Abstract
Background: Several biomarkers of treatment efficacy have been associated with a better prognosis in patients with metastatic renal cell carcinoma (mRCC). The prognostic significance of biomarkers in the early treatment phase is unclear.Material and methods: In a complete national cohort of mRCC patients receiving first-line tyrosine kinase inhibitors (TKI) or interleukin-2 based immunotherapy (IT) from 2006 to 2010, overall survival (OS) was analysed for baseline International mRCC Database Consortium (IMDC) classification factors and on-treatment time-dependent biomarkers obtained day 1 each cycle week 4–12 after treatment initiation with multivariate analysis and bootstrap validation.Results: A total of 735 patients received first-line TKI (59%) or IT (41%). Median OS was overall 14.0 months and 33.4, 18.5, and 5.8 months for baseline IMDC favourable, intermediate, and poor risk groups, respectively (p < 0.0001). Systolic blood pressure ≥140 mmHg, neutrophils < lower level of normal (LLN), platelets < LLN, sodium ≥ LLN, and LDH ≤1.5 times upper level of normal after treatment initiation were significantly associated with favourable OS independent of baseline IMDC risk group in multivariate analyses stratified for TKI and IT (p ≤ 0.04). Concordance (C)-index for IMDC classification alone was 0.625 (95% CI 0.59–0.66) and combined with the five-factor biomarker profile 0.683 (95% CI 0.64–0.72). For patients with good (3–5 factors) and poor (0–2 factors) biomarker profile median OS were 23.5 and 9.6 months, respectively (p < 0.0001). Adding the five-factor biomarker profile significantly improved prognostication in IMDC intermediate (25.7 vs. 12.0 months, p < 0.0001) and poor (12.8 vs. 6.4 months, p < 0.0001) risk groups. A trend was seen in IMDC favourable risk group (38.9 vs. 28.7 months, p = 0.112).Conclusion: On-treatment hypertension, neutropenia, thrombocytopenia, LDH below 1.5 times upper level of normal, and normal sodium, obtained week 4–12 of treatment, are independent biomarkers of favourable outcome in mRCC, independent of treatment type.
Highlights
Several biomarkers of treatment efficacy have been associated with a better prognosis in patients with metastatic renal cell carcinoma
If neutrophils or platelets were measured below level of normal (LLN), haemoglobin or sodium at or above LLN, calcium at or below ULN, LDH at or below 1.5 Â ULN, and thyroid-stimulating hormone (TSH) above ULN at any time after baseline but within or equal to 12 week after treatment initiation the patient would remain in the category despite subsequent reversal of values
Hypertension was defined as systolic Blood pressure (BP) (SBP) above or equal to 140 mmHg or diastolic BP (DBP) above or equal to 90 mmHg
Summary
Several biomarkers of treatment efficacy have been associated with a better prognosis in patients with metastatic renal cell carcinoma (mRCC). Median OS was overall 14.0 months and 33.4, 18.5, and 5.8 months for baseline IMDC favourable, intermediate, and poor risk groups, respectively (p50.0001). LLN, and LDH 1.5 times upper level of normal after treatment initiation were significantly associated with favourable OS independent of baseline IMDC risk group in multivariate analyses stratified for TKI and IT (p 0.04). Adding the fivefactor biomarker profile significantly improved prognostication in IMDC intermediate (25.7 vs 12.0 months, p50.0001) and poor (12.8 vs 6.4 months, p50.0001) risk groups. Conclusion: On-treatment hypertension, neutropenia, thrombocytopenia, LDH below 1.5 times upper level of normal, and normal sodium, obtained week 4–12 of treatment, are independent biomarkers of favourable outcome in mRCC, independent of treatment type
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