Relapse-free survival of non-metastatic patients treated with primary androgen deprivation

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.

4 Responses

  1. Mike:

    I have seen that referenced elsewhere (I don’t recall where but could find it) in my research. It did not seem logical to me at the time.

    No explanation was given. My personal take is that maybe certain cancers that seem to react to stimulus more quickly may be able to change more rapidly.

    Who knows — but the guys at MSKCC don’t do ADT3 and have me on 6-month intervals for ADT monotherapy. They don’t really answer direct questions from patients about their protocols but I have inferred that they do not believe in over-stimulating the receptors. This is very different from what I have seen on many of the websites.

  2. Hmmm … Well I have never seen this suggested before, so if you could find your prior source, I would be interested.

    One argument that I have heard before, however, is that the frequency of hormone therapy should be closely tied to testosterone levels. I wonder if there is a connection.

  3. Pondering possibilities: Is it possible that the longer time to PSA nadir is more of a diagnostic result than a result of therapeutic intervention? Could these patients with a delayed PSA nadir have had a similar chance of bPFS with or without PADT?

  4. Dave: I am not sure what you are asking.

    These patients were all treated with PADT. If they had not been treated, their PSA level would not have fallen, so they couldn’t have had a PSA nadir level. I therefore don’t understand what you mean when you ask, “Could these patients with a delayed PSA nadir have had a similar chance of bPFS with or without PADT?”

    There is a certainly a whole other issue here, which is whether some of these men really benefited from hormone therapy at the time it was initially administered. All we know about that is that the jury is still out on when to initiate hormone therapy as a general rule. There are good arguments, for certain types of patients, in favor of early hormone therapy, and there are equally good arguments, for other types of patients, in favor of delaying hormone therapy for as long as possible. But this study was not designed to address that question. It was designed to address the time to bPFS in these two patient groups after PADT.

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