Adjuvant chemotherapy: Many cystectomy patients ineligible
Neoadjuvant therapy may be alternative, especially in younger African-Americans
San Francisco—New data from a single institution show that more patients with urothelial carcinoma are eligible for neoadjuvant chemotherapy before radical cystectomy than for adjuvant chemo following surgery.
Results of the retrospective survey suggest that urologists and their patients should consider neoadjuvant chemo and that new, less toxic regimens are needed.
"Most new bladder cancer diagnoses show superficial disease, but many patients with more invasive disease eventually undergo cystectomy," said lead author Patrick Selph, MD, urology resident at the University of North Carolina School of Medicine, Chapel Hill.
"Median 5-year survival is anywhere from 20% to 80% depending on the extent of disease, with extravesical disease at the lower end of the scale. Studies suggest that median survival can increase up to 5 years with chemotherapy, but there is some controversy surrounding study design and results," added Dr. Selph, who worked on the study with Raj S. Pruthi, MD, and colleagues.
Renal function is a key barrier to adjuvant chemotherapy following radical cystectomy. The standard platinum-based regimen carries significant nephrotoxicity, Dr. Selph noted during an oral presentation at the 2011 American College of Surgeons Clinical Congress in San Francisco. A retrospective analysis of all patients who underwent radical cystectomy at UNC between 2000 and 2009 found that just 46% were eligible for adjuvant chemotherapy. The other 54% had inadequate renal function based on an estimated glomular filtration rate (eGFR) of less than 60.
More Caucasians (62%) were ineligible based on renal insufficiency than African-Americans (14%, p=.0002). A greater percentage of patients over the age of 70 years (70%) were ineligible compared to those under 70 (40%, p=.01). There was no difference in eligibility based on gender.
Inadequate renal function is becoming a more common problem, Dr. Selph pointed out. Chronic kidney disease is increasing, which means even fewer patients will likely be eligible for adjuvant chemotherapy in the future.
"More than half of patients are ineligible for chemotherapy based on renal function alone. Our patients are not going to get any healthier with regard to renal function," he predicted.
While there is some controversy regarding the use of an eGFR of 60 as a cutoff for eligibility, there are alternatives: Develop a less nephrotoxic chemotherapeutic regimen and try neoadjuvant chemotherapy.
Looking at eligibility rates for neoadjuvant chemotherapy from 2000 to 2010, the authors found a total of 198 patients who might have been eligible based on eGFR greater than 60 and other factors. A total of 60% of patients were eligible, with more Caucasians ineligible compared to African-Americans (p=.0087) and more patients over 70 years of age ineligible (p=.008). No significant difference in eligibility based on gender was noted.
Few patients receive neoadjuvant therapy
The eligibility criteria reflect factors known to reduce survival in bladder cancer, including age, pathologic stage, N stage, and receipt of adjuvant chemotherapy. But even though Dr. Selph found that slightly more patients are eligible for neoadjuvant chemotherapy (60%) than for adjuvant (46%), the National Cancer Data Base shows that just 1.2% of patients with stage 3 bladder cancer receive neoadjuvant chemotherapy compared to 11.6% who receive adjuvant chemo.
Co-moderator Tracy Downs, MD, associate professor and director of bladder cancer and intravesical therapy programs at the University of Wisconsin School of Medicine and Public Health, Madison, agreed that more patients and more urologists should consider neoadjuvant chemotherapy.
"Neoadjuvant therapy is easier than adjuvant because the patient is generally in better health before surgery than after," he said. "If we don't give these patients chemo, they die. We have a long way to go."