Prognostic Scoring Systems for RCC 2014

Prognostic Factors for mRCC:
Relevance in Clinical Practice
Daniel Heng MD MPH FRCPC
Chair, GU Tumor Group
Tom Baker Cancer Center
University of Calgary
Prognostic Factors
Patient Factors
Patient X
Performance Status
Symptoms
Patient Y
Tumor Burden
Prior nephrectomy
Sites of metastases
Bone / Liver Metastases
LDH
Anemia
Calcium
Sodium
Proinflammatory
Markers
IL-6
ESR
Neutrophilia
Thrombocytosis
C-reactive protein
Treatment-related
Factors
Patient Z
Prior therapy
Prior radiotherapy
Disease-free interval
Diagnosis to treatment interval
MSKCC Prognostic Profiles
Motzer et al JCO 2002
IKCWG Prognostic Criteria
Manola et al Clin Cancer Res 2011
International mRCC Database Consortium
Currently includes 3700 patients from 25 institutions
Int’l mRCC Database Consortium
Prognostic Factors
KPS < 80%
Dx to Tx Interval <1yr
Anemia
Hypercalcemia
Neutrophilia
Thrombocytosis
Heng et al J Clin Oncol 2009
Prognostic Factors
If patient has 0 factors:
Favorable Prognosis
If patient has 1-2 factors:
Intermediate Prognosis
If patient has 3-6 factors:
Poor Prognosis
Prognostic Factors: Targeted Therapy Era
43 months
23 months
8 months
Heng et al Lancet Oncology 2013
Benchmarks from IMDC
Population (Data from IMDC)
PFS (mon)
(95% CI)
7.2 (6.7-7.7)
n=2659
OS (mon) (95%CI)
1st line therapy in intermediate/poor risk patients &
diagnosis to treatment interval < 1 year (similar to ADAPT
(AGS003) pts)
5.6 (5.3-6.1)
n=1174
14.7 (13.3-16.5)
n=1189
1st line therapy in patients with prior nephrectomy (similar
to TIVO-1 (Tivozanib) pt)
8.2 (7.8-8.6)
n=2080
24.8 (23.1-27.3)
n=2117
2nd line therapy
(similar to INTORSECT patients)
3.9 (3.6-4.3)
n=1151
13.0 (12.2-14.7)
n=1157
3rd line therapy (all pts)
4.0 (3.4-4.5)
n=425
12.1 (10.7-13.9)
n=455
4.4 (3.3-5.2)
n=140
18.0 (11.8-24.0)
n=147
1st line therapy (all pts)
3rd line therapy in patients with 1 prior VEGF and 1 prior
mTOR inhibitor (similar to GOLD (dovitinib) pts)
20.9 (19.6-22.5)
n=2705
Ko et al BJC 2014
Conditional Survival
Our prognostic criteria are used at the
initiation of treatment
 How does survival change as you survive
longer?
 How does survival change as you survive
past the median in your risk group?

Harshman et al Lancet Oncol 2012
Survival of each risk group over
time survived already
Harshman et al Lancet Oncol 2012
Conditional Survival in SEER
Bianchi et al BJU 2013
The future of prognostication
Reached the ceiling of clinical variables
 Need biologic markers to add to the
accuracy of existing models
 IMDC model + X + Y to improve
accuracy

Cancer Genome Atlas Research Network Nature 2013
Why are Prognostic Factors
Important?
Prognostic Factors

Important for patient counseling
 Will you live < 1 year or > 1 year?

