Introduction:

The concept of “trifecta” since its first description has become a convenient tool to assess perioperative outcomes after partial nephrectomy (PN) for renal cell carcinoma (RCC). Emerging studies have demonstrated a positive association between trifecta achievement and improved survival and functional outcomes after PN. Recently, preoperative C-reactive protein (CRP) has been advocated as a useful tool to predict oncological outcome and renal functional decline. Herein we sought to integrate preoperative CRP into trifecta criteria to increase its prognostic capability.

Methods:

We examined our prospective database of patients with localized RCC (cT1-T3) who underwent PN. Trifecta was defined as negative surgical margins, no major postoperative complications of Clavien Dindo grade ≥3, and perioperative eGFR decrease of <30%. The primary outcome was all-cause mortality (ACM), and the secondary outcome was de novo eGFR of <45mL/min/1.73m2 (CKD-S3b). We performed multivariate analysis (MVA) using Cox regression to analyze the association between preoperative CRP and trifecta for ACM. Cut-point analysis using the concordance probability method identified CRP thresholds for low (LCRP) and high (HCRP) levels. Kaplan-Meier analysis (KMA) evaluated the overall survival (OS) and CKD-S3b progression-free survival, stratifying patients based on trifecta achievement and preoperative CRP levels. We proposed a new trifecta stratification based on the survival distributions. The Aikaike Information Criterion (AIC) was used to assess the performance of the proposed classification.

Results:

456 patients over a 34-months follow-up period were analyzed, with 316 (67.9%) achieving trifecta. MVA revealed CRP (HR 1.01, p=0.007) as associated with higher ACM risk. Trifecta was associated with reduced risk (HR 0.38, p=0.004). Cut-point analysis established HCRP as ≥5 mg/L. KMA demonstrated trends in the trifecta group with 5-year OS rates of 95.6% for LCRP and 90.1% for HCRP (p=0.13). In the non-trifecta group, rates were 91.3% for LCRP and 59.7% for HCRP (p<0.001). 5-year CKD-S3b-free survival rates in the trifecta group were 83.9% (LCRP) and 80.9% (HCRP, p=0.80), whereas rates in the non-trifecta group were 91.5% vs. 63.2%, respectively (p<0.001). Proposed risk stratification system is low (trifecta+LCRP), intermediate (trifecta+HCRP; no-trifecta+LCRP), and high (no-trifecta+HCRP). Proposed stratification demonstrated lower AIC, translating to superior performance, in predicting ACM and CKD-S3b compared to trifecta (369.921 vs. 381.272; 661.783 vs.671.321, respectively).

Conclusion:

Our findings suggest that non-trifecta patients with low preoperative CRP demonstrated similar outcomes to patients who achieved trifecta. Together these findings suggest that preoperative CRP could identify a subgroup of patients at risk for adverse outcomes. Further investigation is warranted.

Funding: N/A