BLOOD TEST FOR METASTATIC PROSTATE CANCER

There has been a lot of buzz recently about the use of "liquid biopsies" and how these blood tests that show cancer may be able to replace the need for tissue biopsies.

The latest study shows that such a test could be useful in metastatic prostate cancer, where the biopsy sample would need to be taken from bone, which is painful, risky, and expensive, says an expert.

This study used the Guardant360 test and found that cell-free, circulating tumor DNA (ctDNA) was detected in most patients (94%) with metastatic castration-resistant prostate cancer (mCRPC).

In addition, the test showed several genetic changes that appear to be similar to tumor tissue alterations and provide prognostic information.

"A higher number of overall gene alterations and androgen receptor alterations appeared to be associated with poor clinical outcomes," said lead author, Guru Sonpavde, MD, an associate professor of medicine at the University of Alabama in Birmingham. He was talking about the research at a press briefing held in advance of the upcoming Genitourinary Cancers Symposium (GUCS) 2017, to be held in Orlando, Florida.

The circulating tumor DNA test is a valuable research tool to discover new molecular targets, Dr Sonpavde noted.

New androgen receptor (AR) alterations appeared frequently following therapy, he noted. "These data suggest that developing salvage therapy agents targeting AR alterations holds promise."

Noninvasive alternatives to the traditional tumor biopsy are needed, he pointed out. "Repeated analysis of tumor tissue from patients with metastatic prostate cancer is difficult due to the need for bone biopsies in most cases," he said.

This is "one of the largest clinically annotated data sets looking at ctDNA in metastatic prostate cancer," commented Sumanta Pal, MD, a medical oncologist at the City of Hope Cancer Center in Los Angeles, California, and an expert from the American Society of Clinical Oncology who moderated the presscast.

"It showed that circulating tumor DNA offers a simple and effective way to look at tumor composition, so that clinicians can use that to personalize therapy," he said.

The study showed that 94% of patients had circulating tumor cells in their blood, he reiterated. The only other way to assess the tumor is with a biopsy, he noted. "Bone biopsies can be painful, risky and expensive, and the yield can be low."

"As we work to tailor treatment to the molecular changes driving the growth of cancer in each patient, these blood tests appear very promising, especially for patients who are unable to undergo a tumor biopsy," he added.

Use of Liquid Biopsies 

Cell-free ctDNA can provide comprehensive information on genetic changes in a tumor, which can evolve over time, the researchers noted in their abstract. The use of circulating cells has been gaining ground in cancer for their ability to monitor treatment and assess outcomes.

A study published last year and reported by Medscape Medical News, showed that this technology can be used to assess tumor heterogeneity in prostate cancer. Others studies suggest that it may have applications in ovarian cancer, colon cancer, lung cancer, and lymphoma.

Pinpointed Alterations

In the current study, Dr Sonpavde and colleagues investigated ctDNA profiling in patients with mCRPC and the association with clinical outcomes and evolution with therapy.

They analyzed cell-free ctDNA from 514 patients who had undergone baseline ctDNA analysis for potentially actionable alterations using Guardant360 before beginning new systemic therapy.

In this cohort, most (94%) patients had one or more ctDNA alterations, and the most common recurrent somatic mutations were in TP53 (36% of patients); AR (22%); APC (10%); NF1 (9%); EGFR; CTNNB1and ARID1A (6% each); and BRCA1, BRCA2, and PIK3CA (5% each).

The most common genes with increased copy numbers were AR (30%), MYC (20%), and BRAF (18%).

Clinical outcomes and clinical features were available for 163 patients, and the researchers found that a higher number of ctDNA alterations was associated with shorter time to treatment failure (TTF) (hazard ratio [HR], 1.05; P = .026).

AR alterations trended for shorter TTF (HR, 1.42; P = .053) as well as for shorter survival (HR, 2.51; P = .09).

Dr Sonpavde pointed out that patients who had received prior therapy had new alterations in AR (56% vs 37%; P = .028) compared with those who were treatment naive.

Finally, serial ctDNA profiling of a subset of 63 patients revealed the evolution of alterations in AR, BRCA1, and BRCA2 after therapy.

The study was not funded. Dr Sonpavde has disclosed a consulting or advisory role with Bayer, Genentech, Sanofi, Merck, Novartis, Pfizer, Argos Therapeutics, Agensys; serving on the speakers' bureau for Clinical Care Options/National Comprehensive Cancer Network; other relationships with Boehringer Ingelheim; receiving honoraria from UpToDate, and receiving institutional research funding from Onyx, Bayer, and Boehringer Ingelheim. Several coauthors have also disclosed relationships with industry as noted in the abstract.

Genitourinary Cancers Symposium (GUCS) 2017. Abstract 149. To be presented February 16, 2017.