An article in the June issue of the Journal of Urology provides guidelines from a PSA Working Group defining criteria related to the calulation and application of PSA doubling times in monitoring biochemical recurrence and for stratification of patients in clinical trials.
The authors note that calculation of PSA doubling times (PSADT) can be problematic, not least because of assumptions made in determining the methodology for the calculations. They make several specific recommendations designed to standardize the calculation of PSADT.
They also note that the form of intial treatment (surgery, radiation, etc.) will affect the absolute PSA nadir (lowest PSA value) post-treatment, and that this will also impact the calulation of PSADT.
With these reservations, and accepting that the level of available evidence regarding the applicability of PSADT is only level II (as opposed to level I), the Working Group makes the following statements about the role of PSADT as a predictive factor in prostate cancer recurrence:
- A longer PSADT is associated with a longer time to metastasis, to prostate cancer-specific death, and to death from all causes. Furthermore, as the PSADT increases, so do the time to metastasis and the time to prostate cancer-specific death.
- Men with a PSADT of < 3 months are are at “extremely high risk for adverse clinical outcomes.”
- Men with a PSADT of > 15 months have “an extremely low risk of death from prostate cancer.”
- For men with a PSADT between 3 and 15 months, other clinical factors may have a larger role in determining risk.
With respect to the role of PSADT in stratification of patients for clinical trials, the Working Group makes the following recommendations:
- Patients who are hormone-naive, with PSA-only failure, and who are entered into clinical trials of novel cytotoxic agents should primarily be those with PSADT < 15 months (approx. 58 percent of this patient group). They should be stratified into three groups, as follows: PSADT < 3 months; PSADT between 3 and 9 months; and PSADT 9 to < 15 months.
- Patients who have a PSA nadir > 0.2 ng/mL and a PSADT < 3 months when treated with androgen deprivation therapy after radiotherapy or after surgery have a poor prognosis and should be considered for clinical trials, but no formal PSADT stratcification criteria are available.
- Patients who have androgen-independent prostate cancer (AIPC), no evident metastasis, but a rising PSA should be considered for clinical trials, and should be stratified by PSA kinetics and by PSA concentration, but no formal PSADT stratification criteria are proposed at this time.
- Patients who have AIPC with evident metastasis should be considered for clinical trials, and stratification by pre-therapy PSADT should be considered.
It is worth noting that some of the same issues are also addressed in a review by Ramirez et al., just published in European Urology. This latter article also addresses issues related to the use of PSADT as a prognostic factor in the expectant management of patients under active surveillance.