1. Susman, Ed

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SAN FRANCISCO-Long-term kidney function appears to be preserved following bladder-sparing surgery and chemoradiation, researchers reported here at the 2016 Genitourinary Cancers Symposium (Abstract 453).

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In a retrospective study that focused on renal complications of trimodal treatment, researchers said that renal function decreased during the first year, during which patients were undergoing up to 9 months of therapy, but then the renal function stabilized and was maintained.


"Our follow-up showed that the estimated glomerular filtration rates were statistically stable after the first year with a mean follow-up time of 48 months," said Hannah Roberts, a medical student at Columbia University in New York City who performed her study as a research intern at Massachusetts General Hospital/Harvard Medical School.


The study included 178 patients with bladder cancer who underwent bladder-sparing therapy between 2001 and 2013, Roberts said.


"We collected creatinine values before treatment with maximal transurethral resection in bladder-sparing surgery," she said at her poster presentation. "In the first year, estimate glomerular filtration rates dropped from a mean of 70.1 ml/minute at baseline to 58.9 ml/minute at one year-a significant decrease (P=0.001), then the rate stabilized."


She noted that the 58.9 mL/minute rate is just below the 60 ml/minute cutoff that many doctors consider as kidney dysfunction.


Study Details

The patients in the study were diagnosed with Stage T1, Stage T2, or Stage T3 locally advanced muscle-invasive bladder cancer. About 90 percent of the patients were diagnosed with Stage 2 disease. Their treatment first involved transurethral resection followed by two months of chemoradiation. The patients then returned to the clinic for cystoscopy to see whether there had been a response. If the patient achieved a complete response, they went on to receive additional chemoradiation, followed by adjuvant chemotherapy. The duration of treatment was a mean of eight months, Roberts reported.


Cisplatin chemotherapy was administered to 71.9 percent of the patients. About 69 percent of the patients received cisplatin therapy concurrent with radiation; adjuvant chemotherapy was administered to 110 patients, and 61.5 percent received cisplatin-based therapy.


"Renal function was well preserved in the long term following bladder-sparing therapy," she said. "While there was a decline in estimated glomerular filtration rate in the first year, there was no further statistically significant decline over time.


"Those patients who received adjuvant chemotherapy had greater decline in estimated glomerular filtration rate at one year; however, for most patients this was shortly after completion of chemotherapy," Roberts reported. "Lower initial estimated glomerular filtration rate was associated with less decline in function, though these patients may have been less likely to receive aggressive adjuvant chemotherapy."


She reported that 27.7 percent of the patients in her study had baseline estimated glomerular filtration rates that were less than 60 ml/minute.


In the study, Roberts and her colleagues scrutinized risk factors that might have made a difference in the initial decrease in kidney function. Age, hypertension, diabetes, hydronephrosis, and use of concurrent cisplatin were not associated with a greater initial decline in estimated glomerular filtration rates. The 28 patients who received salvage cystectomy had similar renal function to those who did not require surgical intervention, though longer follow up of this cohort is needed, she said. Creatinine values were assessed a month prior to surgery, then at one, three, five, seven, and nine years after trimodal therapy. The follow-up ranges from one month to 162 months, Roberts reported.


Trimodal Therapy

In commenting on the study, Manish A. Vira, MD, Vice Chair of Urologic Research at the Arthur Smith Institute for Urology in New Hyde Park, New York, told OT: "Many patients with muscle invasive bladder cancer have medical co-morbidities such as cardiovascular disease, hypertension, and diabetes that increase their risk for future renal insufficiency. Standard treatment with cisplatinum based chemotherapy and radical cystectomy with urinary diversion can lead to progressive renal deterioration in a subset of these patients.


"The present study suggests that trimodal therapy as an alternative to radical cystectomy and urinary diversion may have less a detrimental effect on future renal function," Vira said. "Of course, this conclusion can only be definitively shown with a controlled prospective trial comparing patients undergoing cystectomy versus bladder preservation therapy.


"Interestingly, this trial suggests that patients with existing renal insufficiency or at high risk for future renal insufficiency may be better managed with trimodal therapy. However, there remains continued controversy on whether trimodal therapy offers equivalent oncologic efficacy as compared to radical cystectomy."


Roberts concurred. "I think we need to look further at survival with these values," she said, "but our study shows that in terms of their renal function, it is stable after the therapy. In order to compare it with the standard of care treatment, which is radical cystectomy, you would have to look at a prospective trial.


"Maintenance of renal function following treatment of bladder cancer presents an ongoing challenge," she said. "Long-term renal function decline following radical cystectomy is well documented. Renal function in the setting of bladder-sparing therapy is poorly understood."


The patients in the study included 139 men and 39 women, and about a third of the patients were 75 years of age or older. In addition to bladder cancer, 48.9 percent of the patients also had hypertension; 17.9 percent had been diagnosed with diabetes; and 3.9 percent of the patients had been diagnosed with hydronephrosis.