The 1-year decline in estimated glomerular filtration rate (eGFR) after radical nephrectomy in patients with renal masses and matched living kidney donors is the same.

OBJECTIVES: To determine short-term differences in renal function evolution between patients with renal cell carcinoma (RCC) submitted to radical nephrectomy (RN) and living kidney donors matched for age and gender. To assess the role of co-morbidity as a risk factor for developing an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m(2) . PATIENTS AND METHODS: In this retrospective study patients undergoing Radical Nefrectomy (RN) between January 2000 and February 2011 for suspicion of localised RCC were matched by age and gender to living kidney donors. Renal function was compared between the groups using the Modification in Diet and Renal Disease (MDRD) equation at 1 year after RN. Charlson co-morbidity score, incidence of hypertension, diabetes and cardiovascular disease were compared and assessed as predictors for developing an eGFR of <60 mL/min/1.73 m(2) . RESULTS: In all, 196 patients were included, 98 in each group. The mean age was respectively 60.6 (RCC group) and 59.1 years (donors). The 1-year postoperative mean eGFR (available in 89 patients with RCC and 87 donors) was similar, at a mean (sd) of 56.7 (16.4) mL/min/1.73 m(2) in patients with RCC and 56.2 (9.8) mL/min/1.73 m(2) in donors (P = 0.83). In patients with RCC the incidence and severity of co-morbidities was significantly higher. A preoperative eGFR of 60-89 mL/min/1.73 m(2) was the only independent risk factor for developing a postoperative eGFR of <60 mL/min/1.73 m(2) (odds ratio 4.4, confidence interval 2.1-9.5, P < 0.001, 95% confidence interval). CONCLUSIONS: In our cohorts with advanced age the 1-year follow-up eGFR was similar in both groups. Despite increased co-morbidity in the RCC group there was no increased decline in renal function. Only reduced preoperative eGFR could be identified as risk factor for developing a postoperative eGFR of <60 mL/min/1.73 m(2) .

Corticosteroids for Immune-Related Adverse Events and Checkpoint Inhibitor Efficacy: Analysis of Six Clinical Trials.

PURPOSE: Retrospective studies suggest that immunosuppressive treatment of immune-related adverse events (irAEs) impairs survival in patients with melanoma who received immune checkpoint inhibitors. Here, we study this association across tumor types using data from six international phase II/III registrational trials. METHODS: A post hoc analysis was performed on individual patient data from the anti-programmed cell death-1 (anti-PD-1) + anti-cytotoxic T lymphocyte-associated protein-4 (anti-CTLA-4) treatment arms of six clinical trials (CheckMate-067, -142, -214, -648, -743, and -9LA). Among patients who received systemic immunosuppression for treatment-related adverse events (trAEs), associations of peak and cumulative corticosteroid dose, and use of second-line immunosuppression with overall survival (OS) and progression-free survival (PFS) were assessed using multilevel Cox regression with adjustment for age and sex. RESULTS: Of the 1,959 patients who received anti-PD-1 + anti-CTLA-4 therapy, 834 patients who were treated with immunosuppression for trAEs were included. Eight hundred and thirty-two patients (100%) received corticosteroids and 81 patients (10%) received second-line immunosuppressants. High corticosteroid peak dose was associated with worse PFS: adjusted hazard ratio (HRadj), 1.15 (95% CI, 1.02 to 1.29) for 1 versus 0.5 mg/kg prednisolone and HRadj, 1.43 (95% CI, 1.05 to 1.96) for 2 versus 0.5 mg/kg. Similar effects were observed for OS: HRadj, 1.21 (95% CI, 1.06 to 1.39) and HRadj, 1.66 (95% CI, 1.17 to 2.37) for 1 and 2 versus 0.5 mg/kg, respectively. Cumulative corticosteroid dose was not associated with survival. HRadj of use of second-line immunosuppression was 1.23 (95% CI, 0.90 to 1.68) for PFS and 1.25 (95% CI, 0.88 to 1.77) for OS. CONCLUSION: Higher corticosteroid peak dose for trAEs is associated with worse survival across tumor types, while cumulative dose is not. Too few patients received second-line immunosuppressants to confirm or reject an association with survival. These data argue for a reconsideration of irAE management approaches, starting with lower corticosteroid dose whenever feasible.

Age and gender related differences in renal cell carcinoma in a European cohort.

