Cancers · 2026
The Prognostic Value of Clinical and Pathological Response to Neoadjuvant Therapy in Metastatic Renal Cell Carcinoma Undergoing Cytoreductive Nephrectomy: A Systematic Review and Clinical Implications.
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Chernysheva Daria, Hernandez-Peñalver Pedro, Maroto Pablo, Palou Joan, Breda Alberto, Rodriguez-Faba Oscar
Аннотация
BACKGROUND: In the immunotherapy era, cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is increasingly performed after neoadjuvant immune checkpoint inhibitor (ICI)-based therapy. Examination of the nephrectomy specimen may capture the depth of treatment-induced tumor clearance more accurately than size-based radiological criteria alone. However, pathological reporting is highly heterogeneous across studies: residual viable tumor (RVT), necrosis, pT stage, and binary downstaging have all been used, limiting reproducible cross-study comparison. We aimed to characterize this heterogeneity, assess its implications for evidence synthesis, and propose a pragmatic framework for qualitative interpretation.
METHODS: PRISMA-compliant systematic review of studies reporting pathological response and oncological outcomes in mRCC patients undergoing CN after neoadjuvant systemic therapy (PROSPERO CRD420251154068). A qualitative synthesis was performed. A three-category Pathological Response Category (PRC) framework is proposed to harmonize heterogeneous metrics.
RESULTS: Seven retrospective studies (n = 408) were included. Pathological reporting metrics were inconsistent across all studies, preventing formal meta-analysis. Nevertheless, across cohorts reporting survival outcomes, deeper pathological response was directionally associated with more favorable oncologic outcomes. A discordance between radiological and pathological response was observed, including near-complete tumor clearance in patients classified as radiologically stable, reflecting the non-size-based mechanisms of ICI-induced tumor killing.
CONCLUSIONS: The central finding of this review is not that pathological response predicts survival-which is expected-but that current pathological reporting in the mRCC surgical setting is too heterogeneous to quantify the frequency, depth, or prognostic significance of that response in a reproducible way. Prospective adoption of standardized pathological reporting protocols is the most critical next step for this field.
METHODS: PRISMA-compliant systematic review of studies reporting pathological response and oncological outcomes in mRCC patients undergoing CN after neoadjuvant systemic therapy (PROSPERO CRD420251154068). A qualitative synthesis was performed. A three-category Pathological Response Category (PRC) framework is proposed to harmonize heterogeneous metrics.
RESULTS: Seven retrospective studies (n = 408) were included. Pathological reporting metrics were inconsistent across all studies, preventing formal meta-analysis. Nevertheless, across cohorts reporting survival outcomes, deeper pathological response was directionally associated with more favorable oncologic outcomes. A discordance between radiological and pathological response was observed, including near-complete tumor clearance in patients classified as radiologically stable, reflecting the non-size-based mechanisms of ICI-induced tumor killing.
CONCLUSIONS: The central finding of this review is not that pathological response predicts survival-which is expected-but that current pathological reporting in the mRCC surgical setting is too heterogeneous to quantify the frequency, depth, or prognostic significance of that response in a reproducible way. Prospective adoption of standardized pathological reporting protocols is the most critical next step for this field.