Katie Murray, DO

Despite promising renoprotective results in renal ischemia reperfusion injury associated with partial nephrectomy with the use of phosphodiesterase-type-5 inhibitors in murine and rat models, the same beneficial effect was not seen in human patients, according to a recent study.

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	In a randomized, double-blinded, placebo-controlled trial presented at the 2015 Society of Urologic Oncology annual meeting in Washington, patients were assigned to either receive oral sildenafil, 100 mg, or placebo immediately prior to robot-assisted laparoscopic partial nephrectomy. The primary endpoint of this study was accrual and retention of patients with secondary endpoints assessing renal functional outcomes following hilar clamping and safety of the medication. Patients were excluded from the trial if they had significant history of coronary artery disease, solitary kidney, suspected benign pathology, were pregnant, or had prior intolerance of PDE-5 inhibitor therapy.

	This study was completed over a 15-month time frame. Thirty patients were randomized, and all of these patients remained on study and received treatment and had proper follow-up. Lead author Louis Spencer Krane, MD, from the National Cancer Institute in Bethesda, MD said this preliminary study taught him that randomized surgical trials are feasible but can be extremely cumbersome to perform. Despite the challenges of this randomized trial, the investigators were able to randomize and treat patients accordingly with 100% retention. According to the study design and objective, the study was positive in meeting the primary endpoint.

Continue to the next page for study results.

	Randomization allowed for matched groups, with nearly half of both groups being male patients with a median age of 59 and 57 years of age in the sildenafil and placebo group, respectively. Baseline comorbid conditions including diabetes mellitus, hypertension, and chronic obstructive pulmonary disease were not different between the two groups. Tumor size was slightly smaller in the sildenafil group at a median of 2.3 cm (IQR 2.2, 3) and 3 cm (IQR 2.8, 4.1) in the placebo group 

=.045). Although size was slightly different, nephrometry scores were similar.

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	Intraoperative characteristics were similar between the groups, including estimated blood loss, warm ischemia time, use of intraoperative vasopressors, and amount of fluid administration. Serum creatinine values (mg/dL) and estimated glomerular filtration rate (GFR) were obtained on all patients preoperatively and at short term (1-to 2-day) follow-up. Of the 15 patients in each arm, eight in the sildenafil group and 11 in the placebo group had 1 to 3 months follow-up with laboratory values. Baseline serum creatinine and GFR were not different between the groups. The median percent change in GFR at 2 days post-op was decreased by 8% in both groups and decreased 4% and 6% in the sildenafil and placebo groups, respectively at 1 month post-op 

=.31). Of note, the median baseline GFR in patients in both groups was >80.

	In conclusion, the authors were able to report feasibility of this trial but were unable to identify any role that sildenafil may have as a renoprotective agent in patients undergoing robot-assisted laparoscopic partial nephrectomy. Dr. Krane claimed that although the animal studies with sildenafil were promising, any future clinical trial powered to find a difference in GFR after robot-assisted partial nephrectomy would need to be extremely large in number. His institution does not have current plans to perform any of these studies in the near future.

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A recent human study sought to replicate previous success seen in animal models of reperfusion injury, reports Urology Times SUO internship program member Katie Murray, DO.

Data on PDE-5’s renoprotective role fail to match early results

	The results of urine tests for bladder cancer must be interpreted in the context of patient factors including age, gender, and smoking history, according to a study presented at the 2015 Society for Urologic Oncology annual meeting in Washington.

	Urine tests are often used to assist with diagnosis in patients undergoing a workup for hematuria by urologists. These tests are also used for follow-up in the patient population being followed over time following a diagnosis of bladder cancer.

	Researchers from Duke University’s division of urology, Durham, NC wanted to evaluate the extent of differences in results of urine cytology and of UroVysion FISH testing (Abbott Molecular, Des Plaines, IL) among clinically meaningful patient subgroups. This phenomenon of variability across population subgroups is referred to as spectrum effects. The subgroups evaluated were defined by age, gender, smoking history, and race. According to the researchers, led by senior author Brant Inman, MD, MS, failure to acknowledge this heterogeneity may result in inappropriate interpretation and clinical decision making.

	Using white light cystoscopy as the gold standard for diagnosis of bladder cancer or recurrence of disease, standard diagnostic test performance metrics were calculated for all patients and in the subgroups defined above. Pathologic diagnosis was not correlated, but instead only cystoscopic evaluation.

	Over a 9-year time period, more than 4,000 pairs of cytology and cystoscopy were performed and nearly 1,700 pairs of UroVysion FISH and cystoscopy were performed. Subject-specific and population-averaged methodologies that take repeated observations into account were used to calculate test performance metrics for the entire cohort and the predetermined subgroups.

	Of those who had cystoscopy and cytology, 61% of the 990 patients were male and 75% were Caucasian. Smoking status included 9% current smokers, 45% former smokers, and 42% never smokers. For cytology, the sensitivity went up with increased age and specificity declined, with sensitivity around 48% for those age 40 years and up to 65% in those 80 years of age. Sensitivity of the test was also higher in males (65%) than females (45%). Smoking status did not have a major change in sensitivity and specificity for cytology when compared to cystoscopy.

	Of those patients who had cystoscopy and UroVysion FISH, 59% of the 828 were males and 78% were Caucasian. Smoking status included 10% current smokers, 49% former smokers, and 41% and never smokers. For UroVysion FISH, increased age led to increased sensitivity up to 45% and decreased specificity to 70%. Higher sensitivity was found in current and former smokers near the 50% range compared to the 20% range for never smokers.

	“The diagnostic performance of two widely used urine tests for bladder cancer, urine cytology and FISH, varied significantly according to the patient demographic in whom they were used, implying that there is no single sensitivity or specificity value that can summarize the performance of these tests,” the authors wrote.

	They conclude that tests with high sensitivities could be preferentially chosen for high-risk populations such as current and former smokers. This information could also be used to avoid additional unnecessary procedures in elderly comorbid patients by using tests with high specificity and low sensitivity.

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Urology Times SUO internship program member Katie Murray, DO, reports on a study evaluating the differences in urine cytology and UroVysion FISH testing results among clinically meaningful patient subgroups.