Epidemiological Trends in Metastatic Renal Cell Carcinoma (RCC) in the Era of Targeted Therapies

An Analysis of the SEER Registry.

Arpit Rao, Charles Wiggins, Richard C. Lauer
University of New Mexico Comprehensive Cancer Center, Albuquerque, NM
Background

Age at diagnosis: 4,501 (39.4%) patients were 18-59 years, 3,500 (30.6%)

FIGURE 1: DISEASE-SPECIFIC SURVIVAL AT 36

MONTHS

35%

were 60-69 years, and 3,420 (29.9%) were 70 years and above.

Discussion

Clear cell RCC (ccRCC) accounts for 70-75% of all kidney and renal pelvis
cancers with approximately 16% of patients presenting with distant
(metastatic) disease. Five year overall survival (OS) remains dismal at 11.2%
for patients with distant disease [1][3]. Several targeted agents (tyrosine
kinase inhibitors or TKI) were approved by US Food and Drug
Administration (FDA) for use in metastatic RCC between 2005 and 2012 [4]

Disease specific survival from metastatic ccRCC in the United States has

Race/Ethnicity: Non-Hispanic White - 8,139 (71.3%), Hispanic White - 1,457

(12.8%), American Indian - 148 (1.3%), and Black - 1,055 (9.2%).
Gender: Male - 7,681 (67.2%) and female - 3,740 (32.8%)

25%

Residence: Metropolitan area 9,775 (85.7%), non-metropolitan area 1,629

improved significantly between 2001 and 2012 with the advent of TKI. Our
analysis showed that patient specific variables such as younger age at

18-59

diagnosis and female gender afford better outcome. Although survival has

60-69

improved in patients aged 70 and above, the DSS continues to be inferior in

70+

(14.3%)

20%

[6]. While these therapies have been shown to improve outcomes in

metastatic ccRCC [7], [8], the long term impact remains unknown.

Age at
diagnosis
(years)

30%

this age group. Our population-based study does not delineate the reason
for this observation, however, comorbidities, number of therapies since

Survival Trends:

diagnosis, and treatment adherence could affect these outcomes.

15%

Disease-specific survival (DSS) at 12, 24, and 36 months after diagnosis was

Methods

noted to be improving across all age groups from 2001 to 2012 (table 1) and

10%

this effect remained significant after adjusting for covariates (adjusted H.R.

The Surveillance, Epidemiology and End-Results (SEER) database was

0.81, 95% C.I. 0.76-0.86 for year of diagnosis 2010-2012 compared with 2001-

queried for patients aged 18 years and older diagnosed with distant stage

2003.)

2001-2003

2004-2006

2007-2009

2010-2012

Year of Diagnosis

Conclusions

TABLE 2: IMPACT OF DEMOGRAPHIC VARIABLES ON SURVIVAL

(metastatic) ccRCC between January 1, 2001 and December 31, 2012 in the

Our analysis quantifies the improvement in survival outcomes in metastatic

Cox Proportional Hazards

(adjusted)
H.R.
95% C.I.

ccRCC in the United States that correlate with TKI use in this setting.

eighteen SEER registries. Analyses were restricted to histologically

Improvement in DSS was maintained across all age groups at 12. 24. and 36

confirmed cases. Study period was divided into 3-year intervals: 2001-03

months from diagnosis in a subgroup analysis (figure 1.) Specifically, in

Non-Hispanic White

1.00

(pre-TKI era); 2004-06 (TKI trials era); 2007-09 (early TKI era); and 2010-12

ages 70 and above, the 36 month DSS improved from 13.9% in 2001-2003 to

Hispanic White

0.94

0.84-1.04

group is planning a SEER-Medicare analysis to evaluate disparities in TKI in

(late/sequential TKI era.) Stratification was done by age at diagnosis,

18.9% in 2010-2012 (p = 0.011.)

American Indian

0.89

0.71-1.11

the population.

Black

1.16

1.07-1.27

00-59

1.00

60-69

1.10

1.04-1.16

70 and above

1.38

1.31-1.46

Male

1.00

Female

1.07

1.02-1.12

Metropolitan

1.00

Non-Metropolitan

0.96

0.89-1.03

Fourth Quartile (Highest)

1.00

Third Quartile

1.02

0.96-1.09

[3] B. Ljungberg, S. C. Campbell, H. Y. Cho, D. Jacqmin, J. E. Lee, S. Weikert, and L. A. Kiemeney, The Epidemiology

Second Quartile

1.09

1.02-1.17

of Renal Cell Carcinoma, Eur. Urol., vol. 60, no. 4, pp. 615621, Oct. 2011.

