The role of surgery in lung metastases

Rome, 9 - 11 October 2017

Maria Letizia Vita Department of Thoracic Surgery

Policlinico A. Gemelli, Roma

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History of Pulmonary Metastasectomy

• In 1855 was described the first metastasectomy.

• 1882 en bloc resection of the chest wall and adiacent lung metastasis for sarcoma.

• 1939 right lower lobectomy for metastatic renal cell carcinoma; the patient died 23 years later of coronary artery disease.

• 1965 Thomford reported a 31% rate of 5-year survival among patients undergoing unilateral metastasectomy of single or multiple secondaries.

• 1970s, Morton, Joseph ,McCormack and Martini showed that extended survival was possible even in patients with bilateral and multiple disease.

• 1997 Pastorino reported the International Registry of Lung Metatases.

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International Registry of lung metastases

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“Many multicentric studies , meta-analisys or review, supported the rationale for pulmonary metastasis…but they are not randomized or comparative studies.”

Kim , 2014

«Metastasectomy represents15-50% of the workload in European thoracic surgical departments.» Treasure , 2014

Randomized studies

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“No one would argue about offering pulmonary metastasectomy when a solitary , slowly growing and isolated lung metastases is detected after a long disease-free interval. Controversely , it would be unreasonable to recomend pulmonary metastasectomy when numerous metastatic lesions are extensively widespread in both lungs within several months after surgery for primary tumors….”

“Between these extremes however , there are always borderline cases with a combination of favorable and unfavorable features in which the indication of pulmonary metastasectomy is uncertain….” Kim, 2014

Indications

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Pulmonary metastasectomy and histology

epithelial

Sarcoma

Melanoma

Germcellstumors

Epithelialtumors

Colon 32,5%

breast 20%

kidney 19%

Head-neck 12,5%

others 16%

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“Patients with untreated metastatic disease have a median survival of less than 10 months and a 5 year survival of less than 5%” Headrick ,2001 “The metastatic disease was confined to the lungs in more than 1/3 of the patients with pulmonary metastases” Nordholm-Cartsensen, 2015 “In contrast patients with potentially resectable disease who do not undergo surgery historically had a dismal prognosis , with a 5-year survival rate of only 0-2%” Miller , 2007 “From 5%-15% of patients with colorectal cancer develop lung metatasis.” Kim 2014

Colorectal cancer metastases

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author year patients 5yr-survival Prognosticfactor

Saito 2002 165 39,6% LNmets,CEA

Pfannschmidt 2003 167 32,4% Lnmets,CEA,numberofmets

Inoue 2004 128 45,3% Primarytumorstage,distributionofmets

Melloni 2006 81 42% Primarytumorstage,completeresection

Yedibela 2006 153 37% Numberofmets,DFI,Transfusion

Welter 2007 169 39,1% DFI,numberofmets,LNmets

Lin 2009 63 43,9% DFI,typeofresection

Onaitis 2009 378 78% Age,sex,DFI,numberofmets

Watanabe 2009 113 67,8% CEA,Lympahticinvasion

Landes 2010 40 43,4% Priorhistoryoflivermets

Riquet 2010 127 41% Completeresection

Zabaleta 2011 84 54% Priorhistoryoflivermets,LNmets,DFI,nuberofmets

Colorectal cancer metastases

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Author pt 5years-survival 10yearssurvival

Neeff2009 44 27% -

Barlow2009 19 20% -

Joosten2008 21 20% -

Tsukioka2007 34 34% -

Imdahl2005 25 33.5% -

Headrick2001 58 30% 16%

Regnard1998 43 11% -

Murata1998 30 43.8% -

Smith1992 10 52% -

“The 5-year survival rates reported after the last metastasectomy range between 30% and 60%, with a median survival from last metastasectomy of 16 to 41 months.Perioperative morbidity and mortality are consistently low.” Saha 2006

Colorectal cancer metastases

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Author pt 5y-Survival Prognosticfactors

Friedel2002 467 35% NumberlesionsDFIRO

Planchard2004 96 45% Size<2cm

Tanaka2005 52 30,8% R0DFI

Welter2008 47 36% NumberandsizeLesionsReceptorstatus

Chen2009 41 51% Receptorstatus,DFI

10-20% patients with breast cancer develop pulmonary metastasis

Breast cancer metastasis

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• R0 vs R1/R2 103.4 versus 23.6 and 20.2 months

• Single vs 2 or more metastases 103 vs 37.1 months

• Smaller 3 cm vs 3 or more cm 103 vs 39 months • ER/PR positive vs TN 127 vs 27 months

2013

Breast cancer metastasis

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Breast cancer metastasis

“…DFI >3 years, complete resection of metastases, solitary pulmonary metastasis and positive hormone receptor status of metastases were most frequently reported as the significant good prognostic factors.”

2015

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“Pulmonary metastasectomy may not be the primary therapeutic option … surgical resection should be considered as an option of the diagnosis.”

