HSPC: Navigating Risk and Management
Transcript: BCR: Practical tips
Andrew J. Armstrong, MD, ScM, FACP
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Well, it's great to be with you today. I'm displaying my disclosures and relationships, grant funding. Today I'm talking to you about biochemical recurrence, practical tips for the clinic. And biochemical recurrence, or PSA recurrence is a disease state where there's been a detection of a rising PSA following local therapy. After radical prostatectomy and after radiation, we use different definitions of, as I'll go into subsequently, but that PSA rise is often the only manifestation of the disease at that time, and that certainly creates worry and concern among both patients and providers that we're not done with the journey that we may need a, a second shot on goal for either curative treatment or palliative treatment or disease control. There's different periods of disease recurrence and risk. You know, certainly the first two to five years after local therapy is the highest risk, but we certainly see periods of late relapse in the the next 5 to 10 years. So vigilance for PSA monitoring is always recommended after local therapy. On this slide, we show the risks of biochemical recurrence. Now these vary widely with grade group and disease risks. For example, very low risk and low risk patients based on low Gleason score or grade group, low PSA, low stage have a very low risk of biochemical recurrence. And on the converse, very high risk disease, which has multiple patterns of high grade behavior or extra capsular extension, seminal vesical invasion, certainly node positive disease conveys a very high risk of biochemical recurrence. Overall, biochemical recurrence is about a third of patients, and again, surgery is not necessarily superior to radiation.
We do see different patterns and proportions depending on the risk of the patient with increasing risks of biochemical recurrence being associated with the risk of the patient and the disease state they're in. So intermediate high risk patients have a higher risk in that continuum. Biochemical recurrence is not felt to be a surrogate for prostate cancer mortality because we're often able to successfully salvage patients with subsequent radiation or hormones or pelvic radiation, and often predates metastatic disease or distant mortality by many, many years. A subsequent subset of these men will go on to develop further PSA recurrence and metastases, which conveys a higher risk of mortality. Now this slide goes over the different definitions. Recurrence after prostatectomy really indicates a subsequently rising PSA consecutive measures certainly above 0.1 and rising. Other definitions like the AUA have used 0.2. But we know that early salvage radiation saves lives and the higher cure rates are observed with salvage radiation at earlier PSA levels even below 0.2. And so consecutively rising PSAs after prostatectomy, the normal PSA after prostatectomy is essentially zero. And so any detectable rising PSA is abnormal. That doesn't necessarily mean that all men with rising PSAs require treatment. And this is where the individual informed decision making goes in. Now, after radiation, we use the Phoenix criteria, so that's nadir plus two. So a rise of two nanograms per mL over time, and that's how we define biochemical recurrence and those different prior local therapy settings. And that is often the trigger for consultation with a radiation oncologist, a medical oncologist, perhaps PSMA PET imaging to better risk stratify the patient. Now, there's different risk groups within the biochemical recurrence definition.
And on this slide we look at ASCO and AUA and NCCN guidelines. There's also EAU guidelines that risk stratify based on the PSA doubling timing fast, either less than a year or more conventionally nine months as was used in the EMBARK trial, patients with high grade disease, very high PSA are certainly at a higher risk of distant metastases. We also use the PSMA-PET scan as a risk stratifier, so patients that are PSMA-PET negative obviously do a lot better. And so the PSA kinetics, the PSA, the distance between the prostatectomy and the present time and the absolute value of PSA are some of the most important factors. And this is all assuming that these patients are non-metastatic by conventional imaging. So in this final slide as we get into the next part of our treatment discussion, the goals of care for patients with biochemical recurrence is to prevent and delay clinical progression, perhaps even to cure some patients and prevent metastatic disease and a eventual hormone-resistant disease. But that has to be balanced by the over treatments and the side effects of hormonal therapy, particularly potent hormonal therapies. There are some patients with low risk biochemical disease that can be safely observed for many years, or patients who can be treated with radiation alone without hormonal therapy, and we'll get into those discussions. Metastatic disease should be ruled out.
Conventional and PSMA-PET is often used to risk stratify patients and the recommendations for salvage therapy, systemic therapy, pelvic radiation, metastasis directed therapy, are very individualized based on those disease and risk considerations, shared decision making based on the patient in front of you and their comorbidities and preferences. Now we'll get into the multidisciplinary care discussion, where for BCR patients, we have medical oncologists, radiation, urologic oncologists, and primary care all working in tandem with nursing, palliative care, and now genetic counseling to really understand why that patient developed prostate cancer in the first place, what the transgenerational risk may be to siblings and children and how that may impact hormone-sensitive disease management. Thank you.
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MA-MM-19261, February 2026.