Based on several studies, there is no question that carboplatin is inferior to cisplatin in the neoadjuvant setting. Certainly, there are non-responders to neoadjuvant chemotherapy. In a study from Dr. Wright’s own institution, they assessed 80 patients with clinical T2-T4, N0-N1 disease who received neoadjuvant chemotherapy and underwent radical cystectomy. Nonresponse was defined as patients with higher pathologic T stage than clinical stage or patients with nodal involvement identified on final pathology. There were 20% of the patients deemed non-responders and Dr. Wright’s group found no difference between gem-cis therapy and MVAC, whereas patients receiving gem-carbo were four times more likely to not respond to chemotherapy .
Furthermore, a 19-center study of neoadjuvant chemotherapy aimed to assess real-world pathologic response rates to neoadjuvant chemotherapy with different regimens . Among data on 935 patients, gem-cis was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). Overall, the rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving gem-cis was 23.9%, compared with 24.5% for MVAC (p=0.2). Additionally, there was no difference between MVAC and gem-cis in pT0N0 on multivariable analysis (OR 0.89, 95%CI, 0.61-1.34), essentially confirming equivalency of these regimens.
Wright makes the point that just because patients are cisplatin ineligible prior to radical cystectomy doesn’t mean that they may remain ineligible post-cystectomy. Several studies suggest that between 17-27% of patients ineligible preoperatively will become eligible post-operatively, and would be candidates for adjuvant cisplatin if necessary. Other options may be chemoradiation, however only a small subset of patients are good candidates and most clinical trials use cisplatin. Immunotherapy has clinical trials ongoing and may be of use for cisplatin ineligible patients in the future, but are not currently.
Wright emphatically notes that three major guidelines recommend upfront cystectomy in cisplatin ineligible patients:
- AUA/ASCO /ASTRO/SUO guidelines: “Clinicians should not prescribe carboplatin-based neoadjuvant chemotherapy for clinically resectable stage cT2-T4N0 bladder cancer. Patients ineligible for cisplatin-based neoadjuvant chemotherapy should proceed to definitive locoregional therapy” (Expert Opinion)
- EAU guidelines: “Do not offer neoadjuvant chemotherapy to patients who are ineligible for cisplatin-based combination chemotherapy”
- NCCN guidelines version 3.2018: “For patients who are not candidates for cisplatin, there are no data to support a recommendation for perioperative chemotherapy. Carboplatin should not be substituted for cisplatin in the perioperative setting”
- A patient unfit for cisplatin-based neoadjuvant chemotherapy should have an upfront cystectomy
- Alternative chemotherapy options to MVAC/gem-cis are inferior and should not be used
- Adjuvant cisplatin may be an option for some, even those preoperatively ineligible
- The future may hold new options, but for now…..take the bladder out
1. Mossanen M, Lee F, Cheng H, et al. Nonresponse to neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma of the bladder. Clin Genitourin Cancer 2014;12(3):210-213.
2. Zargar H, Espiritu PN, Fairey AS, et al. Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol 2015;67(2):241-249.
Presented by: Jonathan Wright, MD, Department of Urology, University of Washington, Seattle, WA
Read the Rebuttal Presentation: Treatment for MIBC for Cis-Platinum Ineligible Patients: Other Systemic Options and Trials
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA