The natural history of low-risk prostate cancer

In a presentation given at the annual meeting of the American Urology Association earlier this year, researchers from Memorial Sloan-Kettering Cancer Center (MSKCC) provided some interesting data on the natural history of prostate cancer in patients initially diagnosed with low-risk disease.

The paper by Adamy et al. was intended to help to provide perspective on the potential risk and benefits of focal therapy compared to active surveillance in low-risk patients, but in doing so it also gives us some interesting data on the natural history of low-risk disease.

Between 1993 and 2009, MSKCC identified 258 men who met inclusion criteria for a study of active surveillance and who elected to participate in their study. To be included in the MSKCC protocol, patients were required to have both a diagnostic and a confirmatory biopsy and an endorectal coil MRI to exclude gross tumor. The inclusion criteria were a PSA level of ≤ 10 ng/ml, a Gleason score of ≤ 6, not more than three positive biopsy cores, and no more than 50 percent of any one biopsy core involved by tumor. (It would be interesting to know how many other patients treated at MSKCC during the same time period met the same criteria but decided not to participate in the study.)

Of these initial 258 patients, 160 went on to have a third prostate biopsy during follow-up. These 160 patients constitute the study cohort for the analysis presented by Adamy et al.

Biochemical progression-free survival (bPFS) of these patients was assessed at 2 and 5 years based on four criteria for disease progression:

  • The ASTRO definition: three consecutive rises in the patient’s PSA
  • The Phoenix definition: the nadir PSA level + 2 ng/ml
  • The Stuttgart definition: the nadir PSA level + 1.2 ng/ml
  • A positive biopsy (showing any amount cancer at all).

The results of this study showed the following:

  • The average (median) age of these 160 patients was 64 years.
  • Their average (median) PSA level was 4.3 ng/ml.
  • 88 percent of the patients were clinical stage T1c at diagnosis.
  • 96 percent of the patients had a Gleason score of 6 at their first biopsy.
  • After the initial biopsy, 119/160 patients (79 percent)  had a decrease in their PSA and achieved a median PSA nadir of 3.45 ng/ml.
  • Using the various criteria defined above
    • ASTRO definition:  bPFS at 2 and 5 years was 84 and 59 percent, respectively.
    • Phoenix definition: bPFS at 2 and 5 years was 70 and 44 percent, respectively.
    • Stuttgart definition: bPFS at 2 and 5 years was  59 and 32 percent, respectively.
    • Negative biopsy: the probability of having only negative biopsy results at 2 and 5 years was 65 and 34 percent respectively.

These results are plotted on a Kaplan-Meier curve that is also available on line.

What these data show us is that, in the very worst case scenario (based on the Stuttgart definition of biochemical failure), 32 percent of low-risk patients show no sign of biochemical progression at 5 years of follow-up. We aren’t talking about clinical progression here, just biochemical progression. If you choose to use the ASTRO definition, nearly 60 percent of these low-risk patients show no sign of biochemical progression at 5 years of follow-up.

For The “New” Prostate Cancer InfoLink, these data provide very compelling information — supportive of data reported from the Sunnybrook, Johns Hopkins, and University of California at San Francisco research groups — of the potential value of active surveillance as a mechanism to defer decisions about immediate treatment for men with low-risk prostate cancer. This is especially the case if you look at the data from this study in combination with the data from the Hölmberg et al. study also discussed on this site this morning.

Clearly it would be helpful to be able to see 10- and 15-year follow-up data on these patients that included specific data on overall survival, incidence of metastatic disease, and prostate cancer-specific mortality.

Adamy et al. used these data to make the point that many men with low-risk prostate cancer who might be considered to be “good” candidates for focal therapy of their prostate cancer would be likely to have an equally good oncologic outcome if they did absolutely nothing!

3 Responses

  1. I once read one definition of the word stupidity was doing the same thing over and over again and expecting a different result. This is the first thing I thought of when I read this post. I was suckered into reading it by the title thinking that maybe someone had come up with a new finding after researching this same senario for the what 100th time. What a fool I am. No wonder cancer treatment has gone nowhere in 40 years. This study didn’t even have different inclusion criteria in it. Didn’t the authors believe the results of all the other studies done on this that yielded the same conclusion. There is no definitive recommendation to people in this situation. For the 100th time. What a waste of time and money again.

  2. Dear Chris: I have never seen data like this analyzed in this way. You may not find it meaningful. Others may see this differently. You are, of course, entitled to your opinion … but then so are others.

  3. Looks like another good study supporting active surveillance to me!

    Chris, if you know of studies ~ 7-100, please let us know. I know of six different major sites (Sunnybrook, Johns Hopkins, MSKCC, The Erasmus Medical Center, UCSF, and Memorial Sloan Kettering), with several studies associated with several of them. However, that is far fewer than your rhetorical “100th time.”

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