Systematic classification and prediction of complications after nephrectomy in patients with metastatic renal cell carcinoma (RCC)

Objective To evaluate and identify factors predictive for morbidity after radical nephrectomy in patients with metastatic renal cell carcinoma (mRCC). Patients and methods We identified patients with mRCC who underwent nephrectomy at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1989 and 2009. Postoperative complications were characterised using a modified version of the Clavien-Dindo classification system. Patient and disease characteristics, including a previously validated MSKCC risk-stratification system using calcium, haemoglobin (Hb), lactate dehydrogenase, and Karnofsky Performance Status (KPS), were evaluated as predictors of postoperative complications using univariate and multivariable logistic regression models. The area under the receiver operating characteristic curve (AUC) was calculated for each model to assess predictive accuracy and corrected for overfit using 10-fold cross validation. Results Over the study period, 195 patients with mRCC underwent nephrectomy; 53 (27%) developed grade ≥2 complications within 8 weeks of surgery. Pulmonary, thromboembolic events and anaemia requiring transfusion were the most common types of complications after nephrectomy in the metastatic setting. In univariate analysis, age, low albumin, low KPS, high corrected serum calcium, low serum Hb, and unfavourable MSKCC risk score were predictive of complications. Patients who sustained postoperative complications were less likely to receive systemic therapy within 56 days (odds ratio [OR] 0.32; 95% confidence interval [CI] 0.12–0.86; P = 0.024). A multivariable model containing KPS (OR 14.5; 95%CI 4.34–48.6; P < 0.001) and age (OR 1.04; 95%CI 1.01–1.08; P = 0.014) showed the greatest predictive accuracy (corrected AUC 0.72; 95%CI 0.63–0.80) for postoperative complications. Conclusion Postoperative complications after radical nephrectomy in the setting of mRCC are common and occur frequently in older patients and those with worse KPS. These complications are important because they may delay or deny receipt of subsequent systemic therapy. Keywords: renal cell carcinoma, metastatic, nephrectomy, sunitinib, complications, Clavien Introduction RCC is diagnosed in > 58 000 Americans annually and results in the death of nearly 13 000 each year [1]. Despite the increasing incidental detection of smaller renal masses the absolute number of patients presenting with metastatic RCC (mRCC) has not changed significantly over the past 20 years [2]. However, in the same time frame, there has been a paradigm shift in the management of these patients. For patients with low metastatic burden and good performance status, nephrectomy followed by interferon-α showed improved survival compared with interferon-α alone [3, 4]. However, nephrectomy is an invasive surgical intervention and may not benefit all patients due to limited survival and risk of significant postoperative morbidity. Tyrosine kinase inhibitors are more effective than interferon-α in prolonging overall survival [5, 6]. This has led to questions about the role and timing of nephrectomy, as patients with significant postoperative morbidity may experience delay or never receive these agents [7–9]. These patients might be more likely to benefit from targeted therapy with their primary tumour in situ. The objective of the present study was to characterise complications among patients undergoing nephrectomy in the setting of metastatic disease, and to identify predictors of complications to better direct early treatment decisions.