For those who fail biochemically after standard treatment with surgery or radiation, the standard thinking has been that such men were failing with occult, widespread metastatic disease, but we are now seeing that probably about half of them will be failing with what we would describe as oligometastatic disease; it could be locoregional, or it could be distant. But we are seeing this space filled with more targeted therapy rather than systemic therapy. So I think this will be a major change in the way we manage the patients. Now, how this improves overall survival remains to be determined. From a review if the literature to date, it does appear to be the case that one can delay the onset of hormonal therapy by using these targeted approaches. Whether that’s a reasonable endpoint or not remains to be determined.

A better understanding of the molecular characteristics of oligometastatic disease would be especially helpful in concert with other advances in the field, such as more sensitive imaging techniques and emerging forms of focal treatment. A molecular signature to discriminate between metastatic disease that is “destined to remain” oligometastatic and disease destined to progress to polymetastatic disease will inform therapeutic decisions. More sensitive imaging will likely identify more metastases in many patients previously classified as “oligometastatic” by conventional modalities such as CT and bone scintigraphy. Likewise, many patients determined to have M0 disease, with no radiographically demonstrable metastases via conventional imaging, may be reclassified as having M1 disease, with an oligometastatic presentation, especially where lower PSA thresholds lead to imaging. Prospective randomized trials to investigate the role of metastasis-directed therapy are ongoing.

Yes, and as relates to improved detection, the field is moving relatively rapidly. We have been doing the gallium PET imaging now for probably 1 to 2 years, scanning hundreds of men with prostate cancer in various disease states, both before treatment and at the time of relapse. In my opinion, novel forms of PET imaging will replace the standard imaging. Now, we need to do the right trials to demonstrate that there is value: randomized trials of PET imaging before surgery or radiation to see influences on treatment choice, outcomes and biochemical-free survival. But I think there is great enthusiasm for these imaging techniques.

How we define metastatic disease with our imaging techniques is a very important question. Historically, we have relied in the last 3 decades on technetium-99m (Tc-99m) bone scan imaging, and I think that bone scan is still the standard in the overwhelming majority of clinical sites throughout the world. That said, I agree there is a rapidly evolving use of different molecular tracers and PET scanning. Over the years, we started with fluorodeoxyglucose (FDG)-PET, carbon-11 (C-11) acetate, C-11 choline radiotracers, and sodium fluoride PET scanning, and all of these have demonstrated some improved accuracy in detecting either soft tissue or bone lesions, depending upon their targeted focus.

Most recently, there has been tremendous interest in gallium PSMA scanning, as well as a new test known as the FACBC (anti-1-amino-3-[18F] fluorocyclobutane-1-carboxylic acid) or AXUMIN (fluciclovine F 18) test that was recently approved in the United States by the Food and Drug Administration (FDA), manufactured by a company known as Blue Earth Diagnostics. There are multiple companies that have gallium PSMA scanning.

Whole body magnetic resonance imaging is another form of radiographic testing that can be very sensitive, with improved specificity, and thus more accurate in picking up smaller lesions, in both bone and soft tissue. The challenges regarding these newer tests include accessibility and affordability throughout the global community.