Upstaging to pT3a in Patients Undergoing Partial or Radical Nephrectomy for cT1 Renal Tumors: A Systematic Review and Meta-analysis of Outcomes and Predictive Factors

Context: Predictors of upstaging from cT1 to pT3a renal masses are poorly inquired, and this remains an area of controversial findings. Objective: To evaluate predictors and outcomes of upstaging from cT1 to pT3a in patients undergoing surgical removal of a renal tumor. Evidence acquisition: A systematic literature search was performed to identify relevant articles using three electronic engines (PubMed, Embase, and Web of Science). Only studies looking at upstaging to pT3a in patients undergoing either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1 renal tumor were included. Study selection was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Evidence synthesis: Thirteen studies, including 21869 patients (cT1/pT3a: 1256 [5.7%]; cT1/pT1: 20613 [93.3%]), were identified. Patients in the upstaged group were older (weighted mean difference [WMD]: 3.89; p < 0.00001) and mostly male (odds ratio [OR]: 1.23; p = 0.04). Renal tumors were larger (WMD: 0.98; p < 0.00001), more complex (OR: 2.38; p < 0.0001), and with a higher rate of cT1b masses (OR: 3.36; p < 0.00001). The cT1/pT3a group had a higher rate of other renal cell carcinoma histological subtypes (OR: 1.59; p = 0.04), as well as higher odds of Fuhrman grade ≥3 (OR: 2.57; p < 0.00001) and positive surgical margins (OR: 1.85; p = 0.007). Five-year recurrence-free survival (RFS) was worse in the upstaged group (OR: 0.31; p = 0.02). Age (OR: 1.03; p < 0.00001), tumor size (OR: 1.51; p < 0.00001), and RENAL score (OR: 2.80; p = 0.0004) were predictors of upstaging. Upstaging was associated with overall survival (hazard ratio [HR]: 1.94; p = 0.05), cancer-specific survival (HR: 2.24; p = 0.007), and RFS (HR: 2.17; p < 0.00001). Conclusions: Upstaging to pT3a in case of surgical removal of a cT1 renal tumor is an uncommon event, which however can translate into worse oncological outcomes. Both patient (older age) and tumor (larger size and higher complexity) characteristics are associated with a higher risk of upstaging. There is very limited evidence regarding whether RN would be better than PN in these cases. There remains an unmet need for tools to better characterize renal masses in the preoperative setting. Patients summary: About 6% of surgically treated localized renal tumors can be found to be locally advanced on final pathology after surgery. This “upstaging” can translate into worse oncological outcomes. There are patient and tumor characteristics that are associated with an increased the risk of upstaging. Upstaging can translate into worse oncological outcomes. Surgeons should be aware of predictors of upstaging during treatment planning. There is an unmet need for tools to better characterize renal masses