Perioperative, oncological and functional outcomes after robotic partial nephrectomy vs. cryoablation in the elderly: A propensity score matched analysis

Objective: To compare perioperative, oncological and functional outcomes of robotic partial nephrectomy (RPN) versus cryoablation in elderly patients (>75 years old), accounting for patient's and tumor's related factors. Methods: Retrospective institutional review of 312 consecutive elderly patients (> 75 years old) who underwent RPN or cryoablation for renal mass (June 2006-December 2016). Demographic, perioperative, functional, and oncological data were evaluated. Sixty-five patients who underwent RPN were propensity-score matched 1:1 to 65 who underwent cryoablation (matching was based on demographics, renal function, comorbidities and tumor characteristics). Perioperative outcomes were compared. Survival analysis was performed to estimate overall (OS), recurrence-free (RFS) and cancer-specific survival (CSS) by Kaplan-Meier method. A linear mixed effect model (LME) estimated the effect of follow-up on estimated glomerular filtration rate (eGFR). Results: After matching, the variables were well balanced with no differences at baseline between groups. Shorter operative time and lower blood losses favored cryoablation (140 vs. 200 min, P < 0.0001 and 100 vs. 195 ml, P = 0.0002, respectively). Overall complications rate was higher for RPN (31% vs. 9%; P = 0.007), but no difference was found in major (Clavien III-IV) complications (6% vs. 1.5%, P = 0.2). At a median follow-up of 37 (29-44) and 46 (38-53) months for RPN and cryoablation, no significant differences were found in CSS (100% vs. 95%, P = 0.3) and OS (80% vs. 75%, P = 0.2) but RFS was higher for RPN (100% vs. 83%, RPN vs. cryoablation, respectively, P = 0.02). eGFR was comparable between the groups at every time point analyzed. Conclusions: Although with a higher rate of recurrences, our data confirm cryoablation as a lower morbidity profile treatment option for small renal masses in the elderly population, with cancer-specific survival comparable to surgery

Cold Versus Warm Ischemia Robot-Assisted Partial Nephrectomy: Comparison of Functional Outcomes in Propensity-Score Matched "at Risk" Patients

Objectives: To compare functional outcomes of warm ischemia RPN (wRPN) to cold ischemia RPN (cRPN) in "at risk" patients. Materials and methods: Retrospective review of institutional database queried for all patients who underwent cRPN/wRPN (January 2007-December 2016). For the study purpose, patients with solitary kidney and/or history of partial nephrectomy and/or multiple tumors and/or preoperative estimated Glomerular Filtration Rate (eGFR) <60 mL/minute were extracted. To reduce inherent biases, groups were matched on key variables related to renal function through a greedy matching algorithm with no replacement. Renal functional outcomes were evaluated by eGFR drops at 1-3 days and at 1, 3, 6, and 12 months postoperatively. A linear mixed effects model was used to assess eGFR at each follow-up who received either cRPN or wRPN. Follow-up was treated as a factor variable to account for nonlinear time trends. Contrast analysis was used to compare cRPN vs wRPN groups at each follow-up, using Sidak-Holm p-value adjustments for multiple comparisons. Results: Out of 19 cRPN patients and 279 wRPN patients, 14 cRPN patients were finally matched 1:1 with no replacement to 14 wRPN. There was no significant difference in preoperative eGFR for matched patients undergoing cRPN vs wRPN. Since the first postoperative day, cRPN patients had higher eGFR. The difference was statistically significant since the third month postoperatively (mean difference = 18.201, 95% confidence interval [CI]: 1.930-34.472) and remained at both the sixth month (mean difference = 18.839, 95% CI: 2.568-35.109) and the 12th month (mean difference = 21.277, 95% CI: 5.006-37.547) follow-up. Conclusions: Accounting for unmodifiable and modifiable factors, in a cohort of highly selected patients "at risk" for postoperative significant decline in renal function after RPN, renal functional outcomes appear to be superior with cold ischemia technique

Transperitoneal Robot-assisted Partial Nephrectomy with Minimum Follow-up of 5 Years: Oncological and Functional Outcomes from a Single Institution

