Comprehensive investigation of clinicopathological and immunological features to determine prognostic impact in metastatic renal cell carcinoma: The JEWEL study.

OBJECTIVES

Current prognostic models for metastatic renal cell carcinoma (mRCC) are likely inaccurate due to recent treatment advances and improved survival outcomes. The JEWEL study used a data set from patients who received tyrosine kinase inhibitors (TKIs) to explore the prognostic impact of the tumor immune environment in the absence of immune checkpoint inhibitor intervention.

METHODS

The primary analysis population comprised 569 of the 770 Japanese patients enrolled in the ARCHERY study who received first-line TKIs. Multivariable Cox proportional hazard models were used to identify factors associated with the primary (overall survival [OS]) and secondary outcomes (treatment duration) using 34 candidate explanatory variables.

RESULTS

Median OS was 34.1 months (95% CI, 30.4-37.6) in the primary analysis population. A considerable negative prognostic impact (descriptive p ≤ 0.0005) on OS was seen with lactate dehydrogenase (LDH) >1.5 × upper limit of normal (adjusted HR [aHR], 3.30; 95% CI, 2.19-4.98), Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (aHR, 2.14; 95% CI, 1.56-2.94), World Health Organization (WHO)/International Society of Urological Pathology (ISUP) Grade 4 (aHR, 1.89; 95% CI, 1.43-2.51), C-reactive protein (CRP) level ≥0.3 (aHR, 1.78; 95% CI, 1.40-2.26), and age ≥75 years (aHR, 1.65; 95% CI, 1.24-2.18) in the multivariable analysis. PD-L1 and immunophenotype affected OS in univariable analyses but were not selected in the multivariable model as explanatory variables.

CONCLUSIONS

JEWEL identified sex, age, ECOG PS, liver and bone metastases, CRP levels, WHO/ISUP grade, LDH, and albumin levels as key prognostic factors for OS after first-line TKI therapy for mRCC.