From the Guidelines
The threshold for biochemical recurrence in prostate cancer is generally defined as a PSA level of 0.2 ng/mL or higher after radical prostatectomy, with a second confirmatory measurement also showing a PSA ≥0.2 ng/mL, as recommended by the American Urological Association 1. For patients who underwent radiation therapy, biochemical recurrence is typically defined as a rise in PSA of 2 ng/mL or more above the nadir (lowest PSA value achieved after treatment) 2. These definitions are important because biochemical recurrence often precedes clinical recurrence by months or years, allowing for earlier intervention. The PSA threshold was established because values below 0.2 ng/mL after surgery may represent residual benign prostate tissue rather than recurrent cancer, while the definition for radiation therapy accounts for the fact that some prostate tissue remains after this treatment and continues to produce small amounts of PSA. Some studies suggest that a cut-point of 0.4 ng/ml followed by another increase may better predict the risk of metastatic relapse 3, but this is not universally accepted as a threshold for initiation of treatment. Regular PSA monitoring is essential for detecting recurrence early, with testing typically recommended every 3-6 months for the first few years after treatment, then annually thereafter if levels remain stable. Key factors to consider in the management of biochemical recurrence include the PSA doubling time, Gleason score, and presence of positive surgical margins, as these can influence the likelihood of local recurrence versus systemic disease 2. In cases of biochemical recurrence, further evaluation with imaging studies such as bone scans, CT/MRI, or radioimmunologic scintigraphy may be necessary to assess for distant metastases, and treatment options may include salvage radiation therapy, androgen deprivation therapy, or observation, depending on the individual patient's risk factors and disease characteristics 2.
From the Research
Biochemical Recurrence Threshold
The threshold for biochemical recurrence in prostate cancer is a topic of ongoing research, with various studies proposing different definitions and thresholds.
- A study published in 2022 4 proposed a serum PSA level of ≥ 0.8 ng/mL as a reasonable threshold for the definition of biochemical recurrence after salvage radiotherapy.
- Another study from 2018 5 found that a prostate-specific antigen (PSA) nadir <0.2 ng/mL is generally considered as tissue ablative and at low risk for recurrence.
- A 2014 study 6 suggested that the optimal definition of biochemical recurrence after radical prostatectomy depends on pathologic risk factors, and proposed different thresholds for different risk groups.
- A 2021 study 7 compared salvage radiation therapy and androgen-deprivation therapy for biochemical recurrence after radical prostatectomy, and found that salvage radiation therapy increased the castration-resistant prostate cancer-free survival rate compared with salvage androgen-deprivation therapy in high-risk patients.
- A 2020 randomized controlled trial 8 compared adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression, and found that adjuvant radiotherapy did not improve biochemical progression-free survival, but increased the risk of urinary morbidity.
Key Findings
- The threshold for biochemical recurrence may vary depending on the specific patient population and treatment context.
- A serum PSA level of ≥ 0.8 ng/mL may be a reasonable threshold for defining biochemical recurrence after salvage radiotherapy 4.
- A PSA nadir <0.2 ng/mL is generally considered as tissue ablative and at low risk for recurrence 5.
- The optimal definition of biochemical recurrence after radical prostatectomy may depend on pathologic risk factors 6.
- Salvage radiation therapy may be more effective than androgen-deprivation therapy in high-risk patients with biochemical recurrence after radical prostatectomy 7.
- Adjuvant radiotherapy may not improve biochemical progression-free survival, but may increase the risk of urinary morbidity 8.