First Quartile (Lowest)

1.13

1.03-1.24

[4] N. J. Vogelzang, Another Step Toward the Cure of Metastatic Renal Cell Carcinoma?, J. Clin. Oncol., vol. 28, no.

Race/Ethnicity

gender, race, residence in metropolitan area, and socio-economic status (as

Age at Diagnosis
(years)

defined by completion of high-school education.) One, two, and three year,

Demographic predictors of survival:

and median cause-specific survival were calculated by Kaplan-Meier

Younger age at diagnosis, female gender, and good socio-economic status

method. Differences in cause-specific survival by time period were

were associated with improved survival. Race and county of residence

assessed with the Log-Rank test. Multivariate Cox proportional hazards

(metropolitan or non-metropolitan) were not associated with survival. These

model was used to assess survival and analyze the impact of covariates.

are further delineated in table 2.

Gender
Residence

Socio-economic
status

Bibliography
[1] Cancer of the Kidney and Renal Pelvis - SEER Stat Fact Sheets. [Online]. Available:
http://seer.cancer.gov/statfacts/html/kidrp.html. [Accessed: 10-Aug-2015].
[2] W.-H. Chow, L. M. Dong, and S. S. Devesa, Epidemiology and risk factors for kidney cancer, Nat. Rev. Urol., vol.
7, no. 5, pp. 245257, May 2010.

34, pp. 50175019, Dec. 2010.

Results

[5] Drugs Approved for Kidney (Renal Cell) Cancer, National Cancer Institute. [Online]. Available:

TABLE 1: CAUSE-SPECIFIC SURVIVAL AT 12, 24, AND 36 MONTHS AFTER DIAGNOSIS

Demographics:

Kaplan-Meier Estimates of Survival

A total of 11,421 patients with metastatic ccRCC were included in the

No. of
Cases

analysis.
Year of diagnosis: 2,655 (23.2%) cases were diagnosed in 2001-2003, 2,656
(23.3%) in 2004-2006, 2,968 (25.9%) in 2007-2009, and 3,142 (27.5%) in 20102012.

Importantly, there has been improvement in DSS across all age groups. Our

Year of
diagnosis

Median
Survival
(Months)

12 months

24 months

36 months

http://www.cancer.gov/about-cancer/treatment/drugs/kidney. [Accessed: 24-Aug-2015].

Multi-Variate Cox Proportional Hazards Analysis

Percent Surviving at

Crude

Kabbinavar, Systemic Therapy for Metastatic Renal Cell Carcinoma: A Review and Update, Rev. Urol., vol. 14, no.
34, pp. 6578, 2012.

Adjusted

[7] L. C. Harshman, W. Xie, G. A. Bjarnason, J. J. Knox, M. MacKenzie, L. Wood, S. Srinivas, U. N. Vaishampayan, M.-

p
<0.0001

[6] J. E. Logan, E. N. Rampersaud, G. A. Sonn, K. Chamie, A. S. Belldegrun, A. J. Pantuck, D. J. Slamon, and F. F.

H. Tan, S.-Y. Rha, F. Donskov, N. Agarwal, C. Kollmannsberger, S. North, B. I. Rini, D. Y. C. Heng, and T. K. Choueiri,

Hazard Ratio

95% C.I.

Hazard Ratio

95% C.I.

1.00

Reference

1.00

Reference

population-based study, Lancet Oncol., vol. 13, no. 9, pp. 927935, Sep. 2012.

in the Cytokine and Targeted Therapy Era, PLoS ONE, vol. 8, no. 5, p. e63341, May 2013.

2001-2003

2,655

7.0

37.0

22.9

17.2

2004-2006

2,656

8.0

42.1

28.2

21.2

0.89

0.84-0.95

0.90

0.85-0.96

2007-2009

2,968

10.0

44.8

28.9

21.7

0.85

0.81-0.91

0.86

0.81-0.92

2010-2012

3,142

11.0

47.2

31.2

24.6

0.79

0.74-0.84

0.81

0.76-0.86

Email: arpitrao@unm.edu; Phone (323) 400-8073

Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy: a
[8] S. K. Pal, R. A. Nelson, and N. Vogelzang, Disease-Specific Survival in De Novo Metastatic Renal Cell Carcinoma