AUA 2018: Comparative Effectiveness of Neoadjuvant and Adjuvant Chemotherapy in the Medicare Bladder Cancer Population

San Francisco, CA ( Neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) prior to radical cystectomy (RC) is supported by Level 1 evidence; yet utilization is not as high as it should be, due to multiple concerns – specifically, delay to RC, complications from chemotherapy, concern for renal function deterioration, etc. On the other hand, there is no strong data to support adjuvant therapy (AC), as of yet – though, there are indicators to suggest it may be effective. 

In this study, the authors compare NAC vs. AC in the medicare bladder cancer population. Yet, as with all such studies, it is severely limited by immortal time bias – patients who get AC are healthy enough after to RC to have made it to AC, whereas many patients who receive RC but never go on to get AC are not included. Similarly, patients scheduled for RC after NAC but only get NAC are not included in this study either. Hence, accurate comparisons are difficult to make – as intent to treat is difficult to capture!

Despite this, the authors used the Surveillance, Epidemiology, and End Results (SEER)-Medicare data, which has more granularity than the SEER database alone, but is limited to patients 65+ on Medicare. 

They identified patients diagnosed with muscle-invasive bladder cancer between 2004-2013 and treated with radical cystectomy. They then stratified patients based on receipt of NAC (676) or AC (666).

  • Patients not receiving chemotherapy were not included in this study – which is a huge flaw, as we discussed below.
In unadjusted analyses, the AC group had worse overall survival compared to the NAC group (HR 1.46; 95% CI: 1.28-1.67), p <0.001). After propensity score adjustment (accounting for the following variables: age, sex, race, Charlson Comorbidity Index, marital status, education, population size, median income, region, year of cystectomy, grade, stage, and nodal status), the overall survival in the AC group was still worse (adjusted HR 1.18; CI 1.02-1.36, p=0.022). 

Regardless of chemotherapy timing, half of the patients in each group survived two years or less after cystectomy. 

Yet, as mentioned earlier, this analysis is plagued by the number of patients it included. Patients who received RC with the intent for AC – but who didn’t end up getting AC – likely did well; and should have been included in an intent-to-treat analysis. As such, the patients receiving AC in this study were selected to do worse – which they did!

On the other hand, as this only included patients who received RC, patients who received NAC but never made it to RC were not included – but should have been!

Hence, this is not a fair comparison between NAC and AC. I am a proponent of NAC, but better comparisons are needed for fair assessment!

Presented by: Mina Fam, University of Pittsburgh, Pittsburgh, Pennsylvania
Co-Authors: Jonathan Yabes, Pittsburgh, PA, Nathan Hale, Charleston, WV, Robert Turner, Jathin Bandari, Liam Macleod, Lee Hugar, Jeffrey Gingrich, Pittsburgh, PA, Tudor Borza, Ted Skolarus, Ann Arbor, MI, Benjamin Davies, Bruce Jacobs, Pittsburgh, PA

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, @tchandra_uromd at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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