Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may benefit patients with this disease. In this multicenter, phase 3 trial, we randomly assigned 626 patients with previously untreated, poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly, 3 million U of interferon alfa (with an increase to 18 million U) subcutaneously three times weekly, or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly. The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group. Patients who received temsirolimus alone had longer overall survival (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P=0.008) and progression-free survival (P<0.001) than did patients who received interferon alone. Overall survival in the combination-therapy group did not differ significantly from that in the interferon group (hazard ratio, 0.96; 95% CI, 0.76 to 1.20; P=0.70). Median overall survival times in the interferon group, the temsirolimus group, and the combination-therapy group were 7.3, 10.9, and 8.4 months, respectively. Rash, peripheral edema, hyperglycemia, and hyperlipidemia were more common in the temsirolimus group, whereas asthenia was more common in the interferon group. There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group (P=0.02). As compared with interferon alfa, temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis. The addition of temsirolimus to interferon did not improve survival. (ClinicalTrials.gov number, NCT00065468.)

Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear. In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated. A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). Overall survival was longer with lenvatinib plus pembrolizumab than with sunitinib (hazard ratio for death, 0.66; 95% CI, 0.49 to 0.88; P=0.005) but was not longer with lenvatinib plus everolimus than with sunitinib (hazard ratio, 1.15; 95% CI, 0.88 to 1.50; P=0.30). Grade 3 or higher adverse events emerged or worsened during treatment in 82.4% of the patients who received lenvatinib plus pembrolizumab, 83.1% of those who received lenvatinib plus everolimus, and 71.8% of those who received sunitinib. Grade 3 or higher adverse events occurring in at least 10% of the patients in any group included hypertension, diarrhea, and elevated lipase levels. Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.)

This document seeks to establish guidance for the evaluation and management of women with recurrent urinary tract infections (rUTI) to prevent inappropriate use of antibiotics, decrease the risk of antibiotic resistance, reduce adverse effects of antibiotic use, provide guidance on antibiotic and non-antibiotic strategies for prevention, and improve clinical outcomes and quality of life by reducing recurrence of urinary tract infection (UTI) events. The systematic review utilized to inform this guideline was conducted by a methodology team at the Pacific Northwest Evidence-based Practice Center. A research librarian conducted searches in Ovid MEDLINE (1946 to January Week 1 2018), Cochrane Central Register of Controlled Trials (through December 2017) and Embase (through January 16, 2018). An update literature search was conducted on September 20, 2018. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low). Such evidence-based statements are provided as Strong, Moderate, or Conditional Recommendations. In instances of insufficient evidence, additional guidance is provided as Clinical Principles and Expert Opinions. Our ability to diagnose, treat, and manage rUTI long-term has evolved due to additional insights into the pathophysiology of rUTI, a new appreciation for the adverse effects of repetitive antimicrobial therapy, rising rates of bacterial antimicrobial resistance (AMR), and better reporting of the natural history and clinical outcomes of acute cystitis and rUTI. As new data continue to emerge in this space, this document will undergo review to ensure continued accuracy.

OBJECTIVE: To evaluate the usefulness of urinary calculi attenuation values from non‐contrast computed tomography (NCCT) in predicting the outcome of treatment by extracorporeal shock wave lithotripsy (ESWL). PATIENTS AND METHODS: We evaluated 112 patients with solitary renal and upper ureteric calculi of 0.5–2 cm undergoing ESWL. All patients had NCCT at 120 kV and 240 mA on a spiral CT scanner. During each ESWL session 3000 shock waves were given to a maximum of 3.0 kV. A final X‐ray of the kidney, ureters and bladder was taken 12 weeks after the last ESWL session. Fragments of ≤ 5 mm were regarded as clinically insignificant residual fragments (CIRF). The calculi retrieved were analysed by X‐ray diffraction and the results assessed by comparing the mean density (as measured in Hounsfield units, HU) with the number of ESWL sessions and clearance. RESULTS: In all, 82 (76%) patients had complete clearance of stones and 26 (24%) had CIRF. There was a linear relationship between the calculus density and number of ESWL sessions required. Of patients with calculi of ≤ 750 HU, 41 (80%) needed three or fewer ESWL sessions and 45 (88%) had complete clearance. Of patients with calculi of > 750 HU, 41 (72%) required three or more ESWL sessions, and 37 (65%) had complete clearance. The best outcome was in patients with calculus diameters of < 1.1 cm and mean densities of ≤ 750 HU; 34 (83%) needed three or fewer ESWL sessions, and the clearance rate was 90%. The worst outcome was in patients with calculus densities of > 750 HU and diameters of > 1.1 cm; 23 (77%) needed three or more ESWL sessions and the clearance rate was only 60%. The calculus density was a stronger predictor of outcome than size alone. CONCLUSIONS: The use of NCCT for determining the attenuation values of urinary calculi before ESWL might help to predict the treatment outcome, and so might help in planning alternative treatment in patients with a likelihood of a poor outcome from ESWL.

While surgical resection is curative in the majority of patients who present with localized renal cell carcinoma (RCC), up to 30% will develop disease recurrence during follow-up, the majority within 5 years.¹ Once the disease progresses to a metastatic state, only high-dose interleukin 2 has been shown to produce durable complete responses, and only in 7% to 10% of patients.^2,3 Thus, there is interest in developing well-tolerated adjuvant therapies for patients at high risk of recurrence following resection of localized RCC. Despite a number of trials evaluating agents for use in RCC in the adjuvant setting, only a single phase 3 adjuvant trial to date has demonstrated any progression-free survival benefit,⁴ and that trial has been criticized for concerns regarding potential bias.⁵ As such, at present, there remains no available clinically proven adjuvant therapy for patients with resected RCC who are at high risk of recurrence.⁶