PURPOSE: We evaluated the influence of age on gender related differences in the renal cell carcinoma presentation of patients operated on between 1995 and 2005 in a European country. We also assessed the trend of missing pathological data. MATERIALS AND METHODS: Data on all patients who underwent radical or partial nephrectomy for renal cell carcinoma during 1995 to 2005 in The Netherlands were retrospectively collected from the prospective PALGA (Pathological Anatomical National Automated Archive) database. Patients were divided into 5 cohorts based on age at surgery, including 40 or less, 41 to 50, 51 to 60, 61 to 70 and greater than 70 years. Variables evaluated were gender differences by age, and tumor size, subtype, stage and Fuhrman grade. RESULTS: A higher mean age in women was only observed in those older than 70 years (p <0.001). The male-to-female ratio was 2:1 at ages 41 to 60 years and 1.2:1 at greater than 70 years. Compared to men women had smaller tumors at ages 51 to 60 years (p = 0.03), stage pT3 was less common at age 41 years or greater (p = 0.02), and grade 2 was less common at age 61 years or greater (p <0.001). The incidence of tumors with missing data on stage (14.9%), subtype (52.2%) and grade (47.1%) decreased substantially during the study period (p <0.001). CONCLUSIONS: Older age in women than in men who present to surgery for RCC was only prevalent in those older than 70 years. The male-to-female ratio was almost equal in patients older than 70 years compared to a 2:1 ratio at ages 41 to 60 years. Women presented with fewer pT3 tumors than men at age 41 years or greater. Missing pathological data decreased significantly between 1995 and 2005.

Prognostic models and factors for patients with renal-cell carcinoma: a survey on their use among urologists.

PURPOSE: To assess the use of prognostic factors and models in renal-cell carcinoma (RCC) and to gain insight in the motivations precluding prognosis estimation and the use of prognosticators. MATERIALS AND METHODS: A questionnaire was sent to 110 urologists involved in the Clinical Research Office of the Endourological Society (CROES) Global Renal Mass Study. Frequencies were gathered using descriptive statistics. RESULTS: The majority of the 86 responders worked in a university hospital in Europe. Most of the urologists (97.7%) used the tumor-node-metastasis (TNM) classification, and 44% performed prognosis estimations in all patients. The main reason not to estimate prognosis was lack of accuracy (20.9%) and of additional benefit (11.6%). In addition, clinical, laboratory, or pathologic factors were used by 89.5% of the urologists and biomarkers by 16.3%. Preoperative models were used by 20.9%, postoperative models by 38.4%, and metastatic models by 38.4%. The Raj and Motzer models were the most used in preoperative and metastatic settings, while no predominance among the different postoperative models was seen. The most important reasons to skip the use of models were "lack of additional value" and "lack of familiarity" reported by 30.2% and 27.9% of the responders, respectively. CONCLUSIONS: The TNM is the mainstay for assessing prognosis in RCC. Our data indicate that penetration of prognostic systems is, at most, moderate, suggesting limited use outside original developmental settings. On the contrary, clinical, laboratory, and pathologic factors are used by almost all urologists for prognosis estimations. The most important reason not to use models is the lack of additional value.

Are there parameters that predict a nondiagnostic biopsy outcome taken during laparoscopic-assisted cryoablation of small renal tumors?

BACKGROUND AND PURPOSE: The histopathologic diagnosis of a small renal mass (SRM) that is managed with cryoablation relies on preoperative or intraoperative biopsies. Because a considerable number of these SRMs are benign, accurate diagnosis has prognostic and follow-up implications. The main problem in SRMs is the high rate of nondiagnostic biopsies. Our purpose was to assess whether certain tumor and biopsy characteristics are correlated with a diagnostic biopsy outcome. PATIENTS AND METHODS: One hundred tumors that were smaller than 4.5 cm in 94 patients were managed with laparoscopic cryoablation. After dissection of the perirenal fat and identification of the tumor by intra-abdominal ultrasonography, one or more biopsies were obtained before freezing. Using the Student t/Mann Whitney U test, the following parameters were evaluated for predicting biopsy outcome: Tumor size, location, and exophytic part of the tumor, size of the biopsy needle, the number of biopsies taken, and presence of nonenhancing areas compatible with necrosis inside the tumors. Correlations among parameters were assessed using a Spearman correlation or Kruskal-Wallis test. RESULTS: Twenty-two (22%) biopsies were nondiagnostic and consisted of normal kidney tissue, connective tissue, fat, fibrosis, necrosis, and/or blood. There were no significant differences in parameters between the diagnostic and nondiagnostic group. There was a positive correlation between tumor size and number of biopsies (P=0.029) and between the presence of nonenhancing areas and both size (P<0.001) and the number of biopsies taken (P<0.001). CONCLUSION: No statistical significant correlation was found between biopsy outcome and tumor or biopsy characteristics. More biopsies were taken in larger tumors, and larger tumors contained more nonenhancing areas that were suspect for necrosis.