PSA and Testosterone Response During Radiation Therapy for Metastatic Prostate Cancer
Yes, it is expected for PSA levels to decrease during radiation therapy for metastatic prostate cancer, while testosterone levels may temporarily decrease but typically recover in most patients without androgen deprivation therapy.
PSA Response During Radiation Therapy
Expected PSA Patterns
- Following radiation therapy, PSA values should fall to a low level and then remain stable 1
- The PSA nadir (lowest point) is an important prognostic indicator of treatment success
- According to consensus guidelines, PSA values < 0.2 ng/mL are uncommon after external beam radiotherapy, which does not ablate all prostate tissue 1
Timing of PSA Response
- The Prostate Cancer Working Group recommends that early PSA changes (within 12 weeks) should not be used for clinical decision making 2
- A minimum exposure of 12 weeks is recommended before making definitive conclusions about treatment efficacy 2
- Various PSA patterns can occur after treatment initiation, including continued rise before decline, plateau, or delayed response 2
PSA Nadir as Prognostic Factor
- Following radiation therapy, biochemical recurrence is defined as a rise in PSA level of 2.0 ng/ml or more above the nadir 1
- A lower PSA nadir after radiation is associated with better long-term outcomes 3
- In patients receiving radiation with neoadjuvant ADT, a pre-radiation PSA nadir ≤0.3 ng/mL was associated with improved 10-year PSA relapse-free survival (74.3% vs 57.7%) 3
Testosterone Response During Radiation Therapy
Expected Testosterone Patterns
- Radiation therapy alone can cause a temporary decrease in testosterone levels 4
- At a median nadir time of 6 months, testosterone typically decreases to an average of 83% of baseline 4
- Approximately 7.5% of patients experience a decrease greater than 50% 4
Recovery of Testosterone
- 97% of patients with normal initial testosterone levels experience recovery to at least normal levels 4
- However, only 60% recover to their individual pretreatment testosterone level 4
- Patients with lower pre-treatment testosterone levels and those treated with larger radiation volumes tend to have a lower testosterone nadir 4
Clinical Significance
- The temporary testosterone decrease after radiation therapy has not been shown to impact subsequent tumor outcomes 4
- PSA doubling times in patients with relapse were not different between those with small or larger testosterone decreases 4
When Combined with Androgen Deprivation Therapy
- When radiation is combined with ADT (common in metastatic disease), testosterone suppression is more pronounced and sustained
- GnRH agonists like goserelin and leuprolide initially cause an increase in LH and FSH, leading to a transient increase in testosterone 5, 6
- Continuous administration then leads to sustained suppression of testosterone to castrate levels (0-50 ng/dL) within approximately 21 days 5
- This suppression can be maintained for the duration of therapy, which may be years 5
Monitoring Considerations
- PSA should not be the sole indicator of treatment response; the overall clinical picture including symptoms and imaging findings is more important 2
- Relying solely on early PSA changes may lead to premature discontinuation of potentially effective therapy 2
- For patients with metastatic disease receiving androgen suppression therapy, failure to achieve a PSA nadir < 4.0 ng/mL seven months after initiation is associated with shorter survival 1
Pitfalls to Avoid
- Do not make treatment decisions based on PSA changes within the first 12 weeks of therapy 2
- Be aware that "PSA bounces" can occur after radiation therapy, particularly with brachytherapy, and should not be mistaken for disease progression 1
- Remember that testosterone recovery is expected in most patients after radiation alone, but will remain suppressed if the patient is on concurrent ADT 5, 4