastases in NSCLC pts is <8%



► Monoclonal antibodies to epithelial markers Monoclonal antibodies to epithelial markers expressed in cancer cells have shown that occult expressed in cancer cells have shown that occult tumor cells are often present in distant sites, even tumor cells are often present in distant sites, even though they cannot be seen using conventional though they cannot be seen using conventional microscopy.microscopy.

► Occult metastasis has correlated with worse Occult metastasis has correlated with worse disease-free survival and a higher rate of recurrens.disease-free survival and a higher rate of recurrens.


Most common sites of exthrathoracic Most common sites of exthrathoracic metastases in NSCLCmetastases in NSCLC

►Brain, bone, liver, adrenal glandsBrain, bone, liver, adrenal glands

►Lung, plevra, subcutaneous tissueLung, plevra, subcutaneous tissue


Liver metastases from lung cancer:is surgical Liver metastases from lung cancer:is surgical resection justified ?resection justified ?

I. Di Carlo . Ann Thorac Surg I. Di Carlo . Ann Thorac Surg 20032003; 76: 291-3.; 76: 291-3.

► Resection of the liver for metastatic lesions Resection of the liver for metastatic lesions has largely been done for secondary has largely been done for secondary colorectal or neuroendocrine tumors, colorectal or neuroendocrine tumors,

► Should it be considered whenever there is Should it be considered whenever there is an isolated lesion.an isolated lesion.

► A successful resection of an isolated A successful resection of an isolated secondary hepatic lesion from a lung secondary hepatic lesion from a lung primary tumor, which wasprimary tumor, which was resected resected approximately 4 years beforehand approximately 4 years beforehand


Isolated solitary splenic metastasis of a pulmonary tumor: a successful

surgicapproach in one stage A. Şanlı ve ark. Türk Göğüs Kalp Damar Cerrahisi DergisiA. Şanlı ve ark. Türk Göğüs Kalp Damar Cerrahisi Dergisi 2006 2006; 14: 73-5.; 14: 73-5.

► T3N0M1 Lung adenocarcinoma, 64 years-oldT3N0M1 Lung adenocarcinoma, 64 years-old

► Left posterolateral thoracotomy + Phrenotomy ,chest Left posterolateral thoracotomy + Phrenotomy ,chest wall resection , left pneumonectomy ve splenectomy .wall resection , left pneumonectomy ve splenectomy .

► Adjuvant chemotherapyAdjuvant chemotherapy

► SSurgical approach in one stageurgical approach in one stage


►The prognosis of the pts with brain The prognosis of the pts with brain metastasis is poor.metastasis is poor.

►The results of surgical treatment of The results of surgical treatment of synchronous brain metastases along synchronous brain metastases along with the primary tumor is controversialwith the primary tumor is controversial


Survival results of surgical resection of brain Survival results of surgical resection of brain metastases and primary tumor metastases and primary tumor

(retrospective studies)(retrospective studies)

NoNo % op % op MortalitMortalityy

MST(m)MST(m) 2y (%)2y (%) 5y (%)5y (%)

MussiMussi 1515 00 1818 -- 6.66.6

MagillianMagillian 4141 22 1313 3131 2121

RossiRossi 4040 22 -- 2525 1313

TorreTorre 2121 00 1313 3535 1010

BonnetteBonnette 103103 22 1212 2828 1111

HoseckHoseck 1212 00 6.26.2 -- --

ChidelChidel 1313 -- 2020 -- --

GranoneGranone 2020 00 2323 4747 14*14*

BillingBilling 2828 00 2424 5454 2121


Prognostic factors pts with NSCLC with syncronous, Prognostic factors pts with NSCLC with syncronous, isolated brain metastases undergoing combined isolated brain metastases undergoing combined

surgical treatmentsurgical treatment

Pts noPts no HistologyHistology N N T T R0(P)R0(P)

Mussi (1996)Mussi (1996) 1212 Y(SCC)Y(SCC) __ __ __

Granone(1989-99)Granone(1989-99) 2020 Y(Adeno)Y(Adeno) YY NN __

Billing (1975-97)Billing (1975-97) 2828 __ YY __ __

Torre (1975-87)Torre (1975-87) 2121 __ YY __ __

Getman (1994-99)Getman (1994-99) 16 16 NN NN NN __

Burt (1992)Burt (1992) 3232 __ NN NN YY

Bonette (1985-98)Bonette (1985-98) 103103 Y(Adeno)Y(Adeno) NN NN NN


Surgical treatment of solitary adrenal metastasis from Surgical treatment of solitary adrenal metastasis from NSCLCNSCLC

O. Mercier.O. Mercier.J Thorac Cardiovasc SurgJ Thorac Cardiovasc Surg 2005;130:136-140 2005;130:136-140

► 1989 - 2003, 23 patients ( synchronous in 6 pts , 1989 - 2003, 23 patients ( synchronous in 6 pts , metachronous in 17 pts. metachronous in 17 pts.

