Bladder Cancer Academy 2017: Neoadjuvant and Adjuvant Chemotherapy Bladder Cancer

Schaumburg, IL ( Dr. Galsky gave an interesting presentation on the usage of chemotherapy in radical cystectomy (RC) patients. Perioperative chemotherapy in the context of RC is needed to eliminate any chance of micrometastatic disease not shown on standard imaging. Grossman et al. was the first to show an added benefit for neoadjuvant chemotherapy (NAC) in the setting of RC with a 5% overall survival benefit of 5%.1 In a meta-analysis of several studies on NAC, a hazards ratio (HR) of 0.86 (95% CI 0.81-0.98), p=0.003, was demonstrated in favour of NAC.2

There are also several randomized trials and observational studies of adjuvant chemotherapy in RC patients showing benefit. Unfortunately, all 3 contemporary randomized controlled studies closed early due to poor accrual.

Unfortunately NAC usage is not very prevalent according to large observational studies. This represents real world data, different from what is shown in randomized clinical trials.  As patients age, their glomerular filtration rate decreases substantially precluding them from receiving cisplatin based NAC. This ranges from less than 10% in patients aged less than 60 to almost 70% in patients aged 80 and above. 

When trying to answer the important question if it matters whether chemotherapy is given before or after RC, Dr. Galsky states that it probably does not matter. However, the NCCN guidelines recommend NAC based on higher level evidence. The recommended regimen is dose dense MVAC given in 3-4 cycles with GCSF, while perioperative gemcitabine and Cisplatinum are a reasonable alternative, given in 4 cycles.

Some work has been done on finding biomarkers to assess good response to NAC. It has been found that mutation in ATM/RB1/FANCC correlates with improved response and survival. For ERCC2 alteration, similar correlations with improved response and survival have been shown. There also trials assessing immune check point inhibitors in MIBC high risk disease.

In summary, Dr. Galsky showed that there is level 1 evidence to support cisplatin based NAC for MIBC. High risk MIBC patients, who did not receive NAC, are reasonable candidates for adjuvant chemotherapy. Lastly, optimizing perioperative systemic therapy will require better biomarkers, better and safer therapies and better informed decisions. 

Presented By: Matt Galsky, MD, Mount Sinai School of Medicine, New York, NY

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre
Twitter: @GoldbergHanan

1. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. The New England journal of medicine 2003; 349(9): 859-66.
2. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. European urology 2005; 48(2): 202-5; discussion 5-6.

at the 2017 Bladder Cancer Academy - June 9 - 10 - Schaumburg, Illinois, USA