Regular blood tests before and after chemotherapy could indicate whether a patient is responding to prostate cancer treatment, research presented at the National Cancer Research Institute Festival suggests.
Caitlin Davies, a PhD research student at Barts Cancer Institute, Queen Mary University of London, UK, and colleagues, explored whether it would be possible to identify docetaxel resistance using blood tests as an alternative to invasive procedures. This allows doctors to recommend other prostate cancer treatment options, such as abiraterone or cabazitaxel, if it is not working.
Resistance to chemotherapy
Men with prostate cancer that has started to spread to other parts of the body (metastasised) and do not respond to lower levels of the hormone androgen are often treated with docetaxel, a type of chemotherapy that can significantly improve survival. However, some patients are resistant or acquire resistance to docetaxel, leading to other prostate cancer treatments.
The researchers investigated the possibility of identifying docetaxel resistance and predicting survival from the number and types of cancer cells that have detached from the tumour and entered the bloodstream; these are known as circulating cancer cells or CTCs.
The study included taking blood samples from 56 patients with advanced prostate cancer who were being treated at St Bartholomew’s Hospital, London. During a period of around six to eight months, samples were taken before they started docetaxel treatment, after their first dose of chemotherapy, prior to their fifth dose, and once all doses had been provided. The study involved a total of 205 samples that could be analysed with patients supplying between two to four units.
“Our ability to collect and analyse CTCs before, during, and after treatment meant that we could monitor changes in CTCs in response to treatment,” Commented Davies.
A blood filtration system called Parsortix was used to identify CTCs based on their larger size compared to other components in the blood, such as white blood cells. Additionally, different subtypes of CTCs were collected.
“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. For instance, 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-personalised and timely manner,” added Davies.
Understanding the blood test results
The blood test results showed that men were less likely to respond to docetaxel, their disease was more likely to recur or progress within three months, and they were more likely to die within 18 months if more than six CTCs per 7.5mL of blood were detected before their first docetaxel dose. This compared to progression-free survival of 17 months and an overall survival time of three years for men with fewer than six CTCs detected per 7.5mL of blood.
Additionally, having more than one ‘classic’ type of CTC (epithelial, cytokeratin positive cells or E-CTCs) before prostate cancer treatment predicted that the disease would progress within two months following treatment, instead of more than a year later. It also predicted survival: nine months versus 32 months for those without E-CTCs.
Furthermore, high numbers of CTCs towards the end of the prostate cancer treatment predicted a shorter time to disease progression and death. The disease was eight times more likely to progress within six months in patients who showed an increase in another type of CTC (CTCs without epithelial features) than those who did not have an increase.
Davies commented: “This insight into how CTC dynamics lead to reduced progression-free and survival times is vital for clinicians. It will enable them to make early changes of treatment from docetaxel to an alternative, which may significantly improve patients’ chances of long-term survival.”
The study uncovered that protein encoded by a gene called KLK2 was significantly better at predicting time to disease progression and death than the current gold standard protein, prostate-specific antigen (PSA), which is encoded by the KLK3 gene.
The future of prostate cancer treatment
Research and validation of the use of CTCs as biomarkers for prostate cancer will continue. The number of genes in CTCs that could be involved in the resistance to docetaxel will be continuously investigated. This will encourage a better understanding of the mechanisms involved and with identifying new targets for anti-cancer drugs.
Hashim Ahmed, Chair of the NCRI Prostate Group and Professor of Urology at Imperial College London, who was not involved in the research, said: “These are promising results and have the potential to change clinical practice if they are confirmed by further research. Assessing the responsiveness of an individual patient’s tumour to docetaxel treatment by means of blood tests will enable clinicians to personalise cancer treatment more easily and effectively, without the patient having to undergo invasive procedures such as tissue biopsies. It could also help to avoid patients undergoing unpleasant systemic treatments that are going to be unsuccessful.”
