What Is the Best Preoperative Tumor-Shrinking Treatment for Bladder Cancer?

Bladder cancer is the most common urinary tract cancer. In Western societies, the median age at diagnosis is around 70, and it is more common in men than women. Smoking is the most important risk factor increasing the likelihood of bladder cancer, followed by aromatic amines, occupational carcinogen exposure (metal, paint, leather and textiles) and HPV infection as additional risks.

The Bladder Has Three Layers:

1. The inner lining of the bladder (urothelium),
2. A thick muscle layer in the middle (detrusor muscle) and
3. The outer covering (adventitia)

In bladder cancer, the disease stage and therefore its treatment are determined by whether the tumor originating in the bladder's inner lining has spread into the middle muscle layer or outward. From this perspective, we assess bladder cancer in 3 stages:

1. Bladder cancer that has not reached the muscle layer (non-muscle-invasive)
2. Bladder cancer that has spread into the muscle layer (muscle-invasive), and
3. Metastatic bladder cancer (spread to other organs)

At diagnosis, around %80 of bladder cancers havenotreached the muscle layer yet, meaning they are at an early stage. The main treatment at this stage is TUR-M (transurethral resection – bladder): a cystoscope with a camera at its tip is passed through the urinary tract to scrape away the tumor-bearing area of the bladder's inner lining.

When it has invaded the muscle layer, bladder cancer is first treated with neoadjuvant (tumor-shrinking) chemotherapy. The first regimen that comes to mind for preoperative tumor-shrinking chemotherapy in bladder cancer is the combination administered every 21 days, cisplatin-gemcitabine as the combination regimen. However, administered every 14 days, methotrexate-vincristine-adriamycin-cisplatin (ddMVAC) is another combination regimen known to produce good results as neoadjuvant bladder cancer treatment, although it is less often preferred. On 30 August 2018, JAMA Oncologypublished a study comparing these two treatment regimens for the first time.

Study Details and Results

Within the study, cystectomy (bladder cancer surgery) patients numbering 1113 were evaluated. Of these, 824 had muscle-invasive or advanced bladder cancer. Of these 824 patients, %40 received neoadjuvant treatment. Among those receiving neoadjuvant treatment;

• % 61 received gemcitabine-cisplatin
• % 10 received gemcitabine-carboplatin
• % 14 received ddMVAC.

According to the Results;

• Tumor downstaging occurred in % 52 of patients receiving ddMVAC, % 41 receiving gemcitabine-cisplatin, and %27 receiving gemcitabine-carboplatin.
• A more striking finding was a pathological complete response in % 41 of patients receiving ddMVAC, meaning no cancer cells were found in surgically removed tissues. This rate was % 24 for gemcitabine-cisplatin and % 9 for gemcitabine-carboplatin.
• Overall survival was higher in bladder cancer patients treated with ddMVAC than in those receiving other treatments, but this difference was not statistically significant.

In conclusion, ddMVAC treatment appears associated with better disease outcomes than other neoadjuvant bladder cancer treatments. Since this was a retrospective study based on analysis of past patient outcomes, a clear comparison of ddMVAC with gemcitabine-cisplatin, regarded as standard treatment, requires a prospective, randomized clinical trial to be conducted.