The return of prostate cancer, known as recurrence, is a common concern for men who have undergone successful initial treatment. Despite the effectiveness of primary therapies like surgery or radiation, cancer cells can sometimes survive and multiply, leading to a disease setback. Recurrence is a frequently encountered challenge in oncology and is often manageable with further treatment. The approach to managing recurrence is a methodical process that begins with laboratory testing, moves to diagnostic imaging, and concludes with a targeted treatment plan.
Defining Recurrence Through Biochemical Failure
The first indication that prostate cancer may have returned is a measurable rise in the Prostate-Specific Antigen (PSA) level, known as biochemical failure. The specific PSA threshold used to define recurrence depends heavily on the initial treatment received.
Following a radical prostatectomy, which removes the entire prostate gland, the PSA level should drop to an undetectable level within a few weeks. Oncologists typically define biochemical recurrence in this setting as a PSA level of 0.2 nanograms per milliliter (ng/mL) or greater, confirmed by a second, similar value.
The definition differs for patients who initially received radiation therapy, as the prostate gland remains in the body and can still produce some PSA. For these patients, recurrence is often defined by the Phoenix criterion, which requires the PSA level to rise to its lowest point (nadir) plus 2.0 ng/mL. A persistently low PSA level after radiation is associated with a much lower chance of recurrence. A rising PSA signals the presence of cancer cells but does not reveal their location, which is the next phase of diagnosis.
Determining the Location of Recurrence
Once biochemical failure is confirmed through a rising PSA, the next step is determining where the cancer has returned, a distinction that fundamentally guides treatment choices. Recurrence may be localized, meaning the cancer is confined to the area where the prostate gland was situated or to surrounding pelvic lymph nodes. Alternatively, the recurrence may be metastatic, indicating the disease has spread to distant sites in the body, such as the bones or other organs.
To pinpoint the recurrence, physicians rely on advanced imaging technologies. Traditional imaging often included CT scans and bone scans, but these conventional methods are limited in their sensitivity, especially when PSA levels are low. The Prostate-Specific Membrane Antigen (PSMA) PET scan has significantly changed this diagnostic landscape, offering a superior method for detection.
This advanced PET scan uses a radioactive tracer that binds to the PSMA protein, which is highly expressed on the surface of most prostate cancer cells. PSMA PET imaging has a much higher detection rate than conventional methods, allowing for earlier and more accurate staging of the recurrent disease. For example, detection rates can range from 31% to 42% when the PSA is below 0.5 ng/mL and increase significantly as the PSA rises. Identifying the exact location of the cancer allows oncologists to select the most appropriate treatment.
Treatment Options for Localized Recurrence
When diagnostic imaging confirms the cancer recurrence is localized to the prostate bed or nearby lymph nodes, the goal of treatment often remains curative. These focused interventions are referred to as “salvage” therapies because they are administered after the initial treatment failed to eradicate the disease.
If the primary treatment was surgery (radical prostatectomy), the standard approach for localized recurrence is typically salvage radiation therapy directed at the surgical bed. Radiation is most effective when the recurrent PSA level is low, ideally 0.5 ng/mL or less, before treatment begins.
If the initial treatment was radiation therapy, the options for local control are more varied. These salvage modalities include cryotherapy, which uses extreme cold to destroy cancerous tissue, or High-Intensity Focused Ultrasound (HIFU), which uses concentrated sound waves to generate heat and ablate the tumor.
Re-irradiation using techniques like brachytherapy or Stereotactic Body Radiation Therapy (SBRT) may also be considered in highly selected patients. The decision between these options depends on factors like the patient’s overall health and the side effects of the original treatment, as local salvage therapies carry a higher risk of complications than primary treatments.
Managing Systemic and Metastatic Disease
If the recurrence is found to be metastatic, the treatment strategy shifts from a local curative approach to systemic disease control and quality of life maintenance. The foundation of systemic treatment is Androgen Deprivation Therapy (ADT), also known as hormone therapy. Prostate cancer growth is driven by male hormones called androgens, primarily testosterone. ADT works by lowering the level of these hormones or blocking their effect on cancer cells throughout the body.
Although highly effective initially, prostate cancer cells often adapt and become resistant to ADT over time, leading to the development of castration-resistant prostate cancer (CRPC). At this stage, physicians introduce a range of secondary systemic treatments.
These treatments can include newer, potent anti-androgen agents like abiraterone or enzalutamide, which further interfere with the cancer cell’s ability to utilize hormones. Chemotherapy, such as docetaxel, is another systemic option, particularly for patients with a high volume of metastatic disease. For cancer that has spread to the bones, targeted systemic radiation with agents like radium-223 can be used to treat the bone metastases and help manage pain. The combination and sequence of these systemic therapies are tailored to the individual patient, aiming to extend survival while minimizing side effects.