Risk Factors for First-Year Recurrence in Patients With Synchronous Metastatic Renal Cell Carcinoma Undergoing Cytoreductive Nephrectomy and Complete Metastasectomy

Abstract

Purpose: Patients with metastatic renal cell carcinoma (mRCC) with oligometastatic disease can achieve radiographic disease-free (M1 NED) status after cytoreductive nephrectomy and concurrent complete metastasectomy. This study aimed to evaluate outcomes and identify risk factors associated with metastatic recurrence and overall survival in patients with mRCC M1 NED.

Materials and methods: Patients with synchronous mRCC who were M1 NED after cytoreductive nephrectomy and concurrent complete metastasectomy from 4 institutions (2010-2020) were identified. Survival outcomes were analyzed by the Kaplan-Meier method. Patients were grouped by early (first year after surgery) recurrence or delayed/no known metastatic recurrence. Logistic regression modeling identified risk factors for first-year recurrence, and decision curve analysis evaluated the utility of a model incorporating identified risk factors.

Results: One hundred and nine M1 NED patients were identified including 36 patients who had recurrence in the first year after surgery and 73 patients with delayed or no recurrence. First-year recurrence resulted in significantly shorter overall survival compared with those with delayed/no recurrence after 1 year (median 15 vs 97 months, respectively, P < .0001). First-year recurrence predictors included liver metastases, increasing primary tumor size, and elevated preoperative C-reactive protein. A prognostic model incorporating these factors demonstrated discriminatory capacity and improved clinical decision-making compared with a universal immediate postoperative systemic therapy or active surveillance strategy.

Conclusions: Liver metastasis, increasing primary tumor size, and elevated preoperative C-reactive protein are associated with increased risk for first-year progression after cytoreductive nephrectomy and complete metastasectomy. Despite radiographic NED status, high-risk patients should be considered for immediate systemic therapy after surgery given poor outcomes.

Keywords: cytoreductive nephrectomy; kidney cancer; metastasectomy; renal cell carcinoma; survival.

Figure 1.. Recurrence-Free, Systemic Therapy Free, and Overall Survival of Patients with M1 NED Renal Cell Carcinoma.

(A) Recurrence-free survival. (B) Systemic Therapy Free Survival (C) Overall Survival. For figures A-C, follow-up started from time of no evidence of disease after cytoreductive nephrectomy and complete metastasectomy. (D) Overall survival from a risk-defining event i.e., survival from time from recurrence for patients who recurred in the first year after achieving NED or from 12 months after achieving no evidence of disease for the delayed/no recurrence group. One patient was excluded from analysis due to death within 12 months without evidence of recurrence. Patients in the first-year recurrence cohort had inferior OS (Log-rank P<0.0001).

Figure 2.. Decision Curve Analysis Demonstrates Improved Decision-making for Early Initiation of Systemic Therapy.

This decision curve analysis evaluates the net benefit of a prognostic model for predicting recurrence within 12 months after surgery based on the presence of liver metastases, elevated preoperative C-reactive protein, and increasing primary tumor size. The x-axis represents the threshold probability of recurrence within 12 months after no clinical evidence of disease, and the y-axis shows net benefit. The blue curve represents the prognostic model. The green and orange lines correspond to a strategy of treating all patients after surgery with systemic therapy and a strategy of surveying all patients after surgery, respectively. The prognostic model provides clinical decision-making benefit across a range of threshold probabilities by offering superior net benefit compared to a treat all or survey all strategy.