More from the GU Oncology symposium — Part 1


We aren’t even going to try to report on all of the presentations and abstracts for this meeting. For people who want to look through this material for themselves, the majority of the prostate cancer abstracts for papers presented yesterday and today are already available on line on the ASCO web site. What we want to do is call out some very specific papers that demonstrated particularly interesting results.

One of these papers, by Lodde et al., reported preliminary results of a Phase II trial designed to investigate the efficacy and safety of 5α-reductase therapy as first-line treatment for men diagnosed with low risk prostate cancer.

The trial enrolled 113 patients. All patients had been diagnosed with low risk prostate cancer and were assigned to receive either dutasteride (n = 59) or finasteride (n= 54). The patients all received a first follow-up biopsy at 6-12 months after starting on drug therapy, with the following results:

  • 31/113 patients (27.4 percent) had Gleason 6 disease
  • 65/113 patients (57.5 percent) had a negative biopsy
  • 17/113 patients (14.2 percent) had a Gleason score ≥ 7

Data on a second follow-up biopsy, after an additional 6-12 months, has been carried out on just 26 patients to date. Of these 26 patients, 20 were biopsy-negative and 6 were biopsy-positive at the first follow-up biopsy. The results of this second follow-up biopsy were:

  • 7/26 patients (26.9 percent) had Gleason 6 disease (3 +/+, 4 –/+)
  • 18/26 patients (69.2 percent) had a negative biopsy (3 +/–, 15 –/–)
  • 1/26 patients (3.8 percent) had a Gleason score ≥ 7 (1 –/+)

Finally, of the original 113 patients enrolled in the trial, 13 have received treatment to date, with a median time to treatment of 12 months from the start of therapy.

The authors make the following points in their conclusions:

  • First-line treatment with a 5α-reductase in low risk patients appears to offer potential benefits based on the available data to date.
  • There was a 60 percent negative biopsy rate at initial follow-up, which is considerably higher than the negative biopsy rates observed in active surveillance series reported to date.
  • The study has had a very low drop-out rate, with only 3 patients withdrawing from the trial for any reason other than a biopsy-based upgrading of their cancer

The second such paper was a study by Donnelly et al., who reported the results of a randomized clinical trial of cryotherapy versus external beam radiotherapy in patients with localized disease. Yes. That’s right. The patients agreed to be treated at random either by cryotherapy or by EBRT!

Now we should be just as clear as Dr. Donnelly was in his presentation. This study was fraught with problems. It was a single institution study; they had originally hoped to enroll 480 patients, but had to settle for 244; the trial was a so-called “non-inferiority” study, and such trials are always problematic; the amount of radiation that patients received had to be increased during the course of the trial; etc. But, despite all these problems, the trial does offer some reasonable guidance as to the relative value of EBRT and cryotherapy as first line therapy.

Here are the key points:

  • For the first 3 years after treatment, outcomes appeared to favor EBRT compared to crotherapy, but …
  • After 5 years of follow-up, outcomes appeared to favor cryotherapy over EBRT
  • There was no difference in overall or disease-specific survival between the two groups of patients
  • There was no difference in quality of life between the two groups of patients
  • About 29 percent of patients were capable of intercourse at last follow-up (although the cryotherapy patients appeared to need more “aids”)

The results of this trial have to be interpreted with great caution for statistical and other reasons, but it is fair to say that this study is important — if for no other reason than proof of the idea that patients will accept randomization to one or other of two very different types of primary treatment!

A second important study presented at the meeting came from Johns Hopkins with the presentation of data on 25-year follow-up of patients with a rising PSA who received no other form of adjuvant or salvage therapy until they showed clear evidence of metastatic disease.

Antonarakis et al. performed a retrospective analysis of data from 774 men treated with a radical prostatectomy between April 1982 and July 2008 who developed PSA recurrence (as indicated by a PSA ≥ 0.2 ng/ml). The average follow-up was 8.5 years with a range of 1 to 25 years. The results of this analysis showed that:

  • The mean time to PSA recurrence was 4.2 years (range from 1 to 19 years) for all 774 men.
  • 295/774 men (38 percent) developed metastases.
  • The mean time to PSA recurrence for the men who went on to develop metastases was 3.1 years (range 0 to 15 years).
  • 433/774 men had data on PSA doubling times.
  • Time to PSA progression, Gleason score, and PSA doubling time were all highly predictive of development of metastases
  • Metastasis-free survival, broken down by PSA doubling time was as follows:
    • Doubling time < 3.0 months = metastasis-free survival of 3 years
    • Doubling time 3.0-8.9 months = metastasis-free survival of 7 years
    • Doubling time 9.0-14.9 months = metastasis-free survival of 16 years
    • Doubling time of ≥ 15 months = metastasis-free survival of 21 years

Staff at Johns Hopkins have long argued that the benefits of early hormonal therapy for many men with a rising PSA after first-line therapy are very questionable because the effects of hormonal therapy on quality of life can be so deleterious. These data would appear to support their argument — at least for those men with a PSA doubling time of ≥ 9.0 months and aged perhaps 60 years and older at the time of initial therapy.

2 Responses

  1. “patients will accept randomization to one or other of two very different types of primary treatment!”

    I don’t know whether to be encouraged or appalled.

  2. I think that one is easy. You should be encouraged. Just because you wouldn’t have made such a decision personally doesn’t mean that others aren’t prepared to. :O)

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