Imaging Agent Can Change Plans for Recurrent Prostate Cancer

SAN FRANCISCO — When men with prostate cancer experience biochemical recurrence, the rise in levels of prostate-specific antigen (PSA) suggests that the disease may have spread.

This is distressing both for clinicians and patients, because it suggests that curative-intent primary therapy has not succeeded.

It also prompts immediate questions: What is the extent of local recurrence and of metastases? And what should be done next therapeutically?

At present, there is uncertainty as to how to address these issues, because when patients experience biochemical recurrence, the PSA level rises, but there is no visual evidence of disease on conventional scans.

A new study shows that adding an imaging agent to the scans provides more information, and this has a "substantial impact" on clinical decisions for such patients.

The imaging agent, 18F-fluciclovine, was used in conjunction with positron-emission tomography (PET)/CT scanning.

The results from the new study, known as FALCON (Fluciclovine [18F] PET/CT in Biochemical Recurrence of Prostate Cancer), were presented here at the Genitourinary Cancers Symposium (GUCS) 2018.

For 52 of 85 men enrolled in the study (61%), clinical management was changed after 18F-fluciclovine PET/CT imaging, reported Eugene Jueren Teoh, MBBS, an oncologist at Oxford University Hospital in the United Kingdom.

For some patients, management was changed to "provide a better chance at cure or to avoid possibly futile salvage therapy," Teoh told the meeting audience.

He also pointed out that 18F-fluciclovine is a synthetic amino acid that is taken up by amino acid transporters that are "massively" upregulated in many cancers, including prostate cancer.

It is already approved in the United States and the European Union for PET/CT imaging in cases of biochemical recurrence of prostate cancer. In the United States, costs are reimbursed by insurance through the Centers for Medicare & Medicaid Services, Teoh said.

Sumanta Pal, MD, a urologic oncologist from the City of Hope Cancer Center in Duarte, California, said the rate of management change in the study was thought provoking: "I think 60% is awfully impressive.

"If I had any other diagnostic test that changed my management more than half of the time, I would definitely implement it," said Pal, who was asked for comment.
He also placed the results in the context of currently used technology.
"We realize that many patients with localized disease [and rising PSA levels] may actually have brewing metastasis. But we just don't have the technology with current modalities, such as CT scans and technetium bone scans, to detect these areas of disease spread," said Pal.

Study Details

In the FALCON study, the investigators recorded the intended management plan for patients being considered for radical salvage treatment after the patients experienced initial biochemical recurrence; the investigators subsequently recorded newly recommended plans following scanning with 18F-fluciclovine.

The primary objective was assessment of the clinical impact of the scanning agent on patient management.
Postscan changes to treatment modality, such as a change from salvage radiotherapy (RT) to systemic therapy, were classed as "major"; changes within a modality (eg, a modification of RT fields) were classed as "other," said Teoh.
Of the 52 men for whom changes in management were made, 31 underwent a major change (for 18 patients, planned salvage treatment was changed to systemic noncurative therapy; for 13 patients, planned salvage treatment was changed to watchful waiting). For 21 patients, changes in management were classified as "other" (planned RT was modified to include a boost to a positive lesion or a widening of the field to include the whole pelvis).

For the 85 enrolled patients, the mean period following initial diagnosis was 4.8 years; the patients' median age was 67 years. Most (56; 65.9%) had previously undergone radical prostatectomy (RP), and 27 had received RT (± other therapy). For 12 men (14.1%), the Gleason score was ≤6; for 60 (70.6%), the score was 7; and for 13 (15.3%), the score was ≥8.

Notably, the median PSA level among the men was 0.63 ng/mL.

That median PSA level worried a clinician in the GUCS audience.
Daniel Lin, MD, an urologist at of the University of Washington in Seattle, said, "I would put someone forward for salvage radiotherapy much before PSA got to 0.6."

Lin wondered whether waiting for disease spread to show up on a scan, even with highly sensitive 18F-fluciclovine PET/CT imaging, might result in "missing the window for cure."

Toeh responded that, in the study, not all the scans were positive. Among men who had already undergone prostatectomy and whose PSA level was <.5, there was a 25% detection rate upon scanning. That would have triggered salvage RT at Toeh's institution at Oxford, he said.

Furthermore, the study was multicenter, and "hypersensitive" PSA tests were used "heterogeneously" in the study, he noted in explaining the relatively high trigger point for progressing to salvage RT.

There is a need for "robust" criteria for employing 18F-fluciclovine scanning, Toeh admitted. "It's not for everyone," he commented. "But I do believe there will be a subset [of patients], particularly post prostatectomy, who will benefit."

Teoh also said there is no cutoff PSA value with regard to not performing the scan. "I would scan patients with a fast doubling time" whose PSA level was ≥0.1, he said.

The inclusion criteria for the study was a PSA level >0.1 and a doubling time <15 months or a PSA >1, regardless of doubling time.

Enrollment in the UK trial was stopped after this interim analysis with 85 patients, said Teoh, because of "overwhelming efficacy."

Toeh said more research is needed. Currently, follow-up is underway to assess whether patients in the current study experienced clinically related outcomes — PSA dropping/stabilizing or increasing — after 18F-fluciclovine scanning. Long-term studies are needed to determine the impact of this tool on disease outcomes, he added.

Teoh said 18F-fluciclovine is "well established" as a diagnostic tool for detecting sites of recurrent prostate cancer. However, a member of the Dana Farber Cancer Institute in Boston, Massachusetts, who attended GUCS, told Medscape Medical News that the cutting-edge center had added 18F-fluciclovine scanning only in the past 6 months.

Pal said it was his impression that the technology was still mostly limited to use in major academic centers. "If we continue to see compelling trends like these — namely, fluciclovine changing patient management upwards of 60% of the time — we may see greater clinical implementation," he added.

"This modality can be used in the confines of most existing radiology practices," Pal also observed.

The new study is an important step for this imaging agent, he suggested. "Assessing the rate of change in management is really key, as opposed to simply identifying the additional sites of metastases that you can pick up with fluciclovine above and beyond standard modalities."

The study was jointly funded by Innovate UK and Blue Earth Diagnostics. Dr Toeh has received research funding from Blue Earth Diagnostics. The study authors included company employees. Dr Pal has financial ties to Eisai, Ipsen, Astellas, Medivation, Bristol-Myers Squibb, Exelixis, Genentech, Myriad Pharmaceuticals, Aveo, Novartis, and Pfizer.

Genitourinary Cancers Symposium (GUCS) 2018. Abstract 165, presented February 8, 2018.

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