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Positive Surgical Margins in Clear Cell Renal Cell Carcinoma: Prognostic Impact and Implications for Risk Stratification and Adjuvant Therapy

  • 0Department of Urology, UC San Diego Health System, San Diego, CA 92121, USA.
Journal of Clinical Medicine +

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June 13, 2025

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June 13, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Positive surgical margins (PSMs) after kidney cancer surgery independently predict worse overall survival (OS) in clear cell renal cell carcinoma (ccRCC), particularly in later stages. This finding impacts risk assessment and adjuvant therapy eligibility for ccRCC patients.

Area Of Science

  • Urology
  • Oncology
  • Nephrology

Background

  • Positive surgical margins (PSMs) in renal cell carcinoma (RCC) surgery are a concern, yet their prognostic value across different stages and impact on adjuvant therapy eligibility remain debated.
  • Landmark clinical trials for adjuvant therapy in clear cell renal cell carcinoma (ccRCC) often excluded patients with PSMs, limiting evidence for this subgroup.

Purpose Of The Study

  • To evaluate the prognostic significance of PSMs following partial or radical nephrectomy for ccRCC across American Joint Committee on Cancer (AJCC) stages.
  • To assess the relevance of PSMs for eligibility in adjuvant therapy for ccRCC patients.

Main Methods

  • Retrospective analysis of 171,151 ccRCC patients undergoing nephrectomy from the National Cancer Database (2004-2020).
  • Exclusion of patients receiving systemic therapy or with missing data; overall survival (OS) analyzed using Kaplan-Meier, log-rank tests, and Cox regression.
  • Subgroup analyses compared specific tumor characteristics (T2 G2/G3 PSM vs. T2 G4 NSM) and assessed PSM impact within KEYNOTE-564 risk groups.

Main Results

  • PSMs were identified in 5.9% of patients and were an independent predictor of worse OS (HR 1.43, p < 0.001).
  • Prognostic impact of PSMs varied by AJCC stage, with significant survival differences noted in stages II, III, and IV, but not stage I.
  • In the KEYNOTE-564 risk population, PSMs were associated with a 62% increased risk of death (HR 1.62, p < 0.001).

Conclusions

  • PSMs are independently linked to poorer OS in ccRCC patients.
  • The prognostic impact of PSMs is stage-dependent, suggesting their utility in refining risk stratification and surveillance strategies.
  • Considering patients with PSMs for adjuvant therapy trials is warranted.

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