A blood test taken at the time metastatic prostate cancer is first diagnosed can forecast how well certain patients will respond to treatments and how long they might survive. This information helps healthcare providers determine whether patients should receive standard treatments or if they might gain from participating in more aggressive and riskier new drug trials. The study, which is part of a phase 3 clinical trial backed by the National Cancer Institute (NCI) from the National Institutes of Health, has been published in JAMA Network Open.
Before prostate cancer spreads, it can often be treated effectively with surgery or radiation. However, once cancer has metastasized and is considered incurable, systemic treatments aim to extend survival as much as possible. Identifying biomarkers that can predict patient responses could facilitate more targeted treatment strategies, though such biomarkers are currently limited.
Recent research suggests that measuring circulating tumor cells (CTCs), which are rare cancer cells released into the bloodstream, is a dependable method for anticipating a patient’s response to treatment and their chances of survival. CTCs have been previously explored in the context of advanced prostate cancer but never before at the initial diagnosis stage.
“No previous studies have assessed whether CTC counts can be a determinant right as a man presents with metastatic prostate cancer, informing us on his potential lifespan or how he will respond to treatment,” noted Amir Goldkorn, MD, the study’s lead author and associate director of translational sciences at the USC Norris Comprehensive Cancer Center at the Keck School of Medicine of USC.
The research utilized CellSearch (Menarini, Inc.), an FDA-approved liquid biopsy technology available at the Norris Comprehensive Cancer Center, to identify and quantify CTCs in blood samples. Patients with a higher CTC count faced shorter median survival rates and an increased likelihood of death during the study. Additionally, those with more CTCs experienced lower “progression-free survival,” which indicates the duration a patient’s disease remains stable under treatment.
“When these men came in, you wouldn’t be able to distinguish them based on any other variables or prognostic indicators, yet they displayed vastly different outcomes,” said Goldkorn, who also serves as a professor of medicine at the Keck School of Medicine.
The study’s findings indicate that the CellSearch blood test, which is widely accessible through commercial laboratories, can effectively pinpoint patients who are unlikely to respond to standard therapies. Identifying these patients early can lead to more comprehensive treatment approaches, including participation in clinical trials for innovative drugs that may carry more side effects but could offer improved survival rates for at-risk patients.
Analyzing CTC counts
This research formed part of a phase 3 clinical trial organized by the NCI-funded SWOG Cancer Research Network, a collaboration of over 1,300 institutions across the nation devoted to cancer research. Baseline blood samples from 503 patients with metastatic prostate cancer in a new drug trial were analyzed by the Keck School of Medicine team.
To examine the blood samples, the researchers employed the CellSearch platform hosted at the Norris Comprehensive Cancer Center’s Liquid Biopsy Research Core, which Goldkorn established and directs. The CellSearch technology utilizes immunomagnetic beads—antibodies linked to tiny magnetic particles that adhere to CTCs in the bloodstream, allowing for their extraction and quantification with specialized equipment.
The findings revealed that patients with five or more CTCs in their blood had the most unfavorable outcomes. In comparison to those with no CTCs, they were 3.22 times more likely to die during the study and 2.46 times more likely to see their cancer progress. Additionally, they had only a 0.26 times likelihood of achieving a complete prostate-specific antigen (PSA) response, indicating a poor treatment reaction.
Men with five or more CTCs had a median survival time of 27.9 months post-blood test, contrasting with 56.2 months for those with one to four CTCs, and over 78 months for men showing no CTCs. (Many in the latter group survived beyond the study’s publication date, precluding a median survival length calculation.)
In summary, a higher CTC count correlates with shorter survival, quicker disease progression, and lower chances of responding to standard treatments.
Identifying candidates for clinical trials
The new findings illustrate that counting CTCs at the beginning of treatment can help predict long-term survival, even for men who receive multiple therapies for metastatic prostate cancer over several years. This capability can assist in identifying candidates for clinical trials focused on new, potentially more aggressive treatments.
“We aim to enhance these clinical trials with men who truly require additional assistance—those who would greatly benefit from treatments involving three drugs instead of two, or from the inclusion of new chemotherapy options, despite possible side effects,” Goldkorn explained.
Goldkorn and his team are currently investigating a novel blood test that assesses not only the CTC count but also the molecular characteristics of CTCs and circulating tumor DNA, along with other relevant factors. Their objective is to develop biomarkers with enhanced predictive capabilities, potentially aiding in matching patients to tailored treatment strategies.
