Validation of preoperative variables and stratification of patients to help predict benefit of cytoreductive nephrectomy in the targeted therapy ERA

Abstract

Objectives To further elucidate which patients with metastatic renal cell carcinoma (mRCC) may benefit from cytoreductive nephrectomy (CN) before targeted therapy (TT), and to assess the overall survival of patients undergoing CN and TT versus TT alone.Materials and Methods We identified 88 patients who underwent CN at our institution prior to planned TT and 35 patients who received TT without undergoing CN. Preoperative risk factors described in the literature were assessed in our patient population (serum albumin, liver metastasis, symptomatic metastasis, clinical ≥T3 disease, retroperitoneal and supradiaphragmatic lymphadenopathy). Patients were stratified by number of pretreatment risk factors and overall survival (OS) was compared.Results TT patients had significantly more risk factors compared to CN patients (3.06 vs. 2.11, p<0.01). Patients who received TT alone had median OS of 5.8 months. All but one patient receiving TT alone had two or more risk factors. A comparison of the CN and TT groups was performed by constructing Kaplan-Meier curves. There was no significant difference in median OS for those patients with exactly two risk factors (447 vs. 389 days, p=0.24), and those with three or more risk factors (184 vs. 155 days, p=0.87).Conclusions Using previously described pretreatment risk factors we found that patients with two or more risk factors derived no significant survival advantage from CN in the TT era. These risk factors should be incorporated in the assessment of patients for CN.

Long-Term Survival Outcomes of Cytoreductive Nephrectomy Combined with Targeted Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Individual Patient Data Meta-Analysis

“…We determined that 96 articles were relevant based on their titles and abstracts, and further evaluated their full texts for eligibility. Fifteen studies (fourteen retrospective cohort studies and one RCT) fulfilled the pre-determined inclusion criteria and were included in our meta-analysis ( Figure 1 ) [ 15 , 16 , 17 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. On one occasion, data from two studies with overlapping populations reporting on different outcomes were combined [ 39 , 47 ].…”

“…We assessed the individual risk of bias of 14 observational studies using the ROBINS-I tool. The overall risk of bias was determined to be low in one study [ 41 ], moderate in twelve studies [ 15 , 17 , 35 , 36 , 37 , 38 , 39 , 40 , 42 , 43 , 44 , 46 ] and serious in one study [ 45 ]. No studies were found to be at critical risk of bias ( Figure 2 A,B).…”

“…The OS curve of the pooled patient cohorts either receiving CN plus targeted therapy ( n = 2205) or targeted therapy alone ( n = 1752) derived from fifteen studies [ 15 , 16 , 17 , 35 , 36 , 37 , 38 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ] is presented in Figure 3 A. The median OS was 23.3 months (95% CI: 22.0 to 24.9) in the CN group and 12.9 months (95% CI: 12.0 to 14.1) in the non-CN group.…”

“…Eleven studies were included for the OS [ 16 , 17 , 35 , 36 , 37 , 38 , 39 , 40 , 44 , 45 , 46 ], six studies for the PFS [ 16 , 17 , 37 , 45 , 46 , 47 ], and two studies for the CSS subgroup analysis [ 17 , 35 ] comparing upfront CN followed by targeted therapy vs. targeted therapy alone. Patients undergoing upfront CN had superior OS compared to those who did not, as shown in both one-stage frequentist (HR: 0.70, 95% CI: 0.63 to 0.78, p < 0.001) ( Figure 4 A) and Bayesian (HR: 0.70, 95% CrI: 0.64 to 0.78) meta-analyses.…”

“…A post-hoc analysis of the CARMENA trial particularly highlights this concern by suggesting that patients with one but not two IMDC risk factors (both classified as intermediate-risk patients) benefited from CN [ 70 ]. Other authors have used their own models to stratify patients based on prognostic factors derived from regression analyses [ 36 , 44 ]. Regardless of the approach, several studies have shown that CN offered a considerable survival advantage, even when accounting for these risk factors by performing subgroup analyses in patients with more favorable prognosis [ 15 , 36 , 42 , 44 ].…”