Progression-free survival and objective response rate as a surrogate end point for overall survival in metastatic renal cell carcinoma: A systematic review and meta-analysis
In brief
Progression and tumor response only moderately track survival in kidney cancer trials
Across 62 trials with 24,518 patients, improvements in progression-free survival and tumor response were only moderately associated with longer overall survival. The links varied across treatment settings and were not consistent enough to reliably predict a survival benefit, so overall survival remains important when judging treatments; evidence was especially limited for less common kidney cancer types.
- Journal
- Cancer (Q1)
- Published
- 1 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Russell Leong, David Chen, Laith Almasri, Nicholas Lum, Karren Xiao, Maryam Soleimani, et al.
- PMID
- 42779347
- DOI
- 10.1002/cncr.70616
Why clinicians should know about it
- Picked for Nephrology (top studies of the week, 27 September 2026): Surrogate endpoints in metastatic renal cell carcinoma
- Picked for Oncology and Radiation Oncology (top studies of the week, 27 September 2026): Moderate correlation PFS/OS, surrogate not reliable
- Picked for Radiation Oncology (top studies of the week, 27 September 2026): Surrogate endpoints in renal cell carcinoma, no radiation
- Picked for Surgical Oncology (top studies of the week, 27 September 2026): Recent Surgical Oncology research from a high-quartile journal
- Picked for Urology (top studies of the week, 27 September 2026): Not relevant to urology clinical practice
- Picked for Histology (top studies of the week, 27 September 2026): PFS‑OS demonstrated a moderate correlation (r = 0.52)
Abstract
The objective of this systematic review and meta-analysis was to evaluate the validity of progression-free survival (PFS) and the objective response rate (ORR) as surrogate end points for overall survival (OS) in randomized controlled trials (RCTs) of metastatic renal cell carcinoma. The MEDLINE, Embase, and Cochrane CENTRAL databases were searched from inception to June 10, 2025. Associations between treatment effects on OS, PFS, and ORR were assessed using Pearson correlation coefficients (r). Surrogate threshold effect (STE) analyses determined the minimum PFS hazard ratio (HR) or ORR odds ratio (OR) required to predict OS benefit. Subgroup analyses were conducted by treatment class, line of therapy, and histology. Sixty-two randomized controlled trials comprising 24,518 patients were included. PFS-OS demonstrated a moderate correlation (r = 0.52; 95% confidence interval [CI], 0.38-0.66), with an STE (HR, 0.92; 95% CI, 0.79-1.09). ORR-OS demonstrated a moderate correlation (r = -0.59; 95% CI, -0.72, -0.45), with an STE (OR, 1.40; 95% CI, 0.99-1.89). Subgroup estimates varied across treatment settings and were frequently imprecise, particularly for ORR and in smaller treatment-class subgroups; limited representation of non-clear cell renal cell carcinoma precluded reliable histology-specific conclusions. Overall, PFS and ORR had moderate trial-level associations with OS in metastatic renal cell carcinoma, but the overall analyses did not demonstrate sufficiently consistent surrogacy to reliably predict OS benefit. These findings should be interpreted cautiously given the substantial heterogeneity of the included trials. Surrogate validity appears to be context-dependent, supporting continued reliance on OS and the need for more robust surrogate end points.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.