Prostate cancer is frequently treated using either radical prostatectomy or radiation therapy. While these treatments are often successful, a measurable rise in prostate-specific antigen (PSA) levels after therapy is a recognized concern. This elevation is known as biochemical recurrence (BCR), indicating that some cancer cells have survived the initial treatment and are once again producing PSA. BCR is a common event and does not immediately signify widespread metastatic disease, but it does signal the need for close monitoring and potential further intervention.
Defining Biochemical Recurrence
Biochemical recurrence is defined differently depending on the type of primary treatment received. After a radical prostatectomy, the entire prostate gland is removed, and the PSA level should ideally drop to an undetectable level within a few weeks. BCR is typically established when the PSA level reaches \(0.2\) nanograms per milliliter (ng/mL) or higher on two separate, consecutive blood tests.
Following radiation therapy, the definition is more complex because the prostate tissue remains and continues to produce some PSA, meaning the level rarely drops to zero. The widely accepted standard for BCR after radiation is called the Phoenix definition. This criterion is met when the PSA level rises by \(2.0\) ng/mL above the lowest value achieved after treatment, known as the nadir.
Regular monitoring of PSA levels is a standard part of follow-up care to detect BCR. For most patients, this involves PSA blood tests every three to six months for the first two years, followed by less frequent testing. The pattern of the PSA rise, rather than the absolute number alone, helps guide future decisions.
Determining the Location of Recurrence
Once biochemical recurrence is confirmed, the next step is determining the location of the recurrent disease. Localization is essential because the management plan depends on whether the cancer is local (in the prostate bed or pelvis) or distant (metastatic, such as in bone or lymph nodes).
Factors such as the initial Gleason score, the time it took for the PSA to begin rising, and the PSA doubling time (PSADT) are used to estimate the risk of metastasis. A short PSADT and a high initial Gleason score suggest a greater likelihood of aggressive, distant disease. Conversely, a slow rise in PSA over several years may suggest a more indolent, localized recurrence.
Traditional imaging methods, such as computed tomography (CT) and bone scans, have limitations, especially at low PSA values. These conventional scans often fail to detect small-volume recurrences; bone scans show negligible yield when the PSA level is below \(10\) ng/mL and the Gleason score is low.
Next-generation imaging, primarily using Prostate-Specific Membrane Antigen Positron Emission Tomography (PSMA PET), has become the preferred method for localizing recurrence. PSMA PET scans can detect disease at much lower PSA levels, offering a detection rate of approximately \(38\%\) even when the PSA is between \(0.2\) and \(0.5\) ng/mL. This increased sensitivity allows clinicians to visualize the exact location of the recurrence earlier, which can alter the treatment strategy.
Management and Treatment Strategies
Management of biochemical recurrence is highly individualized, depending on the recurrence location, the rate of PSA rise, and the patient’s overall health. For men with a slow PSA rise (e.g., doubling time greater than 15 months) and no evidence of metastatic disease on imaging, observation or active surveillance may be appropriate. This approach avoids the side effects of immediate treatment while closely monitoring the cancer’s progression.
If the recurrence is localized to the prostate bed after radical prostatectomy, the primary treatment is salvage radiation therapy (SRT). SRT targets the surgical bed and sometimes the nearby lymph nodes. It may be administered alone or combined with short-course Androgen Deprivation Therapy (ADT). The addition of ADT, typically for four to six months, is recommended for patients with higher-risk features, such as a pre-SRT PSA level greater than \(0.7\) ng/mL or a short PSADT.
For local recurrence following primary radiation therapy, other salvage options exist, including salvage cryotherapy (CRYO) and High-Intensity Focused Ultrasound (HIFU). These minimally invasive techniques use extreme cold or heat, respectively, to destroy the recurrent tissue within the prostate. While effective, these methods carry a higher risk of side effects, such as urinary incontinence, compared to primary treatment.
When imaging confirms a distant, metastatic recurrence, systemic treatment is required. Androgen Deprivation Therapy (ADT) remains the cornerstone of systemic treatment, lowering the body’s testosterone levels to starve hormone-sensitive cancer cells. The choice between continuous ADT and intermittent ADT (where therapy is paused when the PSA drops) depends on the extent of the disease and the patient’s tolerance. Continuous ADT is generally preferred for high-volume metastatic disease.
In contemporary practice, ADT is frequently combined with newer agents. These include Androgen Receptor Signaling Inhibitors (ARSI) like Abiraterone or Enzalutamide, or chemotherapy like Docetaxel. This combination therapy has demonstrated significant improvements in progression-free and overall survival for men with metastatic hormone-sensitive prostate cancer.