► The overall 5-year survival was 23.3% The overall 5-year survival was 23.3%

► All patients with a disease-free interval of less than 6 months All patients with a disease-free interval of less than 6 months died within 2 years of the operation. died within 2 years of the operation.

► Surgical resection of metachronous isolated adrenal Surgical resection of metachronous isolated adrenal metastasis with a DFI of greater than 6 months can provide metastasis with a DFI of greater than 6 months can provide long-term survival in patients previously undergoing complete long-term survival in patients previously undergoing complete resection of the primary NSCLC. resection of the primary NSCLC.


Surgical treatment of solitary adrenal metastasis from Surgical treatment of solitary adrenal metastasis from NSCLC NSCLC H. PorteH. Porte Ann Thorac Surg 2001;71:981-985Ann Thorac Surg 2001;71:981-985

► 43 pts ; 32 synchronously 43 pts ; 32 synchronously ► Median survival was 11 months, and 3 patients Median survival was 11 months, and 3 patients

survived more than 5 years survived more than 5 years

► Survival was not affected by the histology of the Survival was not affected by the histology of the NSCLC, TNM stage, any adjuvant and neoadjuvant NSCLC, TNM stage, any adjuvant and neoadjuvant treatment treatment

► No clinical or pathologic criteria were detected to No clinical or pathologic criteria were detected to identify patients amenable to potential cure. identify patients amenable to potential cure.


Adrenalectomy for solitary adrenal metastases Adrenalectomy for solitary adrenal metastases from NSCLC.from NSCLC. Pfannschmidt J. Lung Cancer 2005;49(2):203Pfannschmidt J. Lung Cancer 2005;49(2):203

► Between 1997 and 2000,Between 1997 and 2000,► 11 pts (11 pts (methacronous -6 pts-, Synchronous-5 pts-methacronous -6 pts-, Synchronous-5 pts-))► Pts with synchronous adrenal metastases Pts with synchronous adrenal metastases

MST; 10.3 m.MST; 10.3 m.


Resected solitary adrenal metastasis from Resected solitary adrenal metastasis from non-small cell lung cancer.non-small cell lung cancer. Aranguren D. Lung Cancer Aranguren D. Lung Cancer

2005;49(2) S2:2342005;49(2) S2:234

► 1984 to 20041984 to 2004► 31 pts (14 synchronously)31 pts (14 synchronously)► R0; a median TTP of 7m, and a MST of 15 m.R0; a median TTP of 7m, and a MST of 15 m.►Non-R0; TTP of 3m, and a MST of 12 m.Non-R0; TTP of 3m, and a MST of 12 m.► 7 (37%) resected pts alive at 3 years (4 7 (37%) resected pts alive at 3 years (4

synch, 3 meta)synch, 3 meta)


Pulmonary MetastasesPulmonary Metastases

► The 1997 staging system classifies a The 1997 staging system classifies a satellite nodule of cancer that is within the satellite nodule of cancer that is within the same lobe as the primary tumor as T4(stage same lobe as the primary tumor as T4(stage IIIb), and additional foci of cancer in IIIb), and additional foci of cancer in different lobes as M1 (stage IV)different lobes as M1 (stage IV)


Pulmonary MetastasesPulmonary Metastases

► The classification of pulmonary metastases The classification of pulmonary metastases is difficult because of the existence of is difficult because of the existence of several factors that appear to influence several factors that appear to influence patient outcome.patient outcome.

-Pts with bronchioalveolar cancers-Pts with bronchioalveolar cancers

-Pts with same-lobe satellite nodules-Pts with same-lobe satellite nodules


Survival following resection of a primary lung Survival following resection of a primary lung cancer and a pulmonary metastasis cancer and a pulmonary metastasis

Detterbeck FC.Lung Cancer. An evidence-based guide for the practicing clinicianDetterbeck FC.Lung Cancer. An evidence-based guide for the practicing clinician

NN % adeno% adeno % BAC% BAC % SLSN% SLSN % 5-year% 5-year

NarukeNaruke 146146 6868 __ 6161 88

DeslauriesDeslauries 8484 2525 55 8181 2222

NakajimaNakajima 5050 8484 5858 9494 3030

WatanabeWatanabe 4949 5656 __ __ 2222

YanoYano 4747 6262 __ 8383 3333

SuzukiSuzuki 4646 100100 MostMost 100100 3636

YoshinoYoshino 4242 7474 __ __ 2424

ShimizuShimizu 4242 6767 __ 8888 2626

FukuseFukuse 4141 6666 __ 4949 2626


Survival following resection of a primary lung Survival following resection of a primary lung cancer and a pulmonary metastasis cancer and a pulmonary metastasis

