In the European Organization for Research and Treatment of Cancer (EORTC) randomized trial 30904, nephron-sparing surgery (NSS) was associated with reduced overall survival compared with radical nephrectomy (RN) over a median follow-up of 9.3 yr (hazard ratio: 1.50; 95% confidence interval [CI], 1.03–2.16).
Objective
To examine the impact of NSS relative to RN on kidney function in EORTC 30904.
Design, setting, and participants
This phase 3 international randomized trial was conducted in patients with a small (≤5 cm) renal mass and normal contralateral kidney who were enrolled from March 1992 to January 2003.
Intervention
Patients were randomized to RN (n = 273) or NSS (n = 268).
Outcome measurements and statistical analysis
Follow-up estimated glomerular filtration rates (eGFR; milliliters per minute per 1.73 m2) were recorded for 259 subjects in the RN arm and 255 subjects in the NSS arm. Percentages of subjects developing at least moderate renal dysfunction (eGFR <60), advanced kidney disease (eGFR <30), or kidney failure (eGFR <15) were calculated for each treatment arm based on the lowest recorded follow-up eGFR (intent-to-treat analysis).
Results and limitations
With a median follow-up of 6.7 yr, eGFR <60 was reached by 85.7% with RN and 64.7% with NSS, with a difference of 21.0% (95% CI, 13.8–28.3); eGFR <30 was reached by 10.0% with RN and 6.3% with NSS, with a difference of 3.7% (95% CI, –1.0 to 8.5); and eGFR <15 was reached by 1.5% with RN and 1.6% with NSS, with a difference of –0.1% (95% CI, –2.2 to 2.1). Lack of longer follow-up for eGFR is a limitation of these analyses.
Conclusions
Compared with RN, NSS substantially reduced the incidence of at least moderate renal dysfunction (eGFR <60), although with available follow-up the incidence of advanced kidney disease (eGFR <30) was relatively similar in the two treatment arms, and the incidence of kidney failure (eGFR <15) was nearly identical. The beneficial impact of NSS on eGFR did not result in improved survival in this study population.
According to a recent systematic review of 20 observational studies, in patients with a small renal mass (T1a and selected T1b tumors), nephron-sparing surgery (NSS) is associated with improved overall survival compared with radical nephrectomy (RN) [1]. These findings were attributed to similar oncologic outcomes after NSS and RN, with better preservation of renal function after NSS [1]. However, these studies were limited by their observational design and thus subject to selection bias.
In 2011, Van Poppel et al. presented results of a randomized trial of NSS versus RN for a small (≤5 cm) solitary renal mass, with a prospective assessment of renal function, oncologic outcomes, and overall and cause-specific survival [2]. Median follow-up for all-cause mortality was 9.3 yr. In the intention-to-treat analysis, overall survival was better in the RN arm compared with the NSS arm (hazard ratio [HR]:1.50; 95% confidence interval [CI], 1.03–2.16; p = 0.03) [2]. This difference, however, could not be attributed to differences in kidney cancer mortality. Among the 273 patients randomized to RN, 4 patients died from kidney cancer and 46 died from other causes. Among the 268 patients randomized to NSS, 8 patients died from kidney cancer and 59 died from other causes. The difference in kidney cancer mortality (NSS vs RN) was not statistically significant (p = 0.23) [2]. The impact of NSS relative to RN on postoperative kidney function as assessed by the estimated glomerular filtration rate (eGFR) has not been previously reported. The main objective of this analysis was to examine the incidence of at least moderate renal dysfunction (eGFR <60), advanced kidney disease (eGFR <30), and kidney failure (eGFR <15) in the RN and the NSS arms of European Organization for Research and Treatment of Cancer (EORTC) trial 30904. In exploratory analyses, we investigated whether the effect of NSS relative to RN on kidney function depends on baseline creatinine and comorbidities.
Section snippets
Study design
This study was a randomized trial of RN versus NSS, with all-cause mortality as the primary end point. Details of the study design were reported elsewhere [2], [3]. Eligibility criteria included a solitary renal mass suspicious for renal cell carcinoma ≤5 cm, a radiographically normal contralateral kidney, and a World Health Organization performance status of 0–2. Preoperative serum creatinine (SC) was documented as ≤1.25 × upper limit of normal (ULN), 1.26–2.5 × ULN, or 2.6–5.0 × ULN (ie, exact
Results
From March 1992 to January 2003, 541 patients from 45 institutions [2] were randomized to undergo RN (n = 273) or NSS (n = 268). In each intervention arm, 12 patients had no information on follow-up SC and were excluded from the current analyses. Among the remaining patients, the sex of two patients in the RN arm and one patient in the NSS arm was unknown. They were also excluded because their eGFR could not be calculated (Fig. 1). Hence the current analyses were based on 259 patients randomized to
Discussion
Our current analyses demonstrated that over a median follow-up of 6.7 yr for eGFR, NSS compared with RN substantially reduced the incidence of at least moderate renal dysfunction stage A (eGFR <60) and stage B (eGFR <45) based on both lowest eGFR and last eGFR, although the incidence of advanced kidney disease (eGFR <30) was relatively similar in the two treatment arms, and the incidence of kidney failure (eGFR <15) was essentially identical. The beneficial impact of NSS on eGFR did not result
Conclusions
In EORTC 30904, the only randomized trial of RN versus NSS completed to date, over a median follow-up of 6.7 yr for eGFR, NSS substantially reduced the incidence of at least moderate renal dysfunction (eGFR <60), although the incidence of advanced kidney disease (eGFR <30) was relatively similar in the two treatment arms and the incidence of kidney failure (eGFR <15) nearly identical. The beneficial impact of NSS on eGFR did not result in improved survival in this study population with a median
Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial.
