Surgery Before Systemic Therapy in metastatic RCC Viraj Master MD, - - PDF document

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Surgery Before Systemic Therapy in metastatic RCC Viraj Master MD, - - PDF document

Jun 04, 2023 212 likes •371 views

Winship Cancer Institute of Emory University Surgery Before Systemic Therapy in metastatic RCC Viraj Master MD, PhD, FACS Department of Urology Emory University Disclosures Nothing relevant to report. 1 Cytoreductive Nephrectomy Trial

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1 Winship Cancer Institute of Emory University

Surgery Before Systemic Therapy in metastatic RCC

Viraj Master MD, PhD, FACS Department of Urology Emory University

Disclosures

  • Nothing relevant to report.
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2

Cytoreductive Nephrectomy – Trial Results

  • EORTC
  • NTX +IFN vs IFN
  • Time to progression:

5 vs 3 months, p=.04

  • Median survival:

17 vs 7 months, p=.03

  • SWOG
  • NTX +IFN vs IFN
  • Difference in

comparison groups

  • Median survival:

11 vs. 8 months, p=.05

Pooled Analysis 331 patients 13.8 months NTX + IFN vs 7.8 months IFN alone, p=.0002 Overall survival advantage ~6 months for the entire group

Flanigan RC, J Urol 2004

NTX=nephrectomy

Selection of Patients for Cytoreductive Nephrectomy (CN)

  • MD Anderson
  • 1991‐2007
  • 566 patients underwent CN
  • 110 received medical tx alone
  • Multivariate analysis conducted

Culp SH Cancer 2010

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Selection of Patients for Cytoreductive Nephrectomy (CN)

  • Albumin < normal
  • LDH > normal
  • cT3/T4
  • Symptomatic from mets
  • Liver metastases
  • Retroperitoneal

Adenopathy

  • Supradiaphragmatic

adenopathy

Culp SH Cancer 2010

Selection of Patients for Cytoreductive Nephrectomy (CN)

  • Albumin < normal
  • LDH > normal
  • cT3/T4
  • Symptomatic from mets
  • Liver metastases
  • Retroperitoneal

Adenopathy

  • Supradiaphragmatic

adenopathy

Culp SH Cancer 2010

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Metastasectomy ‐ Rationale

  • Old view

– Locally confined cancers curable with local therapy – Distant metastatic disease managed with systemic therapy, no role for local therapy

Metastasectomy ‐ Rationale

  • ‘New’ view

– Integrating therapies, local, regional and systemic may provide for better survival – Prototype disease: Testis Cancer

– Old view

– Locally confined cancers curable with local therapy – Distant metastatic disease managed with systemic therapy, no role for local therapy

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Advanced RCC

2002 6thed AJCC RCC Staging – Stage IV

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2002 6thed AJCC Staging

  • Capitanio examined 310 patients

with clinical T4N0‐2 RCC surgery (246) or no surgery (64).

  • + surgery med. survival 48mo
  • ‐ surgery med surv. 6 mo (HR 2.2)
  • The effect of surgery for those

patients (125) who had T4N0 disease even stronger, with a hazard ratio of 3.7, with a cancer specific mortality of approximately 40% at 10 years

Capitanio BJUI 2010

2010 7thed AJCC RCC staging – Stage IV

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Which is better for prognosis?

‘Old’ 2002 TNM staging ‘New’ 2010 TNM staging

Johnson, Master unpublished

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Increasing Incidence of RCC (localized), BUT no change in regional or distant disease

Rise in poorly differentiated cancers

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C-reactive protein

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  • 24 studies, 4100 patients
  • Elevated CRP level independently associated

– higher stage RR 2.90, 95% CI 2.52–3.32, P<0.00001 – higher grade RR 4.31, 95% CI 3.35–5.56, P<0.00001

  • Overall survival HR 1.5, 95% CI 1.09–1.93, P< 0.00001
  • cancer-specific survival HR 3.91, 95% CI 2.18–5.64,

P<0.00001)

  • localized RCC, elevated CRP level was associated with

– Decreased CSS (HR 3.49, 95% CI 2.93–4.05, P<0.00001 – progression-free survival (HR 3.29, 95% CI 2.91–3.67, P<0.00001

  • metastatic RCC, elevated CRP level was associated with

– Decreased overall survival (HR 2.37, 95% CI 2.14–2.60, P<0.00001 – Decreased CSS (HR 3.70, 95% CI 3.19–4.22, P<0.00001

  • ccRCC histology only, elevated CRP level associated with

– higher stage RR 2.92, 95% CI 2.25–3.80, P<0.00001 – CSS HR 2.60, 95% CI 2.32–2.88, P<0.00001 – progression-free survival HR 1.21, 95% CI 0.94–1.47, P<0.00001

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Experience matters!