Detterbeck FC.Lung Cancer. An evidence-based guide for the practicing clinicianDetterbeck FC.Lung Cancer. An evidence-based guide for the practicing clinician

► Yano et al Yano et al ;; 8 pts , 5-year survival 0%8 pts , 5-year survival 0%► Shimizu et alShimizu et al ;; 5 pts, 5-year survival 20%5 pts, 5-year survival 20%► Fukuse et al Fukuse et al ;; 21 pts, 3-year survival 21 pts, 3-year survival

21%21%► Naruke et al Naruke et al ;; 57 pts , 5-year survival 57 pts , 5-year survival

5%5%


Prolonged survival after extracranial metastasectomy from Prolonged survival after extracranial metastasectomy from synchronous resectable lung cancersynchronous resectable lung cancer

V. Ambrogi Ann of Surg Oncology 2001:8;663V. Ambrogi Ann of Surg Oncology 2001:8;663

► 9 pts with NSCLC with synchronous, 9 pts with NSCLC with synchronous, solitarymetastasis: adrenal (5), cutaneous (2), solitarymetastasis: adrenal (5), cutaneous (2), axillary lymph node (1),kidney (1). axillary lymph node (1),kidney (1).

► 5-year survival rate was 55.6%. Five patients who 5-year survival rate was 55.6%. Five patients who had adrenal (3), or skin (1), or axillary (1) had adrenal (3), or skin (1), or axillary (1) metastases, survived more than 5 years. All N2 metastases, survived more than 5 years. All N2 patients (n = 2) died.patients (n = 2) died.

► Unexpected, prolonged survival was demonstrated Unexpected, prolonged survival was demonstrated in our limited series in our limited series


Oligometastatic NSCLC: A Multidisciplinary Approach Oligometastatic NSCLC: A Multidisciplinary Approach in the PET Scanin the PET Scan EraEra

T. M. De Pas, Ann Thorac Surg 2007;83:231-234T. M. De Pas, Ann Thorac Surg 2007;83:231-234

► Analyzed the data from 1509 pts who Analyzed the data from 1509 pts who underwent surgical procedures for a primary underwent surgical procedures for a primary NSCLC from 2000 to 2005 , after a work-up NSCLC from 2000 to 2005 , after a work-up that included a PET scan.that included a PET scan.

► Ten pts (0.7%) exhibited a solitary Ten pts (0.7%) exhibited a solitary hematogenous metastasis.hematogenous metastasis.


Oligometastatic NSCLC: A Multidisciplinary Approach Oligometastatic NSCLC: A Multidisciplinary Approach in the PET Scanin the PET Scan EraEra


► The data from 1,509 pts who underwent surgical procedıres The data from 1,509 pts who underwent surgical procedıres for a primary NSCLC, after a workup that included a PET scanfor a primary NSCLC, after a workup that included a PET scan

► 10 pts (0.7%) . The median overall survival was 26 months, 10 pts (0.7%) . The median overall survival was 26 months, and the median time to progression was 20 months; 6 and the median time to progression was 20 months; 6 patients were alive at the time of analysis, with a median patients were alive at the time of analysis, with a median follow-up of 30 months. follow-up of 30 months.


Oligometastatic NSCLC: A Multidisciplinary Approach Oligometastatic NSCLC: A Multidisciplinary Approach in the PET Scanin the PET Scan Era Era


P stageP stage Site of Site of metmet

Treatment of Treatment of metmet

TTP(m)TTP(m) OS(m)OS(m)

11 ypT2N0ypT2N0 BrainBrain WBRWBR 1919 3030

22 pT1N2pT1N2 BrainBrain S+SRTS+SRT 1818 1818

33 ypT2N0ypT2N0 BrainBrain SRTSRT 3030 3333

44 ypT2N0ypT2N0 BoneBone RTRT 66 1010


66 ypT4N1ypT4N1 AdrenalAdrenal SS 1515 2222


88 ypT2NxypT2Nx AdrenalAdrenal TABTAB 3232 3232


1010 pT2N2pT2N2 BoneBone S+RTS+RT 99 99


►Clear data regarding this issue is Clear data regarding this issue is lackinglacking

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Is The Surgical Treatment for Patients with Advanced Lung Cancer beneficial? Pro and Con