New European guidelines on clinically localized prostate cancer


The European Association of Urology (EAU) has issued updated guidelines on the screening, diagnosis, and treatment of clinically localized prostate cancer. The document also includes guidance about treatment of progressive and castration-resistant prostate cancer.

All 164 pages of the fully revised guidelines are already available on the EAU web site, and a summary article about the new guidelines has just been published in European Urology by Heidenreich et al.

In their summary article, Heidenreich et al. state that:

  • Evidence is not currently sufficient to justify widespread population-based screening for prostate cancer using the PSA test.
  • A systematic prostate biopsy under ultrasound guidance and local anesthesia is the appropriate method for the diagnosis of localized prostate cancer.
  • Active surveillance is a viable method of management for men with low-risk prostate cancer and a long life expectancy.
  • Watchful waiting  is a viable treatment alternative to androgen deprivation therapy (ADT) with equivalent oncologic efficacy for men with locally advanced prostate cancer and for whom local therapy is not mandatory.
  • Active treatment is mostly recommended for patients with localized prostate cancer and a long life expectancy.
    • Radical prostatectomy has been shown to be superior to watchful waiting in a prospective, randomized trial.
    • Nerve-sparing radical prostatectomy is the active treatment of choice in organ-confined disease.
    • Neoadjuvant androgen deprivation in combination with radical prostatectomy has shown no significant benefit.
    • Radiation therapy should be performed with at least 74 Gy and 78 Gy in low-risk and intermediate/high-risk patin ets with prostate cancer, respectively.
    • For patients with locally advanced prostate cancer, adjuvant ADT for 3 years has superior disease-specific and overall survival rates and represents the treatment of choice.
  • Patient follow-up after local therapy should be based on PSA data; a disease-specific history with imaging is indicated only if and when symptoms occur.

The new guideline classifies cryotherapy, high-intensity focused ultrasound (HIFU), and focal therapies under the heading “Experimental” as treatments for localized prostate cancer, which isn’t going to make some people happy. (Don’t shoot the messenger!)

6 Responses

  1. I’d say this:

    Active surveillance is a viable method of management for men with low-risk prostate cancer and a long life expectancy

    is one of the greatest changes I have seen in the treatment options since I was diagnosed in 1996.

    I never thought the day would come that there would be a formal recognition of what was so obvious to me personally.

  2. Pardon my ignorance. Seems to me that there is at least a paradox between:

    “Nerve-sparing radical prostatectomy is the active treatment of choice in organ-confined disease,”

    and

    “For patients with locally advanced prostate cancer, adjuvant ADT for 3 years has superior disease-specific and overall survival rates and represents the treatment of choice.”

    (Although I’m not sure what locally advanced means.)

  3. INTERESTING VIEW OF EUROPEAN PERSPECTIVE

    Once again, thanks so much for calling this [set of guidelines] to our attention. I’ve now read selected brief sections as well as the entire Section 12, Hormonal Therapy, pages 83 through 99. I believe this guideline will help move prostate cancer technology forward in Europe, but I noted a number of what I would term significant flaws in the area on hormonal therapy. That’s a bold statement for a survivor with no enrolled medical education, just 11 years in the school of hard knocks, but I feel I can support it. Here are some comments following excerpts of summary findings from the study, from Sitemaster’s article above.

    “Evidence is not currently sufficient to justify widespread population-based screening for prostate cancer using the PSA test.”

    My comment: The issue facing not only national health systems but individuals is that there is substantial uncertainty: a lot of research-based clues indicating that screening is beneficial for health and reduced mortality; a lot of evidence that widespread screening leads to substantial over-treatment with attendant side effect/complication burden; and there is no fully acceptable, long-term evidence that widespread screening works well.

    To me the European guideline puts the issue in terms that we are used to: widespread screening versus no alternative stated. I hope we well see a future edition of this European guideline move toward screening for as many men as possible who have been educated in the wisdom of active surveillance for low-risk prostate cancer. For such men, hopefully with access to sound information about when biopsies are appropriate, nearly universal PSA testing/DRE exams makes sense to me.

    “Active surveillance is a viable method of management for men with low-risk prostate cancer and a long life expectancy.”

    My comment: I’m glad to see this recognition that AS is acceptable for younger men, a position that matches the consensus statement of the conference of experts on active surveillance in 2007.

    “Watchful waiting is a viable treatment alternative to androgen deprivation therapy (ADT) with equivalent oncologic efficacy for men with locally advanced prostate cancer and for whom local therapy is not mandatory.”

    My comment: To me this is one of the huge flaws in the recommendations. The statement is in line with the guidelines view that ADT is probably best after symptoms of advanced disease have appeared. The medical oncologists whom I see as experts in hormonal therapy are convinced, based on published research as well as observing high numbers of patients in their practices that specialize in PC, that ADT is most effective and very effective when commenced early after primary therapy has failed rather than late. I saw repeated instances where the guideline seems to have taken an almost blind look at study results without thinking what those dated (arguably at times obsolete) results mean in the context of current knowledge. I sensed that rote analysis was triumphing over expert insight.

    “Radical prostatectomy has been shown to be superior to watchful waiting in a prospective, randomized trial.”

    My comment. It’s very important to distinguish watchful waiting (WW), the approach in the research behind the statement, from active surveillance (AS); the research does not apply to AS.

