Experts Delve Into 4 Phenotypes of Advanced Prostate Cancer

Christina T. Loguidice
Published: Monday, Aug 20, 2018
Raoul S. Concepcion, MD, FACS

Raoul S. Concepcion, MD, FACS

Changes in prostate cancer(PC) screening protocols have led to an evolution in the type of disease that physicians are encountering when patients first enter the clinic, a panel of experts said during a recent OncLive Peer Exchange®. “We are seeing, especially in the urology office, patients coming in not having been PSA [prostate specific antigen] screened, higher Gleason patterns, and metastatic disease. And, obviously, they’ve not been hormonally treated up until this point,” Raoul S. Concepcion, MD, said. This has led to a more aggressive treatment stance that includes early combination hormonal therapy and chemotherapy, he said.

PC remains the most commonly diagnosed malignancy in US men.1 In 2015, there were an estimated 3,120,176 US men living with PC, and 164,690 new cases are anticipated in 2018.1 Although PC incidence and mortality rates have steadily decreased since the early 1990s, the reported incidence of metastatic disease has increased.2 One study reported a 72% increase in metastatic disease paired with a 37% decrease in low-risk PC from 2004 to 2013 among a sample of >700,000 men with a PC diagnosis.3 This trend has largely been attributed to changes in US screening protocols.4,5

In 2008, the US Preventive Services Task Force (USPSTF) recommended against routine PSA screenings for men aged ≥70 years and in 2012 recommended against routine PSA-based screenings for men of all ages.4 The USPSTF has since softened its stance, currently recommending against routine PSA-based screenings in men aged ≥70 years but for screening men aged 55 to 69 years if they express a preference for screening after being counseled about its potential harms, such as the risks of false-positives and the potential for overtreatment (Table).6 With fewer PC cases being diagnosed at low-risk stages, healthcare providers have been tasked with treating more advanced PC cases.

As a result, advanced PC is being redefined, the panel said during the OncLive Peer Exchange®. “We’ve traditionally thought of PC as a single continuum and it’s not,” Daniel J. George, MD, said. The panel provided practical definitions for 4 phenotypes of advanced PC: biochemical recurrent (BCR) hormone-naïve nonmetastatic PC, metastatic hormone-naïve advancing PC, nonmetastatic castration-resistant PC (CRPC), and metastatic CRPC. They also discussed treatment advances and offered insights into how improved diagnostics, such as next-generation biological imaging, are affecting treatment decision making.

BCR Hormone-Naive Nonmetastatic PC

Patients with BCR hormone-naïve nonmetastatic PC have no history of hormonal therapy or androgen deprivation therapy (ADT) and have an increasing PSA level after radical prostatectomy (RP) or radiation therapy (RT) for localized PC. BCR is common, affecting up to 40% of men post RP and up to 50% of men post RT, with most cases occurring within 10 years of treatment.7,8

“Post-RP patients should have a PSA of 0, so any rise in PSA is the signal that there’s BCR, whereas post RT, you really need to reach the nadir, and there are different sets of definitions,” Alec S. Koo, MD, explained. In the United States, the Phoenix criterion is commonly used to determine BCR after RT, with a PSA increase of 2 ng/mL over nadir considered BCR, independent of patients’ hormonal therapy exposure.9

Historically, in patients with BCR, it has been challenging to determine when to conduct imaging studies to establish the location of the recurrence and whether metastasis has occurred. “We all know that at low PSA values, bone scans and CT [computed tomography] scans aren’t necessarily that sensitive to pick up metastatic lesions, so typically you’d wait till it reaches a certain level, but that level is highly variable based on the patient,” Alec Koo said. However, the advent of PC-specific positron emission tomography (PET), particularly fluciclovine F 18 (Axumin) with PET/CT, has shifted this thinking, as it enables detection of sites of recurrence at lower PSA levels than required by conventional imaging modalities. In the BED-001 study, the overall detection rate among 595 patients who received ≥1 injection of fluciclovine for the detection of suspected BCR after RP or RT was 67.7%, with an overall detection rate of 41.4% in patients with a PSA <0.8 ng/mL.10

The ability to diagnose and characterize recurrence earlier enables treatment in this population to be better tailored. The imaging presents "a great opportunity to treat low-volume recurrent disease, either with radiation therapy or possibly surgical extubation, rather than reflexively starting ADT," Neal D. Shore, MD, said, noting that several studies are examining this issue and that a lot of data are forthcoming.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis SyndromeJun 30, 20191.0
Community Practice Connections™: 2nd Annual International Congress on Oncology Pathology™Aug 31, 20191.5
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