Time-dependent changes in pathological risk factors of recurrence after renal cell carcinoma surgery

To evaluate time-dependent changes in pathological risk factors for recurrence in patients with renal cell carcinoma (RCC) after surgery, we assessed the impact of prolonged recurrence-free survival (RFS) on subsequent recurrence rates and pathological risk factors using conditional survival (CS) analysis.

This retrospective multicenter study included 994 patients who underwent radical or partial nephrectomy for localized RCC between 2010 and 2019. Conditional RFS (C-RFS) and conditional cumulative incidence of cancer-specific mortality (CCSM) were calculated to assess the time-dependent recurrence risk. The impact of pathological factors on recurrence was evaluated using multivariable Cox regression and hazard function analyses.

The 5-year C-RFS and CCSM remained stable over time, with no significant improvement even as the postoperative duration increased. Although pathological tumor stage and World Health Organization/International Society of Urological Pathology grade were significant predictors of recurrence at baseline, their prognostic values declined over time. In contrast, lymphovascular invasion (LVI) consistently remained a significant risk factor for recurrence throughout the follow-up period, as demonstrated by the CS analysis (baseline: LVI-positive, 64.3%; LVI-negative, 92.5%; 5-year LVI-positive, 74.1%; LVI-negative, 92.3%), multivariate Cox regression analyses (baseline hazard ratio [HR], 3.03; 3-year HR, 4.33), and hazard curves.

Even with longer event-free time after surgery, improvements in subsequent C-RFS and CCSM were limited. Although the influence of most pathological risk factors diminished over time, LVI remained a consistent predictor of recurrence. These findings underscore the importance of postoperative strategies that account for the dynamic changes in pathological risk factors in RCC.