  • All-Canada study
  • 816 cases over 20 yrs
  • In hosp mortality 7%
  • 75% deaths occurred in

the first 2 cases of surgeon experience

  • Overall complication

profile 78%

  • Increasing surgeon

volume, not hospital volume associated with lower mortality on MVA

Toren, P: Urology 2013 82:572

Quality of Pathology Reporting – Implications for Nomograms

  • Evaluated 344 pathology reports in LA (2002-

2006) from community, teaching and cancer center hospitals

  • 10% -no data on histology
  • 20% -no data on Fuhrman grade
  • 30% (27.8%) T-stage absent
  • Only 60% met CAP criteria for tumor

classification, margin, size and grade

Shuch B, BJUI 2010

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Quality of Pathology Reporting – Implications for Nomograms

  • Evaluated 344 pathology

reports in LA from community, teaching and cancer ctr hospitals

  • 10% -no data on histology
  • 20% -no data on Fuhrman

grade

  • 30% (27.8%) T-stage absent
  • Only 60% met CAP criteria

for tumor classification, margin, size and grade

  • CAP criteria satisfied

– 54% community – 71% teaching – 75% cancer center

  • Implications for using

prognositic nomograms

– SSIGN 16% – Kattan 12%

  • UCLA-UISS 66%

Shuch B, BJUI 2010

A quote for Surgeons/ Interventionalists

"From inability to let alone; from too much zeal for the new and contempt for what is old; from putting knowledge before wisdom, and science before art, and cleverness before common sense; from treating patients as cases; and from making cure of the disease more grievous than the endurance of the same, Good Lord, deliver us.”

  • Sir Robert Hutchinson

Courtesy Niall Galloway FRCS

BMJ 1953 1:671

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C-Reactive Protein in patients with advanced mRCC: Usefulness in identifying patients most likely to benefit from initial nephrectomy

  • Retrospective
  • 181 patients

– 52 immuno/TKI only – 129 cytoreductive NTX

  • CRP measured preop
  • ROC curves to

identify 3 ranges (<18, 18-67, >67)

Ito H, BMC Cancer 2013 12:337

Potential Influence of Surgery? (not randomized – selection bias)

Median OS >4 yrs Median OS <1 yrs Surgery NO Surgery Ito H, BMC Cancer 2013 12:337

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Cytoreductive Nephrectomy in metastatic RCC patients with non-clear cell histology

  • SEER, 4914 mRCC

patients diagnosed with metastatic RCC between 2000- 2009

  • 591 non-clear mRCC
  • Median F/U 20 mos
  • CSS
  • 64% underwent

cytoreductive NTX

  • non-clear cell histology pts

with CN displayed lower RCC-specific and all-cause mortality than those who did not (p<.001 in both cases)

  • Adjusted for year, race,

gender, location, histology, CN decreased both

– CSS (HR 0.62, 95% CI 0.48- 0.80, p<.001) – OS (HR 0.45, 95% CI 0.37- 0.55, p<.001)

Aizer AA BJU Int 2014

Cytoreductive Nephrectomy in metastatic RCC patients with non-clear cell histology still relevant in era of TKI’s?

  • Results unchanged when

looking at patients diagnosed 2006-2009 (Targeted therapy era, Sutent/Nexavar Dec 2005)

  • Reductions of 38% and 55%

respectively, when CN performed

  • CSS HR 0.50, 95% CI 0.34-

0.72, p<.001

  • OS HR 0.43, 95% CI 0.31-

0.59, p<.001

  • Reductions of 38% and 55%

respectively, when CN performed

  • Most benefit for chromophobe,

then papillary, collecting duct

Aizer AA BJU Int 2014 CSS

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Cytoreductive Nephrectomy in metastatic RCC patients with non-clear cell histology still relevant in era of TKI’s?

  • Results unchanged when

looking at patients diagnosed 2006-2009 (Targeted therapy era, Sutent/Nexavar Dec 2005)

  • Reductions of 38% and 55%

respectively, when CN performed

  • CSS HR 0.50, 95% CI 0.34-

0.72, p<.001

  • OS HR 0.43, 95% CI 0.31-

0.59, p<.001

  • Reductions of 38% and 55%

respectively, when CN performed

  • Most benefit for chromophobe,

then papillary, collecting duct

Aizer AA BJU Int 2014 OS

Conclusions ?