Improved 5-Factor Prognostic Classification of Patients Receiving Salvage Systemic Therapy for Advanced Urothelial Carcinoma.
OBJECTIVE
Prognostic factors in patients receiving salvage systemic therapy for advanced urothelial carcinoma include performance status, liver metastasis, hemoglobin and time since chemotherapy. We investigated the impact of albumin, and neutrophil, lymphocyte and platelet counts.


METHODS
Patient level data from 10 phase II trials were used. Cox proportional hazards regression was applied to evaluate associations with overall survival. An optimal regression model was constructed using forward stepwise selection and risk groups were defined using the number of adverse factors. Trial was a stratification factor. External validation was done in a separate data set of 5 salvage phase II trials.


RESULTS
Discovery data were obtained on 708 patients. After adjustment for the 4 known factors a platelet count of the upper limit of normal or greater and albumin less than the lower limit of normal were significant poor prognostic factors. Only the addition of albumin was externally validated. For 0 or 1, 2 and 3 or greater risk factors median overall survival was 8.9, 6.4 and 4.5 months in 207, 171 and 113 patients in the discovery data set of 491, and 10.6, 10.0 and 7.0 months in 73, 47 and 47 patients, respectively, in the validation data set of 167. By adding albumin the c-index improved from 0.610 to 0.639 in the discovery set and from 0.616 to 0.646 in the validation set.


CONCLUSIONS
Albumin was externally validated as a prognostic factor for overall survival after accounting for time from prior chemotherapy, hemoglobin, performance status and liver metastasis status in patients receiving salvage systemic therapy for advanced urothelial carcinoma. The discovery of molecular prognostic factors is a priority to further enhance this new preferred 5-factor clinical prognostic model.
University of Alabama-Birmingham Comprehensive Cancer Center, Birmingham, Alabama. Electronic address: gsonpavde@uabmc.edu.
Guru
G
Sonpavde
McMaster University, Hamilton, Ontario, Canada.
Gregory R
GR
Pond
Memorial Sloan Kettering Cancer Center, New York, New York.
Jonathan E
JE
Rosenberg
Memorial Sloan Kettering Cancer Center, New York, New York.
Dean F
DF
Bajorin
Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Toni K
TK
Choueiri
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Andrea
A
Necchi
University Federico II, Naples, Italy.
Giuseppe
G
Di Lorenzo
Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Joaquim
J
Bellmunt
D014408:Biomarkers, Tumor / Q000097:blood; D001772:Blood Cell Count; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D016879:Salvage Therapy; D012709:Serum Albumin / Q000378:metabolism*; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
D014408:Biomarkers, Tumor; D012709:Serum Albumin
albumins; carcinoma; prognosis; urinary tract; urothelium