Frozen section biopsy helps diagnose bladder cancer

A University of São Paulo study examined 131 patients and showed that the method helps in the early identification of invasive lesions.

By Karina Toledo

Agência FAPESP – A study conducted at the University of São Paulo School of Medicine (FMUSP) showed that the rapid result test known as a frozen section biopsy may become the most precise bladder cancer diagnostic test available and enable the early treatment of invasive lesions.

The assessment was made during the doctoral studies of urologist João Alexandre Queiroz Juveniz on 131 patients with urothelial carcinoma treated at the Cancer Institute of the State of São Paulo (ICESP). The study was led by Dr. Alexandre Crippa Sant'Anna, the project coordinator of the FAPESP-funded project called "Analysis of prognostic factors associated with recurrence of bladder cancer."

“Patients would come to the hospital with the diagnosis of bladder tumor, but we didn’t know whether they had muscle-invasive tumors, which are the type that affect the organ’s muscle layer. This determination is made using a procedure called transurethral resection,” Juveniz explained.

The procedure removes the tumor and cauterizes the site with the aid of equipment connected to a camera inserted through the urethra. The collected material is then sent for pathological analysis, and the results are ready within approximately five days.

“If the lesion is determined to be superficial, which occurs in approximately 70% of the cases, that’s the end of the surgical treatment. However, if the exam indicates that the tumor is muscle invasive, the bladder needs to be removed to prevent the spread of the disease [metastasis],” the researcher said.

To make a precise diagnosis, however, the surgeon needs to obtain a sample of the bladder’s muscle layer during the resection procedure for analysis. When this does not occur, a new procedure has to be conducted, and the start of treatment is delayed for at least four more weeks.

“Our objective in performing frozen section biopsy during transurethral resection was to be sure that the collected material included some of the muscle layer. This is not how the test is normally used, and we did this for the first time to attempt to increase the diagnostic accuracy,” Juveniz explained.

The method consists of freezing the collected material using liquid nitrogen and then cutting the sample into thin slices for microscopic analysis. The pathologist’s analysis is performed while the patient is still on the operating table, and the result is ready in approximately 15 to 20 minutes. “If the results show that the resection was not adequately performed, the procedure can be redone immediately,” Juveniz said.

According to the researcher, the frozen section procedure is already used routinely in two circumstances: during surgery, when it is needed to determine whether the tumor is benign or malignant (to guide the treatment options), and after removing the tumor, when it is needed to determine whether the surgical margin is free of lesions.

Research groups

The patients who participated in the study were randomly divided into two groups: 67 in the control group were subjected to the standard protocol; that is, they underwent transurethral resection, and the material was sent for a traditional pathological analysis.

The sample is inserted into a paraffin solution and, once solidified, cut into thin slices for microscopic analysis. “Although this procedure takes longer, it offers some advantages. It allows the sample to be cut into thinner slices, thus providing a better view of the tumor and enabling a more complete analysis,” Juveniz explained.

The other 64 patients, in addition to the standard procedure, had a second sample collected that was subjected to frozen section biopsy. In this group, the samples were collected until they were able to get a muscle layer representation for the frozen section procedure.

In the patients who had not undergone frozen section biopsy, 40% had no muscle layer representation, and another procedure was necessary.

In the study group, the number of lesions that had invaded the muscle layer tested was eight times higher – 23% of the patients compared with only 3% of the control group – demonstrating the effectiveness of the frozen section study in diagnosing muscle-invasive disease.

“Between four and six weeks later, we performed another resection to investigate whether there was any remaining lesion in the original site. In the group that underwent the frozen section biopsy, 90% of the patients were free from lesions compared with only 65% of the control group,” the researcher said.

Although the surgery lasted slightly longer in the group that underwent the frozen section biopsy – 50 minutes compared with 42 minutes in the control group – there was no statistical difference in terms of complications. “Because additional material has to be removed to perform the frozen section biopsy, more complications are possible, such as bladder perforation or increased bleeding. In our study, however, there was no significant difference between the two groups,” the researcher stated.

According to Juveniz, frozen section biopsy is a relatively inexpensive procedure – costing less than R$100 – and provides for earlier diagnosis and treatment of invasive lesions.

“Bladder tumors are usually very aggressive and cause early metastasis. The patient’s prognosis can change drastically in less than three months if the treatment is not performed in a proper manner. We also need to consider that when a patient arrives at a hospital like the ICESP, he has probably already been treated by several institutions,” Juveniz said.

Bladder cancer is strongly linked to smoking and is the fourth leading cause of cancer in men; it is second only to prostate cancer among the tumors affecting the urological system. It is estimated that the disease affects 13.3 of every 100,000 inhabitants of the city of São Paulo. In Brazil, 8,900 cases of bladder cancer were reported in 2012, with 3,100 deaths, according to data from the National Cancer Institute (INCA).