Prostate-specific antigen (PSA) is a protein produced by cells in the prostate gland. PSA levels are often monitored in men to screen for prostate cancer or to check for cancer recurrence after treatment. If PSA levels rise after definitive treatment like surgery or radiation, this may indicate the cancer has returned. However, PSA levels can fluctuate for various reasons, so doctors do not always recommend immediate further treatment when PSA rises. Instead, they may recommend repeating the PSA test over several months to determine if the rise is a sign of recurrent cancer or simply a temporary fluctuation.
When is PSA monitoring recommended after treatment?
PSA monitoring is commonly recommended for men who have been treated for prostate cancer with the goal of cure, such as with surgery, radiation therapy, or androgen deprivation therapy (ADT). PSA is expected to become undetectable after successful definitive treatment for prostate cancer. Any subsequent detectable or rising PSA may suggest cancer recurrence, so monitoring PSA levels regularly allows early detection of potential recurrence.
The National Comprehensive Cancer Network provides the following PSA monitoring recommendations after various treatments:
- After radical prostatectomy: Check PSA every 6 months for 5 years, then annually.
- After radiation therapy: Check PSA every 6 months for 2-5 years, then annually.
- After ADT for localized disease: Check PSA every 6 months while on ADT, then every 6 months for 2 years, then annually.
Closer PSA monitoring every 3-6 months is often done for high-risk cases during the first 5 years when recurrence risk is highest.
What PSA threshold indicates recurrence?
There is no definitive PSA threshold that universally indicates cancer recurrence. However, the following thresholds are often used:
- After radical prostatectomy: PSA level ≥0.2 ng/mL
- After radiation therapy: PSA rise by 2 ng/mL or more above the lowest PSA level (nadir)
With radical prostatectomy, PSA is expected to become undetectable, so any recurrent detectable PSA suggests recurrence. After radiation, some PSA may still be detectable, so a significant rise from the lowest level points to recurrence.
How many rising PSAs warrant further evaluation?
A single elevated PSA does not always require immediate further treatment. PSA levels can temporarily rise due to benign prostatic conditions like inflammation, infection, or trauma. To confirm a rising PSA trend that likely indicates recurrent cancer, most clinicians want to document PSA elevation on 2-3 consecutive tests performed at intervals of 1-3 months.
However, some factors may warrant more rapid evaluation and treatment after a single PSA elevation, such as:
- Very high or rapidly increasing PSA levels
- Short PSA doubling time (time for PSA to double)
- High-risk cancer features like Gleason score, stage, or PSA kinetics prior to treatment
Conversely, slower PSA doubling times (>12 months) may allow observation for more PSA rises before intervening.
What testing is done to confirm recurrence?
If PSA elevation indicates recurrence, the cancer must be localized for targeted treatment. Tests commonly performed include:
- Imaging – CT, MRI, and bone scans to detect metastases
- Biopsy – To confirm cancer and test for aggressiveness
- Genomic testing – Test cancer genes to guide treatment selection
Imaging and biopsy are key to localize the site(s) of recurrence before deciding additional treatments.
What are treatment options if PSA indicates recurrence?
If recurrent prostate cancer is localized, additional local treatments may be curative, including:
- Salvage radiation after prostatectomy recurrence
- Salvage prostatectomy after radiation recurrence
- Cryoablation (freezing) of the prostatic fossa
- High-intensity focused ultrasound (HIFU) ablation
- Brachytherapy implant radiation
Systemic treatments like hormone therapy or chemotherapy may be options if the cancer has spread more extensively. Observation alone may be appropriate for some patients, especially those with very slow PSA rise.
Case Examples of PSA Monitoring after Treatment
Here are some examples of PSA monitoring in hypothetical patients to illustrate how PSA trends inform recurrence management:
Case 1: Prostatectomy, PSA undetectable then rising
- 67 year old man, had prostatectomy in 2019
- Gleason 3+4=7 prostate cancer, staged T2c, N0
- PSA trended down after surgery, reached undetectable in 2020
- PSA rose to 0.1 ng/mL in 12/2021, repeat 0.15 ng/mL 3 months later
This PSA rise after being undetectable indicates likely cancer recurrence. Salvage radiation was done in early 2022.
Case 2: Radiation, PSA rising from nadir
- 72 year old man, external beam radiation in 2017
- Pre-radiation PSA 9 ng/mL, fell to nadir of 1.2 ng/mL in 2019
- PSA rose to 2.1 ng/mL in early 2020, 2.7 ng/mL 3 months later
Rising PSA from nadir by >2 ng/mL suggests recurrence. MRI and biopsy confirmed localized recurrence, treated with salvage prostatectomy.
Case 3: Prostatectomy, slow PSA rise
- 61 year old man, prostatectomy in 2018
- PSA undetectable until 12/2020, rose to 0.05 ng/mL
- PSA 0.06 ng/mL in 6/2021, 0.08 ng/mL in 12/2021
Despite PSA rises, the very slow doubling time of >12 months allowed observation until 2022 when PSA velocity increased.
Table: Summary PSA Monitoring Recommendations after Prostate Cancer Treatment
| Treatment | PSA Monitoring Frequency | PSA Threshold for Recurrence |
|---|---|---|
| Radical Prostatectomy | Every 6 months for 5 years, then annually | PSA ≥0.2 ng/mL |
| Radiation Therapy | Every 6 months for 2-5 years, then annually | PSA rise by ≥2 ng/mL from nadir |
| ADT for Localized Disease | Every 6 months while on ADT, then every 6 months for 2 years, then annually | Any recurrent detectable PSA |
Conclusion
PSA monitoring is important after definitive treatment for prostate cancer to enable early detection of potential cancer recurrence. Consecutive PSA rises above threshold levels generally warrant further evaluation and consideration of additional treatment. However, benign PSA fluctuations can occur, so instant treatment is not always needed with a single elevated PSA. The PSA trends over time guide appropriate management, with regular PSA testing for at least 5 years after initial treatment.