Background: Robot-assisted partial nephrectomy (RAPN) is an established, minimally invasive nephron-sparing technique with excellent perioperative and intermediate oncological outcomes. However, long-term oncological outcomes have not been reported to date. Objective: To report oncological and functional outcomes of RAPN among patients with minimum follow-up of 5 yr. Design, setting, and participants: Data for consecutive patients undergoing RAPN since October 2006 were extracted from a prospectively-maintained institutional PN database. Patients with benign tumors, genetic mutations, prior radical or ipsilateral PN, and those with follow-up of <5 yr were excluded. Intervention: Transperitoneal RAPN for renal cell carcinoma (RCC). Outcomes measurements and statistical analysis: Demographic, perioperative, postoperative, functional, and oncological data were evaluated. A linear random-effects model was used to estimate the effect of follow-up duration on the estimated glomerular filtration rate (eGFR) after adjustment for potential confounders. Univariable competing-risks regression analyses were performed to evaluate the hazard ratio (HR) for cancer-related events for the variables of interest. Results and limitations: A total of 278 RAPNs for RCC were included. eGFR was significantly lower at follow-up time points than at baseline. At last follow-up (median 46 mo, interquartile range 30-58) the mean eGFR difference was -10.6ml/min (95% confidence interval -12.56 to -8.66; p < 0.0001). There were 28 deaths (10.1%) in the cohort during the follow-up period, of which five (1.8%) were related to metastatic RCC. The 5-yr and 7-yr cumulative incidence of RCC deaths was 1.80% at both 5 and 7 yr, while the cumulative incidence of local recurrence was 3.61% and 4.16%, and that of metastasis was 3.24% and 4.57% at 5 and 7 yr, respectively. Univariable competing-risks regression revealed that higher Fuhrman grade (HR 8.76; p = 0.051), larger tumor size (HR 1.67; p < 0.0001), and tumor necrosis (HR 16.73; p = 0.0019) were independent predictors of RCC death. The retrospective design and potential selection bias due to patient selection in the early RAPN experience may limit the generalizability of the findings. Conclusions: This is the first study reporting minimum oncological follow-up of 5 yr after RAPN. The results demonstrate excellent long-term oncological outcomes after RAPN in a selected cohort of patients. Our data confirm that the renal functional deterioration after RAPN remains stable over time after the early postoperative decrease

Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease

BACKGROUND: In a previous trial involving patients with early autosomal dominant polycystic kidney disease (ADPKD; estimated creatinine clearance, ≥60 ml per minute), the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate (GFR) but also caused more elevations in aminotransferase and bilirubin levels. The efficacy and safety of tolvaptan in patients with later-stage ADPKD are unknown. METHODS: We conducted a phase 3, randomized withdrawal, multicenter, placebo-controlled, double-blind trial. After an 8-week prerandomization period that included sequential placebo and tolvaptan run-in phases, during which each patient's ability to take tolvaptan without dose-limiting side effects was assessed, 1370 patients with ADPKD who were either 18 to 55 years of age with an estimated GFR of 25 to 65 ml per minute per 1.73 m2 of body-surface area or 56 to 65 years of age with an estimated GFR of 25 to 44 ml per minute per 1.73 m2 were randomly assigned in a 1:1 ratio to receive tolvaptan or placebo for 12 months. The primary end point was the change in the estimated GFR from baseline to follow-up, with adjustment for the exact duration that each patient participated (interpolated to 1 year). Safety assessments were conducted monthly. RESULTS: The change from baseline in the estimated GFR was -2.34 ml per minute per 1.73 m2 (95% confidence interval [CI], -2.81 to -1.87) in the tolvaptan group, as compared with -3.61 ml per minute per 1.73 m2 (95% CI, -4.08 to -3.14) in the placebo group (difference, 1.27 ml per minute per 1.73 m2; 95% CI, 0.86 to 1.68; P3 times the upper limit of the normal range) occurred in 38 of 681 patients (5.6%) in the tolvaptan group and in 8 of 685 (1.2%) in the placebo group. Elevations in the aminotransferase level were reversible after stopping tolvaptan. No elevations in the bilirubin level of more than twice the upper limit of the normal range were detected. CONCLUSIONS: Tolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period in patients with later-stage ADPKD. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; REPRISE ClinicalTrials.gov number, NCT02160145 .)