    Moreover, it’s doubtful to me that doctors would consider many of the men in the WW arm of this research eligible for that approach. The research has been published with both 10 year follow-up (Holmberg) and 12 year (Bill-Axelson). If you look at the patient makeup of the WW arm of the study, you can see that the Gleason Scores in the WW arm tended toward the more aggressive range than in the RP arm. Approximately equal numbers in both arms had Gleason scores from 2 to 6: 212 (WW), and 211 (RP). However, for Gleason scores of 7 to 8, 103 in the WW but only 91 in the RP arm fell in that range. Additionally, 33 Gleason scores (9.5% of the total number of patients) were unknown in the WW arm, and 46 (13.3%) were unknown in the RP arm, introducing substantial uncertainty. Tumor staging was somewhat less extensive in the WW arm than the RP arm, but aggressiveness (Gleason score) trumps extent (stage) as most of us would see it.

    What that suggests is that the WW arm had a group that could well have had more aggressive cancer at the outset. It also shows that 103 men in the WW group had Gleason 7 to 10 cancer that was likely to progress to death if not countered or short-circuited by death from non-PC causes. In other words, the group studied was far from an ideal group for a balanced comparison of WW to RP. All that said, WW doesn’t make much sense to me except for men with limited life expectancy due to age, other serious health conditions, or both.

    Gleason scoring (see page 11): This was not raised in Sitemaster’s article, but I noticed a minor difference with modern practice, or maybe just American pathology practice. The guideline states the following: ” … The Gleason score ranges between 2 and 10, with 2 being the least aggressive and
    10 the most aggressive. In needle biopsy, it is recommended that the worst grade always should be included, even if it is present in < 5% of biopsy material …”

    My comment: That's how I understood Gleason scoring until touring the Bostwick Laboratory in Richmond, VA, a few months ago. A lead pathologist in the lab explained that, as of a consensus by pathologists reached a few years ago, the second grade is not always the second most common. If there is a less common grade that has a higher Gleason grade, that less common grade will be the second score. Apparently the tertiary 4 or 5 is no longer being used, at least in the US. If anyone can clarify or confirm this, I would appreciate it.

    Hormonal therapy (also not mentioned in Sitemaster’s commentary): I read this section thoroughly and thoughtfully from my perspective as an 11-year survivor with hormonal blockade therapy (mostly triple) as my sole therapy. A lot of the guideline seemed sound to me, and I think it will help improve the use of hormonal therapy. For instance, the guideline endorses the use of intermittent hormonal therapy, stating that it should no longer be regarded as investigational, for patients with an adequate response to hormonal blockade therapy.

    However, I noticed a number of areas that looked misleading to me. For instance, speaking frankly, I'm glad I did not write the section on cost effectiveness of hormonal blockade; I would have been ashamed The research cited was obsolete, and the analysis was not sharp.

    I hope to put together some more detailed comment on the hormonal therapy section of the guideline.

  4. Dear Dave:

    “Locally advanced” prostate cancer in this context is usually referring to patients with clinical stage T3/T4 prostate cancer and (potentially) node-positive (N+) disease. Standard therapy for such patients is considered to be radiation therapy together with ADT.

    By contrast, “organ-confined” prostate cancer is cancer that is confined to the prostate itself (clinical stage T2 disease) or at worst to the prostate and the seminal vesicles (clinical stage T3 disease) with no suspicion of the possibility of node-positive disease.

    There is no paradox here. It is usually possible to differentiate between such patients with some degree of accuracy pre-treatment. There are, however, those who believe that surgery followed by adjuvant radiation and adjuvant ADT may be the most curative form of treatment for some men with locally advanced disease (as defined above).

  5. Dear Jim:

    I think you need to appreciate that the European guideline only says that watchful waiting is “viable” as an alternative to ADT in patients “for whom localized therapy is not mandatory.” This means only that it is an acceptable method of managing selected patients, who are probably the ones you go on to describe — older patients or those with short life expectancies due to comorbid conditions who could reasonably by expected to die from causes other than prostate cancer long before their cancer became clinically significant or who might need deferred hormone therapy after symptoms appeared but only for a brief period of time.

    Also, I would point out that the guideline is very careful to distinguish between active surveillance and watchful waiting. They are not the same thing at all, and their risks and benefits are very different for carefully selected groups of patients.

    Third, it is my understanding (directly from Dr. Bostwick at the AUA meeting this year) that the use of tertiary Gleason grades is very much alive and well worldwide. I think there may have been a communication glitch somewhere in your conversation with the pathologist at Bostwick Laboratories. There are some very detailed subtleties between exactly what is a classified as a secondary Gleason grade and what may need to be identified as a tertiary grade in the biopsy or surgical pathology specimens from an individual patient.

  6. Sitemaster, thanks for your post of 11/17 7:57 AM responding to my earlier post.

    I did not get a chance to ask about tertiary Gleasons when we took our tour, and I’ve sensed that what I heard was not the complete story. I’m glad to learn that Dr. Bostwick said they are used. There should be a source document somewhere, some kind of pathologist’s guideline. It would be good to have that to be able to better interpret Gleasons from current studies versus older studies.

    Yes, I too saw careful and rather emphatic distinction between WW and AS in the guidelines. That may serve to diminish use of the term “watchful waiting” for what is “active surveillance,” which would be a good thing.

    Thanks for clarifying the subtle distinction about use of WW as an alternative to ADT. That one got by me.

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