PET imaging may predict drug response, survival in advanced prostate cancer

By Marilynn Larkin

NEW YORK (Reuters Health) – Positron emission tomography (PET)-based molecular imaging biomarkers may predict therapeutic response and survival in patients with metastatic castration-resistant prostate cancer (mCRPC), researchers say.

“Glycolysis (Glyc) and androgen receptor (AR) expression are two of the most important biochemical characteristics of prostate cancer, particularly once the tumor has escaped from hormone suppression and after it begins to spread from the prostate gland throughout the body, commonly to bone and lymph nodes,” Dr. Steven Larson of Memorial Sloan Kettering Cancer Center told Reuters Health.

“We (hypothesized) that these biochemical tracers would provide a way to distinguish tumor sites or patterns of tumor sites that would adversely affect survival, and identify patient groups likely to respond to or resist drug treatment,” he said by email.

To investigate, Dr. Larson and colleagues performed PET imaging using the molecular biomarkers FDG (glycolysis) and FDHT (androgen receptor) in 133 men (mean age, 68) with mCRPC.

As reported online November 9 in JAMA Oncology, a total of 2,405 lesions (median, 12 per patient) were detected and characterized by computerized image analysis.

“We found three different patterns of biomarker uptake in tumors which were independently predictive of adverse prognosis,” Dr. Larson said. These were AR1Glyc1, present in 71% of lesions; AR1Glyc0, present in 16%; and AR0Glyc1, present in 13%.

Sorted by lesion type, four patient-specific groups emerged:

1. Concordant, with all AR1Glyc1 (25.6%);

2. AR predominant, with AR1Glyc1 and varying numbers of AR1Glyc0 (24.8%);

3. Glyc predominant, with AR1Glyc1 and varying numbers of AR0Glyc1(30.1%); and

4. Mixed, with AR1Glyc1 plus a mixture of varying numbers of AR1Glyc0 and AR0Glyc1 (19.5%).

Median survival across all patients was 91.6 weeks, with an absolute 5-year survival rate of 11.0%.

“The worst lesion type was the absence of AR expression(AR0), with the presence of glycolysis retained (Glyc1),” Dr. Larson noted. “Each lesion of the AR0Glyc1 type found reduced that patient’s survival by (a relative) 11%. We determined that 49% of the patients studied had at least one of these ‘bad prognosis’ lesions.”

“Other adverse prognostic findings were lesion number more than the median of 12 and very high glucose uptake,” he added.

Dr. Larson concluded, “We recommend that AR0Glyc1 lesions should be biopsied, under PET image guidance, to determine if there are other drugs that may be of benefit if these patients do not respond to conventional treatment with AR inhibitors.”

Dr. Adam Ramin, medical director of Urology Cancer Specialists in Los Angeles said in an email to Reuters Health, “Most patients with mCRPC eventually reach a point at which hormone therapy is no longer effective.”

“While . . . there have been significant strides and advances in prolonging the life of patients with AR- positive mCRPC, we have not yet found good treatment options for those without the receptor,” he said by email.

“The first step in finding a treatment for this group of patients is to be able to identify them,” he observed. “This study shows that PET imaging is useful in making that determination.”

“From a clinical point of view, our challenge now is to discover and design an effective treatment for these patients. Such treatment could include targeted therapies such as immune-based therapies against colonies of cancer cells,” he suggested.

“It is important to indicate that the technology in this study is not 100% accurate,” he added. “There will be a subgroup of patients whose cancer may not show up on PET imaging, whether the cells have the androgen receptor or not.”

“Research to find more accurate radioactive tracers (is ongoing),” he noted. “As the sensitivity, and therefore the accuracy, of PET imaging improves, more information maybe gleaned from the heterogeneity of various prostate cancer colonies.”

SOURCE: http://bit.ly/2mqT6bN

JAMA Oncol 2017.

(c) Copyright Thomson Reuters 2017. Click For Restrictions - http://about.reuters.com/fulllegal.asp