This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0–2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual.
Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70–82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7–5·5). All patients enrolled had T1–T2a and N0–N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38–60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred.
To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer.
Cancer Australia Priority-driven Collaborative Cancer Research Scheme.
Nephrectomy is the mainstay of treatment for individuals with localized kidney cancer. However, surgery can potentially result in the loss of kidney function or in kidney failure requiring dialysis/kidney transplantation. There are currently no clinical tools available to preoperatively identify which patients are at risk of kidney failure over the long term. Our study developed and validated a prediction equation for kidney failure after nephrectomy for localized kidney cancer.
Population-level cohort study.
Adults (n = 1,026) from Manitoba, Canada, with non-metastatic kidney cancer diagnosed between January 1, 2004, and December 31, 2016, who were treated with either a partial or radical nephrectomy and had at least 1 estimated glomerular filtration rate (eGFR) measurement before and after nephrectomy. A validation cohort included individuals in Ontario (n = 12,043) with a diagnosis of localized kidney cancer between October 1, 2008, and September 30, 2018, who received a partial or radical nephrectomy and had at least 1 eGFR measurement before and after surgery.
Age, sex, eGFR, urinary albumin-creatinine ratio, history of diabetes mellitus, and nephrectomy type (partial/radical).
The primary outcome was a composite of dialysis, transplantation, or an eGFR < 15 mL/min/1.73 m2 during the follow-up period.
Cox proportional hazards regression models evaluated for accuracy using area under the receiver operating characteristic curve (AUC), Brier scores, calibration plots, and continuous net reclassification improvement. We also implemented decision curve analysis. Models developed in the Manitoba cohort were validated in the Ontario cohort.
In the development cohort, 10.3% reached kidney failure after nephrectomy. The final model resulted in a 5-year area under the curve of 0.85 (95% CI, 0.78-0.92) in the development cohort and 0.86 (95% CI, 0.84-0.88) in the validation cohort.
Further external validation needed in diverse cohorts.
Our externally validated model can be easily applied in clinical practice to inform preoperative discussions about kidney failure risk in patients facing surgical options for localized kidney cancer.
Patients with localized kidney cancer often experience a lot of worry about whether their kidney function will remain stable or will decline if they choose to undergo surgery for treatment. To help patients make an informed treatment decision, we developed a simple equation that incorporates 6 easily accessible pieces of patient information to predict the risk of reaching kidney failure 5 years after kidney cancer surgery. We expect that this tool has the potential to inform patient-centered discussions tailored around individualized risk, helping ensure that patients receive the most appropriate risk-based care.
2023, Urologic Oncology: Seminars and Original Investigations
Highly complex renal masses pose a challenge to urologic surgeons’ ability to perform robotic partial nephrectomy (RPN). Given the increased utilization of the robotic approach for small renal masses, we sought to characterize the outcomes and determine the safety and feasibility of RPN for complex renal masses from our large multi-institutional cohort.
We performed a retrospective analysis of patients with R.E.N.A.L. Nephrometry Scores ≥10 who underwent RPN in our multi-institutional cohort (N = 372). Baseline demographic, clinical and tumor related characteristics were evaluated with the primary endpoint of trifecta achievement (defined as negative surgical margin, no major complications, and warm ischemia time ≤25 min). Relationships between variables were assessed using the chi-square test of independence, Fisher exact test, Mann-Whitney U test, and Kruskal Wallis test. Logistic regression was used to evaluate the relationship between baseline characteristics and trifecta achievement.
Of 372 patients in the study, mean age was 58 years, and median BMI was 30.49 kg/m2. The median tumor size was 4.3 cm (3.0–5.9 cm). Most of the patients had R.E.N.A.L. scores of 10 (n = 253; 67.01%). Overall, trifecta was achieved in 72.04% of patients. Stratifying intraoperative and postoperative outcomes by R.E.N.A.L. scores, there was no significant difference in trifecta achievement, operative time, warm ischemia time (WIT), open conversion, major complication, or positive margin rates. Length of hospital stay was significantly longer for higher R.E.N.A.L. scores (median days 2 vs. 1, P = 0.012). Multivariate analyses for factors associated with trifecta achievement concluded that age and baseline eGFR were independently associated with trifecta achievement.
RPN is a safe and reproducible procedure for complex tumors with R.E.N.A.L. Nephrometry scores ≥10. Our results suggest excellent rates of trifecta achievement and short-term functional outcomes when performed by experienced surgeons. Long-term oncological and functional evaluation are needed to further support this conclusion.
