Blood Tests Can Detect Individual’s Resistance to Docetaxel for Prostate Cancer

Regularly testing before and during chemotherapy can help physicians determine early on if treatment is working.

Regular blood tests before and during chemotherapy can detect whether an individual with prostate cancer is developing resistance or resistant to treatment with docetaxel, results of a study show.

This could help physicians detect early on if treatment is working and switch to alternatives, such as abiraterone or cabazitaxel, if necessary.

Investigators studied the number and types of cancer cells that have detached for the tumor and entered the blood stream. These are called circulating cancer cells (CTC) and can help identify docetaxel resistance and predict survival.

“An increase in CTC numbers may indicate a lack of response to treatment. Furthermore, by monitoring the appearance of potentially drug-resistant CTCs, we can change treatment tactics early on and in a patient-personalized and timely manner,” Davies said.

If more than 6 CTCs per 7.5 mL of blood were detected before their first docetaxel dose, men were less likely to respond to docetaxel, and their disease was more likely to progress or recur within 3 months; they were also more likely to die within 18 months.

Men with fewer than 6 CTCs detected per 7.5 mL of blood were likely to have progression-free survival of 17 months and an overall survival time of 3 years.

Investigators took blood samples from 56 individuals with advance prostate cancer who were being treated at St Bartholomew’s Hospital in London. The samples were taken before treatment, after their first dose of chemotherapy, before their fifth dose, and after they finished all doses, over a total of approximately 6 to 8 months.

The number of samples per individual ranged from 2 to 4 m, depending on availability, with a total of 205 samples.

Investigators used Parsortix, a blood filtration system, to identify CTCs based on their larger size compared with other components in blood. The system also captures different subtypes of CTCs.

“We then looked for patterns in the data from men who responded or did not, or whose disease progressed sooner than others after treatment. Using these patterns, we can apply them to future patients with the goal to predict whether they will respond to therapy and pre-emptively decide on the best course of action that will have maximal benefit,” Caitlin Davies, a PhD research student at Barts Cancer Institute at the Queen Mary University of London, said in the statement.

Among the subtypes of CTCs, investigators found that more than 1 “classic” type of CTC, such as epithelial, cytokeratin positive cells (E-CTCs), before docetaxel treatment predicted that the disease progress within 2 months following treatment, instead of more than a year later.

The subtypes also predicted survival at 9 months compared with 32 months for individuals without E-CTCs.

High number of CTCs toward the end of treatment predicted a shorter time to disease progression and death, and the disease was 8 times more likely to progress within 6 months for individuals who showed an increase in CTCs without epithelial features than those who did not have an increase.

Investigators also found that a protein encoded by a gene called KLK2was better at predicting time to disease progression and death than the current gold standard protein, prostate-specific antigen, encoded by KLK3 gene.

“There were high levels of the KLK2 gene expression in patients who did not respond to docetaxel, and this elevated expression was also associated with a shorter time to disease progression and death,” Davies said.

Investigators are continuing research and validate the use of CTCs as biomarkers for prostate cancer.

The findings were presented at the NCRI Festival.

Reference

Blood tests predict which prostate cancer patients are resistant to chemotherapy drug. EurekAlert, News release. November 9, 2021. Accessed November 10, 2021. https://www.eurekalert.org/news-releases/934115