The value and timing of chemotherapy in patients undergoing cystectomy for clinically localized bladder cancer has long been controversial. There are myriad reasons supporting both neoadjuvant and adjuvant chemotherapies.
The study by Gofrit et al (Urol Oncol Apr. 25, 2008 Epub) provides additional important information about the benefit of chemotherapy in bladder cancer. The authors analyzed a retrospectively identified cohort of 67 patients, half of whom received adjuvant chemotherapy following cystectomy for node positive bladder cancer. The other half did not. They found that those who received chemotherapy lived six times longer than the untreated cohort. Despite an obvious selection bias favoring those receiving chemotherapy (they were younger and had lower stage tumors), adjuvant chemotherapy was an independent predictor of overall survival.
These data are thrilling at first glance; however, closer scrutiny and past experience must temper our enthusiasm and expectations. The authors did not control for comorbidities that could significantly impact overall survival in this elderly population. Possible interactions among age, chemotherapy, and disease stage were unmeasured. Nevertheless, these data establish that adjuvant chemotherapy with gemcitabine and cisplatin (GC) can be administered postoperatively and 80% of patients will tolerate and complete four courses of treatment. In addition, combination chemotherapy with GC after cystectomy may impact survival in select patients. This second finding is particularly important because prior studies of neoadjuvant or adjuvant therapy have used older regimens.
Perhaps more valuable information on this issue will be available from EORTC trial 30994, which has a similar study design, but three different chemotherapy regimens and has progression-free survival as an endpoint.
The availability of chemotherapy that is relatively well tolerated and the suggestive evidence in the literature that adjuvant chemotherapy carries benefit have supported our decision to use adjuvant chemotherapy in the past. However, this new evidence, if supported by additional studies, suggests we may need to rethink this strategy. Larger, adequately powered, randomized prospective trials to assess the value of adjuvant chemotherapy in post-cystectomy patients with high-risk bladder cancer are necessary. But until such data are available, the jury is still out.
Dr. Konety is associate professor and vice chair, urology and epidemiology & biostatistics, University of California, San Francisco.