And now, at 29 years of follow-up …


In this week’s issue of the New England Journal of Medicine, Bill-Axelson et al. offer data from a sixth update to the outcomes from the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial of radical prostatectomy vs. watchful waiting in “early”, but clinically diagnosed prostate cancer (which we would remind readers is a very different “animal” than the type of “early” prostate cancer customarily diagnosed today — primarily on the basis of PSA testing).

The data in this report represent the outcomes of 29 years of follow-up among 695 Scandinavian patients with clinically localized prostate cancer who were randomly assigned to management with either a radical prostatectomy or watchful waiting (i.e., not active surveillance) between October 1989 and February 1999 and followed through 2017.

Here are the core results as of December 31, 2017:

  • The average (median) follow-up was 23 years.
  • Among the men randomized to radical prostatectomy,
    • 261/347 had died of all causes.
    • 71/347 had died of prostate cancer.
  • Compared to the men who had pathologically organ-confined disease at radical prostatectomy, extracapsular extension of the cancer increased risk for prostate cancer-specific death by about five times.
  • Among the men randomized to watchful waiting
    • 292/348 had died of all causes.
    • 110/348 had died of prostate cancer.
  • The absolute difference in risk of dying from prostate cancer was + 11.7 percent in the watchful waiting group over the surgical group.
  • The relative difference in risk of dying from prostate cancer was + 55 percent in the watchful waiting group over the surgical group.
  • The number of patients who needed to be treated to delay one death from any cause was 8.4.
  • Radical prostatectomy as compared to watchful waiting was associated with an average (mean) 2.9-year increase in overall survival.

As far as we know, this is now, by a very considerable time period, the longest set of patients ever followed in any randomized prostate cancer trial. We have previously congratulated the study group (and their patients) for their determination to follow this group of patients over what is now a near-to-30-year time frame

The authors conclude that:

Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer.

The truly critical aspect of this trial is what it tells us about the difference between high-risk and lower-risk forms of prostate cancer.

By far the majority of the patients in this trial would have to have met criteria for, intermediate-, high-risk, or very high-risk prostate cancer by today’s standards because they were all diagnosed clinically. In other words, they displayed clinical signs and/or symptoms that led their physicians to suspect prostate cancer and advise a biopsy. Neither the PSA test nor any other blood test was being used for assessment of risk of localized prostate cancer in Scandinavian countries during the period that this trial was enrolling patients.

Despite this fact:

  • 142/695 men (20.4 percent) were still living at a median of 23 years of follow-up, including
    • 86/347 men (24.8 percent) who had been given a radical prostatectomy
    • 56/348 men (16.1 percent) initially managed on watchful waiting

What we do not, obviously, know is how much earlier the men in this trial might have been diagnosed if modern diagnostic methods had been available and used. In other words, we don’t know the “lead time” between when prostate cancer might have been diagnosed using modern methods and the methods actually used. It is not unreasonable to think that this could have been as high as 10 years for a significant number of these patients.

If we make the assumption that it was (perhaps more reasonably) an average of 7 years, this would imply that something like 20 percent or more of the men followed on watchful waiting in this trial might have lived with their cancer for 30+ years, and it shows us very clearly what the long-term value of active surveillance may turn out to be over a similar time frame.

One Response

  1. The results of this study were published at 8, 10, 15 and 23 years of follow-up.

    Regarding extracapsular extension, it may be interesting to know that in this study seminal vesicle involvement was classified as extracapsular growth. They never mentioned lymph node involvement, so maybe it was also classified as extracapsular growth.

    48 (68%) and 68 (62%) deaths from prostate cancer in the surgery group and the watchful waiting group respectively occurred in the first 10 years of follow-up.

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