Early blood test may predict survival in men newly diagnosed with metastatic prostate cancer, clinical trial finds

A blood test, performed when metastatic prostate cancer is first diagnosed, can predict which patients are likely to respond to treatment and survive the longest. This can help providers decide which patients should receive standard treatment and which might benefit from trials of riskier, more aggressive new drugs.

The research, which is part of a phase III clinical trial, was published in Open JAMA Network.

Before it spreads, prostate cancer can be cured with surgery or radiation therapy. Once the cancer has metastasized and is no longer curable, systemic treatments are used to prolong survival as much as possible. Biomarkers that predict patient response could enable better personalization of treatments, but they are rare.

A new study has found that measuring circulating tumor cells (CTCs), rare cancer cells shed by tumors into the blood, is a reliable way to predict subsequent treatment response and survival prospects. CTCs have already been studied in prostate cancer, but only at its later stages.

“No one, until now, has looked at whether CTC counts can be used early on, when a man first presents with metastatic prostate cancer, to tell us whether he will live a long time or short time, or whether or not it will progress with therapies,” said Amir Goldkorn, MD, senior author of the study and associate director of translational sciences at the USC Norris Comprehensive Cancer Center at the Keck School of Medicine. USC.

The research leveraged CellSearch (Menarini, Inc.), an FDA-approved liquid biopsy technology at the Norris Comprehensive Cancer Center, to detect and measure CTCs in blood samples. Patients with more CTCs had a shorter median survival time and a higher risk of death during the study period. Those who had more CTCs also had less “progression-free survival,” which refers to the length of time a patient’s disease is controlled by treatment without getting worse.

“You couldn’t tell these men apart when they came through the door,” said Goldkorn, who is also a professor of medicine at the Keck School of Medicine. “All their other variables and prognostic factors were apparently the same, and yet they had very, very different results over time.”

Researchers say the CellSearch blood test, already widely available from commercial providers, can help quickly identify patients unlikely to respond to standard treatment options. These men could benefit from a more intensive treatment approach, including clinical trials of new drugs that may have more side effects but could improve survival in these high-risk patients.

Count CTCs

The research was part of a Phase III clinical trial by the SWOG Cancer Research Network, a group of more than 1,300 institutions across the country that collaborate to study various cancers. Baseline blood samples from 503 patients with metastatic prostate cancer, who were participating in a new drug trial, were sent to the Keck School of Medicine team for analysis.

To analyze the blood samples, the researchers used the CellSearch platform at the Liquid Biopsy Research Core at the Norris Comprehensive Cancer Center, a facility founded and led by Goldkorn. CellSearch uses immunomagnetic beads, antibodies attached to small magnetic particles, which bind to CTCs in the blood and extract them to be detected and counted by specialized equipment.

Patients with five or more CTCs in their blood sample had the worst outcomes. Compared to patients without CTC, they were 3.22 times more likely to die during the study period and 2.46 times more likely to have their cancer progress. They were only 0.26 times more likely to have a complete prostate-specific antigen (PSA) response, meaning they responded poorly to treatment.

Men with five or more CTCs had a median survival time of 27.9 months after the blood test, compared to 56.2 months for men with one to four CTCs and at least 78 months for men without CTCs. (Many patients in the latter group survived beyond the publication date, so the median survival time could not yet be calculated.)

The bottom line: more CTCs meant patients survived shorter, progressed much more quickly, and were unlikely to respond to standard treatments.

Clinical trial candidates

The new study shows that measuring CTC counts at the start of treatment can predict long-term survival rates, even in men who receive numerous treatments for metastatic prostate cancer over a period of years. This means the test can help identify men early for trials of new and potentially more aggressive therapies.

“We want to enrich these clinical trials with men who need all that extra help, who would really benefit from three drugs versus just two, or a new chemotherapy drug, even though it may have more side effects.” , Goldkorn said.

Goldkorn and his team are currently testing a new blood test that measures not only the number of CTCs, but also the molecular composition of CTCs and tumor DNA circulating in the blood, as well as other factors. Their goal is to create biomarkers with even greater predictive power, which could ultimately help match patients to specific treatment options.