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Liquid biopsy could help guide prostate cancer treatment
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An experimental blood test designed to analyze circulating tumor cells may be able to predict which patients with prostate cancer could benefit from hormone therapies, according to study results presented at the Genitourinary Cancers Symposium.
Solid tumors release circulating tumor cells into the bloodstream. Each patient can have multiple types of circulating tumor cells, and single-site biopsy may not accurately reflect the diversity of disease, according to study background.
Howard I. Scher
Howard I. Scher, MD, chief of genitourinary oncology service and chair in urologic oncology at Memorial Sloan Kettering Cancer Center, and colleagues evaluated whether a blood test known as liquid biopsy could help identify phenotypic and genomic heterogeneity as a mechanism of resistance to androgen receptor signaling-directed therapy — such as abiraterone acetate (Zytiga, Janssen) or enzalutamide (Xtandi; Astellas, Medivation) — among men with metastatic castration-resistant prostate cancer.
“Not all men respond equally to either enzalutamide or abiraterone, and some men don’t respond at all,” Scher said in a press release. “If the test is validated, it could be used to help select the treatment to which a patient is more likely to respond, sparing the toxicities that may result from one that is ineffective.”
Scher and colleagues stained blood specimens with special dyes to distinguish circulating tumor cells from normal blood cells. They used a liquid biopsy platform developed by Epic Sciences to analyze characteristics of circulating tumor cells, including shape and size.
“Tumor heterogeneity has been proposed as a biomarker of treatment resistance,” Scher said during a press conference. “We studied heterogeneity in circulating tumor cells on a cell-by-cell basis to develop predictive biomarkers of sensitivity for use at decision points in management to better sequence available therapies.”
Scher and colleagues collected 221 blood specimens from patients with metastatic prostate cancer who were about to begin androgen receptor signaling-directed therapy (n = 150) or taxane chemotherapy (n = 71).
Their analysis showed patients with greater variation within circulating tumor cells — both with regard to appearance and genetic composition — did not respond as well to hormone therapy. Patients with high heterogeneity scores experienced shorter median PFS (5 months vs. 17 months), a lower rate of 6-month PFS (OR = 4.5; P < .001) and shorter OS (9 months vs. not reached; HR = 5.51; P < .0001) than those with low heterogeneity scores.
Heterogeneity scores did not appear to predict resistance to taxane chemotherapy.
Because blood samples are easily obtained at any time, they allow for earlier adjustments in treatment.
“The most common place for prostate cancer metastases is in the bone,” Scher said during the press conference. “When you think of a patient with 20 lesions, it would be very difficult to take a biopsy of all those lesions. Some lesions respond, some don’t.
“We think you'll have a greater chance of getting more of an idea of the disease as a whole if you look at the individual cells,” Scher added. “Knowing what is present and tracking that over time will be very relevant. If you don’t track circulating tumor cells, results will be quite poor.”
Sumanta K. Pal
Response rates of the agents studied in first-line settings are pretty similar, Scher said. However, responses vary considerably in the second- and third-line settings, making treatment decisions at those stages more critical.
“In many cases, at that point people are going right to a taxane,” he said. “Obviously we'd like to use the most effective therapy with the least toxicity in those settings.”
Although these findings are early, they are exciting, according to Sumanta K. Pal, MD, assistant clinical professor in the department of medical oncology and therapeutics research at City of Hope and a HemOnc Today Editorial Board member.
“It’s remarkable that a blood test could help us profile cancers in real time, gleaning insights that directly affect patient care decisions,” Pal said in a press release. “Eventually, we may be able to spare some men with prostate cancer the significant side effects of hormone therapy.” – by Anthony SanFilippo
Reference:
Scher HI, et al. Abstract 163. Presented at: Genitourinary Cancers Symposium; Jan. 7-9, 2016; San Francisco.
Disclosure: Scher reports consultant/advisory or speakers bureau roles with, travel accommodations or expenses from, or institutional research funding from Astellas, AstraZeneca, Bristol-Myers Squibb, Genentech, Janssen, Medivation, Pfizer, Sanofi, Takeda and several other pharmaceutical companies. Please see the abstract for a list of all other researchers’ relevant financial disclosures.
Perspective
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Stephen B. Strum, MD, FACP
For decades, I have heard the terms “hormone-refractory,” “androgen-independent” and “castrate-resistant” prostate cancer bandied around, ignoring the well-known fact that the bottom line for the vast majority of men with progressive prostate cancer remains to deliver better therapy directed at the androgen receptor. All of the above terms could have been called ARDPC (androgen receptor-dysregulated prostate cancer).How many men with prostate cancer were misdirected on their anti-prostate cancer treatment because of ignorance related to the importance of the androgen receptor?
Now, Scher and colleagues may well have a handle on targeting true AIPC (androgen-independent prostate cancer) by evaluating the level of heterogeneity of circulating cancer cells, and showing that the higher the level of heterogeneity, the less responsive the patient’s prostate cancer is to those hormonal treatments used in this study — eg, enzalutamide (Xtandi; Astellas, Medivation) or abiraterone acetate (Zytiga, Janssen).
It would be interesting if some of the old drugs now forgotten in the management of prostate cancer might be effective in patients with high levels of heterogeneity. These would include diethylstilbestrol, aminoglutethimide or high-dose ketoconazole combined with triamcinolone (instead of prednisone, which may well induce the promiscuous androgen receptor).
I think the term “liquid biopsy” is cute but may be misleading. The level of heterogeneity is another biomarker, and the concept of evaluating and following biomarkers as biological endpoints truly needs emphasis in all of medicine.
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