External Validation of the 2003 Leibovich Prognostic Score in Patients Randomly Assigned to SORCE, an International Phase III Trial of Adjuvant Sorafenib in Renal Cell Cancer.

Purpose: The 2003 Leibovich score guides prognostication and selection to adjuvant clinical trials for patients with locally advanced renal cell carcinoma (RCC) after nephrectomy. We provide a robust external validation of the 2003 Leibovich score using contemporary data from SORCE, an international, randomized trial of sorafenib after excision of primary RCC.
Methods: Data used to derive the 2003 Leibovich score were compared with contemporary data from SORCE. Discrimination and calibration of the metastasis-free survival outcome were assessed in data from patients with clear-cell RCC, using Cox proportional hazards regression, Kaplan-Meier curves, and calculation of Harrell's c indexes. Secondary analyses involved three important SORCE groups: patients with any non-clear-cell subtype, papillary, and chromophobe carcinomas.
Results: Four hundred seven recurrences occurred in 982 patients in the Leibovich cohort and 520 recurrences were recorded in 1,445 patients in the primary SORCE cohort. Clear discrimination between intermediate-risk and high-risk SORCE cohorts was shown; hazard ratio 2.74 (95% CI, 2.29 to 3.28), c-index 0.63 (95% CI, 0.61 to 0.65). A hazard ratio of 0.61 (95% CI, 0.53 to 0.70) confirmed poor calibration of the two cohorts. Discrimination was observed in secondary populations, with c-indexes of 0.64 (95% CI, 0.59 to 0.69) for non-clear-cell RCC, 0.63 (95% CI, 0.56 to 0.69) for papillary RCC, and 0.65 (95% CI, 0.55 to 0.76) for chromophobe RCC.
Conclusion: The 2003 Leibovich score discriminates between intermediate-risk and high-risk clear-cell and non-clear-cell RCC groups in contemporary data, supporting its use for risk stratification in adjuvant clinical trials. Over time, metastasis-free survival for patients with locally advanced RCC has improved. Contemporary data from adjuvant RCC trials should be used to improve prognostication for patients with RCC.
Competing Interests: Tim EisenEmployment: AstraZeneca, RocheLeadership: AstraZeneca, RocheStock and Other Ownership Interests: AstraZeneca, RocheResearch Funding: Bayer (Inst), Pfizer (Inst), AstraZeneca (Inst)Travel, Accommodations, Expenses: AstraZeneca, RocheOther Relationship: Macmillan Cancer Support, Kidney Cancer UK Grant D. StewartHonoraria: Pfizer, Merck, EUSA PharmaConsulting or Advisory Role: Pfizer, Merck, EUSA Pharma, CMR SurgicalSpeakers' Bureau: PfizerResearch Funding: Pfizer, AstraZeneca, Intuitive Surgical, CRUKTravel, Accommodations, Expenses: Pfizer Axel BexConsulting or Advisory Role: Pfizer (Inst), Novartis (Inst), Bristol Myers Squibb (Inst), Ipsen (Inst), Eisai (Inst), Genentech (Inst)Speakers' Bureau: Pfizer, Novartis, Bristol Myers SquibbResearch Funding: Pfizer (Inst) Rick KaplanResearch Funding: AstraZeneca (Inst) Ian D. DavisResearch Funding: Astellas Pharma (Inst), Pfizer (Inst), Roche/Genentech (Inst), MSD Oncology (Inst), AstraZeneca (Inst), Janssen Oncology (Inst), Eisai (Inst), Bayer (Inst), Amgen (Inst), Bristol Myers Squibb (Inst), Movember Foundation (Inst), Exelixis (Inst), Ipsen (Inst), Medivation (Inst), Seattle Genetics (Inst), ANZUP Cancer Trials GroupPatents, Royalties, Other Intellectual Property: International Patent Application No: PCT/US2004/032147 (NY-ESO-1) through Ludwig Institute for Cancer Research Martin R. StocklerResearch Funding: Astellas Pharma (Inst), Celgene (Inst), Bayer (Inst), Bionomics (Inst), Medivation (Inst), Sanofi (Inst), Pfizer (Inst), AstraZeneca (Inst), Bristol Myers Squibb (Inst), Roche (Inst), Amgen (Inst), Merck Sharp & Dohme (Inst), Tilray (Inst), BeiGene (Inst)Travel, Accommodations, Expenses: Medivation/Pfizer Laurence AlbigesConsulting or Advisory Role: Bristol Myers Squibb (Inst), Ipsen (Inst), Roche (Inst), Novartis (Inst), Amgen (Inst), Pfizer (Inst), Astellas Pharma (Inst), Merck (Inst), MSD (Inst), AstraZeneca (Inst), Exelixis (Inst), Janssen (Inst), Eisai (Inst), Corvus Pharmaceuticals (Inst), Peloton Therapeutics (Inst), Bellerophon Theraeutics (Inst)Research Funding: Bristol Myers Squibb (Inst)Travel, Accommodations, Expenses: BMS, MSD Bernard EscudierHonoraria: Pfizer, Bristol Myers Squibb, Ipsen, OncorenaConsulting or Advisory Role: Pfizer, Bristol Myers Squibb, Ipsen, AVEO, OncorenaResearch Funding: BMS France (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Ipsen, MSD James LarkinHonoraria: Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Novartis, Roche/Genentech, Incyte, iOnctura, Merck Serono, Eisai, Dynavax Technologies, Cancer Research UK, touchIME, touchEXPERTSConsulting or Advisory Role: Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Novartis, Boston Biomedical, Incyte, iOnctura, Iovance Biotherapeutics, Immunocore, YKT Corporation, Apple Tree PartnersResearch Funding: Pfizer (Inst), Novartis (Inst), MSD (Inst), Bristol Myers Squibb (Inst), Achilles Therapeutics (Inst), Roche (Inst), Nektar (Inst), Covance (Inst), Immunocore (Inst), AVEO (Inst), Pharmacyclics (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Pfizer, Novartis, Roche/Genentech, AstraZeneca, Incyte, GlaxoSmithKline, Pierre Fabre, Merck Serono, iOnctura, British Uro-Oncology Group (BUG), ESMO, National Cancer Research Institute (NCRI), EUSA Pharma, Syneos Health, Kidney Cancer Association, Bioevents, MedConcept, RV Mais Steven JoniauConsulting or Advisory Role: Janssen, AstraZeneca, Bayer, Astellas PharmaSpeakers' Bureau: Astellas Pharma, Janssen, IpsenResearch Funding: Janssen (Inst), Astellas Pharma (Inst), Ipsen (Inst), Bayer (Inst), Ferring (Inst)Travel, Accommodations, Expenses: Janssen, Ipsen, Astellas Pharma, Ferring Joaquim BellmuntStock and Other Ownership Interests: Rainier TherapeuticsHonoraria: UpToDateConsulting or Advisory Role: Pierre Fabre, Astellas Pharma, Pfizer, Merck, Genentech, Novartis, AstraZeneca/MedImmune, Bristol Myers SquibbResearch Funding: Millennium (Inst), Sanofi (Inst), Pfizer/EMD Serono (Inst)Travel, Accommodations, Expenses: Pfizer, MSD Oncology, Ipsen Mahesh K.B. ParmarResearch Funding: AstraZeneca (Inst), Astellas Pharma (Inst), Janssen (Inst), Clovis Oncology (Inst) Angela MeadeResearch Funding: AstraZeneca (Inst)No other potential conflicts of interest were reported. Tim EisenEmployment: AstraZeneca, RocheLeadership: AstraZeneca, RocheStock and Other Ownership Interests: AstraZeneca, RocheResearch Funding: Bayer (Inst), Pfizer (Inst), AstraZeneca (Inst)Travel, Accommodations, Expenses: AstraZeneca, RocheOther Relationship: Macmillan Cancer Support, Kidney Cancer UK Grant D. StewartHonoraria: Pfizer, Merck, EUSA PharmaConsulting or Advisory Role: Pfizer, Merck, EUSA Pharma, CMR SurgicalSpeakers' Bureau: PfizerResearch Funding: Pfizer, AstraZeneca, Intuitive Surgical, CRUKTravel, Accommodations, Expenses: Pfizer Axel BexConsulting or Advisory Role: Pfizer (Inst), Novartis (Inst), Bristol Myers Squibb (Inst), Ipsen (Inst), Eisai (Inst), Genentech (Inst)Speakers' Bureau: