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Approche multidisciplinaire dans le traitement du cancer
du rein métastatique
Approche multidisciplinaire dans le traitement du cancer
du rein métastatique
Pierre I. Karakiewicz, MD, MPHUrologic Oncologist,
Associate Professor andSenior Research Scientist,
Director, Cancer Prognostics and Health Outcomes UnitUniversity of Montreal Health Center (CHUM)
Pierre I. Karakiewicz, MD, MPHUrologic Oncologist,
Associate Professor andSenior Research Scientist,
Director, Cancer Prognostics and Health Outcomes UnitUniversity of Montreal Health Center (CHUM)
Canadian cancer facts and figures 2007
Canadian cancer facts and figures 2007
Cancer incidence and mortality 2007 Cancer incidence and mortality 2007
Incidence
Mortality
6th
10th
Five year cancer survivalFive year cancer survival
RCC Stage vs. prognosisRCC Stage vs. prognosis
Cohen HT, McGovern FJ. N Engl J Med. 2005;353:2477-2490.
Stage I
Tumor < 7 cm in greatest dimension and limited to kidney; 5-year survival, 95%
Stage II
Tumor > 7 cm in greatest dimension and limited to kidney; 5-year survival, 88%
Stage III
Tumor in major veins or adrenal gland, tumor within Gerota’s fascia, or 1 regional lymph node involved; 5-year survival, 59%
Stage IV
Tumor beyond Gerota’s fascia or > 1 regional lymph node involved; 5-year survival, 20%
Histology Type % Prognosis Gene
Clear cell 85 Poor VHL
Papillary Type I Papillary Type 2
55
Good Poor
MET, FH, TFE3
Chromophobe 3 Good BHD
Oncocytoma 4 Good BHD
Collecting duct < 1 Poor None known
Sarcomatoid / Other 1–2 Poor None known
Tumor histology vs. prognosisTumor histology vs. prognosis
1. Cohen HT, McGovern FJ. N Engl J Med. 2005;353:2477-2490.2. Cangiano T, Liao J, Naitoh J, et al. J Clin Oncol. 1999;17:523-528.
3. Nelson EC, Evans CP, Lara PN Jr. Cancer Treat Rev. 2007;33:299-313.
Caucasian 85%
Other 15%
SEER RCC demographicsSEER RCC demographicsFemale 38%
Male 62%
Temporal distribution of new RCC diagnoses – all stages SEER
Temporal distribution of new RCC diagnoses – all stages SEER
N=43143
RN 66% PN 7%
No Sx 25%LTD 1%
Rx type
T1-2,N0,M059%
T3-4,N0-2,M019%
M1 22%
Stage
FG 1 20%
FG 2 46%
FG 3 26%
FG 4 8%Grade
Clear cell RCC 85%
Other Histology
SEER Rx by stageSEER Rx by stage
RN 80%
PN 12%No Sx 7%LTD 1%
T1-2, N0, M0
RN 89%
PN 3%No Sx 8%LTD <1%
T3-4, N0-2, M0
RN 28%
PN 1% No Sx 71%
LTD <1%M1
Modes of presentation: locally advanced RCC
Modes of presentation: locally advanced RCC
Nephrectomy rate T3-4, N0-2, M0 RCCNephrectomy rate
T3-4, N0-2, M0 RCC
N=7068n= 6786Range 96.2- 95.7%Χ2 trend p=0.2
Matched:HR 5.1 p<0.001CRR p<0.001
84 months
11 vs. 8 months
17 vs. 7 months
Cohen HT, McGovern FJ. N Engl J Med. 2005;353:2477-2490.
Overall survival RCC specific survival10
months
10 months
n=5372SEER 9: 1988-2004
MVA HR 2.4 p<0.001
CRR p<0.001
Cohen HT, McGovern FJ. N Engl J Med. 2005;353:2477-2490.
Temporal trendsCytoreductive nephrectomy - SEER
Temporal trendsCytoreductive nephrectomy - SEER
N=5372n= 2925Range 56.4- 51.1%Χ2 trend p=0.8
N=2530 N=1377
31
Final Overall SurvivalFinal Overall Survival
0 3 6 9 12 15 18 21 24 27 30 33 36Time (months)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Ove
rall
Surv
ival
Pro
babi
lity
Sunitinib (n=375) Median: 26.4 months (95% CI: 23.0 - 32.9)IFN-α (n=375)
Median: 21.8 months (95% CI: 17.9 - 26.9)
Hazard Ratio = 0.821(95% CI: 0.673 - 1.001)p =0.051 (Log-rank)
375 44 / 326 38 / 283 48 / 229 42 / 180 14 / 61 4 / 2nDeath/nRisk Sunit375 61 / 295 46 / 242 52 / 187 25 / 149 15 / 53 1 / 1nDeath/nRisk IFN-α
Total DeathSunitinib 190IFN-α 200
Total DeathSunitinib 190IFN-α 200
0
20
40
60
80
100
0 2 4 6 8 10 12 14Months
Prob
abili
ty, %
Everolimus (n = 277)Placebo (n = 139)
Hazard ratio = 0.3395 % CI [0.25, 0.43]
Median PFSEverolimus: 4.90 moPlacebo: 1.87 mo
Log rank P value = <0.001
Patients at riskEverolimusPlacebo
277 192 115 51 26 10 1 0139 47 15 6 2 0 0 0
> 25 %
3 mos
Baseline Month 17
Stable Disease to Everolimus Therapy
Stable Disease to Everolimus Therapy
Modes of presentation: metastatic RCCModes of presentation: metastatic RCC
Sequential therapy: PFS projections
• Surgery: 10 months• Sunitinib: 8 months• Sorafenib: 3 months• Avastin: 5 months• Torisel: 3 months• Evorolimus: 3 months
• Total: 32 months
• Overall survival: 32++ months
Sequential therapy: PFS projections
• Surgery: 10 months• Sunitinib: 8 months• Sorafenib: 3 months• Avastin: 5 months• Torisel: 3 months• Evorolimus: 3 months
• Total: 32 months
• Overall survival: 32++ months
40