Results from our recent retrospective study show that surgically managed patients with kidney cancer and comorbid mild to moderate chronic kidney disease (CKD) experience significantly less need for future dialysis.
The findings underscore the importance of careful patient selection and screening for increased body mass index (BMI) and cardiovascular diseases such as hypertension, diabetes, and coronary artery disease to help predict the trajectory of patients’ renal function after surgery.
Published online ahead of print in the Canadian Urological Association Journal, it is the first study to describe differences in preoperative eGFR for patients with CKD who undergo kidney cancer surgery.
Among a cohort of 1,204 patients treated at Memorial Sloan Kettering Cancer Center (MSK) from 1998 to 2016, we observed an improving eGRF for patients with stage 3a CKD, compared to a worsening eGFR for those with stage 3b or higher CKD (p < 0.001) after partial or full nephrectomy for kidney cancer. The two-year and five-year cumulative incidence of dialysis was 1.8 percent (range 1.1 to 2.6 percent) and 3.1 percent (range 2.2 to 4.2 percent), respectively. (1)
Those with stage 3b or higher CKD have a higher risk of further reduction in estimated glomerular filtration rate (eGFR), the need for dialysis, and increased all-cause mortality for both partial and radical nephrectomy.
Balancing Benefits and Risks of Kidney Cancer Surgery in CKD Patients
Surgery is a key modality for managing kidney cancer, but surgical complications can increase the risk of compromised renal function. (2) Partial nephrectomy, when appropriate, reduces the likelihood of developing CKD and cardiovascular morbidity and mortality. (3), (4), (5) Studies have shown that patients with concurrent kidney cancer and CKD have an increased risk of end-stage renal disease (ESRD) and cardiovascular events. (6), (7)
Dependence on dialysis increases mortality and is associated with a decreased quality of life. (8), (9) Therefore, surgeons weigh the benefits of surgery against the risk of harming renal function further when treating kidney cancer in patients with CKD. They carefully assess tumor factors, including size, vascular extension, and clinical staging, as well as the patient’s fitness for surgery, including age, renal function, comorbidities, tobacco use, and BMI.
We previously validated the factors predicting restoration of baseline eGFR after radical nephrectomy: Patients with preoperative CKD, defined as an eGFR less than 60 mL/min/1.73m (2) were more likely than those with normal renal function, defined as an eGFR greater than 60 mL/min/1.73m, (2) to return to 95 percent of baseline eGFR within two years. eGFR recovery was associated with normal blood pressure and larger tumor size. However, we did not assess whether the recovery was durable, prevented long-term dialysis, or improved survival. (10)
For the present study, we queried our prospectively maintained kidney surgery database and identified 1,204 patients with CKD who underwent a partial or radical nephrectomy between 1998 and 2016. A preoperative eGFR less than 60 mL/min/1.73m (2) indicated CKD. (1)
To reduce bias from multiple operations, we followed patients from the time of their last staging or repeat surgery. We censored patients who started permanent or temporary dialysis or received kidney transplantation at the time of the intervention. (1)
Our primary goal was to characterize the long-term renal function trajectory of patients with pre-existing CKD who had kidney cancer surgery. Secondarily, we evaluated overall survival (OS) and cancer-specific survival (CSS). (1)
Among the 1,204 patients in our study, the median age was 68 years (interquartile range (IQR): 64–75), and 37 percent were women. The median time from preoperative eGFR assessment to kidney surgery was eight days (IQR: 5–13). (1)
At baseline, 892 patients (74 percent) had stage 3a, 271 (23 percent) had stage 3b, and 41 (3.4 percent) had stage 4 or 5 CKD. Patients with more advanced CKD tended to be older and more frequently had hypertension and coronary artery disease. Tumor characteristics were comparable across groups with predominantly malignant pathology. (1)
Patients in all groups more often received partial (61 percent) rather than radical (39 percent) nephrectomy. The median follow-up time among live patients who did not receive dialysis was 8.1 years (IQR: 4.6–10). (1)
Our main finding was that patients with stage 3b or stages 4/5 CKD at baseline had decreased eGFR, whereas patients with stage 3a disease at baseline had an increased eGFR over time from surgery. Factors associated with increasing eGFR included partial nephrectomy, female gender, younger age, lower BMI, and the absence of cardiovascular risk factors. (1)
During the study period, 55 patients needed dialysis, and 355 died, of which 99 or 28 percent were deaths due to kidney cancer. The two-year and five-year cumulative incidence of dialysis were 1.8 percent (95% confidence interval (CI): 1.1–2.6%) and 3.1 percent (95% CI: 2.2–4.2%), respectively. The cumulative incidence of dialysis significantly differed according to the preoperative CKD stage. Patients who had a partial nephrectomy had a lower cumulative incidence of dialysis, although the difference was not quite statistically significant.
The preoperative CKD stage was significantly associated with OS, but not CSS; patients with stage 3b and 4/5 disease had lower overall survival than those with stage 3a. Tumor factors, including size and preoperative metastasis, were significantly associated with OS and CSS but not dialysis. Female gender and increased BMI were associated with improved CSS, in line with other studies. Older age was associated with lower OS, and interestingly, a reduced incidence of dialysis, likely due to older patients dying of comorbidities before they needed dialysis.
A radical nephrectomy was associated with a decreased eGFR over time and worse OS and CSS. This finding may reflect a greater reduction in renal volume. Interestingly, tumor size was significantly associated with a lower eGFR over time on univariate analysis (p < 0.001), but the direction of this effect reversed on multivariate analysis, whereby increased tumor size was associated with an increased eGFR over time ( p = 0.101). Other studies have found that resection of larger tumors is associated with an improved postoperative eGFR. (11), (12) This finding may be explained by compensatory upregulation of the contralateral kidney to maintain homeostasis as the diseased kidney declines before surgery.
Advancing Kidney Cancer Outcomes
At MSK, we are dedicated to maximizing outcomes and the quality of life of kidney cancer patients. We are currently conducting 19 clinical trials testing investigational combinations of immunotherapies and targeted therapies for patients with kidney cancer.
The study was supported by funding by the National Cancer Institute. Dr. Russo has no external relationships or financial interests to disclose. For disclosures from other study authors, please refer to the paper.