2013

Breast cancer metastasis

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Author pt %completeresection

5y-Survival Prognosticfactors

Cerfolio1994 96 65% 36% Radicality

Forquier1997 50 90% 44% Radicality

Plitz2002 122 86% 40% Radicality

Murthy2005 92 68% 31% Radicality,N

Meimarakis2011 202 87% 45% Radicality,NPleuralinvasion,size,DFI

Kanzaki2011 48 90% 47% Radicality,DFI

30-50% of patients with renal cell carcinoma develop pulmonary metastases

Renal cell metastasis

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“Lymphatic spread of renal cell carcinoma to mediastinal sites has been well documented”

“For solitary nodules, we recommend anatomic resection when possible, because our bias is that these cancers utilize pulmonary lymphatic drainage similar to lung cancers.” “We have now begun incorporating both mediastinoscopy and lymph node dissection to define metastases to N2 or N3 stations.”

2005

Renal cell metastasis

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2011

Renal cell metastasis

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Renal cell metastasis

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Author year pt 5y-survival Prognosticfactors

Shiono 2009 114 26,55% MaleSexoralcancer,nodalinvolvement,completeresection

Winter 2008 67 20,9% Resectionperioerativecomplication,NAD

Chen 2008 20 59,4% MaleSex,DFI,Histology

Liu 1999 83 50% CompleteresectionAge>50aaDFI≤24mesi

“…there is the potential for a good surgical outcome in carefully selected patients.” Shiono, 2009

Head-neck metastasis

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Germinal cells tumors

Author Pt 5year-survival Prognosticfactors

Kesler2011 431 79% Age,histologyofmetastasis

Basse2009 53 94% Alfafetoprotein

Pfannschmidt2006

52 76% Radicality,alfafetoproteineBhcginblood

“…are highly responsive to chemotherapy, and 90% can be cured. Of those with stage I disease, 8% develop pulmonary metastases.”

“Multiple metastases and the finding of residual malignancy were associated with progression and death. Long-term survival is not attributable to the surgery, but surgery is an established part of the management strategy for cogent evidence-based reasons.”

Treasure 2014

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Author 5y-Survival Prognosticfactors

Predina,2011(48pt,89metastasectomie)

52% Radicalitysize≤2cmNumberlesions≤2

Canter,2007(138pt) 29% Radicality,DFI

Pfannschmidt,2006(50pt)

37,6% Radicality

Suri,2005(103pt) 21% Radicality

25-50% of patients with STS develop isolated lung metastases

“…these results are biased by stringent selection of patients for surgical treatment. “ Pfannschmidt, 2012

Soft tissue sarcoma metastasis

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Author 5y-Survival Prognosticfactors

Briccoli2010(323pt) 37% NumberlesionsDFI

Buddingh2010(56pt) 38% DFI,radicality

Diemel2009(85) 48% Radicality

Chen2008(23pt) 31% Radicality

Harting2006(96pt) 23% DFI

Tsuchiya,2002(280pt) 31% DFI

15-20% of patients with osteosarcoma have a pulmonary metastasis at diagnosis

“In particular , for each additional month in DFI1 and DFI2 , there is a 3% decrease in mortality. “ Briccoli, 2005

Osteosarcomametastasis

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Briccoli, 2005

“…patients with recurrent metastases should always be considered for reoperation. Surgery , combined with chemotherapy can favorably influence prognosis of carefully selected osteosarcoma patients who have repeated lung recurrences.”

Osteosarcomametastasis

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Melanomametastases

Author 5years-survival Prognosticfactors

Riad2013 36% Numbernodules

Schuahn2011 35,1% Numbernodules

Petersen2007 21% histologyNumbernodulesDFIExtrathoracicmetastases

Andrews2006 33% Numbernodules

30% of patients with melanoma develop metastasis…in 80% of cases is a pulmonary metastasis

“In contrast to systemic therapy, surgical management continues to be the primary treatment modality for patients with metastatic melanoma. Unfortunately, surgery is not appropriate for all patients, and patient selection criteria remain controversial.”

Petersen, 2007

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OpenorVATS?

Limphoadenectomy?

Anatomicalvswedgeresection

SurgicalTechnique

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UniportalVATS

Diego Gonzalez Rivas

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UniportalVATS

•  May 2016-september 2017 •  209 resection (45 lobectomy, 15

segmentectomy, 149 wedge resection, of these, 104 for metastases

•  Postoperative days: 2-3 •  Mortality : 0% •  Morbidity: 9,6% (4 FA,4 Atelectasis,16 air

leak) •  2 conversions in thoracotomy for bleeding

control •  complete resection : 100% of cases •  Less pain if compared to thoracotomy. •  VAS score: 2 with complete resolution after

chest tube removal ( normally in third p.o. day)

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ReCIMP

•  In 2010 started data collection

•  More of 1800 patients

•  Actually 3 research protocols are waiting to be evaluated from Italian Thoracic Society

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•  ”…role of surgery in patients with lung metastases remains still controversial due to lack of prospective randomized controlled trials comparing pulmonary metastasectomy with a control of either medical therapy group or observation…

•  …the encouraging outcomes of pulmonary metastasectomy to date might therefore attribuited to the fact that selected candidates already have beneficial prognostic factors, typically resectability , rather than the benefit of surgical resection per se, and is therefore unknown whether the reported good results are due to surgery.”

Conclusions

Kim, 2014

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“An association between survival and metastasectomy may be perceived …. Given the heterogeneity of the disease and in its rate of progression , and the multiplicity and repetition of treatments , it is not possible to distinguish the signal from the noise.” Treasure 2013

Conclusions