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Chemotherapy plus immunotherapy before surgery is beneficial for invasive bladder cancer outcomes

1 Sep 2021
Chemotherapy plus immunotherapy before surgery is beneficial for invasive bladder cancer outcomes

A new study is the first to report the beneficial use of chemotherapy plus immunotherapy before surgical removal of the bladder in muscle-invasive bladder cancer (MIBC).

Researchers at the University of North Carolina Lineberger Comprehensive Cancer Center led the study, reporting that the regimen reduced the invasiveness of the cancer in 56 percent of patients in a phase II clinical trial.

The findings were published in the Journal of Clinical Oncology.

“Downstaging, or treating tumors so that they become less invasive prior to surgical removal, is an important tool in muscle-invasive bladder cancer,” said UNC Lineberger’s Tracy Rose, MD, MPH, assistant professor at the UNC School of Medicine and lead author of this finding.

“If we can treat a tumour pre-surgically so that it regresses to a stage where it is superficial and does not invade the bladder muscle wall, the chances of long-term survival are better.”

Nearly 25 percent of all bladder cancers are muscle invasive. Surgical removal of the bladder is performed in many MIBC cases, but often microscopic cancer cells have already spread to lymph nodes, greatly reducing chances of a cure.

In these cases, clinicians often use cisplatin chemotherapy before removal of the bladder to reduce tumour volume and kill micro-metastases. Despite this aggressive treatment, more than half of patients see their cancer return within two years.

“Optimal management of MIBC is a huge unmet need,” said UNC Lineberger’s Matthew Milowsky, MD, the paper’s corresponding author.

“We think that the combination treatment used in our trial may improve outcomes compared with chemotherapy alone, with the aim of ridding micro-metastatic disease so that even a modest improvement in response rates translates to higher cure rates.”

All of the 39 patients enrolled in the trial had tumours that had grown into the muscle layer of the bladder wall.

The patients intravenously received the immunotherapy drug pembrolizumab in combination with standard cisplatin-based chemotherapy before surgery. What was unique about this trial is that patients received cisplatin on the first and eighth day of their treatment cycles.

This approach, known as ‘split dosing’, helped reduce toxicities compared to single, initial high doses, making the treatment more tolerable, especially in patients with borderline kidney function or other comorbidities.

Pembrolizumab was continued every 21 days for four cycles. All patients except one had their bladders surgically removed after finishing their chemo- and immunotherapies.

Twenty-two patients (56%) saw their tumours regress to a less invasive stage and regress from the muscle layer of the bladder; 14 patients (36%) saw their tumours completely disappear from their bladder.

The most common side effects were low blood platelet counts, anaemia and several other blood and mineral-related deficiencies.

“More than a third of the patients saw a complete regression of their cancer and ultimately may not require surgical bladder removal,” Rose concluded. “More studies will need to be done to identify who can safely avoid surgery. Several ongoing trials are investigating this bladder-sparing approach."

The researchers are now analysing blood and tumour samples to determine which patients were likely to respond to treatment and what changes took place in the tumours, blood, and immune system during and after treatment.

Source: UNC Lineberger Comprehensive Cancer Center