MADISON, WI – It is possible for patients with metastatic renal cell carcinoma (mRCC) with oligometastatic disease to achieve radiographic disease-free (M1 NED) status following cytoreductive nephrectomy and concurrent complete metastasectomy (CNCM). A new study evaluated outcomes and uncovered risk factors associated with metastatic recurrence and overall survival in mRCC M1 NED patients.
The study team led by the University of Wisconsin School of Medicine and Public Health and the William S. Middleton Memorial Veterans Hospital, both in Madison, identified patients with synchronous mRCC who were M1 NED following CNCM from four institutions from 2010–2020. In analyzing survival outcomes, the patients were grouped by early (first year following surgery) recurrence or delayed/no known metastatic recurrence.
Of the 109 M1 NED patients identified, 36 had recurrence in the first year following surgery and 73 patients had delayed or no recurrence.
“First-year recurrence resulted in significantly shorter overall survival (OS) compared to those with delayed/no recurrence after 1 year (median 15 vs. 97 months respectively, P<0.0001),” the researchers wrote in the Journal of Urology. “First-year recurrence predictors included liver metastases, increasing primary tumor size, and elevated preoperative C-reactive protein (CRP). A prognostic model incorporating these factors demonstrated discriminatory capacity and improved clinical decision-making compared to a universal immediate post-operative systemic therapy or active surveillance strategy.”1
The authors concluded that liver metastasis, increasing primary tumor size, and elevated preoperative CRP are associated with increased risk for first-year progression following cytoreductive nephrectomy and complete metastasectomy. “Despite radiographic NED status, high risk patients should be considered for immediate systemic therapy following surgery given poor outcomes,” they advised.
Background information in the article noted that a subset of patients with metastatic renal cell carcinoma (mRCC) present with synchronous low volume or oligometastatic disease. “Although microscopic disease is likely present,” the researchers suggested, “cytoreductive nephrectomy and complete metastasectomy (CNCM) may render select patients radiographically with no evidence of disease (NED) on follow-up imaging. Prior studies demonstrate patients with metastatic RCC who underwent CM and had no clinical evidence of disease (M1 NED) had significantly improved cancer-specific and overall survival.”
The authors advised that, when feasible, the rationale for CNCM includes potentially slowing the rate of disease progression, symptomatic relief in large primary tumors or metastatic sites and delaying initiation of systemic treatments.
They point out that, even in patients treated with aggressive surgery, most patients have microscopic metastatic disease present, which eventually results in radiographic disease progression or recurrence. “It is also important to consider the perioperative morbidity associated with CNCM, given prior reports (albeit historical) demonstrating complications in 25% of patients treated with metastasectomy, including 10% with major complications,” the researchers noted. “Given the risks of CNCM, it is critical to understand which patients may benefit from aggressive surgery and which patients rendered disease free with surgery should initiate immediate post-operative systemic therapy versus conservative management with imaging surveillance.”
The study concluded, “The median OS of this cohort (85 months) is favorable. Unsurprisingly, we found that patients who recurred within 12 months of CNCM had a significantly reduced OS. Thus, it is important to understand which patients are likely to recur early as this will aid preoperative counseling and determining which patients should receive postoperative therapy rather than surveillance.
This study differed from many prior ones of complete metastasectomy because only patients with synchronous mRCC were included” initially present with localized disease and subsequently develop metastatic disease often have a more indolent phenotype, which likely makes the decision for local treatment of oligometastatic disease more straightforward.”
- Ghasemzadeh A, Abel EJ, Karam JA, Spiess PE, Peyton CC, Manley BJ, Sirard RB, Robertson N, Ellis EE, Cotta BH, Patel KR, Nicaise E, Jani A, Sexton WJ, Patil D, Allen GO, Matin SF, Master VA, Shapiro DD. Risk Factors for First-Year Recurrence in Patients With Synchronous Metastatic Renal Cell Carcinoma Undergoing Cytoreductive Nephrectomy and Complete Metastasectomy. J Urol. 2025