Active surveillance and intermediate-risk prostate cancer

A Reuters report on a forthcoming study in the Journal of Clinical Oncology has suggested that some men with intermediate-risk prostate cancer may be able to safely defer treatment in favor of monitoring the disease over time (through active surveillance) for a period of at least 4 years.

The Reuters report addresses a paper by Cooperberg et al. The paper is based on a series of 466 prostate cancer patients who have been managed with active surveillance at the University of California, San Francisco (UCSF).

According to Dr. Cooper, in the USA today, between 25 and 40 percent of all newly diagnosed prostate cancer patients have localized disease that falls into the intermediate-risk category. The wide range is a consequence of the fact that there are varying definitions of “intermediate risk.” However, it has been clear for a while that active surveillance held potential as a management starategy for at least some of these men.

Of the 466 patients managed at UCSF, 90 were categorized as having intermediate-risk disease and the other 376 had low-risk disease. After their initial diagnosis, they received PSA tests and digital rectal exams about every 3 months, ultrasound tests every 6 to 12 months, and follow-up biopsies every 1 to 2 years.

At a median follow-up of 4 years, Cooperberg et al. report that:

  • 55/90 intermediate-risk patients (61 percent) and 203/376 low-risk patients (54 percent) demonstrated no growth in their tumors.
  • The difference in results between the low- and intermediate-risk groups of patients was not statistically significant.
  • Compared to the patients with low-risk tumors, those with intermediate-risk tumors
    • Were older (mean, 64.9 vs. 62.3 years)
    • Had higher mean PSA values (10.9 vs. 5.1 ng/ml)
    • Had a greater degree of tumor involvement (mean, 20.4 vs. 15.3 percent positive biopsy cores)
  • 113/376 low-risk patients (30 percent) and 32/90 of the intermediate-risk patients (35 percent) had opted to initiate treatment after some time on active surveillance.
  • Of the patients who had opted to initiate treatment by surgery (which was the most common form of therapy)
    • None were found to have lymph node positive disease.
    • None had had a post-surgical rise in their PSA level within 3 years of surgery.

Dr. Peter Carroll, the chairman of the Department of Urology at UCSF, and a highly regarded authority on the management of early stage prostate cancer, has apparently “stressed that active surveillance would be an option only for carefully selected men with intermediate-risk cancer” in an e-mail to Reuters, stating that, “Such patients require careful evaluation and an assessment can be made only on the basis of a very well performed biopsy and by experienced clinicians.”

As one might expect, good candidates for active surveillance among patients with intermediate-risk, localized prostate cancer include men with a limited life expectancy (based not only on their chronological age but also on their overall health status and and specific comorbidities such as chronic cardiac conditions). However, according to Reuters, Dr. Carroll has also indicated that “the take-home message for men with prostate cancer is that they should not ‘rush’ into treatment, but seek opinions about all of their options, including active surveillance.”

The “New” Cancer InfoLink has long believed that active surveillance would be shown to be an appropriate management strategy for at least some men initially diagnosed with intermediate-risk prostate cancer, e.g.,

  • Men with a PSA < 10 ng/ml and Gleason 3 + 4 disease (as opposed to Gleason 4 + 3 disease) and a life expectancy of < 15 years.
  • Men with a PSA only slightly greater than 10 ng/ml and a Gleason score of 6 and a life expectancy of < 15 years.

Clearly we will need more data over time to see if we can clarify the opportunity that active surveillance offers for patients initially diagnosed with intermediate-risk disease, but this study does appear to significantly expand the pool of patients for whom active surveillance is a potentially reasonable management option.

6 Responses

  1. Mike,

    I believe that this may be pushing the envelope a bit. I am certain that some men will be OK for AS with 3 + 4 disease, but as in my case, 3 + 4 is commonly changed to higher grade disease and seldom down-graded post-prostatectomy, at least in my observations as a support group leader. As Dr. Carroll states “carefully selected” patients can be qualified, but they are much more difficult to define. That stated, it will be really interesting to see a “Klotz” type study when we have a larger cohort to analyze. I will bet there is a much higher incidence of progression to advanced stages or Gleason grade when all is said and done.

  2. That’s exactly why (at least at present) one wouldn’t want to recommend this for anyone with Gleason 7 disease and of your age at the time of diagnosis (although there are certainly some men of your age with intermediate-risk disease who are practicing active surveillance).

  3. More than the Gleason score or PSA should be considered. Most certainly the number of tissue samples extracted that showed evidence of developing prostate cancer. More than two or three such samples and with percentage development over 15% would be reason for considering other than active surveillance. Of course anyone with any level of PSA, Gleason score, or multiple tissue samples from biopsy with cancer presence can consider active surveillance, but in my opinon that would be playing with fire.

  4. I referenced my case because of the grading change after surgery and certainly would not suggest that AS for a 44-year-old man with intermediate-risk prostate cancer is reasonable. In fact I am not a proponent of active surveillance outside the much clearer guidelines agreed to by the NCCN and other organizations. But there are quite a few men doing it anyway, and doing it well. I can certainly understand AS for men with intermediate-risk prostate cancer who also have other high-risk health factors such as degenerative heart disease (just one example). My point is that it stands to reason that even the “carefully selected” are certainly going to have a higher incidence of disease progression, and it will become increasingly difficult to provide a demarcation point balancing QoL with risky judgement. I understand the research, but I am also glad I am not one of the test subjects.

  5. I was glad to see this paper from UCSF about their active surveillance program, especially about their intermediate-risk patients. It’s interesting that the intermediate-risk patients actually did better than the low-risk group in terms of no tumor growth at 4 years. I’m thinking the evidence is based on Dr. Shinohara’s data as he is well known for his imaging skills.

    UCSF is a highly respected prostate cancer treatment center, of course, so it’s likely these patients were carefully and skillfully characterized through biopsies, Gleason scoring, and DRE exams, as well through PSA and the other usual indicators. Tony’s point about actual widespread practice likely not achieving the same results is pertinent, but what UCSF is doing here is proving the principle. Based on the abstract and the information from Mike, it appears they have done that well.

    Dr. Klotz’s series also includes some intermediate-risk men. I remember seeing some reports about their men with Gleason 7 cancers (with significant co-morbidity and relative short life expectancy, as I recall it), but I don’t recall whether they broke that down by primary and secondary grade or whether they used the original Gleason scoring system or the current modified system. Does anyone know whether the Klotz series also gave leeway to men with a PSA above 10 or a stage beyond T2a?

    It’s a most positive development that active surveillance is being extended and that is is being done cautiously. It is also good that additional criteria are being considered, such as information about cores that Chuck mentioned (though up to 50% of a core is okay for some programs) and tumor vascularity, location, shape, etc., based on color Doppler ultrasound. Based on that report a few days ago, it may not be long before we are also able to consider genetic testing results.

  6. I for one would not recommend active surveillance to anyone unless they are conclusively early-stage prostate cancer patients with a Gleason 4 or less. Moderate-risk patients with a Gleason 7 have no way of knowing if their malignancy might suddenly become more aggressive. Until our science catches up with our diagnosis to predict which tumors might become more advanced, how can we recommend active surveillance for anyone but those with the lowest Gleason scores?

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