<p>Many patients develop prostate cancer biochemical recurrence with rising prostate-specific antigen (PSA) levels following surgery or radiation therapy. Our featured experts discuss their perspectives on US consensus recommendations for treating prostate cancer biochemical recurrence and their approach to treating patients who have biochemical recurrence and negative prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) scans.</p>

I think that the US Prostate Cancer Conference (USPCC) publication did a beautiful job addressing the complexity and number of issues that need to be considered when treating patients with biochemical recurrence. One point they make is on the value of better imaging in this patient population. Many people with high-risk biochemical recurrence have had their prostate cancer detected using PSMA PET/CT imaging, which can help improve the precision of their treatment. Some biochemical recurrences are local disease recurrences, even if other features suggest that a patient is at high risk for distant disease. Another point the USPCC report makes is that there is value in providing a second local treatment to patients who have had prior prostatectomy, as it is potentially curative and may help avoid the need for long-term systemic treatment. The consensus recommendations also included a thoughtful discussion about treatment deescalation and interruption, both of which are valuable considerations in this space.

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Patients who received prior local treatment and whose PSA level is rising might have oligometastatic disease, but physicians will not know this until they image it, which is an area where PSMA PET/CT has been valuable. An interesting dilemma that we often confront is an uninformative PSMA PET/CT scan at a very low PSA value. You can assume that this is a local recurrence. I think that an increasingly attractive approach is to observe the patient until the disease becomes detectable, particularly in those who are not enthusiastic about receiving salvage radiation therapy. There are risks to both approaches, but local salvage radiation therapy may be reasonable when you are on the fence about whether someone is a good candidate to receive it. I would love to see a study done to address whether there is any disadvantage to waiting until you can see the disease.

As a urologist, I encounter patients with prostate cancer biochemical recurrence at pretty much every clinic. We struggle with how to manage a low-level PSA recurrence after a radical prostatectomy. Even though the American Urological Association/American Society for Radiation Oncology/Society of Urologic Oncology (AUA/ASTRO/SUO) consensus definition of PSA recurrence is a PSA level above 0.2 ng/mL, other data suggest that not all patients with a PSA level of 0.2 ng/mL have cancer recurrence.

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Some patients can have benign prostatic tissue left in situ after a prostatectomy, particularly those who have received surgeries with aggressive nerve and bladder neck sparing. Even though ultra-early salvage radiation therapy shows better outcomes in some patients whose PSA level is less than 0.5 ng/mL, my caution is to remember that some patients in these studies may not actually have a cancer recurrence. Sometimes, when the PSA level is less than 0.5 ng/mL—and even when it is less than 1 ng/mL—a PSMA PET/CT scan may be negative. The USPCC guidelines recommend salvage radiation therapy for these patients even when a PSMA PET/CT scan is negative. In general, this is good, but I find that some of my patients do not want to receive salvage radiation therapy if their PSMA PET/CT scan is negative.

In terms of the implications of using PSMA PET/CT scans in the setting of prostate cancer biochemical recurrence, I personally find that this setting is one of the most challenging to treat because of the absence of standardized guidelines incorporating PSMA PET/CT scans into how to treat patients. PSMA PET/CT scans have really changed this field dramatically in the last several years. The USPCC guidelines devote a considerable amount of space to discussing the biochemical recurrence setting because we must use a nuanced approach in our clinics when treating patients. I believe that there will be more individualized treatment in the setting of prostate cancer biochemical recurrence than ever before.