Pfizer, Novartis, Bristol Myers SquibbResearch Funding: Pfizer (Inst) Rick KaplanResearch Funding: AstraZeneca (Inst) Ian D. DavisResearch Funding: Astellas Pharma (Inst), Pfizer (Inst), Roche/Genentech (Inst), MSD Oncology (Inst), AstraZeneca (Inst), Janssen Oncology (Inst), Eisai (Inst), Bayer (Inst), Amgen (Inst), Bristol Myers Squibb (Inst), Movember Foundation (Inst), Exelixis (Inst), Ipsen (Inst), Medivation (Inst), Seattle Genetics (Inst), ANZUP Cancer Trials GroupPatents, Royalties, Other Intellectual Property: International Patent Application No: PCT/US2004/032147 (NY-ESO-1) through Ludwig Institute for Cancer Research Martin R. StocklerResearch Funding: Astellas Pharma (Inst), Celgene (Inst), Bayer (Inst), Bionomics (Inst), Medivation (Inst), Sanofi (Inst), Pfizer (Inst), AstraZeneca (Inst), Bristol Myers Squibb (Inst), Roche (Inst), Amgen (Inst), Merck Sharp & Dohme (Inst), Tilray (Inst), BeiGene (Inst)Travel, Accommodations, Expenses: Medivation/Pfizer Laurence AlbigesConsulting or Advisory Role: Bristol Myers Squibb (Inst), Ipsen (Inst), Roche (Inst), Novartis (Inst), Amgen (Inst), Pfizer (Inst), Astellas Pharma (Inst), Merck (Inst), MSD (Inst), AstraZeneca (Inst), Exelixis (Inst), Janssen (Inst), Eisai (Inst), Corvus Pharmaceuticals (Inst), Peloton Therapeutics (Inst), Bellerophon Theraeutics (Inst)Research Funding: Bristol Myers Squibb (Inst)Travel, Accommodations, Expenses: BMS, MSD Bernard EscudierHonoraria: Pfizer, Bristol Myers Squibb, Ipsen, OncorenaConsulting or Advisory Role: Pfizer, Bristol Myers Squibb, Ipsen, AVEO, OncorenaResearch Funding: BMS France (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Ipsen, MSD James LarkinHonoraria: Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Novartis, Roche/Genentech, Incyte, iOnctura, Merck Serono, Eisai, Dynavax Technologies, Cancer Research UK, touchIME, touchEXPERTSConsulting or Advisory Role: Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Novartis, Boston Biomedical, Incyte, iOnctura, Iovance Biotherapeutics, Immunocore, YKT Corporation, Apple Tree PartnersResearch Funding: Pfizer (Inst), Novartis (Inst), MSD (Inst), Bristol Myers Squibb (Inst), Achilles Therapeutics (Inst), Roche (Inst), Nektar (Inst), Covance (Inst), Immunocore (Inst), AVEO (Inst), Pharmacyclics (Inst)Travel, Accommodations, Expenses: Bristol Myers Squibb, Pfizer, Novartis, Roche/Genentech, AstraZeneca, Incyte, GlaxoSmithKline, Pierre Fabre, Merck Serono, iOnctura, British Uro-Oncology Group (BUG), ESMO, National Cancer Research Institute (NCRI), EUSA Pharma, Syneos Health, Kidney Cancer Association, Bioevents, MedConcept, RV Mais Steven JoniauConsulting or Advisory Role: Janssen, AstraZeneca, Bayer, Astellas PharmaSpeakers' Bureau: Astellas Pharma, Janssen, IpsenResearch Funding: Janssen (Inst), Astellas Pharma (Inst), Ipsen (Inst), Bayer (Inst), Ferring (Inst)Travel, Accommodations, Expenses: Janssen, Ipsen, Astellas Pharma, Ferring Joaquim BellmuntStock and Other Ownership Interests: Rainier TherapeuticsHonoraria: UpToDateConsulting or Advisory Role: Pierre Fabre, Astellas Pharma, Pfizer, Merck, Genentech, Novartis, AstraZeneca/MedImmune, Bristol Myers SquibbResearch Funding: Millennium (Inst), Sanofi (Inst), Pfizer/EMD Serono (Inst)Travel, Accommodations, Expenses: Pfizer, MSD Oncology, Ipsen Mahesh K.B. ParmarResearch Funding: AstraZeneca (Inst), Astellas Pharma (Inst), Janssen (Inst), Clovis Oncology (Inst) Angela MeadeResearch Funding: AstraZeneca (Inst)No other potential conflicts of interest were reported.