Important for clinical trial risk
stratification and retrospective study
adjustment methods
Italian Database





281/2065 had 3 lines of
targeted therapy
VEGF VEGF mTOR vs
VEGF mTOR VEGF
HR 2.59 (1.59-4.22)
after adjusting for
prognostic criteria
Assumes patients make
it to three lines of
therapy
No axitinib in study
Iacovelli et al EJC 2013
Prognostic Factors

Important for planning therapy
 We use temsirolimus for poor risk patients
 Is active surveillance appropriate for small
bulk, not growing, favorable risk, highly
selected patients
 Is cytoreductive nephrectomy appropriate?
Cytoreductive Nephrectomy
3245 mRCC patients
2569 (79%)
patients with
nephrectomy
676/1658 (41%)
No nephrectomy
982/1658 (59%)
Cytoreductive
Nephrectomy
FINAL NUMBERS
EXCLUDED 1587 (49%)
w/ nephrectomy
prior to metastases
Overall Survival
Overall Survival
Median OS 20.6 vs 9.5 months (p<0.0001)
Adjusted HR 0.60 (95%CI 0.52-0.69, p<0.0001)
Cytoreductive nephrectomy
No Cytoreductive nephrectomy
Months Since Initiation of Targeted Therapy
HR adjusted for IMDC criteria:
0.60 (95%CI 0.52-0.69, p<0.0001)
Incremental Benefit
Overall
Survival
(Months)
< 24
<18
<12
<9
<6
<3
No CN OS
(Months)
CN OS
(Months)
P-value
7.1
n=456
6.7
n=430
5.5
n=366
4.5
n=303
3.2
n=230
2.1
n=118
12.3
n=480
10.0
n=395
7.3
n=290
5.5
n=218
4.0
n=151
2.2
n=71
<0.0001
<0.0001
<0.0001
0.0027
0.0084
0.9429
Incremental Benefit
Overall
Survival
(Months)
< 24
<18
<12
<9
<6
<3
No CN OS
(Months)
CN OS
(Months)
P-value
7.1
n=456
6.7
n=430
5.5
n=366
4.5
n=303
3.2
n=230
2.1
n=118
12.3
n=480
10.0
n=395
7.3
n=290
5.5
n=218
4.0
n=151
2.2
n=71
<0.0001
Incremental
Benefit
(Months)
+5.2
<0.0001
+3.3
<0.0001
+2.2
0.0027
+1.0
0.0084
+0.8
0.9429
+0.1
Incremental Benefit
Overall
Survival
(Months)
< 24
<18
<12
<9
<6
<3
No CN OS
(Months)
CN OS
(Months)
P-value
<0.0001
Incremental
Benefit
(Months)
+5.2
7.1
n=456
6.7
n=430
5.5
n=366
4.5
n=303
3.2
n=230
2.1
n=118
12.3
n=480
10.0
n=395
7.3
n=290
5.5
n=218
4.0
n=151
2.2
n=71
Hazard Ratio Adjusted
for IMDC Criteria
0.72 (0.62-0.85) p<0.0001
<0.0001
+3.3
0.85 (0.72-1.00) p=0.0498
<0.0001
+2.2
0.97 (0.81-1.17) p=0.7614
0.0027
+1.0
0.98 (0.79-1.20) p=0.8108
0.0084
+0.8
1.02 (0.80-1.31) p=0.8561
0.9429
+0.1
1.03 (0.72-1.46)
p=0.8782
Using IMDC Prognostic Factors
# of IMDC Criteria
Met
No CN OS months
(N)
CN OS months
(N)
P value
0
92% (65/71) patients had CN, insufficient number to compare
1
22.5 (n=72)
30.4 (n=178)
0.0024
2
10.2 (n=143)
20.2 (n=253)
<0.0001
3
10.0 (n=113)
15.9 (n=106)
<0.0001
4
5.4 (n=103)
6.0 (n=67)
0.1664
5
3.6 (n=36)
2.8 (n=14)
0.5044
6
25% (3/12) patients had CN, insufficient number to compare
Cytoreductive Nephrectomy
Perhaps not appropriate in patients with
survival estimated to be < 1 year
 Perhaps not appropriate in patients with
4 or more adverse prognostic factors

Prognosis
Is important for patient counseling, study
design, and planning therapy
 Prognosis is dynamic
 Prognosis needs to be improved with
biomarkers

THANK YOU!
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