Understanding Treatment Disconnect and Mortality Trends in Renal Cell Carcinoma Using Tumor Registry Data.
The paradoxical rise in overall and cancer-specific mortality despite increased detection and treatment of renal cell carcinoma (RCC) is termed "treatment disconnect." We reassess this phenomenon by evaluating impact of missing data and rising incidence on mortality trends.



Using Surveillance, Epidemiology, and End Results data, we identified patients with RCC diagnosis from 1973 to 2011. We estimated mortality rates by tumor size after accounting for lags from diagnosis to death using multiple imputations for missing data from 1983. Mortality rates were estimated irrespective of tumor size after adjustment for prior cumulative incidence using ridge regression.



A total of 78,891 patients met inclusion criteria. Of 70,212 patients diagnosed since 1983, 10.4% had missing data. Significant attenuation in cancer-specific mortality was noted from 1983 to 2011 when comparing observed with imputed rates: Δobs0.05 versus Δimp0.10 (P=0.001, <2 cm tumors); Δobs0.29 versus Δimp0.18 (P=0.005, 2-4 cm tumors); Δobs0.46 versus Δimp-0.20 (P<0.001, 4-7 cm tumors); Δobs0.93 versus Δimp-0.15 (P<0.001, >7 cm tumors). Holding incidence of RCC constant to 2011 rates, temporal increase in overall mortality for all patients was attenuated (P<0.001) when comparing observed estimates (3.9-6.8) with 2011 adjusted estimates (5.9-7.1), suggesting that rapidly rising incidence may influence reported overall mortality trends. These findings were supported by assessment of mortality to incidence ratio trends.



Missing data and rising incidence may contribute substantially to the "treatment disconnect" phenomenon when examining mortality rates in RCC using tumor registry data. Caution is advised when basing clinical and policy decisions on these data.
*Division of Urologic Oncology †Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center-Temple University Health System, Philadelphia, PA ‡Department of Urology, Michigan University, Ann Arbor, MI §Department of Urology, Yale University, New Haven, CT ∥Division of Medical Oncology, Fox Chase Cancer Center-Temple University Health System, Philadelphia, PA.
Marc C
MC
Smaldone
Brian
B
Egleston
John M
JM
Hollingsworth
Brent K
BK
Hollenbeck
David C
DC
Miller
Todd M
TM
Morgan
Simon P
SP
Kim
Aseem
A
Malhotra
Elizabeth
E
Handorf
Yu-Ning
YN
Wong
Robert G
RG
Uzzo
Alexander
A
Kutikov
D000368:Aged; D002292:Carcinoma, Renal Cell / Q000401:mortality* / Q000628:therapy*; D005260:Female; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends*; D012042:Registries; D018426:SEER Program; D015996:Survival Rate; D014481:United States / Q000453:epidemiology