BERKELEY, CA (UroToday.com) - Although neoadjuvant and adjuvant platinum-based systemic chemotherapy have been studied individually for locally advanced bladder cancer, these two modalities have not been compared comprehensively.
The rationale for neoadjuvant therapy is to eliminate the primary cancer and possible micro-metastases before the morbidity of surgery. However, neoadjuvant therapy is accompanied by the risk of delay for patients who do not respond while receiving treatment. The justification for adjuvant therapy is to decrease local and metastatic recurrence of disease. The patient however, must be a suitable candidate to withstand chemotherapy side effects despite recent cystectomy. Although both sequences of chemotherapy administration carry risks and benefits, there is no prospective study comparing a full course of neoadjuvant systemic chemotherapy to adjuvant systemic chemotherapy for bladder cancer in the existing literature.
Evidence from the United States Intergroup Study (SWOG 8710, among others, demonstrated that three cycles of neoadjuvant systemic chemotherapy followed by cystectomy improved overall survival when compared to cystectomy alone. Data from Stockle et al. and others have shown a benefit to cystectomy followed by adjuvant therapy when compared to cystectomy alone despite flaws in these trials. Despite poor accrual, Paz-Ares et al. (SOGUG99/01) showed the benefit of adjuvant platinum-based chemotherapy when compared with observation in overall survival and disease-specific survival. Svatek et al. also showed the benefit of adjuvant systemic chemotherapy. Milikan et al. compared neoadjuvant plus adjuvant (2 cycles neoadjuvant, 3 cycles adjuvant) therapy to adjuvant (5 cycles) therapy alone and identified no difference in OS or DSS between groups. Additionally there was no increase in perioperative morbidity after neoadjvuant chemotherapy.
There is no current definitive standard timing of platinum-based systemic chemotherapy administration for patients with locally advanced bladder cancer. Over the past 15 years there has existed minimal intra-institutional bias for either neoadjuvant or adjuvant platinum-based chemotherapy at Columbia University Comprehensive Cancer Center. Therefore, we chose to retrospectively compare the effectiveness of adjuvant and neoadjuvant platinum-based chemotherapy for patients with cT2-T4aN0-N2M0 bladder cancer at our institution to elucidate this issue.
Of 146 patients receiving systemic perioperative chemotherapy, 122 received cisplatin-based and 24 received carboplatin-based chemotherapy. 79 patients used MVAC while 43 received gemcitabine/cisplatin. No significant differences were identified in disease-specific survival (p=.46) or overall survival (p=.76) between neoadjuvant or adjuvant chemotherapy groups. Statistical improvement in disease-specific survival was noted for neoadjuvant GC when compared with adjuvant GC (p=.049).
Overall the sequence of perioperative chemotherapy in relation to surgery did not appear to significantly affect survival outcomes. We believe that our results may help guide clinicians considering such therapy for appropriate candidates with bladder cancer. Despite evidence supporting perioperative systemic chemotherapy, neoadjuvant and adjuvant chemotherapy are often underutilized (2.2% vs. 10.4% of patients with stage 3 bladder cancer from the National Cancer Database). In the future, molecular markers to predict platinum-based chemotherapy sensitivity and a prospective randomized controlled trial will be needed to definitively assess the effect of timing on perioperative systemic chemotherapy for advanced bladder cancer.
Matthew Wosnitzer, MD and James M. McKiernan, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.