Many patients with no specific evidence of metastatic disease now receive primary androgen deprivation therapy (PADT) much earlier than was the case before the availability of the PSA test. This includes patients who get hormone therapy for a rising PSA after other forms of first-line therapy and patients who receive hormone therapy as their first-line treatment. Whether such early use of hormone therapy is the most appropriate form of management for these men is a much-disputed question. However, whether it is appropriate or not, there is a relative paucity of data on the biochemical progression-free survival (bPFS) of these patients over time.
Hori et al. have studied the outcomes of two contemporary series of patients treated with PADT in the UK. They also sought to identify predictive risk factors for biochemical recurrence of disease (i.e., a rising PSA) in these two series of patients.
The first series (Cohort A) included 155 patients and the researcher team was interested most specifically in the outcomes of PADT in the patients with bone scan-negative disease. A second series of 84 patients (Cohort B) — all without boney metastases, and all treated at a different institution — were used to validate the data from patients in Cohort A.
Data from this study showed the following:
- The median follow-up of all patients in Cohorts A and B was 70 months (just under 6 years).
- In Cohort A
- 109/155 patients (70 percent) were bone scan negative.
- Of these 109 patients, 49 (45 percent) had a rising PSA during the follow-up period and 26/109 (28 percent) had a rising PSA within 5 years of starting PADT.
- Independent factors predicting biochemical recurrence were a high PSA nadir and a shorter time to achievement of that PSA nadir.
- A PSA nadir of ≤ 0.1 ng/ml and a time to PSA nadir of > 24 months from initiation of PADT specifically identified men with a very good outcome.
- In Cohort B
- 33/84 patients (39 percent) had a rising PSA during the follow-up period and 29/84 patients had a rising PSA within 5 years of starting PADT.
- PSA nadir thresholds identified in Cohort A could be used to define a good prognostic group in Cohort B.
The authors conclude that non-metastatic patients treated with PADT can have durable responses to this form of therapy, and that the majority of such patients remain progression-free at 5 years. These results are hardly surprising.
What, perhaps, is more surprising is the apparent correlation between a longer time to PSA nadir and progression-free status. We have tended to assume that a rapid drop in the PSA level to near zero as a consequence of androgen deprivation was the ideal. We will need more data if we are to substantiate this idea that a slower decline to PSA nadir is necessarily a “good thing” by comparison with a rapid reduction.