Diapositiva 1

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INTEGRAZIONE TRA TERAPIA CHIRURGICA E TERAPIA
MEDICA
Camillo Porta, MD Medical Oncology I.R.C.C.S.
San Matteo University Hospital Foundation, Pavia
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SURGERY AND MEDICINE
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RCC DISEASE BURDEN IN ITALY
Femmine
Maschi
5568 new cases/year in Italy
2639 new cases/year in Italy
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RCC DISEASE BURDEN IN ITALY
Men 2052 deaths/year in Italy
Women 1133 deaths/year in Italy
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NATURAL HISTORY OF RCC

• Presentation at diagnosis1
• 45 with localized disease
• 25 with locally advanced disease
• 30 with metastatic disease

• 33 of patients originally treated for localized
  disease will
• eventually develop metastatic disease2

1National Cancer Institute. SEER cancer
statistics fact-sheet cancer of the kidney and
renal pelvis. 2009 2Flanigan RC, et al. Curr
Treat Options Oncol 20034385-90
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THE ROLE OF SURGERY IN mRCC THE QUESTIONS ARE

• Surgery of primary tumor in mRCC a unique and
  unusual opportunity

• Has metastasectomy a role in mRCC di per se?

• Is there any difference according to specific
  metastatic sites?

• What really changes in the era of molecularly
  targeted agents?

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SURGERY OF PRIMARY mRCC A UNIQUE AND UNUSUAL
OPPORTUNITY
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CYTOREDUCTIVE NEPHRECTOMY IN THE METASTATIC
SETTING
EORTC 30947
SWOG 8949
Flanigan R, et al. NEJM 20013451655-1659
Mickisch G, et al. Lancet 2001358966-970
Anything new in the era of molecularly-targeted
agents?
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HAS METASTASECTOMY A ROLE IN mRCC, DI PER SE?
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RESECTION AND SURVIVAL
1 RECURRENCE 141 PTS ? CURATIVE METASTASECTOMY
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Alt AL, et al. ASCO GU 2010
IMPACT OF R0 STATUS ON CSS AFTER METASTASECTOMY

• 887 pts treated with nephrectomy for RCC from
  1976-2006 with multiple metastases 125 of these
  underwent resection of metastases

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IS THERE ANY DIFFERENCE ACCORDING TO SPECIFIC
METASTATIC SITES?
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HIGHEST BENEFIT IN LUNG AND SYNCHRONOUS METS

• Conclusions patients with multiple metastases
  of RCC can achieve durable survival with complete
  resection of all metastatic lesions, especially
  patients with lung only metastases and those with
  asynchronous metastases

Alt AL, et al. ASCO GU 2010
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HEPATIC METASTASES FROM RCC
Selected patients with hepatic mets from
RCC benefit from hepatic resection
pts

pts
pts
pts
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WHAT REALLY CHANGES IN THE ERA OF MOLECULARLY
TARGETED AGENTS?
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ANTIANGIOGENETIC AGENTS AND WOUND HEALING
Stages of wound healing
II. cell proliferationand matrix deposition
I. inflammation
III. matrix remodelling

• Fibroplasia
• Angiogenesis
• Re-epithelization
• Extracelluar matrix sythesis
• Collagens
• Fibronectin
• Proteoglucans

Maximum response

• Granulocytes
• Phagocytosis

Extracellular matrixsynthesis, degradationand
remodelling ? Tensile strength ? Cellularity ?
Vascularity

• Bleeding
• Coagulation
• Platelet activation
• Complement activation

• Macrophages
• Cytokines

Withholding Tx for at least 2 or 3 half-lives
before and after surgery may prevent AEs on
microvasculature and tissue integrity
0.1 0.3 1 3 10 30 100 300
Days after wounding (log scale)
Potential risk
Rebound phenomenon due to early regrowth of tumor
vascularization after TKI discontinuation
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ANOTHER ISSUE TIMING OF SURGERY
No more than 3-4 cycles of treatment before
surgery
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SURGERY OF METASTATIC SITES AND PALLIATION
Altough the absolute curative impact of
metastasectomy remains uncertain, operative
intervention can provide effective palliation for
symptomatic metastatic disease to sites such as
bone, brain and adrenal glands
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WHAT WOULD WE NEED
Ultimately, a prospective and randomized
clinical trial comparing metastasectomy to best
standard systemic therapy could more clearly
define the effectiveness of metastasectomy in the
face of various selection factors
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SURGERY AND THE GUIDELINES
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THANK YOU FOR YOUR KIND ATTENTION!!!
c.porta_at_smatteo.pv.it